PubMed Health⌕ Search

SEARCH · PubMed Health

Search PubMed Health

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,657 records · Page 92Linked to original sources
PubMed2026

Canonical lymphocyte chemokine receptors CXCR3 and CXCR5 modulate neuronal autophagy.

Autophagy, a conserved cellular degradation process, plays a critical role in clearing toxic aggregate-prone proteins, which are characteristic pathological hallmarks of neurodegenerative diseases. As we previously found that microglia secreted factors impair neuronal autophagy and identified CCL3, CCL4 and CCL5 as causative chemokines, we screened the microglial secretome for soluble factors and neuronal cytokine receptors to identify candidates impacting autophagy in neuronal models. Against our expectations of identifying negative regulators, we found that two receptor-ligand pairs, CXCR3-CXCL10 and CXCR5-CXCL13, stimulated autophagy across several neuronal models, both in vitro (SH-SY5Y, i3Neurons) and in vivo. Mechanistically, CXCL10 and CXCL13 promoted autophagy through a shared mechanism: cognate receptor stimulation led to downstream activation of JNK, which in turn phosphorylates BCL-XL, promoting its disassociation from BECN1. The freed BECN1 interacts with VPS34 to form the autophagy initiation complex, enhancing autophagosome formation and flux. These findings reveal chemokine signalling as a targetable pathway for neuronal autophagy induction in neurodegeneration.

Journal Article↗
PubMed2026

Appreciating diversity: a review of the Iranian genomic landscape.

Understanding population structure is crucial for designing and interpreting human genetic studies. This is of particular importance for Iran as a large, ethnically diverse country whose population has often been treated as a genetically homogenous entity. Here, we synthesize published literature on the genetic structure of the Iranian population. We further complement this by recapitulating the geographic, historic, and ethnic background, by comparisons with neighboring countries, and by reviewing autozygosity in Iran. This synthesis confirms large genetic diversity, likely building upon an autochthonous component that was reshaped by multiple migrations. The substantial autosomal substructure falls apart into groups of largely shared genetic ancestry (Central Iranian Cluster) and those with substantial admixture in the past. Structure with respect to uniparental markers is less pronounced. We also find consistency for generally high but varying levels of autozygosity, influenced by ethnicity, residence, and socioeconomic factors. Finally, we recapitulate some examples for geographical differences in disease prevalence and (founder) mutation carrier frequency. Our synthesis emphasizes the need to account for this diversity in human genetic studies in the Iranian population. We provide conclusions for the design of such studies and state expectations on the transferability of genetic findings and genomic predictions, such as polygenic scores, within Iran as well as to neighboring countries. Iran's diversity and geographic location provide renewed motivation for conducting population genetic and ancient DNA studies as well as providing genomic reference resources in this part of the world.

Journal Article↗
PubMed2026

Integrating multi-omics technologies to decipher microbiome functions.

Multi-omics approaches have revolutionized our understanding of microbial communities by enabling simultaneous interrogation of genomic, transcriptomic, proteomic, and metabolomic data. The systematic integration and analysis of these deep datasets help decipher the functional roles of microbiomes, providing critical insights into microbial activities, interactions, and dynamics across diverse environments. Biological complexity makes multi-omics analysis of a single, isolated organism demanding but highly informative, yet this complexity increases further when samples comprise hundreds to thousands of individual species. As microbiome research continues to expand into clinical, environmental, and engineered systems, standardized workflows, benchmarked datasets, and community-driven initiatives are essential to ensure reproducibility, standardization and interpretability. Establishing and disseminating best practices for experimental design, data processing, and integrative analyses will be critical for maximizing comparability and scientific rigor across studies. This perspective highlights recent advances in multi-omics microbiome research, outlines key obstacles in data integration and metadata harmonization, and proposes a collaborative roadmap for scalable, FAIR-compliant multi-omics investigations and potentially disruptive Artificial Intelligence (AI) advances comparable to those of AlphaFold in the field of microbiome science.

Multiomics↗
PubMed2026

Flexible use of conserved motifs constrains genome access in cell type evolution.

Cell types can be organized into related families, but the regulatory mechanisms that define and maintain these families across deep evolutionary time remain unknown. Here, combining single-nucleus multi-omic sequencing with deep learning to analyse the accessible genomes of two groups of vastly divergent animals including flatworms and vertebrates, we find that hundreds of accessibility-dictating sequence motifs partition into distinct yet conserved sets, or 'vocabularies', each associated with a specific cell type family. However, combinatorial relationships among these motifs preferred by individual cell types are largely species specific. Deep-learning models trained on one species accurately predict family-level chromatin accessibility in distantly related species, albeit frequently rely on different motifs from shared vocabularies to reach convergent predictions. By contrast, models trained on individual cell types within a family lose cross-species predictive power, indicating that the regulatory syntax governing cell type-level identity evolves rapidly. We propose a 'collective maintenance' model in which motif vocabularies defining cell type families are evolutionarily stable, while recombination of these motifs generates cell type-specific regulatory programmes. This suggests that family identity is maintained collectively by large, conserved pools of regulatory factors, analogous to the logic of developmental homology, where character identity persists through network-level conservation despite extensive rewiring.

