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PubMed2026

Pan-cancer analysis identifies APOC1 as a TAM-derived modulator of adaptive immune resistance and predictor of therapeutic response.

BACKGROUND: Apolipoprotein C1 (APOC1) has been implicated in several malignancies, yet its expression patterns, clinical significance, and immunomodulatory roles across cancer types remain poorly characterized. METHODS: We performed a comprehensive multi-omic analysis of APOC1 across 33 cancer types integrating transcriptomic, proteomic, genomic, epigenomic, and pharmacogenomic data from TCGA, GTEx, CPTAC, and multiple independent external cohorts. Immune infiltration was assessed using seven complementary algorithms. Spatial transcriptomics and single-cell RNA sequencing were employed to determine the cellular source of APOC1 expression. RESULTS: APOC1 upregulation in most cancers was associated with cancer type-specific prognosis. After adjustment for clinical covariates and macrophage infiltration, high APOC1 remained an independent adverse factor in KIRC, LGG, and STAD. APOC1 expression positively correlated with genomic instability hallmarks, including homologous recombination deficiency and aneuploidy, with these associations largely independent of immune infiltration; in contrast, associations with tumor mutational burden were substantially confounded by macrophage abundance. Immune infiltration analysis revealed a pattern consistent with adaptive immune resistance: APOC1 correlated positively with immune-activating signatures (STAT1, MHC-II, TCR signaling) and immunosuppressive M2 macrophages and Tregs, yet negatively with anti-tumor effectors (activated NK cells, dendritic cells). Spatial transcriptomics and single-cell RNA sequencing identified tumor-associated macrophages (TAMs) as the primary cellular source of APOC1, with transcripts co-localizing with CD68 in tissue sections. APOC1 expression correlated with multiple immune checkpoint molecules and was elevated in responders to immune checkpoint blockade, consistent with an inflamed yet regulated tumor microenvironment. Pharmacogenomic analyses revealed that APOC1-high tumors display distinct drug response profiles, characterized by resistance to MAPK pathway inhibitors and potential sensitivity to the HDAC inhibitor Entinostat. CONCLUSION: This pan-cancer analysis establishes APOC1 as a context-dependent biomarker and a TAM-derived modulator of adaptive immune resistance, with prognostic and therapeutic implications across malignancies. APOC1-expressing TAMs represent a potential target for combination immunotherapy strategies.

APOC1↗

PubMed2026

Impact of Genomic Mutations on the Transcriptional Pathways and Tumor Microenvironment Landscape of Localized Early Prostate Cancer.

BACKGROUND: The management of intermediate-risk early prostate cancer (PCa) is challenging due to the difficulty in distinguishing indolent from aggressive tumors. This study explores the association between genomic alterations and the tumor and its microenvironment (TME) and implications for disease progression. METHODS: We performed multi-omic profiling in a cohort of 53 localized PCa using targeted sequencing, transcriptional, and proteomic spatial profiling. RESULTS: Somatic mutations and copy number alterations in RB1 (21%), PTEN (18%), and TP53 (9%) were identified. Kaplan-Meier analysis revealed that alterations in the RB and Cell Cycle pathways, particularly aberrations in PTEN, TP53, or RB1, were associated with shorter biochemical recurrence-free survival (p < 0.001). Spatial proteomic analysis demonstrated a complex immune landscape in patients with mutations. The tumor compartment demonstrated higher expression of immune checkpoint markers, T-cell activation proteins, and proliferation markers; and a TME that is enriched with CD8 + T cells and antigen-presenting cells, but also with immunosuppressive M2 macrophages, suggesting adaptive immune resistance. CONCLUSIONS: Our analysis demonstrates that genomic alterations in PTEN, TP53, or RB1 are not only prognostic for poor outcomes but are also associated with a unique, immunologically complex TME in this Brazilian cohort.

Humans↗

PubMed2026

Cyclin-dependent kinase 4 and 6 inhibitors and the breast cancer immune ecosystem: immune remodeling, resistance, and therapeutic reprogramming.

Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6 inhibitors) combined with endocrine therapy have become a therapeutic backbone for hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer, yet durable disease control is frequently limited by intrinsic and acquired resistance. Canonical tumor-cell mechanisms, including retinoblastoma-pathway escape, cyclin E-cyclin-dependent kinase 2 (CDK2) activation, endocrine adaptation, and phosphoinositide 3-kinase (PI3K)-AKT-mechanistic target of rapamycin (mTOR) signaling, explain only part of this failure because they do not fully capture dynamic immune and stromal remodeling. Preclinical and translational studies indicate that early CDK4/6 inhibition can enhance antigen presentation, activate interferon-related programs, restrain regulatory T cells, and promote a T-cell-inflamed state. These effects are conditional and may not persist during prolonged treatment. Sustained therapy can instead drive heterogeneous resistant niches characterized by stromal remodeling, myeloid recruitment, checkpoint adaptation, and T-cell dysfunction. This immune-state dependence provides a rationale for immune checkpoint blockade, although clinical combinations have shown mixed efficacy and clinically relevant hepatic, pulmonary, and hematologic toxicities. Sequential or lead-in strategies therefore warrant prospective evaluation. Oxidative phosphorylation (OXPHOS) and redox adaptation may sustain selected resistant states and expose context-dependent ferroptotic vulnerabilities. Ferroptosis may connect tumor-cell killing with immune regulation, whereas nanomedicine may improve tumor-selective delivery. Both strategies remain largely preclinical and require further evaluation of pharmacokinetics, biodistribution, toxicity, manufacturability, and immune-cell safety. This Review distinguishes intrinsic from acquired resistance across interpatient, intratumoral, spatial, and temporal dimensions. It integrates tumor-cell escape with cytokine, immune, stromal, vascular, and metabolic remodeling and summarizes emerging therapeutic strategies. We further propose a candidate biomarker-informed framework that integrates genomic profiling, spatial immune architecture, circulating biomarkers, T-cell receptor (TCR) dynamics, transcriptomic and single-cell analyses, artificial intelligence (AI)-assisted multimodal integration, and longitudinal sampling. This framework is intended to support biomarker development and prospective trial design rather than current clinical decision-making, providing a translational basis for testing state-informed and sequence-aware therapeutic strategies.

Humans↗

PubMed2025

Adaptation of the Cyst Nematode Globodera pallida to the Colinear Potato Resistant QTLs GpaVvrn and GpaVspl Involved Distinct Genomic Regions and Absence of Cross-Virulence.

The use of alternative methods to control cyst nematode populations has accelerated since the ban of chemical nematicides in Europe. The resistant QTL GpaVvrn, derived from the wild species Solanum vernei, is widely present in resistant European potato cultivars and provides strong protection against Globodera pallida populations although a risk of resistance breakdown has already been demonstrated in both experimental evolution studies and field populations. The wild relative S. sparsipilum, harbouring the resistant QTL GpaVspl, would be an interesting alternative source of resistance to control virulent G. pallida. The goal of the present study was to understand the genomics of adaptation of the nematode to these two colinear resistant QTLs. Starting with two natural populations, an experimental evolution approach allowed, after 10 generations on resistant potato genotypes, selecting independent nematode lineages adapted to each QTL. These virulent lineages were analysed through a combination of phenotyping and genome scans approaches. Phenotyping enabled the quantification of virulence levels and confirmed resistance breakdowns. Pool-Seq whole genome sequencing followed by genome scan analyses identified genomic regions under selection, potentially involved in the adaptive mechanisms to each resistance factor. Candidate genes within these regions provided insights into the genetic basis of adaptation, revealing effectors known to suppress plant immunity. As genome scans highlighted distinct genomic regions for the adaptation to both resistant factors, we were able to predict and phenotypically confirm the absence of cross-virulence between nematode lineages evolving on GpaVvrn and GpaVspl. These findings have significant implications for the design of effective and sustainable resistance management strategies.

