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Differential methylation patterns in paternally imprinted gene promoter regions in sperm from hepatitis B virus infected individuals

Hepatitis B virus (HBV) infection poses a substantial threat to human health, impacting not only infected individuals but also potentially exerting adverse effects on the health of their offspring. The underly...

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Circulating microRNAs as potential biomarkers of physical activity in geriatric patients with HCV

Circulating microRNAs have been implicated in a diverse array of biological and pathological phenomena. Their potential utility as noninvasive biomarkers for screening and diagnosing various diseases has been ...

Correction: The primary cilium dampens proliferative signaling and represses a G2/M transcriptional network in quiescent myoblasts

The original article was published in BMC Molecular and Cell Biology 2020 21 :25

Upregulated dual oxidase 1-induced oxidative stress and caspase-1-dependent pyroptosis reflect the etiologies of heart failure

Oxidative stress is implicated in the pathogenesis of heart failure. Dual oxidase 1 (DUOX1) might be important in heart failure development through its mediating role in oxidative stress. This study was design...

Comparing chemical transfection, electroporation, and lentiviral vector transduction to achieve optimal transfection conditions in the Vero cell line

Transfection is an important analytical method for studying gene expression in the cellular environment. There are some barriers to efficient DNA transfection in host cells, including circumventing the plasma ...

High-fat diet enhances cell proliferation and compromises intestinal permeability in a translational canine intestinal organoid model

Emerging evidence underscores the responsiveness of the mammalian intestine to dietary cues, notably through the involvement of LGR5 + intestinal stem cells in orchestrating responses to diet-driven signals. H...

mTOR signaling pathway regulation HIF-1 α effects on LPS induced intestinal mucosal epithelial model damage

Sepsis-induced small-intestinal injury is associated with increased morbidity and mortality. Our previous study and other papers have shown that HIF-1α has a protective effect on intestinal mucosal injury in s...

Long non-coding RNA SOX2OT in tamoxifen-resistant breast cancer

Hormone receptor (HR)-positive breast cancer can become aggressive after developing hormone-treatment resistance. This study elucidated the role of long non-coding RNA (lncRNA) SOX2OT in tamoxifen-resistant (T...

Mice lacking DIO3 exhibit sex-specific alterations in circadian patterns of corticosterone and gene expression in metabolic tissues

Disruption of circadian rhythms is associated with neurological, endocrine and metabolic pathologies. We have recently shown that mice lacking functional type 3 deiodinase (DIO3), the enzyme that clears thyroi...

Optimization of seeding density of OP9 cells to improve hematopoietic differentiation efficiency

OP9 mouse stromal cell line has been widely used to induce differentiation of human embryonic stem cells (hESCs) into hematopoietic stem/progenitor cells (HSPCs). However, the whole co-culture procedure usuall...

Development of an in vitro human alveolar epithelial air-liquid interface model using a small molecule inhibitor cocktail

The alveolar epithelium is exposed to numerous stimuli, such as chemicals, viruses, and bacteria that cause a variety of pulmonary diseases through inhalation. Alveolar epithelial cells (AECs) cultured in vitr...

Mechanical stretch leads to increased caveolin-1 content and mineralization potential in extracellular vesicles from vascular smooth muscle cells

Hypertension-induced mechanical stress on vascular smooth muscle cells (VSMCs) is a known risk factor for vascular remodeling, including vascular calcification. Caveolin-1 (Cav-1), an integral structural compo...

Melatonin reduces lung injury in type 1 diabetic mice by the modulation of autophagy

In recent years, the role of autophagy has been highlighted in the pathogenesis of diabetes and inflammatory lung diseases. In this study, using a diabetic model of mice, we investigated the expression of auto...

TonEBP/NFAT5 expression is associated with cisplatin resistance and migration in macrophage-induced A549 cells

Macrophages promote angiogenesis, metastasis, and drug resistance in several cancers. Similarly, TonEBP/NFAT5 induces metastasis in renal carcinoma and colon cancer cells. However, the role of this transcripti...

Optimizing combination therapy in prostate cancer: mechanistic insights into the synergistic effects of Paclitaxel and Sulforaphane-induced apoptosis

Combination therapies in cancer treatment have demonstrated synergistic or additive outcomes while also reducing the development of drug resistance compared to monotherapy. This study explores the potential of...

CTC together with Shh and Nrf2 are prospective diagnostic markers for HNSCC

The lack of appropriate prognostic biomarkers remains a significant obstacle in the early detection of Head and Neck Squamous Cell Carcinoma (HNSCC), a cancer type with a high mortality rate. Despite considera...

Prioritization of Trypanosoma brucei editosome protein interactions interfaces at residue resolution through proteome-scale network analysis

Trypanosoma brucei is the causative agent for trypanosomiasis in humans and livestock, which presents a growing challenge due to drug resistance. While identifying novel drug targets is vital, the process is dela...

Sumoylation of SAP130 regulates its interaction with FAF1 as well as its protein stability and transcriptional repressor function

Fas-associated factor 1 (FAF1) is a multidomain protein that interacts with diverse partners to affect numerous cellular processes. Previously, we discovered two Small Ubiquitin-like Modifier (SUMO)-interactin...

Loss of Dec1 inhibits alcohol-induced hepatic lipid accumulation and circadian rhythm disorder

Chronic alcohol exposure increases liver damage such as lipid accumulation and hepatitis, resulting in hepatic cirrhosis. Chronic alcohol intake is known to disturb circadian rhythms in humans and animals. DEC...

Association between plasma L-carnitine levels and mitochondrial DNA copy number

Mitochondria are key cytoplasmic organelles in eukaryotic cells that generate adenosine triphosphate (ATP) through the electron transport chain and oxidative phosphorylation. Mitochondrial DNA (mtDNA) copy num...

Effect of Emi1 gene silencing on the proliferation and invasion of human breast cancer cells

Breast cancer is the most common malignant tumour in women. The early silk-splitting inhibitor protein 1 Emi1 is responsible for mediating ubiquitin protein degradation. The present study investigated the effe...

TNFα induces Caspase-3 activity in hematopoietic progenitor cells CD34+, CD33+, and CD41 + of myelodysplastic syndromes

Cytopenia is the primary feature of Myelodysplastic Syndrome, even in the presence of hypercellular bone marrow. TNFα is recognized as both a proinflammatory, and proapoptotic cytokine with a well established ...

From network analysis to experimental validation: identification of regulators of non-muscle myosin II contractility using the folded-gastrulation signaling pathway

The morphogenetic process of apical constriction, which relies on non-muscle myosin II (NMII) generated constriction of apical domains of epithelial cells, is key to the development of complex cellular pattern...

Simple, low-cost, and well-performing method, the outgrowth technique, for the isolation of cells from nasal polyps

Epithelial cells are an important part of the pathomechanism in chronic rhinosinusitis with nasal polyps. It is therefore essential to establish a robust method for the isolation and culture of epithelial cell...

Comprehensive brain tissue metabolomics and biological network technology to decipher the mechanism of hydrogen-rich water on Radiation-induced cognitive impairment in rats

Hydrogen-rich water (HRW) has been shown to prevent cognitive impairment caused by ionizing radiation. This study aimed to investigate the pharmacological effects and mechanisms of HRW on ionizing radiation by...

Mineral elements and adiposity-related consequences in adolescents with intellectual disabilities

Patients with intellectual disabilities are shown to have a limited capacity for cooperation, communication,and other biological consequences, which significantly require a specialized interest in healthcare p...

Glycyrrhizin inhibits LPS-induced inflammatory responses in goat ruminal epithelial cells in vitro

Inflammation plays a crucial role in the progression of Subacute Ruminal Acidosis (SARA). The experiment was designed to investigate anti-inflammatory effects of glycyrrhizin on goats ruminal epithelial cells ...

D-galactose-induced mitochondrial oxidative damage and apoptosis in the cochlear stria vascularis of mice

Age-related hearing loss, known as presbycusis, is the result of auditory system degeneration. Numerous studies have suggested that reactive oxygen species (ROS) and mitochondrial oxidative damage play importa...

Keratin 19 binds and regulates cytoplasmic HNRNPK mRNA targets in triple-negative breast cancer

Heterogeneous nuclear ribonucleoprotein K (HNRNPK) regulates pre-mRNA processing and long non-coding RNA localization in the nucleus. It was previously shown that shuttling of HNRNPK to the cytoplasm promotes ...

A computational peptide model induces cancer cells’ apoptosis by docking Kringle 5 to GRP78

Cells can die through a process called apoptosis in both pathological and healthy conditions. Cancer development and progression may result from abnormal apoptosis. The 78-kDa glucose-regulated protein (GRP78)...

BMP9 maintains the phenotype of HTR-8/Svneo trophoblast cells by activating the SDF1/CXCR4 pathway

Bone morphogenetic protein 9 (BMP9) has been shown to regulate processes such as angiogenesis, endothelial dysfunction, and tumorigenesis. However, the role of BMP9 in preeclampsia (PE) is unclear. The purpose...

Emodin and aloe-emodin, two potential molecules in regulating cell migration of skin cells through the MAP kinase pathway and affecting Caenorhabditis elegans thermotolerance

Emodin and aloe-emodin are two anthraquinones having positive effects in wound healing. However, their mechanism of action of wound healing is not fully understood. The MAP kinase family, which plays an active...

Knockdown of ELF4 aggravates renal injury in ischemia/reperfusion mice through promotion of pyroptosis, inflammation, oxidative stress, and endoplasmic reticulum stress

Renal ischemia/reperfusion (I/R) injury is a major cause of acute kidney injury (AKI). Dysfunction of E74-like ETS transcription factor 4 (ELF4) leads to inflammation. This research intended to look into the f...

Janus Kinase 3 phosphorylation and the JAK/STAT pathway are positively modulated by follicle-stimulating hormone (FSH) in bovine granulosa cells

Janus kinase 3 (JAK3) is a member of the JAK family of tyrosine kinase proteins involved in cytokine receptor-mediated intracellular signal transduction through the JAK/STAT signaling pathway. JAK3 was previou...

Genetic and protein interaction studies between the ciliary dyslexia candidate genes DYX1C1 and DCDC2

DYX1C1 (DNAAF4) and DCDC2 are two of the most replicated dyslexia candidate genes in genetic studies. They both have demonstrated roles in neuronal migration, in cilia growth and function and they both are cytosk...

SUMOylation of PDGF receptor α affects signaling via PLCγ and STAT3, and cell proliferation

The platelet-derived growth factor (PDGF) family of ligands exerts their cellular effects by binding to α- and β-tyrosine kinase receptors (PDGFRα and PDGFRβ, respectively). SUMOylation is an important posttra...

Myogenic differentiation of human myoblasts and Mesenchymal stromal cells under GDF11 on Poly-ɛ-caprolactone-collagen I-Polyethylene-nanofibers

For the purpose of skeletal muscle engineering, primary myoblasts (Mb) and adipogenic mesenchymal stem cells (ADSC) can be co-cultured and myogenically differentiated. Electrospun composite nanofiber scaffolds...

Computational analysis of missense variant CYP4F2*3 (V433M) in association with human CYP4F2 dysfunction: a functional and structural impact

Cytochrome P450 4F2 (CYP4F2) enzyme is a member of the CYP4 family responsible for the metabolism of fatty acids, therapeutic drugs, and signaling molecules such as arachidonic acid, tocopherols, and vitamin K...

Using RNA-seq to identify suitable housekeeping genes for hypoxia studies in human adipose-derived stem cells

Hypoxic culture conditions have been used to study the impact of oxygen deprivation has on gene expression in a number of disease models. However, hypoxia response elements present in the promoter regions of s...

SCAT8/miR-125b-5p axis triggers malignant progression of nasopharyngeal carcinoma through SCARB1

Nasopharyngeal carcinoma is a tumor with high malignancy and poor prognosis, which severely affects the health of the patients. LncRNAs and microRNAs are crucial for the occurrence and development of nasophary...

ARNTL2 upregulation of ACOT7 promotes NSCLC cell proliferation through inhibition of apoptosis and ferroptosis

Recent studies have reported that the circadian transcription factor aryl hydrocarbon receptor nuclear translocator like 2 (ARNTL2) promotes the metastatic progression of lung adenocarcinoma. However, the mole...

Evolutionary relevance of single nucleotide variants within the forebrain exclusive human accelerated enhancer regions

Human accelerated regions (HARs) are short conserved genomic sequences that have acquired significantly more nucleotide substitutions than expected in the human lineage after divergence from chimpanzees. The f...

The DNA demethylation-regulated SFRP2 dictates the progression of endometriosis via activation of the Wnt/β-catenin signaling pathway

Endometriosis cause decreases in life quality and pelvic pain in reproductive-age women. Methylation abnormalities played a functional role in the progression of endometriosis, this study aimed to explore the ...

Pre-treatment with IL-6 potentiates β-cell death induced by pro-inflammatory cytokines

Type I Diabetes mellitus (T1D) is characterized by a specific destruction of β-cells by the immune system. During this process pro-inflammatory cytokines are released in the pancreatic islets and contribute for β...

Role of the human solute carrier family 14 member 1 gene in hypoxia-induced renal cell carcinoma occurrence and its enlightenment to cancer nursing

Hypoxia is considered a critical contributor to renal cell carcinoma progression, including invasion and metastasis. However, the potential mechanisms by which it promotes invasion and metastasis have not yet ...

Cyclic tensile force modifies calvarial osteoblast function via the interplay between ERK1/2 and STAT3

Mechanical therapies, such as distraction osteogenesis, are widely used in dental clinics. During this process, the mechanisms by which tensile force triggers bone formation remain of interest. Herein, we inve...

Urine-derived mesenchymal stem cells-derived exosomes enhances survival and proliferation of aging retinal ganglion cells

This study was designed to investigate to test the effect of exosomes from urine-derived mesenchymal stem cells (USCs) on the survival and viability of aging retinal ganglion cells (RGCs), and explored the pre...

RPL11 promotes non-small cell lung cancer cell proliferation by regulating endoplasmic reticulum stress and cell autophagy

Abnormal biogenesis and ribosome free function of ribosomal proteins (RPs) is important for tumorgenesis and development. Ribosomal protein L11 (RPL11) is a component of ribosomal 60 S large subunit with diffe...

Sperm capacitation and transcripts levels are altered by in vitro THC exposure

Delta-9-tetrahydrocannabinol (THC) is the primary phytocannabinoid responsible for the psychoactive properties of cannabis and is known to interact with the endocannabinoid system, which is functionally presen...

The dual role of Nrf2 in melanoma: a systematic review

Melanoma is the most lethal type of skin cancer that originates from the malignant transformation of melanocytes. Although novel treatments have improved patient survival in melanoma, the overall prognosis rem...

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Citation Impact 2023 Journal Impact Factor: 2.4 5-year Journal Impact Factor: 2.5 Source Normalized Impact per Paper (SNIP): 0.684 SCImago Journal Rank (SJR): 0.797 Speed 2023 Submission to first editorial decision (median days): 17 Submission to acceptance (median days): 143 Usage 2023 Downloads: 582,382 Altmetric mentions: 193

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Endothelial adherens junctions and the actin cytoskeleton: an 'infinity net'?

A recent paper in BMC Biology reports that actin stress fibers in adjacent cultured endothelial cells are linked through adherens junctions. This organization might provide a super-cellular network that could ena...

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Robust and specific inhibition of microRNAs in Caenorhabditis elegans

MicroRNAs (miRNAs) are small non-coding RNAs that regulate the expression of numerous target genes. Yet, while hundreds of miRNAs have been identified, little is known about their functions. In a recent report...

Genome of a songbird unveiled

An international collaborative effort has recently uncovered the genome of the zebra finch, a songbird model that has provided unique insights into an array of biological phenomena.

The mathematics of sexual attraction

Pollen tubes follow attractants secreted by the ovules. In a recent paper in BMC Plant Biology , Stewman and colleagues have quantified the parameters of this attraction and used them to calibrate a mathematical m...

Diversity lost: are all Holarctic large mammal species just relict populations?

Population genetic analyses of Eurasian wolves published recently in BMC Evolutionary Biology suggest that a major genetic turnover took place in Eurasian wolves after the Pleistocene. These results add to the gr...

Hybridization and speciation in angiosperms: arole for pollinator shifts?

The majority of convincingly documented cases of hybridization in angiosperms has involved genetic introgression between the parental species or formation of a hybrid species with increased ploidy; however, ho...

Evolution underground: shedding light on the diversification of subterranean insects

A recent study in BMC Evolutionary Biology has reconstructed the molecular phylogeny of a large Mediterranean cave-dwelling beetle clade, revealing an ancient origin and strong geographic structuring. It seems li...

A modern circadian clock in the common angiosperm ancestor of monocots and eudicots

The circadian clock enhances fitness through temporal organization of plant gene expression, metabolism and physiology. Two recent studies, one in BMC Evolutionary Biology , demonstrate through phylogenetic analys...

