Search Results (98)

Background: The development of advanced genomic sequencing techniques now makes it possible to identify novel biomarkers and guide the design of targeted therapeutic strategies. For advanced squamous non-small cell lung cancer (NSCLC), V-Raf murine sarcoma viral oncogene homolog B1 (BRAF) fusions have not been evaluated as a therapeutic target. However, agents that block the pathway activated by these fusions have shown efficacy in other solid tumors, such as melanoma, astrocytoma, acinar carcinoma of the pancreas, and papillary thyroid tumors. Case Report: Here, we present the case of a patient with locally advanced squamous NSCLC and minimal smoking history who was found to harbor a TMEM178B::BRAF fusion. Following curative-intent chemoradiotherapy (CRT) and subsequent maintenance immunotherapy, the patient achieved a complete radiological response at 12 months, accompanied by a marked improvement in both quality of life and overall clinical status. Conclusions: The findings in this patient underscore the importance of extending molecular genetic studies to patients with squamous histology who lack toxic habits or known risk factors. Gene alterations such as BRAF rearrangements may not only predict the response to immunotherapy-based treatments but also represent a promising avenue for the development of new therapeutic strategies. Full article

Assessing genetic diversity in various native poultry breeds, including bantam/dwarf ones, is instrumental for their conservation as genetic resources, identifying their specific genetic features, and exploring the history of their genetic divergence. Rare chicken breeds are usually carriers of peculiar phenotypic traits, including adaptations to local conditions, disease resistance, and unique performance features. Here, we report for the first time SNP-based genetic characterization of the Russian Korolyok, translated as “kinglet,” relative to five other dwarf/small breeds: Cochin Bantam, Hamburg Bantam Silver Spangled, Polish White-crested Black, Red White-tailed Dwarf and Silkie White. We estimated phenotypes, heterozygosity, inbreeding, effective population size, and runs of homozygosity (ROHs). Some breeds had higher genetic diversity and others showed elevated inbreeding rates in their genomes. With lower effective population sizes (both presently and in the past), rare breeds came from a limited number of ancestors or were under strong selection pressure over many generations. Within 22 ROHs, we identified 26 prioritized candidate genes (GRB10, RPRD1A, APOOL, EAF2, SEMA5, HACD2, GALANT1, DACH2, CHM, POF1B, HDX, SLC15A2, PDIA5, SEC22, NR2F2, ARRDC4, IGF1R, SYNM, TMEM263, etc.). Our data offer whole-genome insights into genetic variability, history, phylogeny, selective sweeps, and candidate genes of a distinct indigenous Russian chicken breed and other bantam/dwarf breeds. Full article

A growing body of work has linked the dysregulation of transmembrane (TMEM) proteins to the proliferation, metastasis, drug resistance, and tumor microenvironment remodeling of lung cancer, the leading global cause of cancer mortality. Renamed members such as STING1 (stimulator of interferon response cGAMP interactor 1, TMEM173), ANO1 (anoctamin-1, TMEM16A), ORAI1 (ORAI calcium release-activated calcium modulator 1, TMEM142A), ORAI3 (TMEM142C), and NDC1 (NDC1 transmembrane nucleoporin, TMEM48) are among the most extensively studied ones. Mechanisms of TMEM dysregulation in lung cancer span the modulation of Ca²⁺ influx, lysosomal exocytosis, ferroptosis, Wnt and β-catenin signaling, and immune cell infiltration and immune checkpoint rewiring, among others. Epigenetic silencing and targetable fusions (i.e., TMEM106B-ROS1 and TMEM87A-RASGRF1) create DNA-level vulnerabilities, while miRNA sponges offer RNA-level druggability. A subset of studies revealed context-specific expression (endothelial, B cell, and hypoxic EV) that can be exploited to remodel the tumor microenvironment. One study specifically focused on how isoform-specific expression and localization of TMEM88 determine its functional impact on tumor progression. Yet for most TMEMs, only pre-clinical or early-phase data exist, with many supported by a single study lacking independent validation. This review brings together scattered evidence on TMEM proteins in lung cancer, with the aim of guiding future work on their possible use as biomarkers or therapeutic targets. Full article