Animals↗

PubMed2026

The Adaptive Roles of Active Transposable Elements in Insect Hosts.

Active transposable elements (TEs) are capable of generating new insertions in genomes and have historically been viewed as genomic parasites due to their largely detrimental or neutral effects. However, emerging evidence suggests that these elements also play a crucial role in driving adaptive evolution in insects. This mini-review synthesizes recent findings on how active TEs contribute to insect adaptation through various mechanisms, including regulation of gene expression, structural variation, and epigenetic effects. Notable examples of adaptation driven by active TEs include their roles in insecticide resistance, morphological adaptations, tolerance to harsh climates, and antiviral immune responses. We argue that while host silencing mechanisms, such as the piRNA pathway, tightly regulate TE activity to minimize harmful effects, the context-dependent activation of active TEs can generate beneficial genetic variation that enhances insect adaptations to anthropogenic and climatic pressures. Future research that integrates long-read sequencing, single-cell omics, and gene editing techniques will provide a robust mechanistic foundation for understanding the adaptive significance of active TEs in insects, with important implications for pest management, pollinator protection, and evolutionary biology.

Journal Article↗

PubMed2025

HLA-E and NKG2A Mediate Resistance to BCG Immunotherapy in Non-Muscle-Invasive Bladder Cancer.

Bacillus Calmette-Guérin (BCG) is the first-line therapy for high-grade non-muscle-invasive bladder cancer (NMIBC), yet many patients experience recurrence due to immune evasion. We identify HLA-E and NKG2A as mediators of adaptive resistance involving chronic activation of NK and T cells in BCG-unresponsive tumors. Prolonged IFN-γ exposure enhances HLA-E and PD-L1 expression on recurrent tumors, accompanied by the accumulation of NKG2A+ NK and CD8 T cells. HLA-Ehigh tumor cells preferentially cluster near CXCL12-rich stromal regions with dense effector cell presence, underscoring a spatially segregated tumor architecture. Although cytotoxic lymphocytes retain effector potential, their activity is restrained by HLA-E/NKG2A and PD-L1/PD-1 pathways located in their immediate neighborhood within the bladder tumor microenvironment. These data reveal a spatially organized immune escape program that limits anti-tumor immunity. Our findings support dually targeting NKG2A and PD-L1 checkpoint blockade as a rational, bladder-sparing strategy for patients with BCG-unresponsive NMIBC.

BCG-unresponsive↗

PubMed1979

Maintenance of the adequate function is a general principle of survival of organisms.

A general theory which describes the existence of live organisms is introduced; this theory is the Principle of Adequate Function and it describes all the situations in which live organisms may exist, whether healthy or sick at both physiological and pathological conditions. In biology, so far, the existence of living organisms under physiological conditions is described by homeostasis, and under pathological conditions specific immunity is used. As it is shown below, adaptation and non-specific resistance provide a much broader basis of how living organisms exist under both physiological and pathological conditions. This general theory does not interfere with the notions of homeostasis, adaptation, and specific immunity but includes them as particular cases. It is proposed that the principle of adequate function supplements the description of life processes by the evolutionary principle; it describes the laws of existence and function of a particular individual.

Adaptation, Biological↗

PubMed1979

Macrophage immunity to influenza virus: in vitro and in vivo studies.

Using M-TUR, a macrophage-adapted avian influenza A virus (Hav1, Nav3), antiviral resistance of peritoneal macrophages obtained from specifically or nonspecifically immunized mice towards in vitro infection was assessed. M-TUR grew to high titers in macrophages from nonimmune mice thereby causing a marked cytopathic effect. In contrast, peritoneal macrophages from mice specifically immunized with TUR virus were not affected by infection with M-TUR in vitro. This antiviral immunity was specific: mice immunized with antigenetically unrelated influenza strains such as influenza A/Hong Kong/1/68 (H3, N2) or influenza B/Lee yielded susceptible macrophages. Specific macrophage immunity could be abrogated by trypsin treatment in vitro. Susceptible macrophages from nonimmune hosts became resistant following in vitro exposure to homologous anti-TUR sera. Peritoneal exudate cells from BCG-infected animals were less susceptible to in vitro challenge with M-TUR than control macrophages. In vivo treatment of mice with the unspecific immunostimulants BCG or Corynebacterium parvum did not protect the animals against lethal infection with a hepatotropic variant of TUR.