Scale-eating cichlids: from hand(ed) to mouth

Two recent studies in BMC Biology and Evolution raise important questions about a textbook case of frequency-dependent selection in scale-eating cichlid fishes. They also suggest a fascinating new line of researc...

Top dogs: wolf domestication and wealth

A phylogeographic analysis of gene sequences important in determining body size in dogs, recently published in BMC Biology , traces the appearance of small body size to the Neolithic Middle East. This finding stre...

No better time to FRET: shedding light on host pathogen interactions

Understanding the spatio-temporal subversion of host cell signaling by bacterial virulence factors is key to combating infectious diseases. Following a recent study by Buntru and co-workers published in BMC Biolo...

Making progress in genetic kin recognition among vertebrates

A recent study in BMC Evolutionary Biology has shown that genetically similar individual ring-tailed lemurs are also more similar in their scent composition, suggesting a possible mechanism of kin recognition. Th...

Regeneration review reprise

There have been notable advances in the scientific understanding of regeneration within the past year alone, including two recently published in BMC Biology . Increasingly, progress in the regeneration field is be...

Acoel and platyhelminth models for stem-cell research

Acoel and platyhelminth worms are particularly attractive invertebrate models for stem-cell research because their bodies are continually renewed from large pools of somatic stem cells. Several recent studies,...

Madm (Mlf1 adapter molecule) cooperates with Bunched A to promote growth in Drosophila

The TSC-22 domain family (TSC22DF) consists of putative transcription factors harboring a DNA-binding TSC-box and an adjacent leucine zipper at their carboxyl termini. Both short and long TSC22DF isoforms are ...

Bunched and Madm: a novel growth-regulatory complex?

By combining Drosophila genetics and proteomics Gluderer et al. report in this issue of Journal of Biology the isolation of a novel growth-regulatory complex consisting of Bunched and Madm. Future study of this c...

Q&A: What can microfluidics do for stem-cell research?

Regulation of metabolism in caenorhabditis elegans longevity.

The nematode Caenorhabditis elegans is a favorite model for the study of aging. A wealth of genetic and genomic studies show that metabolic regulation is a hallmark of life-span modulation. A recent study in BMC ...

Reprogramming of the non-coding transcriptome during brain development

A recent global analysis of gene expression during the differentiation of neuronal stem cells to neurons and oligodendrocytes indicates a complex pattern of changes in the expression of both protein-coding tra...

The THO complex as a key mRNP biogenesis factor in development and cell differentiation

The THO complex is a key component in the co-transcriptional formation of messenger ribonucleoparticles that are competent to be exported from the nucleus, yet its precise function is unknown. A recent study in B...

SnoPatrol: how many snoRNA genes are there?

Small nucleolar RNAs (snoRNAs) are among the most evolutionarily ancient classes of small RNA. Two experimental screens published in BMC Genomics expand the eukaryotic snoRNA catalog, but many more snoRNAs remain...

Sometimes one just isn't enough: do vertebrates contain an H2A.Z hyper-variant?

How much functional specialization can one component histone confer on a single nucleosome? The histone variant H2A.Z seems to be an extreme example. Genome-wide distribution maps show non-random (and evolutio...

Apical polarity in three-dimensional culture systems: where to now?

Delineation of the mechanisms that establish and maintain the polarity of epithelial tissues is essential to understanding morphogenesis, tissue specificity and cancer. Three-dimensional culture assays provide...

The water flea Daphnia - a 'new' model system for ecology and evolution?

Daphnia pulex is the first crustacean to have its genome sequenced. Availability of the genome sequence will have implications for research in aquatic ecology and evolution in particular, as addressed by a series...

Top ten in Journal of Biology in 2009: stem cells, influenza, pit bulls, Darwin, and more

The bacterial pathogen listeria monocytogenes : an emerging model in prokaryotic transcriptomics.

A major challenge in bacterial pathogenesis is understanding the molecular basis of the switch from saprophytism to virulence. Following a recent whole-genome transcriptomic analysis using tiling arrays, an ar...

Forward genetics in Tribolium castaneum : opening new avenues of research in arthropod biology

A recent paper in BMC Biology reports the first large-scale insertional mutagenesis screen in a non-drosophilid insect, the red flour beetle Tribolium castaneum . This screen marks the beginning of a non-biased, '...

Mapping the protistan 'rare biosphere'

The use of cultivation-independent approaches to map microbial diversity, including recent work published in BMC Biology , has now shown that protists, like bacteria/archaea, are much more diverse than had been re...

Scribble at the crossroads

Although proteins involved in determining apical-basal cell polarity have been directly linked to tumorigenesis, their precise roles in this process remain unclear. A recent report in BMC Biology clarifies the si...

Q&A: Quantitative approaches to planar polarity and tissue organization

Gene regulation, evolvability and the limits of genomics, the transcriptome of human monocyte subsets begins to emerge.

Human monocytes can be divided into subsets according to their expression or lack of the cell-surface antigen CD16. In papers published recently in the Journal of Proteome Research and in BMC Genomics , two groups...

Chromatin 'programming' by sequence - is there more to the nucleosome code than %GC?

The role of genomic sequence in directing the packaging of eukaryotic genomes into chromatin has been the subject of considerable recent debate. A new paper from Tillo and Hughes shows that the intrinsic therm...

Fishing for the signals that pattern the face

Zebrafish are a powerful system for studying the early embryonic events that form the skull and face, as a model for human craniofacial birth defects such as cleft palate. Signaling pathways that pattern the p...

Coordinated gene expression by post-transcriptional regulons in African trypanosomes

The regulation of gene expression in trypanosomes is unique. In the absence of transcriptional control at the level of initiation, a subset of Trypanosoma brucei genes form post-transcriptional regulons in which ...

Promoter architecture and the evolvability of gene expression

Evolutionary changes in gene expression are a main driver of phenotypic evolution. In yeast, genes that have rapidly diverged in expression are associated with particular promoter features, including the prese...

Adaptations of proteins to cellular and subcellular pH

Bioinformatics-based searches for correlations between subcellular localization and pI or charge distribution of proteins have failed to detect meaningful correlations. Recent work published in BMC Biology finds ...

TBP2 is a general transcription factor specialized for female germ cells

The complexity of the core promoter transcription machinery has emerged as an additional level of transcription regulation that is used during vertebrate development. Recent studies, including one published in BM...

Generalized immune activation as a direct result of activated CD4 + T cell killing

In addition to progressive CD4 + T cell immune deficiency, HIV infection is characterized by generalized immune activation, thought to arise from increased microbial exposure resulting from diminishing immunity.

Life and death as a T lymphocyte: from immune protection to HIV pathogenesis

Detailed analysis of T cell dynamics in humans is challenging and mouse models can be important tools for characterizing T cell dynamic processes. In a paper just published in Journal of Biology , Marques et al . s...

What we still don't know about AIDS

The gene complement of the ancestral bilaterian - was urbilateria a monster.

Expressed sequence tag analyses of the annelid Pomatoceros lamarckii , recently published in BMC Evolutionary Biology , are consistent with less extensive gene loss in the Lophotrochozoa than in the Ecdysozoa, but ...

The nature of cell-cycle checkpoints: facts and fallacies

The concept of checkpoint controls revolutionized our understanding of the cell cycle. Here we revisit the defining features of checkpoints and argue that failure to properly appreciate the concept is leading ...

An expanded evolutionary role for flower symmetry genes

CYCLOIDEA (CYC) -like TCP genes are critical for flower developmental patterning. Exciting recent breakthroughs, including a study by Song et al. published in BMC Evolutionary Biology , demonstrate that CYC -like ge...

Mechanisms of ubiquitin transfer by the anaphase-promoting complex

The anaphase-promoting complex (APC) is a ubiquitin-protein ligase required for the completion of mitosis in all eukaryotes. Recent mechanistic studies reveal how this remarkable enzyme combines specificity in...

Targeting TNF-α for cancer therapy

As the tumor vasculature is a key element of the tumor stroma, angiogenesis is the target of many cancer therapies. Recent work published in BMC Cell Biology describes a fusion protein that combines a peptide pre...

TEs or not TEs? That is the evolutionary question

Transposable elements (TEs) have contributed a wide range of functional sequences to their host genomes. A recent paper in BMC Molecular Biology discusses the creation of new transcripts by transposable element i...

Molecular machines or pleiomorphic ensembles: signaling complexes revisited

Signaling complexes typically consist of highly dynamic molecular ensembles that are challenging to study and to describe accurately. Conventional mechanical descriptions misrepresent this reality and can be a...

Ockham's broom: A new series

Adaptation by introgression.

Both selective and random processes can affect the outcome of natural hybridization. A recent analysis in BMC Evolutionary Biology of natural hybridization between an introduced and a native salamander reveals th...

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The science and philosophy of the brain and the future of neuroscience.

Conflicts of Interest

• Sepahvand, T.; Power, K.D.; Qin, T.; Yuan, Q. The Basolateral Amygdala: The Core of a Network for Threat Conditioning, Extinction, and Second-Order Threat Conditioning. Biology 2023 , 12 , 1274. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Skolariki, K.; Vrahatis, A.G.; Krokidis, M.G.; Exarchos, T.P.; Vlamos, P. Assessing and Modelling of Post-Traumatic Stress Disorder Using Molecular and Functional Biomarkers. Biology 2023 , 12 , 1050. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Lawson, L.; Spivak, S.; Webber, H.; Yasin, S.; Goncalves, B.; Tarrio, O.; Ash, S.; Ferrol, M.; Ibragimov, A.; Olivares, A.G.; et al. Alterations in Brain Activity Induced by Transcranial Magnetic Stimulation and Their Relation to Decision Making. Biology 2023 , 12 , 1366. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Nguyen, G.H.; Oh, S.; Schneider, C.; Teoh, J.Y.; Engstrom, M.; Santana-Gonzalez, C.; Porter, D.; Quevedo, K. Neurofeedback and Affect Regulation Circuitry in Depressed and Healthy Adolescents. Biology 2023 , 12 , 1399. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Pham, T.Q.; Matsui, T.; Chikazoe, J. Evaluation of the Hierarchical Correspondence between the Human Brain and Artificial Neural Networks: A Review. Biology 2023 , 12 , 1330. [ Google Scholar ] [ CrossRef ] [ PubMed ]
• Zhang, R.; Zeng, Y.; Tong, L.; Yan, B. Specific Neural Mechanisms of Self-Cognition and the Application of Brainprint Recognition. Biology 2023 , 12 , 486. [ Google Scholar ] [ CrossRef ] [ PubMed ]

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Keenan, J.P. The Science and Philosophy of the Brain and the Future of Neuroscience. Biology 2024 , 13 , 607. https://doi.org/10.3390/biology13080607

Keenan JP. The Science and Philosophy of the Brain and the Future of Neuroscience. Biology . 2024; 13(8):607. https://doi.org/10.3390/biology13080607

Keenan, Julian Paul. 2024. "The Science and Philosophy of the Brain and the Future of Neuroscience" Biology 13, no. 8: 607. https://doi.org/10.3390/biology13080607

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Editorials are written in-house by members of the editorial staff or by members of the Editorial Board.

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The Perspectives section provides experts with a forum to comment on topical or controversial issues of broad interest. They address controversial issues or those at the interface between science and policy or science and society; present a policy position aimed at influencing policy decisions; examine and make recommendations on scientific and publishing practices. These are meant to be short, opinionated, Op-ed type of pieces.

The ideal Perspective conveys a sense of urgency. Some things to think about would be:

• Is this topic of immediate concern?
• Is the topic relevant to a pressing regional or global issue
• Does the piece offer a novel point of view on a scientific or policy issue, or on topical events?
• Does is make specific, practical proposals to address the issue?

Controversial articles are welcomed, but the text should acknowledge that a position is in fact controversial and provide readers with enough background on the differing views.

Our Perspectives aim to engage a broad and diverse audience—it is therefore important to ensure that they are written in an accessible, persuasive, and stimulating style that appeals to both specialists and non-specialist readers. Perspectives are usually assessed in-house with our Editorial Board, but we reserve the right to peer-review them if needed. Commissioning does not guarantee publication. Editors work closely with authors to ensure that articles are written in an engaging, succinct, yet rigorous manner.

Guidelines for a Perspective

Example Perspectives

Lowe-Power T, Dyson L, Polter AM (2021) A generation of junior faculty is at risk from the impacts of COVID-19. PLoS Biol 19(5): e3001266. https://doi.org/10.1371/journal.pbio.3001266

Bourne PE (2021) Is “bioinformatics” dead? PLoS Biol 19(3): e3001165. https://doi.org/10.1371/journal.pbio.3001165

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Above all, Primers should demystify an area of biology, avoid and/or explain technical jargon and provide critical and forward-thinking analysis about how the research article fits into the current state of the field and its future. A good Primer will briefly discuss (but not exhaustively review) what we know and what questions we have yet to answer for a particular field. It will then introduce the new findings and describe in roughly three paragraphs the advance represented in the related research article, highlighting its significance, not only for the discipline in question, but across disciplines. The Primer should then explain what the findings suggest in terms of next steps: what new avenues of investigation are opened, what new experiments can be tried, what new ideas can now be tested going forward? Ideally, Primers also offer insight into what big questions are likely to remain unanswered for many years (for whatever reasons).

We encourage the use of a figure to illustrate key concepts/mechanism/conclusions in an informative, easy-to-understand manner.

Primers are usually assessed by our Editorial Board, but we reserve the right to peer-review externally if needed. Commissioning does not guarantee publication. Editors work closely with authors to ensure that articles are written in an engaging, succinct, yet rigorous manner.

Guidelines for a Primer

Example Primer

Kazanova A, Rudd CE (2021) Programmed cell death 1 ligand (PD-L1) on T cells generates Treg suppression from memory. PLoS Biol 19(5): e3001272. https://doi.org/10.1371/journal.pbio.3001272

Guizetti J, Frischknecht F (2021) Apicomplexans: A conoid ring unites them all. PLoS Biol 19(3): e3001105. https://doi.org/10.1371/journal.pbio.3001105

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Community Pages are peer-reviewed and commissioning does not guarantee publication. Editors work closely with authors to ensure that articles are written in an engaging, succinct, yet rigorous manner.

Guidelines for a Community Page

Example Community Pages

Weissgerber TL (2021) Training early career researchers to use meta-research to improve science: A participant-guided “learn by doing” approach. PLoS Biol 19(2): e3001073. https://doi.org/10.1371/journal.pbio.3001073

McCullagh EA, Nowak K, Pogoriler A, Metcalf JL, Zaringhalam M, Zelikova TJ (2019) Request a woman scientist: A database for diversifying the public face of science. PLoS Biol 17 (4): e3000212. https://doi.org/10.1371/journal. pbio.3000212

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Example Formal Comment

Rees WE, Wackernagel M (2013) The Shoe Fits, but the Footprint is Larger than Earth. PLoS Biol 11(11): e1001701. https://doi.org/10.1371/journal.pbio.1001701​ ​

Example Formal Comment - Response

Blomqvist L, Brook BW, Ellis EC, Kareiva PM, Nordhaus T, Shellenberger M (2013) The Ecological Footprint Remains a Misleading Metric of Global Sustainability. PLoS Biol 11(11): e1001702. https://doi.org/10.1371/journal.pbio.1001702

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Essays are opinionated articles on a topic of interest to scientists and to a broader audience, including the general public. Unlike traditional review articles, which include a comprehensive account of a field, Essays take an imaginative approach to a provocative question, with an engaging but rigorous investigation of the problem. We encourage authors of Essays to select the most representative references to convey their points and avoid exhaustively covering the relevant literature.

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• take stock of progress in a field from a personal point of view
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• discuss key ideas or educational strategies to enhance understanding of fundamental biological questions
• offer historical/philosophical reflections on contemporary biology
• analyze scientific issues with policy implications

Our Essays aim to engage a broad and diverse audience—it is therefore important to ensure that they are written in an accessible, semi-journalistic style that captures the interest of both specialists and non-specialist readers. We encourage the use of figures to illustrate key concepts in an informative, easy to grasp manner; as well as the use of text boxes for background, self-contained information.

Essays are peer-reviewed and commissioning does not guarantee publication.