Background: Tracheobronchopathia osteochondroplastica (TO) is a rare benign disorder characterized by submucosal cartilaginous and osseous nodules of the tracheobronchial tree, typically sparing the posterior membranous wall. Involvement of the vocal cords is exceedingly rare and may result in critical airway obstruction. The underlying genetic and molecular mechanisms of TO remain largely unexplored. Case presentation: We report a rare case of TO extending from the vocal cords to the bronchi in a 76-year-old man who initially presented with pneumonia and later developed acute respiratory failure due to severe airway narrowing, necessitating emergency tracheostomy. Bronchoscopy and computed tomography revealed diffuse calcified nodules involving the anterior and lateral airway walls, including the subglottic region. Histopathology demonstrated chronic inflammatory cell infiltration with squamous metaplasia. To explore the molecular basis of this condition, whole-genome sequencing (WGS) was performed using peripheral blood samples—the first such application in TO. WGS identified 766 germline mutations (including 27 high-impact variants) and 66 structural variations. Candidate genes were implicated in coagulation and inflammation (KNG1), arachidonic acid metabolism and extracellular matrix remodeling (PLA2G4D), ciliary dysfunction and mineralization (TMEM67), vascular calcification (CDKN2B-AS1), smooth muscle function (MYLK4), abnormal calcification (TRPV2, SPRY2, BAZ1B), fibrotic signaling (AHNAK2), and mucosal barrier integrity (MUC12/MUC19). Notably, despite systemic germline mutations, calcification was restricted to the airway. Conclusions: This case highlights that TO with vocal cord involvement can progress beyond a benign course to cause life-threatening airway obstruction. Integrating clinical, histological, and genomic findings, we propose a novel pathophysiological model in which systemic genetic susceptibility interacts with local immune cell infiltration and fibroblast-driven extracellular matrix remodeling, resulting in airway-restricted dystrophic calcification. This first genomic characterization of TO provides new insights into its pathogenesis and suggests that multi-omics approaches may enable future precision medicine strategies for this rare airway disease. Full article

Osteogenesis imperfecta (OI) type XIV is a rare recessive disorder caused by TMEM38B pathogenic variants that disrupt an endoplasmic reticulum protein essential for calcium homeostasis and bone mineralization. This leads to severe bone fragility, early-onset fractures, skeletal deformities, low bone mass, scoliosis, and variable features like blue sclerae or dental abnormalities. We present a case report of a 21-year-old Italian male with a novel homozygous TMEM38B splice variant (c.112 + 1G > T), detailing the clinical presentation, genetic findings, and therapeutic outcomes. The patient exhibited multiple skeletal deformities and showed a moderate response to bisphosphonate therapy (neridronate). In addition, a systematic review of PubMed and Scopus identified 12 relevant studies from an initial set of 82 publications, encompassing data from 56 patients diagnosed with OI type XIV. Unlike classical collagen-related OI, TMEM38B-related OI necessitates genetic screening beyond classical collagen genes (COL1A1 and COL1A2). While bisphosphonates provide some clinical benefit, persistent fractures underscore the need for long-term management and innovative therapies. This case report and systematic review enhance understanding of OI type XIV and underscore the clinical importance of TMEM38B variants in bone fragility disorders. Full article

Although experimental evidence indicates that mitochondrial collapse is a common effect of both Chagas disease and post-ischemic heart failure and that cardiac anatomy and function are partially restored by stem cell therapy, the responsible molecular mechanisms are still under debate. Gene expression data from our publicly accessible transcriptomic dataset obtained by profiling the left ventricle myocardia of mouse models of Chagas disease and post-ischemic heart failure were re-analyzed from the perspective of the Genomic Fabric Paradigm. In addition to the regulation of the gene expression levels, we determined the changes in the strength of the homeostatic control of transcript abundance and the remodeling of the gene networks responsible for the mitochondrial respiration. The analysis revealed that most of the mitochondrial genes assigned to the five complexes of the respiratory chain were significantly downregulated by both Chagas disease and ischemia but exhibited outstanding recovery of the normal expression levels following direct injection of bone-marrow-derived stem cells. However, instead of regaining the original expression control and gene networking, the treatment induced novel mitochondrial arrangements, suggesting that multiple transcriptomic topologies might be compatible with any given physiological or pathological state. This study confirmed several established mechanisms and identified novel gene expression signals, especially Cox4i2, Cox6b1, Cox7b, Ndufb11, and Tmem186, that warrant further investigations. Their broad rescue with cell therapy underscores mitochondria as a convergent, tractable target for cardiac repair. Full article