Animals↗

PubMed2025

Evaluating selection at intermediate scales within genes provides robust identification of genes under positive selection in M. tuberculosis clinical isolates.

Multiple studies have reported genes in the M. tuberculosis (Mtb) genome that are under diversifying selection, based on genetic variants among Mtb clinical isolates. These might reflect adaptions to selection pressures associated with modern clinical treatment of TB. Many, but not all, of these genes under selection are related to drug resistance. Most of these studies have evaluated selection at the gene-level. However, positive selection can be evaluated on different scales, including individual sites (codons) and local regions within an ORF. In this paper, we use GenomegaMap, a Bayesian method for calculating selection, to evaluate selection of genes in the Mtb genome at all three levels. We present evidence that the intermediate analysis (windows of codons) yields the most credible list of candidate genes under selection (excluding PPE and PE_PGRS genes, which are predicted less reliably due to frequent sequencing errors). A further advantage of this approach is that it identifies specific regions within proteins that are under selective pressure, which is useful for structural and functional interpretation. In an analysis of two separate collections of Mtb clinical isolates (from Moldova; and a globally-representative set), we observed 53 and 173 significant genes under selection, with 36% overlap. The lists of genes under selection include many drug-resistance genes, as well as other genes that have previously been reported to be under selection (resR, phoR). The specific regions under selection identified within drug-resistance genes are shown to correspond to protein structural features known to be involved in resistance, supporting accuracy of the method. Positive selection in several ESX-1-related genes was also observed, suggesting adaptation to immune pressure.

adaptation↗

PubMed2026

Regnase-1-mediated regulation of neutrophils modulates SARS-CoV-2 pneumonia.

The innate immune response to viral infection needs to be tightly regulated to ensure effective pathogen clearance while avoiding excessive immune activation. During SARS-CoV-2 infection, however, the immune system often fails to elicit appropriate responses, resulting in cytokine-release syndrome in patients with COVID-19. In this study, we show that reduced expression of Regnase-1, an RNase that negatively regulates immune cell activation, confers resistance to infection with the mouse-adapted SARS-CoV-2 MA10 strain. In Regnase-1+/- mice, altered neutrophil function contributed to the amelioration of MA10-induced pneumonia. Single-cell RNA sequencing of lung tissue during MA10 infection revealed four distinct neutrophil subsets, and among these, a subset characterized by an interferon-stimulated gene (ISG) signature was decreased in Regnase-1+/- mice. Furthermore, Regnase-1+/- neutrophils exhibited reduced ISG expression without corresponding changes in proinflammatory gene expression. Regnase-1 was found to repress the expression of Tsc22d3, a gene involved in the negative regulation of interferon responses, through its 3' untranslated region. Collectively, these findings suggest that Regnase-1 attenuates resistance to SARS-CoV-2 MA10 infection by promoting excessive interferon responses in neutrophils.

Animals↗

PubMed2026

A cis-regulatory allele of ZmNPR1I spatially uncouples flowering from stalk-rot resistance in maize.

