Search Results (7,917)

Background: The pathophysiological mechanisms of Abdominal Aortic Aneurysm (AAA) are not elucidated. Alterations in mitochondrial function, such as a reduction in oxidative phosphorylation (OXPHOS), have been observed at genome level and functionally in vascular smooth muscle cells. Metformin reduces AAA development and growth in diabetic patients, but the precise mechanisms are not known. In this paper we aim to demonstrate the feasibility of measuring mitochondrial functional capacity ex vivo in intact murine aneurysmal tissue and confirm a decrease in OXPHOS, and to determine if the protective effect of metformin on AAA is mediated by mitochondrial function. Methods: AAA was induced in ApoE KO mice by administration of angII (1000 ng/kg/min) through osmotic minipumps. Metformin was administered in drinking water at a dose of 100 mg/kg/day. The abdominal aorta was isolated in situ and mitochondrial functional capacity was analyzed ex vivo in whole permeabilized tissue by high-resolution respirometry. Results: Mitochondrial respiration was successfully measured ex vivo in whole aneurysmal tissue. Mitochondrial function was impaired in angII-treated mice, with decreased fold change in Complex I and Complex I+II oxygen consumption, relative to basal levels. Complex II oxygen consumption was also decreased in angII-treated mice. Rescue treatment of mice with metformin did not affect or restore mitochondrial function. Conclusions: Mitochondrial function can be evaluated in murine whole aneurysmal tissue, providing a method for a physiological approach to the study of mitochondrial function in AAA. Mitochondrial function is impaired in AAA. However, rescue treatment with metformin is not sufficient to recover mitochondrial function and seems not to be the mechanism behind prevention of aneurysm. Full article

Inbreeding is a quantitative measure of autozygosity that underlies the assessment of genetic risks and the management of genetic progress in livestock populations. The development of methods for its estimation reflects a transition from probabilistic pedigree-based models to the direct analysis of genome structure. This review systematizes the evolution of approaches to inbreeding assessment—from the classical inbreeding coefficient F based on identity by descent (IBD) to marker-based, segment-based runs of homozygosity (ROH) and probabilistic homozygous-by-descent (HBD) models. It is shown that the coefficients F_ped, F_GRM, F_ROH, and F_HBD capture related but distinct aspects of autozygosity and are therefore not fully interchangeable. Particular attention is paid to the transition from integral indicators to spatially and temporally stratified analyses of autozygosity, enabling the differentiation between ancient and recent inbreeding. Methodological assumptions, limitations, and the sensitivity of various approaches to marker density, detection parameters, and population demographic structure are discussed. A comparative analysis of methods for calculating F_ROH and segment-based autozygosity is presented. The necessity of a comprehensive assessment of inbreeding and the standardization of analytical protocols for its application in modern breeding programs is substantiated. Full article

The reciprocal relationship between genes and nutrients, known as nutrigenetics and nutrigenomics, has been established in many studies. However, current investigations of maternal and neonatal nutrition using a precision nutrition approach focused on genomics are limited, especially in the Middle East and North Africa (MENA) region. This review aims to summarize the impacts of the dietary micronutrients, folic acid, thiamine, and cobalamin on optimal health outcomes during pregnancy, fetal development, lactation, and infant growth. In this review, the roles of folic acid, thiamine, and cobalamin are discussed in the context of various aspects of pregnancy, such as preconception, fetal development, and lactation, highlighting how genetic events occurring during developmental periods can have consequential impacts on health outcomes later in life. Deficiency rates and related health consequences as well as the prevalence of genetic mutations related to these nutrients of interest in the MENA region are also elaborated on. How to advance knowledge and applications of precision nutrition, how genes interact with the neurochemical changes during pregnancy, and how this interaction impacts maternal eating behaviors, and consequently fetal development and infant and child growth and health, should be further explored in future studies. This includes taking advantage of cutting-edge technologies and the role of artificial intelligence in this endeavor. Full article