Reproductive and growth traits are key economic traits in sheep. This study aims to identify key single nucleotide polymorphisms (SNPs) and candidate genes associated with reproductive and growth traits in Tianmu polytocous sheep through a genome-wide association study (GWAS). The findings are expected to provide both a theoretical foundation for molecular breeding in this breed and novel insights into the genetic basis of ovine reproductive and growth performance. This study took 483 adult Tianmu polytocous ewes as the research subjects, collected their lambing records, measured their phenotypic values of growth traits (3 weight and 11 body size traits), and collected their blood samples for whole-genome resequencing to identify SNPs in the Tianmu polytocous sheep genome. The results identified a total of 9,499,019 (3× coverage) and 27,413,216 (30× coverage) high-quality SNPs in the Tianmu polytocous sheep genome. Subsequently, the association analysis between SNPs and reproductive and growth traits was conducted using a mixed linear model. A total of 92, 66, 18, 28, 6, 42, 3, 3, 6, 1, 12, 3, 22, 8, 6, and 3 SNPs were found associated with litter size at first parity, litter size at second parity, litter size at third parity, litter size at fourth parity, birth weight, weaning weight, body height, withers height, body length, head length, head width, cannon bone circumference, forelimb height, chest girth, chest depth, and withers width, respectively. Further, based on SNP annotation, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, candidate genes associated with the reproductive and growth traits were identified. Among these genes, 11 LOC, DEPTOR, GNG12, GRM7, PTH, PTH2R, WWOX, INHA, and NRG3 are candidate genes associated with litter size at first parity or litter size at third parity. These genes are involved in the G protein-coupled receptor signaling pathway, G protein-coupled receptor activity, ovarian tissue development, and hormone secretion. Additionally, TFRC and NTN1 are candidate genes associated with birth weight, while five UGT1A and CASR are candidate genes associated with weaning weight. These candidate genes are primarily involved in lipid metabolism. Finally, the following genes were identified as candidates associated with specific traits: DLG2, TMEM126A, and TMEM126B with body height; DSCAM and SCN8A with body length; BARX1 with cannon bone circumference; four LOC genes with forelimb height; EPHA4 with chest depth; and MRS2 with withers width. Full article

The ability of common carp to withstand both short-term and long-term oxygen deprivation has been well documented; however, the potential genetic mechanisms behind common carp’s hypoxia response remain unclear. Therefore, to understand the possible genetic foundation of their response to hypoxia, comparative genomic analyses were conducted among six common carp varieties: Color, Songpu, European, Yellow, Mirror, and Hebao common carps. We identified 118 single-copy orthologous positively selected genes (PSGs) (dN/dS > 1) in all common carps under study, with GO functions directly related to the cellular responses to hypoxia in Color and European common carp PSGs, such as oxygen transport activity, oxygen binding activity, respiratory burst activity, and superoxide anion production. The Bayes Empirical Bayes (BEB) technique identified possible amino acid substitutions in mitochondrial and hypoxic genes under positive selection. Exonic and intronic structural variations (SVs) were discovered in the CYGB2 hypoxia-related gene of Color and European common carps, as well as in several mitochondrial genes, including MRPL20, MRPL32, NSUN3, GUF1, TMEM17B, PDE12, ACAD6, and COX10 of Color, European, Songpu, Yellow, and Hebao common carps. Moreover, Color common carp and Songpu common carp were found to share the greatest percentage of collinear genes (49.8%), with seven Songpu common carp chromosomes (chr A2, chr A9, chr A13, chr B13, chr B15, chr B2, and chr B12) showing distinct translocation events with the corresponding chromosomes of Color common carp. Additionally, we found 570 translocation sites that contained 3572 translocation-related genes in Color common carp, some of which are directly relevant to mitochondrial and hypoxic GO functions and KEGG pathways. Our results offer strong genome-wide evidence of the possible evolutionary response of Cyprinus carpio to hypoxia, providing important insights into the potential molecular mechanisms that explain their survival in hypoxic environments and guiding future research into carp hypoxia tolerance. Full article