Pleiotropic effects of adaptive genes frequently constrain crop improvement by coupling beneficial traits with unfavorable trade-offs. In maize, ZmCCT10 confers strong stalk-rot resistance but causes delayed flowering under long-day conditions, limiting its deployment in temperate breeding. Here, we identify qPss3 as a cis-regulatory locus that governs its downstream target gene, ZmNPR1I. The ZmNPR1I protein represses ZmCCT10 transcription and, together with ZmNPR1-3, facilitates ZmCCT10 protein degradation. The favorable qPss3A5 allele reduces ZmNPR1I expression in leaves, relieving repression of ZmCCT10, ZmSPL32, and ID1, which collectively enhance ZCN8 expression to accelerate flowering. In roots, however, pathogen-induced activation of the resistant ZmCCT10H5 allele largely bypasses qPss3 regulation, thereby preserving stalk-rot resistance. Introgression of qPss3A5 into ZmCCT10H5-containing maize germplasm restores flowering adaptation without compromising disease resistance, improving yield stability under disease pressure. Our work reveals a tissue-specific qPss3A5-ZmNPR1I regulatory module that uncouples the developmental and immune functions of a pleiotropic adaptive gene, providing a general strategy for optimizing beneficial alleles in crop breeding.

flowering time↗

PubMed2026

Genome-wide identification and characterization of ABC transporters and their expression in response to saline-alkaline stress and WSSV infection in Fenneropenaeus chinensis.

ATP-binding cassette (ABC) transporters play crucial roles in stress responses across organisms, yet their functions in Fenneropenaeus chinensis remain largely unknown. In this study, we identified 42 FcABC genes (FcABCs) in the F. chinensis genome and analyzed their phylogenetic relationships, gene structures, and chromosomal distributions. Phylogenetic analysis grouped the FcABCs into eight subfamilies (ABCA-ABCH), with conserved motif and domain compositions within each subfamily. Expression analysis showed that several FcABC genes, including FcABCG5, FcABCA1, and FcABCC3, were significantly induced under saline-alkaline stress in gill and hepatopancreas tissues. In contrast, most FcABCs were downregulated after WSSV challenge, though a subset (e.g., FcABCB1, FcABCC1) exhibited early upregulation. Functional validation via RNA interference demonstrated that knockdown of FcABCG5 increased shrimp mortality under saline-alkaline stress. Cis-regulatory element analysis revealed an enrichment of stress- and immune-related elements in FcABC promoters. Protein-protein interaction network predictions indicated potential roles for FcABCs in cholesterol metabolism and organic anion transport. Our findings provide insights into the roles of FcABC genes in stress adaptation and immune defense, offering candidate genes for the breeding of stress-resistant shrimp varieties.

Animals↗

PubMed2026

Chaperone-mediated autophagy as a regulator of hallmarks of cancer.

Chaperone-mediated autophagy (CMA) is a selective lysosomal degradation pathway that maintains cellular homeostasis by degrading soluble proteins containing KFERQ-like motifs. Although CMA has traditionally been recognized for its role in protein quality control and cellular stress adaptation, increasing evidence shows that it is frequently altered in cancer, where it regulates multiple processes that promote tumor initiation, progression, and therapy resistance. The growing number of identified CMA substrates involved in cell proliferation, apoptosis, metabolism, DNA damage response, immune regulation, inflammation, and cellular plasticity suggests that CMA is much more than a protein degradation pathway; it is an important regulator of tumor adaptation. In this review, we bring together current evidence to provide a comprehensive understanding of how CMA contributes to the Hallmarks of Cancer, including sustained proliferative signaling, resistance to cell death, metabolic reprogramming, invasion and metastasis, immune evasion, and the enabling characteristics of genome instability and tumor-promoting inflammation. We further explore the emerging roles of CMA in cellular plasticity and cancer stem cell maintenance, two interconnected processes that drive tumor progression, metastasis, and therapeutic resistance. By integrating evidence from diverse tumor types, this review provides a comprehensive understanding of how CMA shapes multiple hallmarks of cancer by selectively degrading key regulatory proteins. Finally, we highlight the context-dependent roles of CMA, identify key gaps in our current understanding, and discuss the opportunities and challenges of targeting CMA for cancer therapy. Overall, this hallmark-based perspective provides an integrated understanding of how CMA contributes to multiple hallmarks of cancer and supports its potential as a therapeutic target.

autophagy↗

PubMed2026

Decoding glioblastoma evolution and heterogeneity through mechanistic modeling: implications for clinical translation.