Guidelines for an Essay

Example Essays

Rees T, Bosch T, Douglas AE (2018) How the microbiome challenges our concept of self. PLoS Biol 16(2): e2005358. https://doi.org/10.1371/journal.pbio.2005358 Konig C, Weigelt P, Schrader J, Taylor A, Kattge J, Kreft H (2019) Biodiversity data integration—the significance of data resolution and domain. PLoS Biol 17(3): e3000183. https://doi.org/10.1371/journal.pbio.3000183

Unsolved Mysteries

Unsolved Mysteries discuss a topic of biological or medical importance that is poorly understood and in need of research attention—e.g., an unexplored or challenging question, an emerging opportunity, or a recent puzzling phenomenon. The articles are intended to stimulate the scientific community to think about future research possibilities outside their areas of expertise. The articles should be aimed at a very broad audience of biologists—an unsolved mystery in a neuroscience topic should be accessible to ecologists and biophysicists, for example.   The article should include a discussion of the basic science relevant to the topic, why it is biologically or medically important, what work has been done on the topic (if any), major challenges to understanding the question at hand, competing hypotheses, and what advances would be necessary to shed light on the problem. Ideally the structure of the article should reflect the mystery (e.g. subsections with questions as headings). The article should end with a discussion of possible means to a solution

Unsolved Mysteries are peer-reviewed and commissioning does not guarantee publication. Editors work closely with authors to ensure that articles are written in an engaging, succinct, yet rigorous manner.

Guidelines for an Unsolved Mystery

Example Unsolved Mysteries

Margolis L, Sadovsky Y (2019) The biology of extracellular vesicles: The known unknowns. PLoS Biol 17(7): e3000363. https://doi.org/10.1371/journal.pbio.3000363

Vogels CBF, Ru¨ckert C, Cavany SM, Perkins TA, Ebel GD, Grubaugh ND (2019) Arbovirus coinfection and co-transmission: A neglected public health concern? PLoS Biol 17(1): e3000130. https://doi.org/10.1371/journal.pbio.3000130

Consensus View

Consensus View articles present a comprehensive analysis by an independent and usually multidisciplinary panel of experts who make specific recommendations on important scientific, publishing or policy issues.

Consensus Views are peer-reviewed and commissioning does not guarantee publication. Editors work closely with authors to ensure that articles are written in an engaging, succinct, yet rigorous manner.

Guidelines for a Consensus View

Example Consensus View

Brown TM, Brainard GC, Cajochen C, Czeisler CA, Hanifin JP, Lockley SW, et al. (2022) Recommendations for daytime, evening, and nighttime indoor light exposure to best support physiology, sleep, and wakefulness in healthy adults. PLoS Biol 20(3): e3001571. https://doi.org/10.1371/journal.pbio.3001571

Kent BA, Holman C, Amoako E, Antonietti A, Azam JM, Ballhausen H, et al. (2022) Recommendations for empowering early career researchers to improve research culture and practice. PLoS Biol 20(7): e3001680. https://doi.org/10.1371/journal.pbio.3001680

Vimercati G, Probert AF, Volery L, Bernardo-Madrid R, Bertolino S, Céspedes V, et al. (2022) The EICAT+ framework enables classification of positive impacts of alien taxa on native biodiversity. PLoS Biol 20(8): e3001729. https://doi.org/10.1371/journal.pbio.3001729

Retired Article Types

Book Review/Science in the Media. These short reviews critiqued books, films, plays, and other media that deal with some aspect of the biological sciences.  

• Education. Although we no longer publish Education articles as a separate article type, we continue publishing them as part of the Education Series. The format selected (Essay, Perspective, or Community Page) depends on the aims of each article.
• Historical and Philosophical Perspectives. The Historical and Philosophical Perspectives section provided professional historians and philosophers of science with a forum to reflect on topical issues in contemporary biology.
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• Series. Series were recurrent themed articles on specific topics, including Education, Public Engagement with Science, Cool Tools, and Where Next?
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PLOS publishes Editorial Notes, Corrections, Expressions of Concern, and Retraction notices, as needed, to address issues that arise after a PLOS article has been published.

Biological Research

Special series on Microbial Interactions

The nine articles of this special issue of  Biological Research  address biochemical and genetic determinants of microbial response and tolerance to stressors in different biological models and environmental contexts. Individual articles provide a broad exploration of our current knowledge of response to stressors, with a special emphasis on metal metabolism and toxic compounds.

Special series on Antarctic Research

This special issue on Antarctic research in Biological Research comprises of recent studies, related to the discovery of several new enzymes and biotechnological applications that allow to expand the knowledge of Antarctic organisms and their potential applications.

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Editor’s profile

Manuel J Santos, Editor-in-Chief

Dr Santos is an Associate Professor in the Faculty of Biological Sciences and Medicine at the Pontificia Catholic University of Chile.

Dr Santos received his MD from the University of Chile and his PhD in Cell and Molecular Biology from the Pontificia Catholic University of Chile. He majored in Medical Genetics at The John Hopkins University (USA) and The René Descartes University of Paris (France), and held a post doctorate position in Cell Biology and Genetics at the Rockefeller University (USA).

His research has focused on the biogenesis of cellular organelles, particularly peroxisomes. A pioneer in this field, his research lead him to discover a new type of human genetic disease, the peroxisomal biogenesis disorders, which include Zellweger Syndrome. More recently his research has centered on studying the role of peroxisomes in Alzheimer’s disease, and he also works in the field of bioethics.

Over the span of his career, Dr Santos has published more than 70 peer reviewed papers and been the President of the Society of Biology of Chile, the Genetics Society of Chile and the Bioethical Society of Chile.

About the Society

The Chilean Biology Society (Sociedad de Biología de Chile), previously the Biological Society of Santiago, was founded in late 1928 as a subsidiary of The Societé de Biologie of Paris, France. For several years the summaries of its communications were published in Comps Rendú of the Societé de Biologie du Paris. The Society is currently a member of the International Union of Biological Sciences (IUBS).

The Chilean Biology Society promotes theoretical and experimental studies and research leading to advancement in and dissemination of the biological sciences for the benefit of the community. To accomplish this, the Society organizes periodic scientific meetings in which scientists communicate, comment and discuss research carried out in Chilean or foreign research laboratories. In addition, relations and cooperation with similar domestic and foreign institutions are stimulated, and communication by all appropriate means of biological research carried out in Chile. 

Members of the Society will receive a discount on Biological Research 's article-processing charge when they provide a discount code (which members can obtain by emailing the Society) during the submission process.  The discounted article-processing charge for Society members is £1150 in 2023.

The Society also publishes Revista Chilena de Historia Natural ( Chilean Journal of Natural History, founded in 1897).

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• Cancer Control
• v.28; Jan-Dec 2021

Cancer Biology, Epidemiology, and Treatment in the 21st Century: Current Status and Future Challenges From a Biomedical Perspective

Patricia piña-sánchez.

1 Oncology Research Unit, Oncology Hospital, Mexican Institute of Social Security, Mexico

Antonieta Chávez-González

Martha ruiz-tachiquín, eduardo vadillo, alberto monroy-garcía, juan josé montesinos, rocío grajales.

2 Department of Medical Oncology, Oncology Hospital, Mexican Institute of Social Security, Mexico

Marcos Gutiérrez de la Barrera

3 Clinical Research Division, Oncology Hospital, Mexican Institute of Social Security, Mexico

Hector Mayani

Since the second half of the 20th century, our knowledge about the biology of cancer has made extraordinary progress. Today, we understand cancer at the genomic and epigenomic levels, and we have identified the cell that starts neoplastic transformation and characterized the mechanisms for the invasion of other tissues. This knowledge has allowed novel drugs to be designed that act on specific molecular targets, the immune system to be trained and manipulated to increase its efficiency, and ever more effective therapeutic strategies to be developed. Nevertheless, we are still far from winning the war against cancer, and thus biomedical research in oncology must continue to be a global priority. Likewise, there is a need to reduce unequal access to medical services and improve prevention programs, especially in countries with a low human development index.

Introduction

During the last one hundred years, our understanding of the biology of cancer increased in an extraordinary way. 1 - 4 Such a progress has been particularly prompted during the last few decades because of technological and conceptual progress in a variety of fields, including massive next-generation sequencing, inclusion of “omic” sciences, high-resolution microscopy, molecular immunology, flow cytometry, analysis and sequencing of individual cells, new cell culture techniques, and the development of animal models, among others. Nevertheless, there are many questions yet to be answered and many problems to be solved regarding this disease. As a consequence, oncological research must be considered imperative.

Currently, cancer is one of the illnesses that causes more deaths worldwide. 5 According to data reported in 2020 by the World Health Organization (WHO), cancer is the second cause of death throughout the world, with 10 million deaths. 6 Clearly, cancer is still a leading problem worldwide. With this in mind, the objective of this article is to present a multidisciplinary and comprehensive overview of the disease. We will begin by analyzing cancer as a process, focusing on the current state of our knowledge on 4 specific aspects of its biology. Then, we will look at cancer as a global health problem, considering some epidemiological aspects, and discussing treatment, with a special focus on novel therapies. Finally, we present our vision on some of the challenges and perspectives of cancer in the 21 st century.

The Biology of Cancer

Cancer is a disease that begins with genetic and epigenetic alterations occurring in specific cells, some of which can spread and migrate to other tissues. 4 Although the biological processes affected in carcinogenesis and the evolution of neoplasms are many and widely different, we will focus on 4 aspects that are particularly relevant in tumor biology: genomic and epigenomic alterations that lead to cell transformation, the cells where these changes occur, and the processes of invasion and metastasis that, to an important degree, determine tumor aggressiveness.

Cancer Genomics

The genomics of cancer can be defined as the study of the complete sequence of DNA and its expression in tumor cells. Evidently, this study only becomes meaningful when compared to normal cells. The sequencing of the human genome, completed in 2003, was not only groundbreaking with respect to the knowledge of our gene pool, but also changed the way we study cancer. In the post-genomic era, various worldwide endeavors, such as the Human Cancer Genome Project , the Cancer Genome ATLAS (TCGA), the International Cancer Genome Consortium, and the Pan-Cancer Analysis Working Group (PCAWG), have contributed to the characterization of thousands of primary tumors from different neoplasias, generating more than 2.5 petabytes (10 15 ) of genomic, epigenomic, and proteomic information. This has led to the building of databases and analytical tools that are available for the study of cancer from an “omic” perspective, 7 , 8 and it has helped to modify classification and treatment of various neoplasms.

Studies in the past decade, including the work by the PCAWG, have shown that cancer generally begins with a small number of driving mutations (4 or 5 mutations) in particular genes, including oncogenes and tumor-suppressor genes. Mutations in TP53, a tumor-suppressor gene, for example, are found in more than half of all cancer types as an early event, and they are a hallmark of precancerous lesions. 9 - 12 From that point on, the evolution of tumors may take decades, throughout which the mutational spectrum of tumor cells changes significantly. Mutational analysis of more than 19 000 exomes revealed a collection of genomic signatures, some associated with defects in the mechanism of DNA repair. These studies also revealed the importance of alterations in non-coding regions of DNA. Thus, for example, it has been observed that various pathways of cell proliferation and chromatin remodeling are altered by mutations in coding regions, while pathways, such as WNT and NOTCH, can be disrupted by coding and non-coding mutations. To the present date, 19 955 genes that codify for proteins and 25 511 genes for non-coding RNAs have been identified ( https://www.gencodegenes.org/human/stats.html ). Based on this genomic catalogue, the COSMIC (Catalogue Of Somatic Mutations In Cancer) repository, the most robust database to date, has registered 37 288 077 coding mutations, 19 396 fusions, 1 207 190 copy number variants, and 15 642 672 non-coding variants reported up to August 2020 (v92) ( https://cosmic-blog.sanger.ac.uk/cosmic-release-v92/ ).

The genomic approach has accelerated the development of new cancer drugs. Indeed, two of the most relevant initiatives in recent years are ATOM (Accelerating Therapeutics for Opportunities in Medicine), which groups industry, government and academia, with the objective of accelerating the identification of drugs, 13 and the Connectivity Map (CMAP), a collection of transcriptional data obtained from cell lines treated with drugs for the discovery of functional connections between genes, diseases, and drugs. The CMAP 1.0 covered 1300 small molecules and more than 6000 signatures; meanwhile, the CMAP 2.0 with L1000 assay profiled more than 1.3 million samples and approximately 400 000 signatures. 14

The genomic study of tumors has had 2 fundamental contributions. On the one hand, it has allowed the confirmation and expansion of the concept of intratumor heterogeneity 15 , 16 ; and on the other, it has given rise to new classification systems for cancer. Based on the molecular classification developed by expression profiles, together with mutational and epigenomic profiles, a variety of molecular signatures have been identified, leading to the production of various commercial multigene panels. In breast cancer, for example, different panels have been developed, such as Pam50/Prosigna , Blue Print , OncotypeDX , MammaPrint , Prosigna , Endopredict , Breast Cancer Index , Mammostrat, and IHC4 . 17

Currently, the genomic/molecular study of cancer is more closely integrated with clinical practice, from the classification of neoplasms, as in tumors of the nervous system, 18 to its use in prediction, as in breast cancer. 17 Improvement in molecular methods and techniques has allowed the use of smaller amounts of biological material, as well as paraffin-embedded samples for genomic studies, both of which provide a wealth of information. 19 In addition, non-invasive methods, such as liquid biopsies, represent a great opportunity not only for the diagnosis of cancer, but also for follow-up, especially for unresectable tumors. 20

Research for the production of genomic information on cancer is presently dominated by several consortia, which has allowed the generation of a great quantity of data. However, most of these consortia and studies are performed in countries with a high human development index (HDI), and countries with a low HDI are not well represented in these large genomic studies. This is why initiatives such as Human Heredity and Health in Africa (H3Africa) for genomic research in Africa are essential. 21 Generation of new information and technological developments, such as third-generation sequencing, will undoubtedly continue to move forward in a multidisciplinary and complex systems context. However, the existing disparities in access to genomic tools for diagnosis, prognosis, and treatment of cancer will continue to be a pressing challenge at regional and social levels.

Cancer Epigenetics

Epigenetics studies the molecular mechanisms that produce hereditable changes in gene expression, without causing alterations in the DNA sequence. Epigenetic events are of 3 types: methylation of DNA and RNA, histone modification (acetylation, methylation, and phosphorylation), and the expression of non-coding RNA. Epigenetic aberrations can drive carcinogenesis when they alter chromosome conformation and the access to transcriptional machinery and to various regulatory elements (promoters, enhancers, and anchors for interaction with chromatin, for example). These changes may activate oncogenesis and silence tumor-suppressor mechanisms when they modulate coding and non-coding sequences (such as micro-RNAs and long-RNAs). This can then lead to uncontrolled growth, as well as the invasion and metastasis of cancer cells.

While genetic mutations are stable and irreversible, epigenetic alterations are dynamic and reversible; that is, there are several epigenomes, determined by space and time, which cause heterogeneity of the “epigenetic status” of tumors during their development and make them susceptible to environmental stimuli or chemotherapeutic treatment. 22 Epigenomic variability creates differences between cells, and this creates the need to analyze cells at the individual level. In the past, epigenetic analyses measured “average states” of cell populations. These studies revealed general mechanisms, such as the role of epigenetic marks on active or repressed transcriptional states, and established maps of epigenetic composition in a variety of cell types in normal and cancerous tissue. However, these approaches are difficult to use to examine events occurring in heterogeneous cell populations or in uncommon cell types. This has led to the development of new techniques that permit marking of a sequence on the epigenome and improvement in the recovery yield of epigenetic material from individual cells. This has helped to determine changes in DNA, RNA, and histones, chromatin accessibility, and chromosome conformation in a variety of neoplasms. 23 , 24

In cancer, DNA hypomethylation occurs on a global scale, while hypermethylation occurs in specific genomic loci, associated with abnormal nucleosome positioning and chromatin modifications. This information has allowed epigenomic profiles to be established in different types of neoplasms. In turn, these profiles have served as the basis to identify new neoplasm subgroups. For example, in triple negative breast cancer (TNBC), 25 and in hepatocellular carcinoma, 26 DNA methylation profiles have helped to the identification of distinct subgroups with clinical relevance. Epigenetic approaches have also helped to the development of prognostic tests to assess the sensitivity of cancer cells to specific drugs. 27

Epigenetic traits could be used to characterize intratumoral heterogeneity and determine the relevance of such a heterogeneity in clonal evolution and sensitivity to drugs. However, it is clear that heterogeneity is not only determined by genetic and epigenetic diversity resulting from clonal evolution of tumor cells, but also by the various cell populations that form the tumor microenvironment (TME). 28 Consequently, the epigenome of cancer cells is continually remodeled throughout tumorigenesis, during resistance to the activity of drugs, and in metastasis. 29 This makes therapeutic action based on epigenomic profiles difficult, although significant advances in this area have been reported. 30

During carcinogenesis and tumor progression, epigenetic modifications are categorized by their mechanisms of regulation ( Figure 1A ) and the various levels of structural complexity ( Figure 1B ). In addition, the epigenome can be modified by environmental stimuli, stochastic events, and genetic variations that impact the phenotype ( Figure 1C ). 31 , 32 The molecules that take part in these mechanisms/events/variations are therapeutic targets of interest with potential impact on clinical practice. There are studies on a wide variety of epidrugs, either alone or in combination, which improve antitumor efficacy. 33 However, the problems with these drugs must not be underestimated. For a considerable number of epigenetic compounds still being under study, the main challenge is to translate in vitro efficacy of nanomolar (nM) concentrations into well-tolerated and efficient clinical use. 34 The mechanisms of action of epidrugs may not be sufficiently controlled and could lead to diversion of the therapeutic target. 35 It is known that certain epidrugs, such as valproic acid, produce unwanted epigenetic changes 36 ; thus the need for a well-established safety profile before these drugs can be used in clinical therapy. Finally, resistance to certain epidrugs is another relevant problem. 37 , 38

Epigenetics of cancer. (A) Molecular mechanisms. (B) Structural hierarchy of epigenomics. (C) Factors affecting the epigenome. Modified from Refs. 31 and 32 .