The guinea fowl (Numida meleagris), a thermo-tolerant and disease-resilient poultry species, holds great potential for sustainable poultry production in climate-vulnerable regions. The genomic aspects of this species remain largely understudied. The present study aims to delineate the patterns of domestication and understand the evolutionary dynamics of guinea fowl populations (wild and domestic) across three continents, utilizing whole-genome sequencing data from 122 genomes. The population structure analyses (ADMIXTURE, PCA, phylogeny, F_ST, LD, and MAF) revealed that Indian guinea fowl (CARI) shared close ancestry with Iranian (IRAD) and Chinese (CHID) domesticated populations while remaining distinct from wild lineages. The runs of homozygosity (ROH) identified 49,088 segments, with short fragments (ROHs) preponderant in Indian and domestic populations, reflecting historical inbreeding and effects of domestication cum selection. Copy number variation (CNV) analysis revealed 105,178 CNVs concatenated into 40,067 CNV regions (CNVRs) across 11 populations, establishing the first CNV atlas for guinea fowl at the global level. Gene annotation of overlapping ROH and CNVRs revealed 1080 common candidates across Asian guinea fowl populations, i.e., the Indian guinea fowl (CARI), IRAD, and CHID, including FOS, EPAS1, CD74, and CSF1R. These genes have earlier been associated with immune regulation, stress response, and thermal adaptation. Selection signature scans, integrating intra-population (iHS) and inter-population (XP-EHH) approaches, uncovered genes under positive selection linked to immune response (like BCL11B, IL18, and GPC3), thermo-tolerance (like TRPV4 and BAG3), lipid metabolism (like AACS and ELOVL4), and pigmentation (BCO2). These signatures highlight the molecular basis of resilience in guinea fowl and their potential to withstand climate-induced stresses. This study presents the first global CNV atlas for guinea fowl and provides the first comprehensive genomic characterization of the Indian domestic population, integrating ROH, CNV, and selection signature analyses. It offers a comprehensive assessment of guinea fowl genomes (wild and domesticated) across three continents, offering insights into domestication, evolutionary dynamics, and the genetic basis of their adaptation and resilience. Full article

Metagenomic and targeted next-generation sequencing (NGS) technologies are rapidly transforming diagnosis and management for infectious diseases. This review comprehensively examines the current applications of metagenomic NGS (mNGS) and targeted NGS (tNGS) in clinical microbiology, highlighting their roles in pathogen detection, antimicrobial resistance profiling, virulence characterization, and outbreak investigation—particularly in complex cases such as pneumonia, critical illness with pulmonary infections, and pediatric acute respiratory illnesses. We discuss the diagnostic performance, advantages, and limitations of these approaches, including challenges related to sensitivity, specificity, standardization, bioinformatic complexity, and cost-effectiveness. Furthermore, we explore emerging opportunities for integrating NGS-based surveillance with public health strategies, such as wastewater epidemiology, to monitor healthcare-associated infections (HAIs) and antimicrobial resistance (AMR) at the population level. Finally, we outline key steps needed to translate these powerful genomic tools from research settings into routine clinical and public health practice. Full article

The remarkable evolution of oncological therapies has dramatically improved cancer survival rates but has simultaneously introduced a significant burden of cardiovascular complications. Cardio-oncology has emerged as a critical multidisciplinary field focused on mitigating the “collateral damage” of life-saving anticancer treatments, ranging from traditional chemotherapeutics to novel immunotherapies. This review provides a comprehensive analysis of the pathophysiological mechanisms, clinical phenotypes, and evolving management strategies for cancer therapy-related cardiac dysfunction (CTRCD). An extensive synthesis of the current literature was conducted, focusing on the molecular pathways of cardiotoxicity, including Topoisomerase IIβ inhibition by anthracyclines, HER2 signaling disruption by targeted agents, and immune-mediated myocarditis triggered by checkpoint inhibitors (ICIs). Cardiotoxicity is increasingly recognized as a spectrum of phenotypes. Heart failure with reduced ejection fraction (HFrEF) remains a primary concern with cytotoxic agents, while heart failure with preserved ejection fraction (HFpEF) is emerging as a critical complication of radiation therapy and tyrosine kinase inhibitors (TKIs). The integration of advanced diagnostic tools—specifically Global Longitudinal Strain (GLS) and Cardiac Magnetic Resonance (CMR) mapping—has shifted the clinical focus toward subclinical detection. Furthermore, pivotal clinical trials such as PRADA and SUCCOUR have validated early pharmacological prophylaxis and strain-guided interventions. Emerging challenges, including the management of CAR-T cell-induced cytokine release syndrome and the specific cardiovascular needs of pediatric and geriatric populations, are also explored. The future of cardio-oncology lies in precision medicine, leveraging genomic profiling and artificial intelligence to identify high-risk individuals. A proactive, multidisciplinary approach is essential to ensure that the success of modern oncology is not compromised by irreversible cardiovascular morbidity. Full article