Glioblastoma (GBM) is one of the most aggressive and lethal primary brain tumors in adults, characterized by dynamic clonal evolution and extensive genomic, cellular, spatial, and microenvironmental heterogeneity. Multi-omics studies have revealed that GBM follows complex evolutionary trajectories involving genetic, epigenetic, transcriptional, and immune-microenvironmental remodeling as tumors grow, adapt to the brain microenvironment, and acquire therapeutic resistance. Increasing evidence suggests that GBM may originate from aberrant neural stem or progenitor cells, including those residing in the subventricular zone, and that glioblastoma stem cells (GSCs) contribute to tumor propagation, heterogeneity, and recurrence. A key conceptual challenge is to reconcile hierarchical cancer stem cell models, in which GSCs are viewed as relatively stable tumor-propagating subpopulations, with dynamic state plasticity models, in which stem-like properties can be reversibly acquired or lost during transitions among proneural-like, mesenchymal-like, invasive, and therapy-tolerant states. Recent advances in single-cell profiling, spatial transcriptomics, lineage tracing, organoid culture, 3D bioprinting, genetically engineered models, and artificial intelligence (AI)-assisted computational modeling have substantially improved the ability to study these processes. However, no currently available model fully recapitulates human GBM heterogeneity, recurrence, treatment history, and tumor-microenvironment interactions. Therefore, model selection should be guided by clearly defined mechanistic questions rather than by reliance on any single platform. This review summarizes current advances in in vitro, ex vivo, in vivo, and computational models for studying GBM evolution and heterogeneity, and discusses how integrated model pipelines may improve preclinical drug testing, treatment-response prediction, and precision neuro-oncology.

Humans↗

PubMed2026

Virus-induced gene silencing as a tool for functional genomics in weeds: Challenges and future directions.

Virus-induced gene silencing (VIGS) has evolved from a conceptual demonstration of antiviral defense into a pivotal reverse-genetics platform for plant functional genomics. By exploiting engineered DNA- or RNA-based viral vectors, VIGS enables rapid, sequence-specific transcript knockdown through RNA-mediated degradation of target transcripts. Recent refinements in vector design, inoculation strategies, and viral species selection, such as TRV, BSMV, and FoMV, have expanded its application to previously recalcitrant plants, including major crops and emerging weed models. In weeds, functional genomics remains particularly challenging due to high genetic variability, limited genomic resources, and incompatibility with conventional viral vectors and transformation systems. In this context, VIGS provides a tractable approach to investigate genes associated with herbicide resistance, metabolic adaptation, and stress tolerance. Beyond weed biology, its application to studies of immune signaling, hormonal crosstalk, and secondary metabolism highlights VIGS as a versatile biotechnology for elucidating gene function and supporting next-generation strategies in plant improvement and integrated pest management.

Journal Article↗

PubMed2025

Experimental evolution of a pathogen confronted with innate immune memory increases variation in virulence.

Understanding the drivers and mechanisms of virulence evolution is still a major goal of evolutionary biologists and epidemiologists. Theory predicts that the way virulence evolves depends on the balance between the benefits and costs it provides to pathogen fitness. Additionally, host responses to infections, such as resistance or tolerance, play a critical role in shaping virulence evolution. But, while the evolution of pathogens has been traditionally studied under the selection pressure of host adaptive immunity, less is known about their evolution when confronted to simpler and less effective forms of immunity such as immune priming. In this study, we used a well-established insect model for immune priming - red flour beetles and their bacterial pathogen Bacillus thuringiensis tenebrionis - to test how this form of innate immune memory drives the pathogen evolution. Through controlled experimental evolution of the pathogen in primed versus non-primed hosts, we found no change in average virulence after eight selection cycles in primed host. Nonetheless, we observed a notable rise in the variability of virulence, defined as the ability to kill hosts, among independent pathogen lines that evolved in primed hosts, and the bacteria were unable to develop resistance to host priming. Whole genome sequencing revealed increased activity in the bacterial mobilome (prophages and plasmids). Expression of the Cry toxin - a well-known virulence factor - was linked to evolved differences in copy number variation of the cry-carrying plasmid, though this did not correlate directly with virulence. These findings highlight that innate immune memory can drive variability in pathogen traits, which may favor adaptation to variable environments. This underscores the need to consider pathogen evolution in response to innate immune memory when applying these mechanisms in medicine, aquaculture, pest control, and insect mass production.