Background/Objectives: Omentin, also known as intelectin-1, is a secreted adipokine with anti-inflammatory, insulin-sensitizing, and immune-modulatory functions, primarily expressed in visceral adipose tissue. While omentin has been associated with favorable metabolic outcomes, its role in cancer pathogenesis appears context-dependent and remains poorly understood. This review investigates the biological functions, expression patterns, and clinical relevance of omentin across gastrointestinal malignancies. Methods: A comprehensive review of the literature was conducted using PubMed, Scopus, and Web of Science up to August 2025 to evaluate the role of omentin in gastrointestinal cancers. Both preclinical and clinical studies evaluating omentin, its analogues and omentin-enhancing agents in gastric, colorectal, hepatic, pancreatic, and esophageal cancers were included. Results: Omentin exhibits anti-proliferative, anti-inflammatory, and anti-angiogenic effects within the tumor microenvironment in several GI malignancies. However, evidence also indicates a dual role. High intratumoral omentin expression correlates with improved prognosis in colorectal, gastric, and hepatic cancers; in contrast, elevated circulating levels–particularly in colorectal and pancreatic cancers–have been paradoxically associated with increased cancer risk and poor outcomes. Mechanistically, omentin modulates PI3K/Akt, NF-κB, AMPK, and oxidative stress pathways, and interacts with TMEM207. However, most available studies are small-scale and heterogeneous, with methodological inconsistencies and limited multi-omics integration, leaving major knowledge gaps. Conclusions: This review highlights omentin’s distinct systemic and local roles across GI cancers, underscoring its translational implications. Omentin emerges as a promising but context-dependent biomarker and therapeutic target, with future research needed to address heterogeneity, standardize assays, and validate its clinical utility in large-scale prospective studies. Full article

Background: Correlation of genes within tissues has attracted much attention. In contrast, genes that are INDependent In Expression (INDIE) remain poorly understood, even though they may represent tissue admixtures, reflect new regulatory mechanisms, either transcriptional or post-transcriptional, and contribute to biomarkers or machine learning algorithms. We hypothesised that INDIE genes can be found, may remain uncorrelated across tissues, and replicate within tissues in external datasets. Methods: Biweight midcorrelation was calculated for each gene against all other genes with sufficiently high expression in the given tissue from the GTEx dataset v8, along with the means of absolute values of obtained correlation coefficients. The threshold for gene designation as INDIE was both absolute (r) and relative (Z-score), while the threshold for external validation in the whole blood (four datasets) and the ileum (two datasets) was relative. Results: Only one gene, RPL13P12, was INDIE in all the analysed GTEx tissues, but it did not replicate in the external datasets. In contrast, HIST1H2AD and TMEM176B were not only INDIE in GTEx whole blood but also replicated in all four external datasets, despite their heterogeneity. Moreover, ACAT2 replicated in both external ileal datasets. The haemoglobin gene HBB belonged to most widespread INDIE genes in various GTEx tissues and was validated in an external ileal dataset, pointing towards the importance of tissue heterogeneity in bulk samples. Conclusions: A set of genes exhibiting independent expression patterns across various tissues of GTEx was described. Results for each tissue are made available. Even though many findings can be explained by tissue heterogeneity, some results point towards interesting mechanisms of gene expression regulation. Full article