Background: Gene expression and cellular identity are regulated by epigenetics that occurs through chromatin modifications, RNA changes, chromatin accessibility, and three-dimensional genome organization. Although DNA methylation has been the focus of most epigenetics studies in the past, other non-methyl epigenetic processes, including histone post-translational modifications (PTMs), epitranscriptomic marks, and chromatin remodeling, are dynamic, reversible, and context-dependent, and thus are difficult to accurately interrogate using endpoint sequencing-based assays, especially in heterogeneous tissues, developing systems, and therapeutic response environments. Scope and Approach: The present review discusses epigenetic modifications other than DNA methylation regarding sensor-based technologies that can measure live, dynamic, and spatially resolved measurements. Epigenetic sensors include any genetically encoded sensors (GECs) based on resonance energy transfer, CRISPR/dCas-derived sensors, or aptamer-based sensors, and hybrid biochemical/imaging sensors that can be used in live or semi-live settings. It lays emphasis on the technologies, which have been developed recently, that allow real-time kinetic measurements, working in three-dimensional and organoid models, and being applied to disease-relevant perturbations. On these platforms, performance properties such as specificity, sensitivity, spatial and temporal resolution, ability to perform dynamic versus locus-specific interrogation, and perturbed endogenous chromatin states are compared. Key Conclusions and Outlook: Together, these sensing strategies are complementary to the traditional methods of measuring epigenomics in that they show epigenetic dynamics unobservable with static measurements. We list the important technical issues, including specificity, quantitation, multiplexing, and chromatin perturbation, and report the barriers and solutions in development and design. Lastly, we provide a conceptual map of how live epigenetic sensing and multi-omics and translational models can be integrated, and how the two methodologies can be used to develop functional epigenetics and guide disease modeling and drug development. Full article

Background/Objectives: Influenza, RSV, and SARS-CoV-2 co-circulate and evolve under immune and therapeutic pressures, complicating decision-making for both vaccine formulation and antiviral use. Fragmented, pathogen-specific sequencing approaches limit cross-virus comparability. Methods: We applied a standardized, multiplexed, amplicon-based next-generation sequencing (NGS) workflow to 34 diagnostic specimens (Ct < 35) positive for influenza A/B, RSV-A/B, or SARS-CoV-2. Sequencing libraries were generated and run on an Illumina MiSeq platform (2 × 250 bp). Although the wet-lab workflow is standardized across pathogens, consensus generation and annotation utilized two different analysis environments: Geneious Prime for influenza and MicrobioChek for RSV and SARS-CoV-2. Quality metrics included genome breadth and depth of coverage. Results: Near-complete genomes (mean coverage ≥98%) were recovered for all samples. Influenza A(H1N1)pdm09 sequences clustered in clade 6B.1A; A(H3N2) clustered in subclade 3C.2a1b.2a.2; and influenza B belonged to the Victoria lineage V1A.3a.2. RSV sequences were assigned to Nextclade clades A.D.5.1, A.D.1.10, A.D.2.1, and A.D.3 (RSV-A) and to B.D.4.1.3 and B.D.E.1 (RSV-B), consistent with the ON1 (RSV-A) and BA (RSV-B) genotypes prevalent in recent seasons. Clinically relevant mutations included changes in the influenza HA site and neuraminidase substitutions, RSV F-protein polymorphisms, and spike protein substitutions associated with recent Omicron sublineages (L455F/S, F456L) in SARS-CoV-2. Conclusions: A unified amplicon–NGS approach yields harmonized genomic data across respiratory viruses, enabling timely detection of antigenic drift and resistance markers while supporting integrated, cross-pathogen surveillance. Full article