As we learn about the epigenome of specific cell populations in cancer patients, a door opens to the evaluation of sensitivity tests and the search for new molecular markers for detection, prognosis, follow-up, and/or response to treatment at various levels of molecular regulation. Likewise, the horizon expands for therapeutic alternatives in oncology with the use of epidrugs, such as pharmacoepigenomic modulators for genes and key pathways, including methylation of promoters and regulation of micro-RNAs involved in chemoresponse and immune response in cancer. 39 There is no doubt that integrated approaches identifying stable pharmagenomic and epigenomic patterns and their relation with expression profiles and genetic functions will be more and more valuable in our fight against cancer.

Cancer Stem Cells

Tumors consist of different populations of neoplastic cells and a variety of elements that form part of the TME, including stromal cells and molecules of the extracellular matrix. 40 Such intratumoral heterogeneity becomes even more complex during clonal variation of transformed cells, as well as influence the elements of the TME have on these cells throughout specific times and places. 41 To explain the origin of cancer cell heterogeneity, 2 models have been put forward. The first proposes that mutations occur at random during development of the tumor in individual neoplastic cells, and this promotes the production of various tumor populations, which acquire specific growth and survival traits that lead them to evolve according to intratumor mechanisms of natural selection. 42 The second model proposes that each tumor begins as a single cell that possess 2 functional properties: it can self-renew and it can produce several types of terminal cells. As these 2 properties are characteristics of somatic stem cells, 43 the cells have been called cancer stem cells (CSCs). 44 According to this model, tumors must have a hierarchical organization, where self-renewing stem cells produce highly proliferating progenitor cells, unable to self-renew but with a high proliferation potential. The latter, in turn, give rise to terminal cells. 45 Current evidence indicates that both models may coexist in tumor progression. In agreement with this idea, new subclones could be produced as a result of a lack of genetic stability and mutational changes, in addition to the heterogeneity derived from the initial CSC and its descendants. Thus, in each tumor, a set of neoplastic cells with different genetic and epigenetic traits may be found, which would provide different phenotypic properties. 46

The CSC concept was originally presented in a model of acute myeloid leukemia. 47 The presence of CSCs was later proved in chronic myeloid leukemia, breast cancer, tumors of the central nervous system, lung cancer, colon cancer, liver cancer, prostate cancer, pancreatic cancer, melanoma, and cancer of the head and neck, amongst others. In all of these cases, detection of CSCs was based on separation of several cell populations according to expression of specific surface markers, such as CD133, CD44, CD24, CD117, and CD15. 48 It is noteworthy that in some solid tumors, and even in some hematopoietic ones, a combination of specific markers that allow the isolation of CSCs has not been found. Interestingly, in such tumors, a high percentage of cells with the capacity to start secondary tumors has been observed; thus, the terms Tumor Initiating Cells (TIC) or Leukemia Initiating Cells (LIC) have been adopted. 46

A relevant aspect of the biology of CSCs is that, just like normal stem cells, they can self-renew. Such self-renewal guarantees the maintenance or expansion of the tumor stem cell population. Another trait CSCs share with normal stem cells is their quiescence, first described in chronic myeloid leukemia. 49 The persistence of quiescent CSCs in solid tumors has been recently described in colorectal cancer, where quiescent clones can become dominant after therapy with oxaliplatin. 50 In non-hierarchical tumors, such as melanoma, the existence of slow-cycling cells that are resistant to antimitogenic agents has also been proved. 51 Such experimental evidence supports the idea that quiescent CSCs or TICs are responsible for both tumor resistance to antineoplastic drugs and clinical relapse after initial therapeutic success.

In addition to quiescence, CSCs use other mechanisms to resist the action of chemotherapeutic drugs. One of these is their increased numbers: upon diagnosis, a high number of CSCs are observed in most analyzed tumors, making treatment unable to destroy all of them. On the other hand, CSCs have a high number of molecular pumps that expulse drugs, as well as high numbers of antiapoptotic molecules. In addition, they have very efficient mechanisms to repair DNA damage. In general, these cells show changes in a variety of signaling pathways involved in proliferation, survival, differentiation, and self-renewal. It is worth highlighting that in recent years, many of these pathways have become potential therapeutic targets in the elimination of CSCs. 52 Another aspect that is highly relevant in understanding the biological behavior of CSCs is that they require a specific site for their development within the tissue where they are found that can provide whatever is needed for their survival and growth. These sites, known as niches, are made of various cells, both tumor and non-tumor, as well as a variety of non-cellular elements (extracellular matrix [ECM], soluble cytokines, ion concentration gradients, etc.), capable of regulating the physiology of CSCs in order to promote their expansion, the invasion of adjacent tissues, and metastasis. 53

It is important to consider that although a large number of surface markers have been identified that allow us to enrich and prospectively follow tumor stem cell populations, to this day there is no combination of markers that allows us to find these populations in all tumors, and it is yet unclear if all tumors present them. In this regard, it is necessary to develop new purification strategies based on the gene expression profiles of these cells, so that tumor heterogeneity is taken into account, as it is evident that a tumor can include multiple clones of CSCs that, in spite of being functional, are genetically different, and that these clones can vary throughout space (occupying different microenvironments and niches) and time (during the progression of a range of tumor stages). Such strategies, in addition to new in vitro and in vivo assays, will allow the development of new and improved CSC elimination strategies. This will certainly have an impact on the development of more efficient therapeutic alternatives.

Invasion and Metastasis

Nearly 90% of the mortality associated with cancer is related to metastasis. 54 This consists of a cascade of events ( Figure 2 ) that begins with the local invasion of a tumor into surrounding tissues, followed by intravasation of tumor cells into the blood stream or lymphatic circulation. Extravasation of neoplastic cells in areas distant from the primary tumor then leads to the formation of one or more micrometastatic lesions which subsequently proliferate to form clinically detectable lesions. 4 The cells that are able to produce metastasis must acquire migratory characteristics, which occur by a process known as epithelial–mesenchymal transition (EMT), that is, the partial loss of epithelial characteristics and the acquirement of mesenchymal traits. 55

Invasion and metastasis cascade. Invasion and metastasis can occur early or late during tumor progression. In either case, invasion to adjacent tissues is driven by stem-like cells (cancer stem cells) that acquire the epithelial–mesenchymal transition (EMT) (1). Once they reach sites adjacent to blood vessels, tumor cells (individually or in clusters) enter the blood (2). Tumor cells in circulation can adhere to endothelium and extravasation takes place (3). Other mechanisms alternative to extravasation can exist, such as angiopelosis, in which clusters of tumor cells are internalized by the endothelium. Furthermore, at certain sites, tumor cells can obstruct microvasculature and initiate a metastatic lesion right there. Sometimes, a tumor cells that has just exit circulation goes into an MET in order to become quiescent (4). Inflammatory signals can activate quiescent metastatic cells that will proliferate and generate a clinically detectable lesion (5).

Although several of the factors involved in this process are currently known, many issues are still unsolved. For instance, it has not yet been possible to monitor in vivo the specific moment when it occurs 54 ; the microenvironmental factors of the primary tumor that promote such a transition are not known with precision; and the exact moment during tumor evolution in which one cell or a cluster of cells begin to migrate to distant areas, is also unknown. The wide range of possibilities offered by intra- and inter-tumoral heterogeneity 56 stands in the way of suggesting a generalized strategy that could resolve this complication.

It was previously believed that metastasis was only produced in late stages of tumor progression; however, recent studies indicate that EMT and metastasis can occur during the early course of the disease. In pancreatic cancer, for example, cells going through EMT are able to colonize and form metastatic lesions in the liver in the first stages of the disease. 52 , 57 Metastatic cell clusters circulating in peripheral blood (PB) are prone to generate a metastatic site, compared to individual tumor cells. 58 , 59 In this regard, novel strategies, such as the use of micro-RNAs, are being assessed in order to diminish induction of EMT. 60 It must be mentioned, however, that the metastatic process seems to be even more complex, with alternative pathways that do not involve EMT. 61 , 62

A crucial stage in the process of metastasis is the intravasation of tumor cells (alone or in clusters) towards the blood stream and/or lymphatic circulation. 63 These mechanisms are also under intensive research because blocking them could allow the control of spreading of the primary tumor. In PB or lymphatic circulation, tumor cells travel to distant parts for the potential formation of a metastatic lesion. During their journey, these cells must stand the pressure of blood flow and escape interaction with natural killer (NK) cells . 64 To avoid them, tumor cells often cover themselves with thrombocytes and also produce factors such as VEGF, angiopoietin-2, angiopoietin-4, and CCL2 that are involved in the induction of vascular permeability. 54 , 65 Neutrophils also contribute to lung metastasis in the bloodstream by secreting IL-1β and metalloproteases to facilitate extravasation of tumor cells. 64

The next step in the process of metastasis is extravasation, for which tumor cells, alone or in clusters, can use various mechanisms, including a recently described process known as angiopellosis that involves restructuring the endothelial barrier to internalize one or several cells into a tissue. 66 The study of leukocyte extravasation has contributed to a more detailed knowledge of this process, in such a way that some of the proposed strategies to avoid extravasation include the use of integrin inhibitors, molecules that are vital for rolling, adhesion, and extravasation of tumor cells. 67 , 68 Another strategy that has therapeutic potential is the use of antibodies that strengthen vascular integrity to obstruct transendothelial migration of tumor cells and aid in their destruction in PB. 69

Following extravasation, tumor cells can return to an epithelial phenotype, a process known as mesenchymal–epithelial transition and may remain inactive for several years. They do this by competing for specialized niches, like those in the bone marrow, brain, and intestinal mucosa, which provide signals through the Notch and Wnt pathways. 70 Through the action of the Wnt pathway, tumor cells enter a slow state of the cell cycle and induce the expression of molecules that inhibit the cytotoxic function of NK cells. 71 The extravasated tumor cell that is in a quiescent state must comply with 2 traits typical of stem cells: they must have the capacity to self-renew and to generate all of the cells that form the secondary tumor.

There are still several questions regarding the metastatic process. One of the persisting debates at present is if EMT is essential for metastasis or if it plays a more important role in chemoresistance. 61 , 62 It is equally important to know if there is a pattern in each tumor for the production of cells with the capacity to carry out EMT. In order to control metastasis, it is fundamental to know what triggers acquisition of the migratory phenotype and the intrinsic factors determining this transition. Furthermore, it is essential to know if mutations associated with the primary tumor or the variety of epigenetic changes are involved in this process. 55 It is clear that metastatic cells have affinity for certain tissues, depending on the nature of the primary tumor (seed and soil hypothesis). This may be caused by factors such as the location and the direction of the bloodstream or lymphatic fluid, but also by conditioning of premetastatic niches at a distance (due to the large number of soluble factors secreted by the tumor and the recruitment of cells of the immune system to those sites). 72 We have yet to identify and characterize all of the elements that participate in this process. Deciphering them will be of upmost importance from a therapeutic point of view.

Epidemiology of Cancer

Cancer is the second cause of death worldwide; today one of every 6 deaths is due to a type of cancer. According to the International Agency for Research on Cancer (IARC), in 2020 there were approximately 19.3 million new cases of cancer, and 10 million deaths by this disease, 6 while 23.8 million cases and 13.0 million deaths are projected to occur by 2030. 73 In this regard, it is clear the increasing role that environmental factors—including environmental pollutants and processed food—play as cancer inducers and promoters. 74 The types of cancer that produce the greatest numbers of cases and deaths worldwide are indicated in Table 1 . 6

Total Numbers of Cancer Cases and Deaths Worldwide in 2020 by Cancer Type (According to the Global Cancer Observatory, IARC).

Data presented on this table were obtained from Ref. 6.

As shown in Figure 3 , lung, breast, prostate, and colorectal cancer are the most common throughout the world, and they are mostly concentrated in countries of high to very high human development index (HDI). Although breast, prostate, and colorectal cancer have a high incidence, the number of deaths they cause is proportionally low, mostly reflecting the great progress made in their control. However, these data also reveal the types of cancer that require further effort in prevention, precise early detection avoiding overdiagnosis, and efficient treatment. This is the case of liver, lung, esophageal, and pancreatic cancer, where the difference between the number of cases and deaths is smaller ( Figure 3B ). Social and economic transition in several countries has had an impact on reducing the incidence of neoplasms associated with infection and simultaneously produced an increase in the types related to reproductive, dietary, and hormonal factors. 75

Incidence and mortality for some types of cancer in the world. (A) Estimated number of cases and deaths in 2020 for the most frequent cancer types worldwide. (B) Incidence and mortality rates, normalized according to age, for the most frequent cancer types in countries with very high/& high (VH&H; blue) and/low and middle (L&M; red) Human Development Index (HDI). Data include both genders and all ages. Data according to https://gco.iarc.fr/today , as of June 10, 2021.

In the past 3 decades, cancer mortality rates have fallen in high HDI countries, with the exception of pancreatic cancer, and lung cancer in women. Nevertheless, changes in the incidence of cancer do not show the same consistency, possibly due to variables such as the possibility of early detection, exposure to risk factors, or genetic predisposition. 76 , 77 Countries such as Australia, Canada, Denmark, Ireland, New Zealand, Norway, and the United Kingdom have reported a reduction in incidence and mortality in cancer of the stomach, colon, lung, and ovary, as well as an increase in survival. 78 Changes in modifiable risk factors, such as the use of tobacco, have played an important role in prevention. In this respect, it has been estimated that decline in tobacco use can explain between 35% and 45% of the reduction in cancer mortality rates, 79 while the fall in incidence and mortality due to stomach cancer can be attributed partly to the control of Helicobacter pylori infection. 80 Another key factor in the fall of mortality rates in developed countries has been an increase in early detection as a result of screening programs, as in breast and prostate cancer, which have had their mortality rates decreased dramatically in spite of an increase in their incidence. 76

Another important improvement observed in recent decades is the increase in survival rates, particularly in high HDI countries. In the USA, for example, survival rates for patients with prostate cancer at 5 years after initial diagnosis was 28% during 1947–1951; 69% during 1975–1977, and 100% during 2003–2009. Something similar occurred with breast cancer, with a 5-year survival rate of 54% in 1947–1951, 75% in 1975–1977, and 90% in 2003–2009. 81 In the CONCORD 3 version, age-standardize 5-year survival for patients with breast cancer in the USA during 2010–2014 was 90%, and 97% for prostate cancer patients. 82 Importantly, even among high HDI countries, significant differences have been identified in survival rates, being stage of disease at diagnosis, time for access to effective treatment, and comorbidities, the main factors influencing survival in these nations. 78 Unfortunately, survival rates in low HDI countries are significantly lower due to several factors, including lack of information, deficient screening and early detection programs, limited access to treatment, and suboptimal cancer registration. 82 It should be noted that in countries with low to middle HDI, neoplasms with the greatest incidence are those affecting women (breast and cervical cancer), which reflects not only a problem with access to health services, but also a serious inequality issue that involves social, cultural, and even religious obstacles. 83

Up to 42% of incident cases and 47% of deaths by cancer in the USA are due to potentially modifiable risk factors such as use of tobacco, physical activity, diet, and infection. 84 It has been calculated that 2.4 million deaths by cancer, mostly of the lung, can be attributed to tobacco. 73 In 2020, the incidence rate of lung cancer in Western Africa was 2.2, whereas in Polynesia and Eastern Asia was 37.3 and 34.4, respectively. 6 In contrast, the global burden of cancer associated with infection was 15.4%, but in Sub-Saharan Africa it was 30%. 85 Likewise, the incidence of cervical cancer in Eastern Africa was 40.1, in contrast with the USA and Canada that have a rate of 6.2. This makes it clear that one of the challenges we face is the reduction of the risk factors that are potentially modifiable and associated with specific types of cancer.