Journal Article↗
PubMed2026

Charge-switching ionizable lipids lower the toxicity of lipid nanoparticles.

Lipid nanoparticles (LNPs) have great potential as nucleic acid delivery vehicles; however, they trigger the production of inflammatory cytokines, which limits their medical applications. Developing non-inflammatory LNPs is challenging because the LNP's ionizable lipid and the process of endosomal disruption are the major sources of LNP toxicity but are also essential for delivering nucleic acids. Here we demonstrate that ionizable lipids containing a carboxylic acid and an amine (termed S-lipid) switch their charged state between the pHs of 7.4 and 4.0, allowing them to generate LNPs (termed switchable nanoparticles) that efficiently encapsulate nucleic acid and trigger endosomal release without activation of the TLR4, complement, galectin-8 and platelet activating factor signalling pathways. Finally, we demonstrate that switchable nanoparticles are better at treating lipopolysaccharide-induced acute lung injury than traditional LNPs because they do not exacerbate pre-existing inflammation. Collectively, these results demonstrate that negatively charged ionizable lipids can mitigate the toxicity of LNPs.

Journal Article↗
PubMed2026

A single-cell lens into the co-evolution of genotypes and phenotypes in cancer.

Genetic heterogeneity and clonal outgrowths are observed even in otherwise healthy human tissues, shaping the genetic composition of cell populations in non-malignant disease and during physiological ageing. This clonal mosaicism likely provides the pre-cancerous seeds for malignant transformation. Once a tumour arises, clonal evolution poses a major challenge to achieving cure, as clonal diversification provides an expanded number of substrates upon which therapy can act as a selective pressure, leading to the selection of resistant clones that ultimately fuel disease recurrence. Understanding somatic clonal evolution requires not only mapping genetic diversity but also defining the resulting phenotypes that provide a fitness advantage to mutated clones. This Review discusses multimodal single-cell technologies that enable the measurement of genotypes and additional molecular features from the same cell. These technologies unveil mutant-specific phenotypic traits, often show cell-state specificity in genotype-phenotype effects and can define therapeutic vulnerabilities for precision elimination of disease-propagating mutant cells. Furthermore, the combination of phylogenetic reconstruction with phenotypic measurements allows for the temporal mapping of clonal evolution and phenotypic plasticity. These breakthroughs have created a unique opportunity to define, directly in primary human samples, the mechanisms underlying clonal expansion in both healthy and malignant tissues.

Journal Article↗
PubMed2026

The mechanistic and evolutionary diversity of programmed DNA elimination.

Beyond somatic mutations, the genetic makeup of an organism is often assumed to remain constant across all cells or nuclei within individuals. However, some organisms exhibit programmed DNA elimination (PDE), whereby specific cell lineages lose DNA segments or whole chromosomes. Building evidence indicates that PDE occurs in a wide range of eukaryotes and is linked to diverse cellular processes including gene silencing, germline differentiation, genome defence and sex determination. Here we compare PDE across broad phylogenetic groups, highlighting the mechanistic diversity, overlooked plasticity in genome integrity and the considerable gaps in our understanding of why PDE emerged recurrently and is maintained across the Tree of Life.

Journal Article↗
PubMed2026

Cohesin prevents local mixing of condensed euchromatic domains in living human cells.

The human genome is folded into chromatin loops by the cohesin complex, forming functional chromatin domains that underlie transcription and DNA replication/repair. However, how cohesin organizes these domains in living cells, especially in active euchromatin, remains elusive. Here, to address this question, we combined single-nucleosome imaging/tracking and super-resolution three-dimensional structured illumination microscopy with euchromatin-specific labeling of histone variant H3.3. Using this nanoscopic approach, we revealed that euchromatin forms condensed domains that are constrained by cohesin-mediated loops. This organization refines the classical view of euchromatin as largely open, in line with emerging evidence. Transcription machinery appears to be located near the condensed domain surfaces/borders. Cohesin loss increased nucleosome-level fluidity within these domains without altering their overall compaction, leading to local mixing of domains and compromising transcriptional insulation. These findings suggest a physical role of cohesin in maintaining the integrity of condensed euchromatic domains and ensuring proper higher-order regulation of gene expression.

Humans↗
PubMed2026

Human and mouse adrenal glands are characterized by species-specific steroidogenic states and tissue turnover.