Oral squamous cell carcinoma (OSCC) remains a major global health burden due to aggressive invasion, early metastasis, therapeutic resistance, and poor long-term survival. Beyond tumor-intrinsic genetic and epigenetic alterations, accumulating evidence highlights the critical role of the tumor microenvironment in shaping OSCC progression and clinical outcomes. Cancer-associated fibroblasts (CAFs) and immune cells orchestrate tumor initiation, immune evasion, and recurrence through extracellular matrix remodeling, cytokine signaling, angiogenesis, and metabolic and redox regulation. Key oncogenic pathways, including EGFR/PI3K/AKT/mTOR, TGF-β, Wnt, and Notch, integrate with non-coding RNA networks to reinforce stemness, epithelial–mesenchymal transition, and therapy resistance. Moreover, PD-1/PD-L1-mediated immune escape, CAF-driven biomechanical remodeling, and metabolic reprogramming such as aerobic glycolysis and lipid metabolism contribute to OSCC heterogeneity. This review synthesizes current insights into OSCC across genomic, epigenetic, metabolic, and microenvironmental dimensions, emphasizing CAF biology, immune landscape reprogramming, and non-coding RNA regulation. We further discuss emerging biomarkers, liquid biopsy approaches, and targeted therapeutic strategies, providing a system-level framework for biomarker-guided stratification and precision combination therapies in OSCC. Full article

Wuweiganlu (WGL) is a traditional formulation widely applied in the treatment of rheumatoid arthritis (RA), yet the identity of its bioactive constituents remains inadequately defined. In this study, ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and untargeted serum metabolomics were employed to characterize the active components of WGL. Fraxin was identified as a principal compound from WGL. To investigate its therapeutic mechanism in RA, a series of in silico and experimental approaches were conducted. Network pharmacology analysis and RNA sequencing identified heat shock protein family member 8 (HSPA8) as a potential molecular target of Fraxin, which was further validated by molecular docking studies. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that Fraxin exerts its effects primarily by modulating cell apoptosis through the PI3K signaling pathway. In vitro experiments demonstrated that Fraxin significantly reduced inflammatory responses and downregulated HSPA8 expression in lipopolysaccharide (LPS)-stimulated fibroblast-like synoviocytes (FLs) and macrophages. In vivo, Fraxin administration markedly reduced paw swelling, alleviated bone deformities, and improved bone volume fraction (BV/TV) in male IL1RA-deficient mice exhibiting spontaneous arthritis. Histological analysis confirmed that Fraxin attenuated joint inflammation by modulating the inflammatory microenvironment. Additionally, Fraxin inhibited synovial hyperplasia by regulating mitochondrial membrane potential collapse in FLs. Functional assays revealed that this regulation occurred via the inhibition of HSPA8/PI3K/AKT signaling axis, thereby suppressing aberrant FLS proliferation and contributing to the attenuation of RA progression. Full article

Background: Precision oncology has traditionally relied on genomic biomarkers to guide therapy selection; however, static molecular profiling often fails to predict real-world responses to cytotoxic chemotherapy. Increasing evidence suggests that treatment outcomes are determined by the interaction between tumor-intrinsic biology and host-specific pharmacology. Functional ex vivo platforms, including patient-derived organoids and tumor slice cultures, provide a complementary phenotypic readout of drug sensitivity that reflects tumor architecture and microenvironmental interactions. Methods: This narrative review integrates recent experimental, translational, and clinical evidence on molecular oncodiagnostics combining tumor transcriptomics, germline pharmacogenetics, and ex vivo drug sensitivity testing. Relevant literature was identified through targeted searches of major biomedical databases, focusing on studies describing multi-omic predictive models, functional precision oncology platforms, and patient-derived tumor models. Results: Converging data indicate that integrated oncodiagnostic strategies can improve prediction of chemotherapy response beyond genomics-only approaches. Transcriptomic profiling captures dynamic pathway activity and resistance programs, pharmacogenetic testing informs host-specific toxicity and dosing constraints, and ex vivo assays enable direct phenotypic validation of drug efficacy. Together, these complementary approaches provide a biologically grounded framework for individualized therapy selection. Conclusions: The convergence of molecular profiling and functional phenotyping represents an emerging paradigm in precision oncology. Integrating multi-omic and functional data may enhance treatment prediction and reduce ineffective therapy, although prospective validation and standardization remain necessary for routine clinical implementation. Full article