Improvement of survival rates and its disparities worldwide are also important challenges. Five-year survival for breast cancer—diagnosed during 2010-2014— in the USA, for example, was 90%, whereas in countries like South Africa it was 40%. 82 Childhood leukemia in the USA and several European countries shows a 5-year survival of 90%, while in Latin-American countries it is 50–76%. 86 Interestingly, there are neoplasms, such as pancreatic cancer, for which there has been no significant increase in survival, which remains low (5–15%) both in developed and developing countries. 82

Although data reported on global incidence and mortality gives a general overview on the epidemiology of cancer, it is important to note that there are great differences in coverage of cancer registries worldwide. To date, only 1 out of every 3 countries reports high quality data on the incidence of cancer. 87 For the past 50 years, the IARC has supported population-based cancer registries; however, more than one-third of the countries belonging to the WHO, mainly countries of low and middle income (LMIC), have no data on more than half of the 18 indicators of sustainable development goals. 88 High quality cancer registries only cover 4% of the population in Africa, 8% in Asia, and 7% in Latin America, contrasting with 83% in the USA and Canada, and 33% in Europe. 89 In response to this situation, the Global Initiative for Cancer Registry Development was created in 2012 to generate improved infrastructure to permit greater coverage and better quality registries, especially in countries with low and middle HDI. 88 It is expected that initiatives of this sort in the coming years will allow more and better information to guide strategies for the control of cancer worldwide, especially in developing regions. This will enable survival to be measured over longer periods of time (10, 15, or 20 years), as an effective measure in the control of cancer. The WHO has established as a target for 2025 to reduce deaths by cancer and other non-transmissible diseases by 25% in the population between the ages of 30–69; such an effort requires not only effective prevention measures to reduce incidence, but also more efficient health systems to diminish mortality and increase survival. At the moment, it is an even greater challenge because of the effects of the COVID-19 pandemic which has negatively impacted cancer prevention and health services. 90

Oncologic Treatments

A general perspective.

At the beginning of the 20th century, cancer treatment, specifically treatment of solid tumors, was based fundamentally on surgical resection of tumors, which together with other methods for local control, such as cauterization, had been used since ancient times. 91 At that time, there was an ongoing burst of clinical observations along with interventions sustained on fundamental knowledge about physics, chemistry, and biology. In the final years of the 19 th century and the first half of the 20th, these technological developments gave rise to radiotherapy, hormone therapy, and chemotherapy. 92 - 94 Simultaneously, immunotherapy was also developed, although usually on a smaller scale, in light of the overwhelming progress of chemotherapy and radiotherapy. 95

Thus began the development and expansion of disciplines based on these approaches (surgery, radiotherapy, chemotherapy, hormone therapy, and immunotherapy), with their application evolving ever more rapidly up to their current uses. Today, there is a wide range of therapeutic tools for the care of cancer patients. These include elements that emerged empirically, arising from observations of their effects in various medical fields, as well as drugs that were designed to block processes and pathways that form part of the physiopathology of one or more neoplasms according to knowledge of specific molecular alterations. A classic example of the first sort of tool is mustard gas, originally used as a weapon in war, 96 but when applied for medical purposes, marked the beginning of the use of chemicals in the treatment of malignant neoplasms, that is, chemotherapy. 94 A clear example of the second case is imatinib, designed specifically to selectively inhibit a molecular alteration in chronic myeloid leukemia: the Bcr-Abl oncoprotein. 97

It is on this foundation that today the 5 areas mentioned previously coexist and complement one another. The general framework that motivates this amalgam and guides its development is precision medicine, founded on the interaction of basic and clinical science. In the forecasts for development in each of these fields, surgery is expected to continue to be the fundamental approach for primary tumors in the foreseeable future, as well as when neoplastic disease in the patient is limited, or can be limited by applying systemic or regional elements, before and/or after surgical resection, and it can be reasonably anticipated for the patient to have a significant period free from disease or even to be cured. With regards to technology, intensive exploration of robotic surgery is contemplated. 98

The technological possibilities for radiotherapy have progressed in such a way that it is now possible to radiate neoplastic tissue with an extraordinary level of precision, and therefore avoid damage to healthy tissue. 99 This allows administration of large doses of ionizing radiation in one or a few fractions, what is known as “radiosurgery.” The greatest challenges to the efficacy of this approach are related to radio-resistance in certain neoplasms. Most efforts regarding research in this field are concentrated on understanding the underlying biological mechanisms of the phenomenon and their potential control through radiosensitizers. 100

“Traditional” chemotherapy, based on the use of compounds obtained from plants and other natural products, acting in a non-specific manner on both neoplastic and healthy tissues with a high proliferation rate, continues to prevail. 101 The family of chemotherapeutic drugs currently includes alkylating agents, antimetabolites, anti-topoisomerase agents, and anti-microtubules. Within the pharmacologic perspective, the objective is to attain a high concentration or activity of such molecules in specific tissues while avoiding their accumulation in others, in order to achieve an increase in effectiveness and a reduction in toxicity. This has been possible with the use of viral vectors, for example, that are able to limit their replication in neoplastic tissues, and activate prodrugs of normally nonspecific agents, like cyclophosphamide, exclusively in those specific areas. 102 More broadly, chemotherapy also includes a subgroup of substances, known as molecular targeted therapy, that affect processes in a more direct and specific manner, which will be mentioned later.

There is no doubt that immunotherapy—to be explored next—is one of the therapeutic fields where development has been greatest in recent decades and one that has produced enormous expectation in cancer treatment. 103 Likewise, cell therapy, based on the use of immune cells or stem cells, has come to complement the oncologic therapeutic arsenal. 43 Each and every one of the therapeutic fields that have arisen in oncology to this day continue to prevail and evolve. Interestingly, the foreseeable future for the development of cancer treatment contemplates these approaches in a joint and complementary manner, within the general framework of precision medicine, 104 and sustained by knowledge of the biological mechanisms involved in the appearance and progression of neoplasms. 105 , 106

Immunotherapy

Stimulating the immune system to treat cancer patients has been a historical objective in the field of oncology. Since the early work of William Coley 107 to the achievements reached at the end of the 20 th century, scientific findings and technological developments paved the way to searching for new immunotherapeutic strategies. Recombinant DNA technology allowed the synthesis of cytokines, such as interferon-alpha (IFN-α) and interleukin 2 (IL-2), which were authorized by the US Food and Drug Administration (FDA) for the treatment of hairy cell leukemia in 1986, 108 as well as kidney cancer and metastatic melanoma in 1992 and 1998, respectively. 109

The first therapeutic vaccine against cancer, based on the use of autologous dendritic cells (DCs), was approved by the FDA against prostate cancer in 2010. However, progress in the field of immunotherapy against cancer was stalled in the first decade of the present century, mostly due to failure of several vaccines in clinical trials. In many cases, application of these vaccines was detained by the complexity and cost involved in their production. Nevertheless, with the coming of the concept of immune checkpoint control, and the demonstration of the relevance of molecules such as cytotoxic T-lymphocyte antigen 4 (CTLA-4), and programmed cell death molecule-1 (PD-1), immunotherapy against cancer recovered its global relevance. In 2011, the monoclonal antibody (mAb) ipilimumab, specific to the CTLA-4 molecule, was the first checkpoint inhibitor (CPI) approved for the treatment of advanced melanoma. 110 Later, inhibitory mAbs for PD-1, or for the PD-1 ligand (PD-L1), 111 as well as the production of T cells with chimeric receptors for antigen recognition (CAR-T), 112 which have been approved to treat various types of cancer, including melanoma, non-small cell lung cancer (NSCLC), head and neck cancer, bladder cancer, renal cell carcinoma (RCC), and hepatocellular carcinoma, among others, have changed the paradigm of cancer treatment.

In spite of the current use of anti-CTLA-4 and anti-PD-L1 mAbs, only a subgroup of patients has responded favorably to these CPIs, and the number of patients achieving clinical benefit is still small. It has been estimated that more than 70% of patients with solid tumors do not respond to CPI immunotherapy because either they show primary resistance, or after responding favorably, develop resistance to treatment. 113 In this regard, it is important to mention that in recent years very important steps have been taken to identify the intrinsic and extrinsic mechanisms that mediate resistance to CPI immunotherapy. 114 Intrinsic mechanisms include changes in the antitumor immune response pathways, such as faulty processing and presentation of antigens by APCs, activation of T cells for tumor cell destruction, and changes in tumor cells that lead to an immunosuppressive TME. Extrinsic factors include the presence of immunosuppressive cells in the local TME, such as regulatory T cells, myeloid-derived suppressor cells (MDSC), mesenchymal stem/stromal cells (MSCs), and type 2 macrophages (M2), in addition to immunosuppressive cytokines.

On the other hand, classification of solid tumors as “hot,” “cold,” or “excluded,” depending on T cell infiltrates and the contact of such infiltrates with tumor cells, as well as those that present high tumor mutation burden (TMB), have redirected immunotherapy towards 3 main strategies 115 ( Table 2 ): (1) Making T-cell antitumor response more effective, using checkpoint inhibitors complementary to anti-CTLA-4 and anti-PD-L1, such as LAG3, Tim-3, and TIGT, as well as using CAR-T cells against tumor antigens. (2) Activating tumor-associated myeloid cells including monocytes, granulocytes, macrophages, and DC lineages, found at several frequencies within human solid tumors. (3) Regulating the biochemical pathways in TME that produce high concentrations of immunosuppressive molecules, such as kynurenine, a product of tryptophan metabolism, through the activity of indoleamine 2,3 dioxygenase; or adenosine, a product of ATP hydrolysis by the activity of the enzyme 5’nucleotidase (CD73). 116

Current Strategies to Stimulate the Immune Response for Antitumor Immunotherapy.

Abbreviations: TME, tumor microenvironment; IL, interleukin; TNF, Tumor Necrosis Factor; TNFR, TNF-receptor; CD137, receptor–co-stimulator of the TNFR family; OX40, member number 4 of the TNFR superfamily; CD27/CD70, member of the TNFR superfamily; CD40/CD40L, antigen-presenting cells (APC) co-stimulator and its ligand; GM-CSF, granulocyte-macrophage colony-stimulating factor; IFN, interferon; STING, IFN genes-stimulator; RIG-I, retinoic acid inducible gene-I; MDA5, melanoma differentiation-associated protein 5; CDN, cyclic dinucleotide; ATP, adenosine triphosphate; HMGB1, high mobility group B1 protein; TLR, Toll-like receptor; HVEM, Herpes virus entry mediator; GITR, glucocorticoid-induced TNFR family-related gene; CTLA4, cytotoxic T lymphocyte antigen 4; PD-L1, programmed death ligand-1; TIGIT, T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibition motives; CSF1/CSF1R, colony-stimulating factor-1 and its receptor; CCR2, Type 2 chemokine receptor; PI3Kγ, Phosphoinositide 3-Kinase γ; CXCL/CCL, chemokine ligands; LFA1, lymphocyte function-associated antigen 1; ICAM1, intercellular adhesion molecule 1; VEGF, vascular endothelial growth factor; IDO, indolamine 2,3-dioxigenase; TGF, transforming growth factor; LAG-3, lymphocyte-activation gene 3 protein; TIM-3, T-cell immunoglobulin and mucin-domain containing-3; CD73, 5´nucleotidase; ARs, adenosine receptors; Selectins, cell adhesion molecules; CAR-T, chimeric antigen receptor T cell; TCR-T, T-cell receptor engineered T cell.

Apart from the problems associated with its efficacy (only a small group of patients respond to it), immunotherapy faces several challenges related to its safety. In other words, immunotherapy can induce adverse events in patients, such as autoimmunity, where healthy tissues are attacked, or cytokine release syndrome and vascular leak syndrome, as observed with the use of IL-2, both of which lead to serious hypotension, fever, renal failure, and other adverse events that are potentially lethal. The main challenges to be faced by immunotherapy in the future will require the combined efforts of basic and clinical scientists, with the objective of accelerating the understanding of the complex interactions between cancer and the immune system, and improve treatment options for patients. Better comprehension of immune phenotypes in tumors, beyond the state of PD-L1 and TME, will be relevant to increase immunotherapy efficacy. In this context, the identification of precise tumor antigenicity biomarkers by means of new technologies, such as complete genome sequencing, single cell sequencing, and epigenetic analysis to identify sites or subclones typical in drug resistance, as well as activation, traffic and infiltration of effector cells of the immune response, and regulation of TME mechanisms, may help define patient populations that are good candidates for specific therapies and therapeutic combinations. 117 , 118 Likewise, the use of agents that can induce specific activation and modulation of the response of T cells in tumor tissue, will help improve efficacy and safety profiles that can lead to better clinical results.

Molecular Targeted Therapy

For over 30 years, and based on the progress in our knowledge of tumor biology and its mechanisms, there has been a search for therapeutic alternatives that would allow spread and growth of tumors to be slowed down by blocking specific molecules. This approach is known as molecular targeted therapy. 119 Among the elements generally used as molecular targets there are transcription factors, cytokines, membrane receptors, molecules involved in a variety of signaling pathways, apoptosis modulators, promoters of angiogenesis, and cell cycle regulators. 120

Imatinib, a tyrosine kinase inhibitor for the treatment of chronic myeloid leukemia, became the first targeted therapy in the final years of the 1990s. 97 From then on, new drugs have been developed by design, and today more than 60 targeted therapies have been approved by the FDA for the treatment of a variety of cancers ( Table 3 ). 121 This has had a significant impact on progression-free survival and global survival in neoplasms such as non-small cell lung cancer, breast cancer, renal cancer, and melanoma.

FDA Approved Molecular Targeted Therapies for the Treatment of Solid Tumors.

Abbreviations: mAb, monoclonal antibody; ALK, anaplastic lymphoma kinase; CDK, cyclin-dependent kinase; CTLA-4, cytotoxic lymphocyte antigen-4; EGFR, epidermal growth factor receptor; FGFR, fibroblast growth factor receptor; GIST, gastrointestinal stroma tumor; mTOR, target of rapamycine in mammal cells; NSCLC, non-small cell lung carcinoma; PARP, poli (ADP-ribose) polimerase; PD-1, programmed death protein-1; PDGFR, platelet-derived growth factor receptor; PD-L1, programmed death ligand-1; ER, estrogen receptor; PR, progesterone receptor; TKR, tyrosine kinase receptors; SERM, selective estrogen receptor modulator; TKI, tyrosine kinase inhibitor; VEGFR, vascular endothelial growth factor receptor. Modified from Ref. [ 127 ].

Most drugs classified as targeted therapies form part of 2 large groups: small molecules and mAbs. The former are defined as compounds of low molecular weight (<900 Daltons) that act upon entering the cell. 120 Targets of these compounds are cell cycle regulatory proteins, proapoptotic proteins, or DNA repair proteins. These drugs are indicated based on histological diagnosis, as well as molecular tests. In this group there are multi-kinase inhibitors (RTKs) and tyrosine kinase inhibitors (TKIs), like sunitinib, sorafenib, and imatinib; cyclin-dependent kinase (CDK) inhibitors, such as palbociclib, ribociclib and abemaciclib; poli (ADP-ribose) polimerase inhibitors (PARPs), like olaparib and talazoparib; and selective small-molecule inhibitors, like ALK and ROS1. 122

As for mAbs, they are protein molecules that act on membrane receptors or extracellular proteins by interrupting the interaction between ligands and receptors, in such a way that they reduce cell replication and induce cytostasis. Among the most widely used mAbs in oncology we have: trastuzumab, a drug directed against the receptor for human epidermal growth factor-2 (HER2), which is overexpressed in a subgroup of patients with breast and gastric cancer; and bevacizumab, that blocks vascular endothelial growth factor and is used in patients with colorectal cancer, cervical cancer, and ovarian cancer. Other mAbs approved by the FDA include pembolizumab, atezolizumab, nivolumab, avelumab, ipilimumab, durvalumab, and cemiplimab. These drugs require expression of response biomarkers, such as PD-1 and PD-L1, and must also have several resistance biomarkers, such as the expression of EGFR, the loss of PTEN, and alterations in beta-catenin. 123

Because cancer is such a diverse disease, it is fundamental to have precise diagnostic methods that allow us to identify the most adequate therapy. Currently, basic immunohistochemistry is complemented with neoplastic molecular profiles to determine a more accurate diagnosis, and it is probable that in the near future cancer treatments will be based exclusively on molecular profiles. In this regard, it is worth mentioning that the use of targeted therapy depends on the existence of specific biomarkers that indicate if the patient will be susceptible to the effects of the drug or not. Thus, the importance of underlining that not all patients are susceptible to receive targeted therapy. In certain neoplasms, therapeutic targets are expressed in less than 5% of the diagnosed population, hindering a more extended use of certain drugs.