The adult adrenal cortex undergoes constant renewal, yet underlying human-specific mechanisms remain poorly understood. Here we generated single-cell and spatial transcriptomic atlases of adult human and mouse adrenal glands, leveraging single-cell-resolution spatial data and a rare clonal mosaic case for lineage inference. In humans, we identified age-associated zona glomerulosa (ZG) cell states with direct cortisol synthesis capacity and sex-specific differences in inferred cholesterol balance. Cross-species comparison revealed conserved aldosterone-producing ZG but notable divergence in zona fasciculata markers, absence of zona reticularis homologs in mice and differential SHH-WNT4 signaling in proliferating cells. We uncovered human WT1- capsule-to-ZG transition and vascular smooth muscle cell-to-steroidogenic transitions supported by mosaic lineage evidence. We revealed dispersed proliferating cortical SF1+EZH2+ cells throughout the human cortex in contrast with ZG restriction in mice. Taken together, our data expand the centripetal renewal model and establish a comparative framework for human adrenocortical biology.

Animals↗
PubMed2026

Mechanisms underlying disease-causing variants in promoters and enhancers.

The study of human monogenic disorders has been a powerful tool for generating a deep understanding of protein function/dysfunction and for uncovering underlying biological mechanisms. Here we explore the insights that an expanding catalog of noncoding monogenic disease variants can provide into the functions of the noncoding genome. We focus on small genetic alterations (one to a few tens of base pairs) in cis-regulatory elements-promoters, enhancers and silencers-and their potential mechanisms of action, such as loss or gain of function. We discuss the challenges in determining pathogenicity for variants in the noncoding genome, discuss why there might be so few concrete examples and highlight the opportunities for advancing this area of human genetics by using experimental and machine-learning tools.

Journal Article↗
PubMed2026

Chemogenomic maps reveal a PRDX1-dependent iron-damage axis in the DNA damage response.

The DNA damage response (DDR) is a sophisticated network of cellular pathways whose perturbation leads to genome instability and is a key hallmark of oncogenesis. Here, we present data from 32 genome-scale loss-of-function CRISPR interference chemical-genetic screens with inhibitors targeting core constituents of the DDR machinery (PARP, ATR, ATM, DNAPK and WEE1), as both single agents and in combination with poly(ADP-ribose) polymerase inhibitors. These experiments identify >1,000 genes whose perturbation modifies the DDR and provides a rich resource to the DDR community. In addition, this compendium of functional genomics data reveals key principles governing the DDR and highlights a strong chemical-genetic interaction between loss of activity of the peroxiredoxin PRDX1 and all tested DDR inhibitors through a mechanism involving iron availability mediated by an MRGBP-PAX7-IREB2 axis. Our data position PRDX1 as a key suppressor of DNA damage accumulation and potential druggable target in combination with DDR inhibitors.

Journal Article↗
PubMed2026

Intestinal infections establish antigen-specific, long-lived memory CD4+ T cells in the brain and meninges.

The meninges form the border between the brain and periphery and house a rich network of immune cells. Here we show that gastrointestinal challenges (intracellular or extracellular bacteria and parasites) reshape the nature of CD4+ T cells in the dura mater, the outer meningeal layer, changing the dominant polarization states to T helper (TH) 1, TH17 and TH2 cells, respectively, with differing cytokine profiles. This occurs via CXCR6-CXCL16-dependent migration of gut-activated CD4+ T cells to the central nervous system, where they establish long-lived memory populations around the dural venous sinuses, within dural lymphoid aggregates and in the brain. Functionally, these orally primed dural CD4+ T were capable of rapid, antigen-specific recall responses, proliferating and producing cytokines upon intravenous rechallenge. Our findings reveal a direct link between intestinal and dural immunity, enabling the central nervous system borders to acquire immunological memory of gut microorganisms, a major source of bloodborne pathogens capable of reaching the brain via fenestrated dural vasculature.

Journal Article↗
PubMed2026

Genome-wide identification, characterization, evolutionary analysis, and expression profiling of the FCS-like zinc finger (FLZ) gene family in soybean (Glycine max L.) under abiotic stresses.