Infertility is a prevalent clinical issue which disrupts normal human life and exerts an impact on fertility rates within the population. The increase in environmental pollutants, including acetyl tributyl citrate (ATBC), has given rise to concerns regarding their potential toxicity in infertility-related disorders. Icariin exhibits therapeutic effects on infertility, yet its mechanism of action against plasticiser-induced reproductive disorders remains unclear. This study aims to elucidate the potential toxicological targets and molecular mechanisms of ATBC-induced infertility, as well as the therapeutic targets and mechanisms of icariin in treating ATBC-induced reproductive disorders, through network toxicology, molecular-docking techniques and molecular dynamics simulation. Utilising the component-target database SwissTargetPrediction, the Similarity Ensemble Approach, PharmMapper, the ChEMBL database, and disease databases including the Therapeutic Target Database, OMIM, GeneCards, and DrugBank, 63 targets for ATBC-induced infertility and 33 targets for icariin treatment were identified. Screening via the STRING platform and Cytoscape 3.10.1 software yielded four core targets for ATBC-induced infertility—HSP90AA1, PIK3CA, CASP3, HRAS—and four core targets for icariin treatment—IL6, TNF, STAT3, and INS. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that ATBC-induced infertility correlates with pathways including pathways in cancer, prostate cancer, and PI3K-Akt signalling pathways. Conversely, the core targets of icariin therapy for related reproductive disorders are closely associated with tumour-associated signalling pathways and the AGE-RAGE signalling pathway. Molecular-docking and molecular dynamics simulation further confirmed the strong binding interactions between ATBC and infertility-related targets, as well as between icariin and core targets for treating reproductive disorders. This provides a theoretical foundation for understanding ATBC’s toxicological targets and the complex molecular mechanisms underpinning icariin’s treatment of infertility. It informs the development of strategies for icariin to prevent and treat infertility caused by exposure to ATBC-containing plastics or excessive ATBC contact. Full article

To comprehend the current state and future of newborn screening (NBS), it is essential to understand its history. Over the past six decades, this well-established and exemplary population-based screening program has been guided by screening principles dating back more than half a century. Advances in laboratory and point-of-care testing, diagnostic methods, and a surge of available treatments and even cures have made it challenging to balance screening criteria that have not kept pace with the current landscape. The availability to screen as well as the demand from parents and stakeholders to screen for more and increasingly complex conditions while limiting the retention of NBS specimens and genetic material has been both exciting and challenging. This paper shares the history of NBS in the United States, followed by the development and integration of genomic sequencing as a complement to current practice. It explores evidence supporting the concomitant use of biomarker- and DNA-sequencing-based approaches for NBS, how disorders are selected for inclusion, and available treatments, and offers recommendations regarding what to consider and how to proceed in this ever-changing NBS landscape. Full article

The raspberry (Rubus idaeus L.), an economically important crop, is affected by the crumbly fruit disorder, a malformation that leads to fruit disintegration at harvest due to poor drupelet cohesion. Despite previous efforts to identify genetic determinants of this phenotype, its complex inheritance and strong environmental component have limited the development of robust predictive markers. This study assessed the behavior and transferability of previously reported SSR and SNP markers associated with crumbly fruit across plants from a diverse panel of 34 R. idaeus cultivars, including in adjacent genomic regions not screened previously. Phenotyping was based on multi-season fruit performance and drupelet cohesion, and genetic variation was analysed using PCR-based genotyping within a multilocus approach. Consistent clustering patterns were observed across multiple SSR and SNP loci, suggesting a reproducible association between these genomic regions and the crumbly phenotype. Overall, the results support a multilocus genetic architecture underlying crumbly fruit, but also demonstrate that previously reported markers are not universally transferable across genetic backgrounds. These findings highlight the importance of integrated, population-aware marker validation to enable more reliable implementation of marker-assisted strategies in raspberry breeding programs. Full article

Advances in sequencing technologies have transformed human microbiome research, yet most analyses still rely on species-level profiles. However, strains rather than species represent the true ecological and functional units of the microbiome. Individual strains can vary substantially in gene content, metabolic capacity, virulence factors, antimicrobial resistance, and host-interaction properties. These differences critically influence immune responses, epithelial barrier integrity, disease susceptibility, and therapeutic outcomes. Here, we synthesize recent human microbiome studies that provide robust strain-resolved evidence, focusing on three major themes: (i) the emergence and long-term persistence of personalized strain repertoires, (ii) strain-specific pathobiont traits that drive host pathology, and (iii) the implications of strain-level ecology for the development of next-generation microbiome therapeutics. We also highlight key methodological innovations including high-resolution amplicon profiling, advanced metagenomic and single-cell genomics, and culture-based functional approaches that collectively enable strain-level resolution and are reshaping the field. Full article