The identification of biomarkers and the use of new generation sequencing on tumor cells has shown predictive and prognostic relevance. Likewise, mutation analysis has allowed monitoring of tumor clone evolution, providing information on changes in canonic gene sequences, such as TP53, GATA3, PIK3CA, AKT1, and ERBB2; infrequent somatic mutations developed after primary treatments, like SWI-SNF and JAK2-STAT3; or acquired drug resistance mutations such as ESR1. 124 The study of mutations is vital; in fact, many of them already have specific therapeutic indications, which have helped select adequate treatments. 125

There is no doubt that molecular targeted therapy is one of the main pillars of precision medicine. However, it faces significant problems that often hinder obtaining better results. Among these, there is intratumor heterogeneity and differences between the primary tumor and metastatic sites, as well as intrinsic and acquired resistance to these therapies, the mechanisms of which include the presence of heterogeneous subclones, DNA hypermethylation, histone acetylation, and interruption of mRNA degradation and translation processes. 126 Nonetheless, beyond the obstacles facing molecular targeted therapy from a biological and methodological point of view, in the real world, access to genomic testing and specific drugs continues to be an enormous limitation, in such a way that strategies must be designed in the future for precision medicine to be possible on a global scale.

Cell Therapy

Another improvement in cancer treatment is the use of cell therapy, that is, the use of specific cells as therapeutic agents. This clinical procedure has 2 modalities: the first consists of replacing and regenerating functional cells in a specific tissue by means of stem/progenitor cells of a certain kind, 43 while the second uses immune cells as effectors to eliminate malignant cells. 127

Regarding the first type, we must emphasize the development of cell therapy based on hematopoietic stem and progenitor cells. 128 For over 50 years, hematopoietic cell transplants have been used to treat a variety of hematologic neoplasms (different forms of leukemia and lymphoma). Today, it is one of the most successful examples of cell therapy, including innovative modalities, such as haploidentical transplants, 129 as well as application of stem cells expanded ex vivo . 130 There are also therapies that have used immature cells that form part of the TME, such as MSCs. The replication potential and cytokine secretion capacity of these cells make them an excellent option for this type of treatment. 131 Neural stem cells can also be manipulated to produce and secrete apoptotic factors, and when these cells are incorporated into primary neural tumors, they cause a certain degree of regression. They can even be transfected with genes that encode for oncolytic enzymes capable of inducing regression of glioblastomas. 132

With respect to cell therapy using immune cells, several research groups have manipulated cells associated with tumors to make them effector cells and thus improve the efficacy and specificity of the antitumor treatment. PB leckocytes cultured in the presence of IL-2 to obtain activated lymphocytes, in combination with IL-2 administration, have been used in antitumor clinical protocols. Similarly, infiltrating lymphocytes from tumors with antitumor activity have been used and can be expanded ex vivo with IL-2. These lymphocyte populations have been used in immunomodulatory therapies in melanoma, and pancreatic and kidney tumors, producing a favorable response in treated patients. 133 NK cells and macrophages have also been used in immunotherapy, although with limited results. 134 , 135

One of the cell therapies with better projection today is the use of CAR-T cells. This strategy combines 2 forms of advanced therapy: cell therapy and gene therapy. It involves the extraction of T cells from the cancer patient, which are genetically modified in vitro to express cell surface receptors that will recognize antigens on the surface of tumor cells. The modified T cells are then reintroduced in the patient to aid in an exacerbated immune response that leads to eradication of the tumor cells ( Figure 4 ). Therapy with CAR-T cells has been used successfully in the treatment of some types of leukemia, lymphoma, and myeloma, producing complete responses in patients. 136

CAR-T cell therapy. (A) T lymphocytes obtained from cancer patients are genetically manipulated to produce CAR-T cells that recognize tumor cells in a very specific manner. (B) Interaction between CAR molecule and tumor antigen. CAR molecule is a receptor that results from the fusion between single-chain variable fragments (scFv) from a monoclonal antibody and one or more intracellular signaling domains from the T-cell receptor. CD3ζ, CD28 and 4-1BB correspond to signaling domains on the CAR molecule.

Undoubtedly, CAR-T cell therapy has been truly efficient in the treatment of various types of neoplasms. However, this therapeutic strategy can also have serious side effects, such as release of cytokines into the bloodstream, which can cause different symptoms, from high fever to multiorgan failure, and even neurotoxicity, leading to cerebral edema in many cases. 137 Adequate control of these side effects is an important medical challenge. Several research groups are trying to improve CAR-T cell therapy through various approaches, including production of CAR-T cells directed against a wider variety of tumor cell-specific antigens that are able to attack different types of tumors, and the identification of more efficient types of T lymphocytes. Furthermore, producing CAR-T cells from a single donor that may be used in the treatment of several patients would reduce the cost of this sort of personalized cell therapy. 136

Achieving wider use of cell therapy in oncologic diseases is an important challenge that requires solving various issues. 138 One is intratumor cell heterogeneity, including malignant subclones and the various components of the TME, which results in a wide profile of membrane protein expression that complicates finding an ideal tumor antigen that allows specific identification (and elimination) of malignant cells. Likewise, structural organization of the TME challenges the use of cell therapy, as administration of cell vehicles capable of recognizing malignant cells might not be able to infiltrate the tumor. This results from low expression of chemokines in tumors and the presence of a dense fibrotic matrix that compacts the inner tumor mass and avoids antitumor cells from infiltrating and finding malignant target cells.

Further Challenges in the 21st Century

Beyond the challenges regarding oncologic biomedical research, the 21 st century is facing important issues that must be solved as soon as possible if we truly wish to gain significant ground in our fight against cancer. Three of the most important have to do with prevention, early diagnosis, and access to oncologic medication and treatment.

Prevention and Early Diagnosis

Prevention is the most cost-effective strategy in the long term, both in low and high HDI nations. Data from countries like the USA indicate that between 40-50% of all types of cancer are preventable through potentially modifiable factors (primary prevention), such as use of tobacco and alcohol, diet, physical activity, exposure to ionizing radiation, as well as prevention of infection through access to vaccination, and by reducing exposure to environmental pollutants, such as pesticides, diesel exhaust particles, solvents, etc. 74 , 84 Screening, on the other hand, has shown great effectiveness as secondary prevention. Once population-based screening programs are implemented, there is generally an initial increase in incidence; however, in the long term, a significant reduction occurs not only in incidence rates, but also in mortality rates due to detection of early lesions and timely and adequate treatment.

A good example is colon cancer. There are several options for colon cancer screening, such as detection of fecal occult blood, fecal immunohistochemistry, flexible sigmoidoscopy, and colonoscopy, 139 , 140 which identify precursor lesions (polyp adenomas) and allow their removal. Such screening has allowed us to observe 3 patterns of incidence and mortality for colon cancer between the years 2000 and 2010: on one hand, an increase in incidence and mortality in countries with low to middle HDI, mainly countries in Asia, South America, and Eastern Europe; on the other hand, an increase in incidence and a fall in mortality in countries with very high HDI, such as Canada, the United Kingdom, Denmark, and Singapore; and finally a fall in incidence and mortality in countries like the USA, Japan, and France. The situation in South America and Asia seems to reflect limitations in medical infrastructure and a lack of access to early detection, 141 while the patterns observed in developed countries reveal the success, even if it may be partial, of that which can be achieved by well-structured prevention programs.

Another example of success, but also of strong contrast, is cervical cancer. The discovery of the human papilloma virus (HPV) as the causal agent of cervical cancer brought about the development of vaccines and tests to detect oncogenic genotypes, which modified screening recommendations and guidelines, and allowed several developed countries to include the HPV vaccine in their national vaccination programs. Nevertheless, the outlook is quite different in other areas of the world. Eighty percent of the deaths by cervical cancer reported in 2018 occurred in low-income nations. This reveals the urgency of guaranteeing access to primary and secondary prevention (vaccination and screening, respectively) in these countries, or else it will continue to be a serious public health problem in spite of its preventability.

Screening programs for other neoplasms, such as breast, prostate, lung, and thyroid cancer have shown outlooks that differ from those just described, because, among other reasons, these neoplasms are highly diverse both biologically and clinically. Another relevant issue is the overdiagnosis of these neoplasms, that is, the diagnosis of disease that would not cause symptoms or death in the patient. 142 It has been calculated that 25% of breast cancer (determined by mammogram), 50–60% of prostate cancer (determined by PSA), and 13–25% of lung cancer (determined by CT) are overdiagnosed. 142 Thus, it is necessary to improve the sensitivity and specificity of screening tests. In this respect, knowledge provided by the biology of cancer and “omic” sciences offers a great opportunity to improve screening and prevention strategies. All of the above shows that prevention and early diagnosis are the foundations in the fight against cancer, and it is essential to continue to implement broader screening programs and better detection methods.

Global Equity in Oncologic Treatment

Progress in cancer treatment has considerably increased the number of cancer survivors. Nevertheless, this tendency is evident only in countries with a very solid economy. Indeed, during the past 30 years, cancer mortality rates have increased 30% worldwide. 143 Global studies indicate that close to 70% of cancer deaths in the world occur in nations of low to middle income. But even in high-income countries, there are sectors of society that are more vulnerable and have less access to cancer treatments. 144 Cancer continues to be a disease of great social inequality.

In Europe, the differences in access to cancer treatment are highly marked. These treatments are more accessible in Western Europe than in its Eastern counterpart. 145 Furthermore, highly noticeable differences between high-income countries have been detected in the cost of cancer drugs. 146 It is interesting to note that in many of these cases, treatment is too costly and the clinical benefit only marginal. Thus, the importance of these problems being approached by competent national, regional, and global authorities, because if these new drugs and therapeutic programs are not accessible to the majority, progress in biomedical, clinical and epidemiological research will have a limited impact in our fight against cancer. We must not forget that health is a universal right, from which low HDI countries must not be excluded, nor vulnerable populations in nations with high HDI. The participation of a well-informed society will also be fundamental to achieve a global impact, as today we must fight not only against the disease, but also against movements and ideas (such as the anti-vaccine movement and the so-called miracle therapies) that can block the medical battle against cancer.

Final Comments

From the second half of the 20th century to the present day, progress in our knowledge about the origin and development of cancer has been extraordinary. We now understand cancer in detail in genomic, molecular, cellular, and physiological terms, and this knowledge has had a significant impact in the clinic. There is no doubt that a patient who is diagnosed today with a type of cancer has a better prospect than a patient diagnosed 20 or 50 years ago. However, we are still far from winning the war against cancer. The challenges are still numerous. For this reason, oncologic biomedical research must be a worldwide priority. Likewise, one of the fundamental challenges for the coming decades must be to reduce unequal access to health services in areas of low- to middle income, and in populations that are especially vulnerable, as well as continue improving prevention programs, including public health programs to reduce exposure to environmental chemicals and improve diet and physical activity in the general population. 74 , 84 Fostering research and incorporation of new technological resources, particularly in less privileged nations, will play a key role in our global fight against cancer.

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding: The author(s) received no financial support for the research, authorship, and/or publication of this article.

Hector Mayani https://orcid.org/0000-0002-2483-3782

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49 Most Interesting Biology Research Topics

August 21, 2023

In need of the perfect biology research topics—ideas that can both showcase your intellect and fuel your academic success? Lost in the boundless landscape of possible biology topics to research? And afraid you’ll never get a chance to begin writing your paper, let alone finish writing? Whether you’re a budding biologist hoping for a challenge or a novice seeking easy biology research topics to wade into, this blog offers curated and comprehensible options.

And if you’re a high school or transfer student looking for opportunities to immerse yourself in biology, consider learning more about research opportunities for high school students , top summer programs for high school students , best colleges for studying biomedical engineering , and best colleges for studying biology .

What is biology?

Well, biology explores the web of life that envelops our planet, from the teeny-tiny microbes to the big complex ecosystems. Biology investigates the molecular processes that define existence, deciphers the interplay of genes, and examines all the dynamic ways organisms interact with their environments. And through biology, you can gain not only knowledge, but a deeper appreciation for the interconnectedness of all living things. Pretty cool!

There are lots and lots of sub-disciplines within biology, branching out in all directions. Throughout this list, we won’t follow all of those branches, but we will follow many. And while none of these branches are truly simple or easy, some might be easier than others. Now we’ll take a look at a few various biology research topics and example questions that could pique your curiosity.

Climate change and ecosystems

The first of our potentially easy biology research topics: climate change and ecosystems. Investigate how ecosystems respond and adapt to the changing climate. And learn about shifts in species distributions , phenology , and ecological interactions .

1) How are different ecosystems responding to temperature changes and altered precipitation patterns?2) What are the implications of shifts in species distributions for ecosystem stability and functioning?

2) Or how does phenology change in response to climate shifts? And how do those changes impact species interactions?

3) Which underlying genetic and physiological mechanisms enable certain species to adapt to changing climate conditions?

4) And how do changing climate conditions affect species’ abilities to interact and form mutualistic relationships within ecosystems?

Microbiome and human health

Intrigued by the relationship between the gut and the rest of the body? Study the complex microbiome . You could learn how gut microbes influence digestion, immunity, and even mental health.

5) How do specific gut microbial communities impact nutrient absorption?

6) What are the connections between the gut microbiome, immune system development, and susceptibility to autoimmune diseases?

7) What ethical considerations need to be addressed when developing personalized microbiome-based therapies? And how can these therapies be safely and equitably integrated into clinical practice?

8) Or how do variations in the gut microbiome contribute to mental health conditions such as anxiety and depression?

9) How do changes in diet and lifestyle affect the composition and function of the gut microbiome? And what are the subsequent health implications?

Urban biodiversity conservation

Next, here’s another one of the potentially easy biology research topics. Examine the challenges and strategies for conserving biodiversity in urban environments. Consider the impact of urbanization on native species and ecosystem services. Then investigate the decline of pollinators and its implications for food security or ecosystem health.

10) How does urbanization influence the abundance and diversity of native plant and animal species in cities?

11) Or what are effective strategies for creating and maintaining green spaces that support urban biodiversity and ecosystem services?

12) How do different urban design and planning approaches impact the distribution of wildlife species and their interactions?

13) What are the best practices for engaging urban communities in biodiversity conservation efforts?

14) And how can urban agriculture and rooftop gardens contribute to urban biodiversity conservation while also addressing food security challenges?

Bioengineering

Are you a problem solver at heart? Then try approaching the intersection of engineering, biology, and medicine. Delve into the field of synthetic biology , where researchers engineer biological systems to create novel organisms with useful applications.

15) How can synthetic biology be harnessed to develop new, sustainable sources of biofuels from engineered microorganisms?

16) And what ethical considerations arise when creating genetically modified organisms for bioremediation purposes?

17) Can synthetic biology techniques be used to design plants that are more efficient at withdrawing carbon dioxide from the atmosphere?

18) How can bioengineering create organisms capable of producing valuable pharmaceutical compounds in a controlled and sustainable manner?

19) But what are the potential risks and benefits of using engineered organisms for large-scale environmental cleanup projects?

Neurobiology

Interested in learning more about what makes creatures tick? Then this might be one of your favorite biology topics to research. Explore the neural mechanisms that underlie complex behaviors in animals and humans. Shed light on topics like decision-making, social interactions, and addiction. And investigate how brain plasticity and neurogenesis help the brain adapt to learning, injury, and aging.

20) How does the brain’s reward circuitry influence decision-making processes in situations involving risk and reward?

21) What neural mechanisms underlie empathy and social interactions in both humans and animals?

22) Or how do changes in neural plasticity contribute to age-related cognitive decline and neurodegenerative diseases?

23) Can insights from neurobiology inform the development of more effective treatments for addiction and substance abuse?

24) What are the neural correlates of learning and memory? And how can our understanding of these processes be applied to educational strategies?

Plant epigenomics

While this might not be one of the easy biology research topics, it will appeal to plant enthusiasts. Explore how epigenetic modifications in plants affect their ability to respond and adapt to changing environmental conditions.

25) How do epigenetic modifications influence the expression of stress-related genes in plants exposed to temperature fluctuations?

26) Or what role do epigenetic changes play in plants’ abilities to acclimate to changing levels of air pollution?

27) Can certain epigenetic modifications be used as indicators of a plant’s adaptability to new environments?

28) How do epigenetic modifications contribute to the transgenerational inheritance of traits related to stress resistance?

29) And can targeted manipulation of epigenetic marks enhance crop plants’ ability to withstand changing environmental conditions?

Conservation genomics

Motivated to save the planet? Conservation genomics stands at the forefront of modern biology, merging the power of genetics with the urgent need to protect Earth’s biodiversity. Study genetic diversity, population dynamics, and how endangered species adapt in response to environmental changes.

30) How does genetic diversity within endangered species influence their ability to adapt to changing environmental conditions?

31) What genetic factors contribute to the susceptibility of certain populations to diseases, and how can this knowledge inform conservation strategies?

32) How can genomic data be used to inform captive breeding and reintroduction programs for endangered species?

33) And what are the genomic signatures of adaptation in response to human-induced environmental changes, such as habitat fragmentation and pollution?

34) Or how can genomics help identify “hotspots” of biodiversity that are particularly important for conservation efforts?

Zoonotic disease transmission

And here’s one of the biology research topics that’s been on all our minds in recent years. Investigate the factors contributing to the transmission of zoonotic diseases , like COVID-19. Then posit strategies for prevention and early detection.