Animals↗

PubMed2026

Overcoming cancer resistance in pancreatic cancer: toward dynamic precision oncology.

Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy, largely because of its profound and evolving therapeutic resistance. Resistance is not determined by a single molecular alteration but arises from interconnected mechanisms, including intrinsic resistance, treatment-induced adaptive resistance, acquired resistance, genomic evolution, clonal selection, cancer stemness, phenotypic plasticity, metabolic adaptation, and tumor microenvironment-mediated effects. Emerging therapeutic approaches targeting KRAS/RAS signaling, stromal and immune components, metabolic dependencies, and DNA damage repair pathways offer opportunities to address these mechanisms, although durable efficacy remains limited by biological heterogeneity and adaptive responses. In this review, we examine therapeutic resistance as an evolutionary and multidimensional process and summarize emerging strategies for overcoming resistance. We further propose a Dynamic Precision Oncology (DPO) framework that extends conventional precision oncology beyond baseline molecular profiling by integrating longitudinal assessment of tumor genomics, circulating tumor DNA, CA19-9, imaging, radiomics, and clinical characteristics. This framework emphasizes iterative detection and characterization of emerging resistance, mechanism-informed treatment adaptation, and subsequent reassessment rather than automatic treatment modification based on a single biomarker. DPO may provide a conceptual framework for integrating evolving tumor biology into treatment decision-making, while prospective studies are needed to validate biomarkers, define actionable thresholds, and determine whether longitudinal resistance-guided strategies improve clinical outcomes in PDAC.

Humans↗

PubMed2026

Comprehensive profiling of antibiotic resistance genes and functional clusters of orthologous groups annotation of gut microbiota in Indonesian Kedu chickens.

Antibiotic resistance is a growing global health concern, with poultry systems acting as important reservoirs of antibiotic resistance genes (ARGs). However, resistome and functional profiles of indigenous chickens raised under traditional systems remain underexplored. This study aimed to characterize the antibiotic resistome, virulence factor genes, and metabolic potential of gut microbiota in Indonesian Kedu chickens using a shotgun metagenomic approach. Digesta samples from five gastrointestinal segments of 21 healthy adult chickens were analyzed through high-throughput sequencing. ARGs were identified using the Comprehensive Antibiotic Resistance Database (CARD) and Antibiotic Resistance Genes Databases (ARDB), while virulence factors and functional genes were annotated using Virulence Factor Database (VFDB), Clusters of Orthologous Groups (COG), and Carbohydrate-Active EnZymes (CAZy) databases. Results revealed a diverse resistome dominated by multidrug resistance and efflux pump mechanisms, with prominent genes associated with fluoroquinolone, tetracycline, β-lactam, and glycopeptide resistance. The detection of clinically relevant ARGs suggests that genetic determinants associated with antimicrobial resistance are present in the gut microbiota of traditionally raised Kedu chickens, although metagenomic data alone cannot determine whether these genes are actively expressed or confer phenotypic resistance. Virulence factor analysis showed functions related to adherence, immune evasion, iron acquisition, quorum sensing, and efflux activity, reflecting strong microbial adaptability. Functional profiling demonstrated enrichment in translation, carbohydrate and amino acid metabolism, genome maintenance, and cell envelope biogenesis. Additionally, CAZyme analysis indicated a high capacity for complex polysaccharide degradation, supporting efficient utilization of fiber-rich traditional diets. In conclusion, this study provides a comprehensive metagenomic overview of antibiotic resistance and functional potential in Kedu chicken gut microbiota, emphasizing the importance of incorporating indigenous poultry into antimicrobial resistance surveillance within a One Health framework.

Antibiotic resistance genes↗