Drought and salinity limit soybean yield. Despite their role in the SnRK1 energy-sensing complex, a systematic study of FCS-Like Zinc Finger (FLZ) proteins in soybean has not been reported. We performed a genome-wide identification of the GmFLZ gene family, identifying 40 members distributed across 18 of the 20 soybean chromosomes. Phylogenetic analysis of 87 FLZ proteins from Glycine max, Arabidopsis thaliana, and Oryza sativa revealed four major evolutionary clades, suggesting that diversification predates the separation of monocots and dicots. Structural analysis identified ten conserved motifs, with Motifs 1 and 2 present in all family members. Gene duplication analysis identified 304 paralogous pairs, most arising from segmental duplication. Ka/Ks analysis indicated localized positive selection in six gene pairs and purifying selection in 97.9% of pairs. Tissue-specific expression profiling across nine tissues showed that GmFLZ5, GmFLZ15, GmFLZ25, and GmFLZ34 had the highest expression levels detected across the GmFLZ family, with GmFLZ5 the most highly expressed member in leaves, nodules, and stem and showing moderate expression in pod, root, and root hairs, whereas GmFLZ18, GmFLZ23, and GmFLZ37 showed root-preferential expression. RT-qPCR validation under drought (20% PEG-6000) and salt (200 mM NaCl) treatments in the Giza 5 cultivar showed that 36 and 34 of the 40 GmFLZ genes, respectively, exhibited at least a two-fold change in expression, with GmFLZ21 and GmFLZ35 among the most strongly induced under salt stress. These findings provide an evolutionary and functional framework for the GmFLZ family and identify candidate genes for future functional studies in soybean stress tolerance.

Glycine max↗
PubMed2026

Integrative multi-omics analysis reveals lipid/metabolite dysregulation and temporal decoupling in disease progression.

Our study presents and applies a metabolomics-driven multi-omics integration strategy to elucidate dynamic pathway interactions during disease progression. We analyzed longitudinal metabolomics datasets from a Duchenne muscular dystrophy (DMD) mouse model (6-30 weeks) and an acute Bothrops asper envenomation model (1-24 h) to contrast chronic versus acute inflammation. In the DMD model, we predicted phased cross-talk between sphingolipid metabolism and neurotrophin signaling: an early proteomic surge followed by lipid-mediated amplification and a late convergence at the protein level. Arginine and proline metabolism exhibited early metabolite accumulation preceding delayed inferred protein changes, consistent with impaired nitric oxide synthesis and argininemia-like effect. We also predicted late-stage activation of the AGE-RAGE pathway in DMD, likely triggered by ceramide buildup, and an autophagy-related lipid metabolic shift at mid-stage. In the envenomation model, tryptophan-kynurenine and nicotinamide pathways for NAD⁺ biosynthesis were rapidly perturbed at the metabolite level (1-3 h) but induced corresponding predicted enzymes only by 24 h. Thyroid hormone signaling showed an early coupling of substrate availability (tyrosine surge at 1 h) with predicted stress-response proteins and a second, delayed wave of inferred transcriptional regulators at 24 h. Acute envenomation also triggered immediate glycine/serine utilization possibly for antioxidant defense and glycerophospholipid breakdown (via phospholipase A₂), whereas chronic DMD showed sustained glycine/serine engagement and inferred, unresolved phospholipid perturbation without protein-level compensation, which may result from chronic oxidative stress. Overall, our integrative analysis revealed time-specific, multi-layer molecular perturbations distinguishing acute toxin injury from chronic muscle degeneration. Key metabolic control points (ceramide accumulation, arginine flux diversion, autophagy-lipid cross-talk, NAD⁺ salvage timing) were identified, highlighting potential targets for stage-specific therapeutic or nutritional interventions.

Animals↗
PubMed2026

A Boveri perspective on cancer biomarker testing using artificial intelligence.

Artificial intelligence (AI) can predict genomic alterations from histology, yet its adoption is slowed by a lack of trust. We argue that deliberate morphology (i.e., a cognitive understanding of histological features supported by standardized annotations) creates a bidirectional feedback loop between clinical practice and model outputs.We translate these observations into an actionable hypothesis for clinical and computational teams: that by enhancing explainability, deliberate morphology could facilitate the responsible deployment of AI biomarkers in oncology.

Journal Article↗
PubMed2026

Cell-body curvature reduces stall frequency to enhance Vibrio cholerae swimming and chemotaxis through hydrogels.

The swimming motility of the bacterial pathogen Vibrio cholerae is a virulence factor that aids in breaching the mucus layer. V. cholerae has a curved cell shape, and previous work demonstrated that loss of curvature decreases infectivity. Here, we investigate the mechanism by which curvature affects single-cell motility. We compared the chemotactic performance of wild-type curved cells and straight mutants. The two exhibit similar swimming properties in liquid and viscous solutions but differ significantly in mucus-mimicking hydrogels, where curved cells demonstrate an 86% increase in chemotactic drift. Trajectory analysis indicates comparable swimming speeds, but straight mutants experience more frequent stalls, reducing total swimming time. Stalls further reduce chemotactic performance by imposing an average reorientation down the chemical gradient, regardless of cell shape. Coarse-grained molecular dynamics simulations corroborate these results across intestinal mucus hydrogel stiffnesses and identify an optimal curvature for movement through hydrogel-like meshes, close to the pathogen's median curvature. These findings highlight cell shape's role in pathogenicity and the need to study bacterial behaviors under conditions more closely mimicking the host environment.

Vibrio cholerae↗