35) What are the ecological and genetic factors that facilitate the spillover of zoonotic pathogens from animals to humans?

36) Or how do changes in land use, deforestation, and urbanization impact the risk of zoonotic disease emergence?

37) Can early detection and surveillance systems be developed to predict and mitigate the spread of zoonotic diseases?

38) How do social and cultural factors influence human behaviors that contribute to zoonotic disease transmission?

39) And can strategies be implemented to improve global pandemic preparedness?

Bioinformatics

Are you a data fanatic? Bioinformatics involves developing computational tools and techniques to analyze and interpret large biological datasets. This enables advancements in genomics, proteomics, and systems biology. So delve into the world of bioinformatics to learn how large-scale genomic and molecular data are revolutionizing biological research.

40) How can machine learning algorithms predict the function of genes based on their DNA sequences?

41) And what computational methods can identify potential drug targets by analyzing protein-protein interactions in large biological datasets?

42) Can bioinformatics tools be used to identify potential disease-causing mutations in human genomes and guide personalized medicine approaches?

43) What are the challenges and opportunities in analyzing “omics” data (genomics, proteomics, transcriptomics) to uncover novel biological insights?

44) Or how can bioinformatics contribute to our understanding of microbial diversity, evolution, and interactions within ecosystems?

Regenerative medicine

While definitely not one of the easy biology research topics, regenerative medicine will appeal to those interested in healthcare. Research innovative approaches to stimulate tissue and organ regeneration, using stem cells, tissue engineering, and biotechnology. And while you’re at it, discover the next potential medical breakthrough.

45) How can stem cells be directed to differentiate into specific cell types for tissue regeneration, and what factors influence this process?

46) Or what are the potential applications of 3D bioprinting in creating functional tissues and organs for transplantation?

47) How can bioengineered scaffolds enhance tissue regeneration and integration with host tissues?

48) What are the ethical considerations surrounding the use of stem cells and regenerative therapies in medical treatments?

49) And can regenerative medicine approaches be used to treat neurodegenerative disorders and restore brain function?

Biology Research Topics – Final thoughts

So as you take your next steps, try not to feel overwhelmed. And instead, appreciate the vast realm of possibilities that biology research topics offer. Because the array of biology topics to research is as diverse as the ecosystems it seeks to understand. And no matter if you’re only looking for easy biology research topics, or you’re itching to unravel the mysteries of plant-microbe interactions, your exploration will continue to deepen what we know of the world around us.

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Mariya holds a BFA in Creative Writing from the Pratt Institute and is currently pursuing an MFA in writing at the University of California Davis. Mariya serves as a teaching assistant in the English department at UC Davis. She previously served as an associate editor at Carve Magazine for two years, where she managed 60 fiction writers. She is the winner of the 2015 Stony Brook Fiction Prize, and her short stories have been published in Mid-American Review , Cutbank , Sonora Review , New Orleans Review , and The Collagist , among other magazines.

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Biology Research Topics

Are you in need of captivating and achievable research topics within the field of biology? Your quest for the best biology topics ends right here as this article furnishes you with 100 distinctive and original concepts for biology research, laying the groundwork for your research endeavor.

Table of Contents

Our proficient researchers have thoughtfully curated these biology research themes, considering the substantial body of literature accessible and the prevailing gaps in research.

Should none of these topics elicit enthusiasm, our specialists are equally capable of proposing tailor-made research ideas in biology, finely tuned to cater to your requirements. 

Thus, without further delay, we present our compilation of biology research topics crafted to accommodate students and researchers.

Research Topics in Marine Biology

• Impact of climate change on coral reef ecosystems.
• Biodiversity and adaptation of deep-sea organisms.
• Effects of pollution on marine life and ecosystems.
• Role of marine protected areas in conserving biodiversity.
• Microplastics in marine environments: sources, impacts, and mitigation.

Biological Anthropology Research Topics

• Evolutionary implications of early human migration patterns.
• Genetic and environmental factors influencing human height variation.
• Cultural evolution and its impact on human societies.
• Paleoanthropological insights into human dietary adaptations.
• Genetic diversity and population history of indigenous communities.

Biological Psychology Research Topics 

• Neurobiological basis of addiction and its treatment.
• Impact of stress on brain structure and function.
• Genetic and environmental influences on mental health disorders.
• Neural mechanisms underlying emotions and emotional regulation.
• Role of the gut-brain axis in psychological well-being.

Cancer Biology Research Topics 

• Targeted therapies in precision cancer medicine.
• Tumor microenvironment and its influence on cancer progression.
• Epigenetic modifications in cancer development and therapy.
• Immune checkpoint inhibitors and their role in cancer immunotherapy.
• Early detection and diagnosis strategies for various types of cancer.

Also read: Cancer research topics

Cell Biology Research Topics

• Mechanisms of autophagy and its implications in health and disease.
• Intracellular transport and organelle dynamics in cell function.
• Role of cell signaling pathways in cellular response to external stimuli.
• Cell cycle regulation and its relevance to cancer development.
• Cellular mechanisms of apoptosis and programmed cell death.

Developmental Biology Research Topics 

• Genetic and molecular basis of limb development in vertebrates.
• Evolution of embryonic development and its impact on morphological diversity.
• Stem cell therapy and regenerative medicine approaches.
• Mechanisms of organogenesis and tissue regeneration in animals.
• Role of non-coding RNAs in developmental processes.

Also read: Education research topics

Human Biology Research Topics

• Genetic factors influencing susceptibility to infectious diseases.
• Human microbiome and its impact on health and disease.
• Genetic basis of rare and common human diseases.
• Genetic and environmental factors contributing to aging.
• Impact of lifestyle and diet on human health and longevity.

Molecular Biology Research Topics 

• CRISPR-Cas gene editing technology and its applications.
• Non-coding RNAs as regulators of gene expression.
• Role of epigenetics in gene regulation and disease.
• Mechanisms of DNA repair and genome stability.
• Molecular basis of cellular metabolism and energy production.

Research Topics in Biology for Undergraduates

• 41. Investigating the effects of pollutants on local plant species.
• Microbial diversity and ecosystem functioning in a specific habitat.
• Understanding the genetics of antibiotic resistance in bacteria.
• Impact of urbanization on bird populations and biodiversity.
• Investigating the role of pheromones in insect communication.

Also read: Psychology Research Topics

Synthetic Biology Research Topics 

• Design and construction of synthetic biological circuits.
• Synthetic biology applications in biofuel production.
• Ethical considerations in synthetic biology research and applications.
• Synthetic biology approaches to engineering novel enzymes.
• Creating synthetic organisms with modified functions and capabilities.

Animal Biology Research Topics 

• Evolution of mating behaviors in animal species.
• Genetic basis of color variation in butterfly wings.
• Impact of habitat fragmentation on amphibian populations.
• Behavior and communication in social insect colonies.
• Adaptations of marine mammals to aquatic environments.

Also read: Nursing research topics

Best Biology Research Topics 

• Unraveling the mysteries of circadian rhythms in organisms.
• Investigating the ecological significance of cryptic coloration.
• Evolution of venomous animals and their prey.
• The role of endosymbiosis in the evolution of eukaryotic cells.
• Exploring the potential of extremophiles in biotechnology.

Biological Psychology Research Paper Topics

• Neurobiological mechanisms underlying memory formation.
• Impact of sleep disorders on cognitive function and mental health.
• Biological basis of personality traits and behavior.
• Neural correlates of emotions and emotional disorders.
• Role of neuroplasticity in brain recovery after injury.

Biological Science Research Topics: 

• Role of gut microbiota in immune system development.
• Molecular mechanisms of gene regulation during development.
• Impact of climate change on insect population dynamics.
• Genetic basis of neurodegenerative diseases like Alzheimer’s.
• Evolutionary relationships among vertebrate species based on DNA analysis.

Biology Education Research Topics 

• Effectiveness of inquiry-based learning in biology classrooms.
• Assessing the impact of virtual labs on student understanding of biology concepts.
• Gender disparities in science education and strategies for closing the gap.
• Role of outdoor education in enhancing students’ ecological awareness.
• Integrating technology in biology education: challenges and opportunities.

Biology-Related Research Topics

• The intersection of ecology and economics in conservation planning.
• Molecular basis of antibiotic resistance in pathogenic bacteria.
• Implications of genetic modification of crops for food security.
• Evolutionary perspectives on cooperation and altruism in animal behavior.
• Environmental impacts of genetically modified organisms (GMOs).

Biology Research Proposal Topics

• Investigating the role of microRNAs in cancer progression.
• Exploring the effects of pollution on aquatic biodiversity.
• Developing a gene therapy approach for a genetic disorder.
• Assessing the potential of natural compounds as anti-inflammatory agents.
• Studying the molecular basis of cellular senescence and aging.

Biology Research Topic Ideas

• Role of pheromones in insect mate selection and behavior.
• Investigating the molecular basis of neurodevelopmental disorders.
• Impact of climate change on plant-pollinator interactions.
• Genetic diversity and conservation of endangered species.
• Evolutionary patterns in mimicry and camouflage in organisms.

Biology Research Topics for Undergraduates 

• Effects of different fertilizers on plant growth and soil health.
• Investigating the biodiversity of a local freshwater ecosystem.
• Evolutionary origins of a specific animal adaptation.
• Genetic diversity and disease susceptibility in human populations.
• Role of specific genes in regulating the immune response.

Cell and Molecular Biology Research Topics 

• Molecular mechanisms of DNA replication and repair.
• Role of microRNAs in post-transcriptional gene regulation.
• Investigating the cell cycle and its control mechanisms.
• Molecular basis of mitochondrial diseases and therapies.
• Cellular responses to oxidative stress and their implications in ageing.

These topics cover a broad range of subjects within biology, offering plenty of options for research projects. Remember that you can further refine these topics based on your specific interests and research goals.

Frequently Asked Questions 

What are some good research topics in biology?

A good research topic in biology will address a specific problem in any of the several areas of biology, such as marine biology, molecular biology, cellular biology, animal biology, or cancer biology.

A topic that enables you to investigate a problem in any area of biology will help you make a meaningful contribution. 

How to choose a research topic in biology?

Choosing a research topic in biology is simple. 

Follow the steps:

• Generate potential topics. 
• Consider your areas of knowledge and personal passions. 
• Conduct a thorough review of existing literature.
•  Evaluate the practicality and viability. 
• Narrow down and refine your research query. 
• Remain receptive to new ideas and suggestions.

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212 Unique Biology Research Topics For Students And Researchers

Every student studying something related to biology — botany, marine, animal, medicine, molecular or physical biology, is in an interesting field. It’s a subject that explores how animate and inanimate objects relate to themselves. The field unveils the past, the present, and what lies in the future of the relationship between the living and nonliving things.

This is precisely why you need custom and quality biology topics for your college and university essay or project. It’ll make it easy to brainstorm, research, and get to writing straight away. Before the deep dive, what is biology?

What Is Biology?

Everyone knows it’s the scientific study of life, but beyond that, biology facilitates the comprehension of living and nonliving things. It’s a branch that explores their anatomy, behavior, distribution, morphology, and physiology.

For example, it understands how genes are classified and constituted into generations. It encompasses various branches, including botany, medicine, genetics, ecology, marine biology, zoology, and molecular biology.

Here are what some of these mean:

Botany: This study of plants examines their structure, physiology, ecology, economic importance, and distribution, among others. It also deals with their biochemical processes, properties, and social interactions between plants. It extends to how plants are vital for human life, survival, and growth and how they play a significant role in stabilizing environmental health. Zoology: Zoology studies animal behavior, brain, structure, physiology, class, and distribution. It’s the general study of the lives of both living and extinct animals. It explains animal classification, the animal kingdom, evolution, habitat, embryology, and life span. Physiology: Physiology deals with the daily functions of the human body: How it works and the factors that make it work. It examines molecular behavior, the chemistry and physics behind locomotion, and how the cells in the living organisms’ body function. It helps understand how humans and animals get sick and what can be done to alleviate pain. Microbiology: Dealing with microorganisms, it examined how viruses, algae, fungi, bacteria, protozoa, and slime molds become parts of human life. They’re regarded as microbes, which play substantial roles in the human biochemical processes, including climate change, biodegradation, biodeterioration, food spoilage, biotech, and epidemiology. Marine Biology: This is the scientific study of organs in the sea. It understands their family classification, how they survive, and what makes wild marine animals different from domesticated and consumable ones. It also explores their interaction with the environment through several processes. The marine biologist studies marines in their natural environment, collects data on their characteristics, human impact on their living, and how they relate with themselves.

Now that you know all these, here are some custom biology topics to research for your university or college essay and paper.

Controversial Biology Topics

There are many controversial subjects in every field, and biology isn’t exempt from controversy. If you’d like to create an original essay through diverse opinions, here are biology topics for you:

• What are your thoughts on the post-Roe V Wade world?
• How can the post-Roe V Wade policy affect developing countries looking up to America for their laws?
• Abortion and feminism: discuss
• Does saving life justify cloning?
• Explain the principle of abortion in medical practice
• The effects of cloning in medicine
• How does genetics contribute to obesity?
• Explain why a parent could have Hepatitis B virus and only one of five offspring have the virus
• Is homosexuality really in the gene?
• How does depression correlate with genetics?
• Additives and how they affect the genes
• Examine how genetic mutations work
• Discuss the grounds that you could prove for legalizing human cloning
• Which is more immoral: Human or animal cloning?
• How is nanotechnology different from biotechnology?
• Discuss the manifestation of nanotechnology in science
• Explain three instances where public opinion has held back scientific inventions
• How does transgenic crop work?
• Would you say genetically modified food is safe for consumption?
• Explain why sexual abuse leads to trauma.

Biology Research Paper Topics

You’d need to write an extensive paper on biology one day. This could be when you’re in your final year in college or the university or submitting to a competition. You’d need Biology topics to research for brainstorming, and here are 30 of them:

• Stem cells and tissue formation processes
• Why are there different congenital disabilities?
• Mixtures in anticancer drugs?
• What are the complexities of existing HIV drugs?
• What is the contribution of chemotherapy to cancer?
• Examine the chemotherapy process and why it doesn’t work for some patients.
• Explain the origin of developmental diseases
• How do germs affect the cells?
• What are the consequences of the sun on the white person’s and black person’s skin?
• Why are some diseases treatable through drugs while some are not?
• Scientific lessons learned from COVID-19 and ideas to tackle the next virus
• If animals are carriers of the virus, what should be done to them?
• Examine five animals in extinction and what led to it
• Discuss the subject of endangered species and why people should care
• Is a plant-based diet sustainable for human health?
• Account for the consequence of living on Mars on human health
• Discuss the inconveniences involved in space travel
• How does space flight contribute to environmental disasters
• Discuss the emergence of leukemia
• Explain how the immune systems in humans work
• Evaluate the factors that weaken the immunological system
• What would you consider the deadliest virus?
• Autoimmune: what is it, origin and consequences
• Immune disorder: origin and how it affects the body
• Does stress affect the ability to have sex?
• Contribution of vaccine to eradicating disease: Discuss
• What are the complexities in taking the Hepatitis B vaccine while being positive?
• Allergies: why do humans have them?
• DNA modification: how does it work?
• Explain the misconceptions about the COVID-19 vaccines.

Interesting Biology Topics

Biology doesn’t have to be boring. Different aspects of biology could be fun to explore, especially if you’ve had a flair for the study since your elementary school classes.

You can either write an essay or paper with the following interesting biology research topics:

• Human emotions and conflicts with their intellectual intelligence
• Emotions: Its influence on art and music and how the perception of art influences the world
• The consequences of marijuana and alcohol on teenagers
• Compare and contrast how alcohol affects teenagers and adults
• Discuss the contributions of neuroscience to the subject of emotional pain
• Explain how the brain process speech
• Discuss the factors that cause autism
• Explain what is meant when people say humans are animals
• Why do scientists say humans are pessimists?
• Factors contributing to the dopamine levels human experience
• How does isolation affect the human brain?
• What factors contribute to instinctive responses?
• Noise pollution: how it affects living organisms
• Fire ecology: The contributions of plants to fire outbreak
• Explain the science behind how hot temperature, soil, and dry grass start a fire
• Microbes: what do you understand by bioremediation?
• Explain urban ecology and the challenges it pokes to solve
• Discuss how excessive internet usage affects the human memory
• Evaluate how conservation biology contributes to the extinction prevention efforts
• Discuss the role of satellites and drones in understanding the natural world
• Why do we need space travel and studies?
• Explain the limitations of limnology studies
• What are infectious-disease-causing agents all about?
• Discuss what epigenetics studies encompass
• Why is cancer research essential to the world?
• Discuss climate change: Governments are not interested, and there is no alternative
• How is behavioral science studies a core part of the understanding of the world?
• Discuss the issues with genetic engineering and why it’s a challenge
• Evaluate the strengths and weaknesses in the arguments for a plant-based diet
• Create a survey amongst students of biology asking why they chose to study the course.

Biology Research Topics For College Students

If you find any of the above beyond your intellectual and Research capacity, here are some topics you can handle. You can use these for your essays, projects, quizzes, or competitions.

These custom yet popular biology research topics will examine famous personalities and other discourse in biology:

• Effects of the human hormone on the mind
• Why do men get erect even when they’re absentminded?
• How does women’s arousal work?
• How can melatonin be valuable for therapy?
• Risky behavior: Hormones responsible for the risk
• Stem and cloning: what is the latest research on the subject?
• Hormones: changes in pregnancy
• Why do pregnant women have an appetite for random and remote things?
• The role of physical activities in hormone development
• Examine the benefits and threats of transgenic crops
• The fight against COVID-19: assess current successes
• The fight against smallpox: assess current successes
• The fight against HIV: history, trends, and present research
• Discuss the future of prosthetic appliances
• Examine the research and the future of mind-controlled limbs
• What does cosmetic surgery mean, and why is it needed?
• Analyze the meaning and process of vascular surgery
• Discuss the debate around changes in genital organs for males and females in transgender bodies
• How do donors and organ transplants work?
• Account for the work of Dr. Malcom E Miller
• Discuss the contribution of Charles Darwin to human evolution
• Explain the trends in biomedicine
• Discuss the functions of x-rays in botany
• Assess the most efficient systems for wildlife preservation
• Examine how poverty contributes to climate hazards
• Discuss the process involved in plant metabolism
• The transformation of energy into a living thing: discuss
• Prevention for sexually transmitted disease: What are the misconceptions?
• Analyze how the human body reacts to poison
• Russian Poisoning: What are the lessons scientists must learn?
• COVID-19: Discuss the efforts by two or three governments to prevent the spread
• Discuss the contributions of Pfizer during the pandemic.

Marine Biology Research Topics

This subject explains orgasms in the sea, how they survive, and their interaction with their environment. If you have a flair for this field, the following Biology research topics may interest you:

• Discuss what quantitative ecology through modeling means
• Smallest diatoms and marine logistics: discuss
• How is the shark studied?
• Acidification of seas: Causes and consequences
• Discuss the concept of the immortality of Jellyfishes
• Discuss the differences between seawater and freshwater in marine study
• Account for some of the oldest marine species
• Discuss the evolution of the deep sea
• Explain whales’ communication techniques
• What does plankton ecology encompass?
• The importance of coral reefs to seawater
• Challenges that encompass geological oceanography
• How tourism affects natural animal habitat
• Discuss some instances of the domestication of wild marine animals
• Coastal zone: pros and cons of living in such areas
• How do sharks perceive enemies?
• Analyze why some animals can live in water but can’t live on land
• Explain how plants survive in the sea
• Compare and contrast the different two species of animals in the water
• How can marine energy be generated, stored, and used?

Molecular Biology Research Topics

Focusing on the construct of cells and analysis of their composition, it understands the alteration and maintenance of cellular processes. If you’d like to focus on molecular biology, here are 15 good biology research topics for you:

• Ethical considerations in molecular genetics
• Discuss the structure and component of the gene
• Examine the restrictions in DNA
• What are the peculiarities in modern nucleic acid analysis
• What goes into the Pharmaceutical production of drugs
• Evaluate the building blocks of life
• Discuss the systems of RNA translation to protein
• PCR: How DNA is tested and analyzed
• Why is prion disease so dangerous?
• Compare and contrast recessive genes vs. dominant genes
• Can there be damage to the human DNA, and can it be repaired?
• Constraints in the research of microarray data analysis
• Protein purification: How it evolves
• Objectives of nucleic acid
• Explain the structure of a prion.

Biology Research Topics For High School

Your teachers and professors will be awed if you create impeccable essays for your next report. You need to secure the best grades as you move closer to graduation, and brainstorming any of these popular biology research topics will help:

• Identify the most endangered species
• The challenges to animal extinction
• What are the things everyone should know about sea life?
• Discuss the history of genetics
• Explain the biological theory of Charles Darwin
• How did the lockdown affect social interaction?
• Why do some people refuse the vaccine?
• Origin of genetics
• What is animal hunting, and why is it fashionable
• Explain the evolution of a virus
• Role of lockdown in preventing deaths and illnesses
• Invasive species: What does it mean?
• Endangered animals: How do they survive in the face of their hazards?
• Lockdown and their role in reducing coronavirus transmission
• Vaccine distribution: Ideas for global distribution
• Why can viruses become less virulent?
• Discuss the evolution of the world
• Explain the evolution of the planet
• Explain what Elon Musk means when he says life on Mars is possible
• What does herd immunity mean?
• Flu: why is there a low incidence in 2020?
• Relationship between archaeology and biology
• Antiviral drug: What it means
• Factors leading to the evolution of humans
• Give instances of what natural selection means
• What is considered the dead branches of evolution
• Whale hunting: What it means and the present trends
• Who is Stephen Jay, and what is his role in paleontology?
• Origin of diseases: why must humans fall sick?
• Why are humans called higher animals?

Human Biology Research Topics

Human biology understands humans and their relationship between themselves and their environment. It also studies how the body works and the impediments to health. Here are some easy biology research topics to explore on the subject:

• How do gut bacteria affect the brain?
• What are the ethical concerns around organ transplants?
• The consequence of alcohol on the liver
• The consequences of extreme salt on the human body
• Why do humans need to deworm regularly?
• The relationship between obesity and genetics
• Genetically modified foods: Why are they needed?
• How sun exposure affects human skin
• Latest trends: Depression is hereditary
• Influence of music on the human brain
• What are the stages of lung cancer
• Forensic DNA: latest trends
• How visual consumptions affect how humans think
• What is the process that leads to pregnancy?
• Explain the role of nanotechnology in HIV research
•  Discuss any experiment with stem cells you know about
• Explain how humans consume food
• Discuss the process of metabolism as well as its criticality to human health
• Explore the consistent challenges technology poses to human health
• Explain the process of body decay to a skeleton.

Cell Biology Research Topics

There are many evolutionary biology research paper topics formed not by the nomenclature but for what they stand for. Cell biology is one of the most complex branches of the field.

It examines minor units and the living organisms that make them up. The focus is on the relationship between the cytoplasm, membrane, and parts of the cell. Here are some topics to explore for your scientific dissertation writing :

• How does chromatin engage in the alterations of gene expression?
• What are the usual cell infections, and why does the body have immunity defections?
• Identify and account for the heritage of Robert Brown in his core career focus
• Explain the structure of the animal cell and why It’s what it is
• Identify the cells in the human body as well as their functions
• Explain a scenario and justify the context of animals photosynthesizing like plants
• Why do bacteria invade the body, and how do they do it?
• Why are mitochondria considered the powerhouse of the cell
• Use the molecular analysis tool to explain multicellular organisms
• Examine how the White blood cells fight disease
• What do you understand about the role of cell biology in the treatment of Alzheimer’s Disease
• What are the latest research methods in cell biology?
• Identify the characteristics of viruses and why they threaten human existence.
• Discuss the differences between DNA and RNA
• What part of the body is responsible for human functionality for as long as the individual wants?

Get Biology Research Help As Soon As Possible

Creating the best essays or papers is easier now that you have custom biology research topics. However, you may still need support writing your paper beyond these topic ideas. After all, the first stage of writing like experts is brainstorming ideas and researching which is most feasible to write about.

If you truly want to wow your professor or teacher but can’t afford to dedicate all the required time, here’s an alternative. You can hire writing helpers online for quality papers at a cheap price, and we can help with that. We are a team of writers with many years of writing experience for students in Europe and North America. You can even buy thesis online with us, as well as editing services.

Each paper is assigned to writers with expertise in a specific field. This enables them to provide in-depth analysis as your assignment requires. We’re based online, which means you won’t have issues with accessibility and availability. Just tell us what you need, and we will get it done.

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Retraction Watch

Tracking retractions as a window into the scientific process

Former Maryland dept. chair with $19 million in grants faked data in 13 papers, feds say

A former department chair engaged in research misconduct in work funded by 19 grants from the National Institutes of Health, according to the U.S. Office of Research Integrity. 

Richard Eckert, formerly the chair of the Department of Biochemistry and Molecular Biology at the University of Maryland, Baltimore, and deputy director of the university’s Marlene and Stewart Greenebaum Comprehensive Cancer Center, faked data in 13 published papers and two grant applications, ORI found. 

The ORI finding stated Eckert “engaged in research misconduct in research supported by” every NIH grant on which he served as principal investigator, totaling more than $19 million. The finding also lists multiple “ Center Core Grants ” worth hundreds of millions for shared resources and facilities at research centers. 

Of the 13 papers in which Eckert faked Western blot and microscopy image data, according to ORI, four have been corrected and one retracted, and Eckert must request corrections or retractions for the remaining eight. The 13 papers have been cited 488 times, according to Clarivate’s Web of Science. 

“ Suppression of AP1 Transcription Factor Function in Keratinocyte Suppresses Differentiation ,” originally appeared in PLOS ONE in 2012 and has been cited 20 times. The journal retracted it in 2021, citing the University of Maryland’s investigation. 

“The investigation committee recommended retraction of the article and concluded that it is compromised in light of their findings” about two of the figures, the retraction notice states. 

According to ORI’s findings, Eckert erased a band in one of the paper’s figures “to falsely show a favorable result.” 

In the 13 papers and two grant applications, Eckert used and reused images “representing unrelated experiments, with or without manipulating them, and falsely relabeling them as data representing different proteins and/or experimental results,” ORI found.  

Eckert agreed to forgo contracting with the federal government or receiving government funding for eight years, longer than the three-year bans or supervision periods that ORI typically imposes . Eckert also agreed not to serve on any advisory or peer review committees for the U.S. Public Health Service, which includes the NIH, for eight years. 

Eckert has not responded to our request for comment sent to his university email address, which did not bounce. The finding is the fourth announced by the ORI this year .

According to the University of Maryland’s 2019 announcement naming him deputy director of the university’s cancer center, Eckert “is internationally-renowned for his pioneering discoveries in the area of surface epithelial biology.” His studies “have led to enhanced understanding of normal skin biology and to insights regarding the mechanisms that drive skin diseases including cancer.”

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23 thoughts on “former maryland dept. chair with $19 million in grants faked data in 13 papers, feds say”.

All penalties assessed by the ORI are completely ridiculous. “not to serve on any advisory or peer review committees” is something like a Christmas gift. And 8 years are better than 3.

The bottomline is he is out of academia.

“Trust the science”

Is that true? It sounds like he’s still at the University of Maryland, in the Cancer Center.

It sounds like he should be charged criminally

He was born in 1953, so is now 70 or 71. He can easily retire, and live off his state pension / TIAA-CREF account! Am sure he is laughing all the way to the bank… ORI did not make him personally pay back the funding for the fraudulent grants.

Yes, he has had a good career! He gets to retire comfortably, while the others who did not get his grants were denied tenure and are now high school teachers or unemployed/homeless!

I resemble that remark….. 40 published papers but couldn’t break through the wall of them that has gits!

> ORI did not make him personally pay back the funding > for the fraudulent grants. > I’d expect this to be well outside the range of penalties that ORI is even allowed to consider. The contract was almost certainly with UM, not with Eckert, so clawing back the money would need him to be fined for the same amount, and I’d be very surprised if ORI as a non judicial body can inflict fines. They’d need to sue him I suspect…

If it was a regular person, they would already be in jail. He’s just a normal person that broke the law and should be serving jail time and be made to pay the grants back!

Not surprised that why our human beings still haven’t solved the cancer.

So much progress has been made in cancer despite the complex nature of the disease.

Unfortunately, not nearly enough progress has been made, hindered by charlatans like this guy Eckert who fake data to push incorrect hypothese and pharma companies that push ineffective drugs for $ (e g., Avastin)

Why is research conduct involving grants not prosecuted as fraud? Is there some reason it shouldn’t be? Martha Stewart did time for much less.

You “nailed it!”

Eight years just long enough for the infamy to dissipate? Why would someone be allowed to participate in ANY research in ANY capacity after this kind of gross misconduct.

Dishonest faculty should not be in academia where they could penalize a student who cheats while they are doing the same…we should not tolerate cheating in any form by any one.

You are so very correct! This taints the integritiy of my favorite health care Provider…UMMS. I wonder how Len Stoler feels about this; he and his wife just donated millions for a new Cancer Wing for UMMS!

People like him should be criminally charged and never allowed to work again. What about the people who used his data and passed away? Our world has no remorse. Let criminals be criminals and keep going.

Many people mistakenly believe that research fraud is a crime without victims, but this is clearly not the case. Among the victims are: 1. The institution suffers a blow to its reputation. 2. The credibility of the NIH peer review process is compromised. 3. Taxpayers are cheated out of $19 million in funding. 4. Stories of fraud undermine public trust and fuel anti-science movements. 5. Researchers who embarked on new projects based on this fraudulent work have wasted both time and resources. 6. Administrators wasted time and effort on processing fraudulent applications. 7. Many deserving researchers may have missed out on grants or even lost their jobs because fraudulent projects were prioritized.

You left out the most important victim: 8. Patients.

The fraudulent results find their way into clinicians’ practices, killing or harming millions of people.

The harm can have 2 forms: Either the fraudulent recommendations are dangerous: following them will directly harm the patient. Or, as the least invasive scenario, the fraudulent recommendation is a useless but harmless sham; patients will still be harmed by losing precious golden time and opportunity to treat while they are busy trying a useless sham.

Must be nice to screw the taxpayers I think he should pay it back and plus 2 times that amount in interest

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The proposed method relies on the transformer architecture, which is particularly effective for processing sequential data. The researchers have utilized various pre-trained models, including ESM-2, a protein language model trained on over 250 million protein sequences, and Geneformer, a single-cell language model trained on 30 million single-cell transcriptomes. These models employ masked language modeling, where parts of the sequence are hidden, and the model is trained to predict the missing elements. This training enables the model to learn the underlying patterns and relationships within the sequences, making it possible to predict outcomes such as protein stability, gene expression levels, and variant effects. The models can be further fine-tuned for specific tasks, such as integrating multi-modal data that includes gene expression, chromatin accessibility, and protein abundance.

The proposed language models demonstrated substantial improvements across various biological tasks. For protein sequence analysis, the model achieved higher accuracy in predicting protein stability and evolutionary constraints, significantly outperforming existing methods. In single-cell data analysis, the model effectively predicted cell types and gene expression patterns with enhanced precision, offering superior performance in identifying subtle biological variations. These results underscore the models’ potential to transform biological research by providing accurate, scalable, and efficient tools for analyzing complex biological data, thereby advancing the capabilities of computational biology.

In conclusion, this proposed method offers a significant contribution to AI-driven biological research by effectively adapting language models for the analysis of biological sequences. The approach addresses a critical challenge in the field by leveraging the strengths of transformer-based models to overcome the limitations of traditional methods. The use of models like ESM-2 and Geneformer provides a scalable and accurate solution for a wide range of biological tasks, with the potential to revolutionize fields such as genomics, proteomics, and personalized medicine by enhancing the efficiency and accuracy of biological data analysis.

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• Published: 09 August 2024

Language models for biological research: a primer

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Nature Methods volume  21 ,  pages 1422–1429 ( 2024 ) Cite this article

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Language models are playing an increasingly important role in many areas of artificial intelligence (AI) and computational biology. In this primer, we discuss the ways in which language models, both those based on natural language and those based on biological sequences, can be applied to biological research. This primer is primarily intended for biologists interested in using these cutting-edge AI technologies in their applications. We provide guidance on best practices and key resources for adapting language models for biology.

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Acknowledgements

We would like to thank M. Karelina, F. Ekman, S. Simon and J. Chang for feedback and Z. Huang for help with the figures. K.S. acknowledges support from the Knight-Hennessy Scholarship. E.S. acknowledges support from the National Institutes of Health (T15LM007033). J.Z. is supported by funding from the CZ Biohub.

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These authors contributed equally: Elana Simon, Kyle Swanson.

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Department of Biomedical Data Science, Stanford University, Stanford, USA

Elana Simon & James Zou

Department of Computer Science, Stanford University, Stanford, USA

Kyle Swanson & James Zou

Chan-Zuckerberg Biohub, San Francisco, USA

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E.S. and K.S. wrote and edited the manuscript. J.Z. supervised and edited the manuscript.

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Simon, E., Swanson, K. & Zou, J. Language models for biological research: a primer. Nat Methods 21 , 1422–1429 (2024). https://doi.org/10.1038/s41592-024-02354-y

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Received : 20 March 2024

Accepted : 18 June 2024

Published : 09 August 2024

Issue Date : August 2024

DOI : https://doi.org/10.1038/s41592-024-02354-y

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