Fiber fineness is a critical determinant of wool quality and is of great significance in enhancing the overall quality of wool. The aim of this research was to pinpoint the key proteins that participate in the regulation of wool fineness. To achieve this, we utilized Astral—DIA proteomics technology to examine the disparities in proteins, pathways, and GO terms among the wool tissues of Gansu alpine fine-wool sheep with varying mean fiber diameters (MFD). The experiment was divided into two groups: coarse (group C, MFD = 22.36 ± 0.75 μm, n = 4) and fine (group F, MFD = 16.89 ± 0.36 μm, n = 4). The results indicated that 67 differentially expressed proteins (DEPs) were identified from the wool tissues of Gansu alpine fine-wool sheep in groups C and F. Functional enrichment analysis demonstrated that several key differential proteins, including MGST3, KRT26, KRT72, KRT74, KRT71, etc., were mainly enriched in multiple functional pathways. These pathways included glutathione metabolism, oxidative phosphorylation, the degradation of valine, leucine, and isoleucine, intermediate filaments, serine protease activity, and cysteine protease activity (p < 0.05). Furthermore, protein–protein interaction (PPI) network analysis suggested that type II keratin and type I keratin (such as CTSF, PSAP, TMEM106B, LYPD3, KRT71, KRT72), along with glutathione metabolism (MGST3, W5QDB7), are closely related to hair follicle development and the regulation of wool fineness. In summary, this study enriches the existing sheep proteinome database and offers novel perspectives on the regulatory mechanisms of wool fineness. Full article

Lung adenocarcinoma (LUAD) is characterized by substantial genetic heterogeneity, making it challenging to identify reliable biomarkers for diagnosis and treatment. Tumor mutational burden (TMB) is widely recognized as a predictive biomarker due to its association with immune response and treatment efficacy. In this study, we take a different approach by treating TMB as a response variable to uncover its genetic drivers using multiomics data. We conducted a thorough evaluation of recent feature selection methods through extensive simulations and identified three top-performing approaches: projection correlation screening (PC-Screen), distance correlation sure independence screening (DC-SIS), and Wasserstein distance-based screening (WD-Screen). Unlike traditional approaches that rely on simple statistical tests or dataset splitting for validation, we adopt a method-based validation strategy, selecting top-ranked features from each method and identifying consistently selected genes across all three. Using The Cancer Genome Atlas (TCGA) dataset, we integrated copy number alteration (CNA), mRNA expression, and DNA methylation data as predictors and applied our selected methods. In the two-platform analysis (mRNA + CNA), we identified 13 key genes, including both previously reported LUAD-associated genes (CCNG1, CKAP2L, HSD17B4, SHROOM1, TIGD6, and TMEM173) and novel candidates (DTWD2, FLJ33630, NME5, NUDT12, PCBD2, REEP5, and SLC22A5). Expanding to a three-platform analysis (mRNA + CNA + methylation) further refined our findings, with PCBD2 and TMEM173 emerging as the robust candidates. These results highlight the complexity of multiomics integration and the need for advanced feature selection techniques to uncover biologically meaningful patterns. Our multiomics strategy and robust selection approach provide insights into the genetic determinants of TMB, offering potential biomarkers for targeted LUAD therapies and demonstrating the power of Wasserstein distance-based feature selection in complex genomic analysis. Full article

Cervical cancer is the second leading cause of cancer-related death in Mexico, primarily due to persistent infection with high-risk Alpha-papillomavirus genotypes, such as HPV16 and 18. Next-generation sequencing (NGS) has revealed a high prevalence of Beta- and Gamma-HPVs, mainly Beta-2 types 38b, 80, 107, and 122, in cervical cancer samples from Mexico. Our group previously reported that HPVs 38b, 107, and 122 possess transforming properties in primary fibroblasts; however, the oncogenic potential of E6/E7-HPV80 has not yet been elucidated. For this purpose, primary human fibroblasts were transduced with E6/E7-HPV80 (FB-E6/E7-HPV80), and functional assays were conducted to evaluate changes in proliferation, metabolic activity, and cell migration. RNA-seq analysis identified differentially expressed genes (DEGs) and enriched pathways. Fibroblasts transduced with E6/E7-HPV16 (FB-E6/E7-HPV16) or empty vector (FB-pLVX) served as controls. FB-E6/E7-HPV80 extended their lifespan and exhibited increased proliferation, metabolic activity, and migration capacity. RNA-seq analysis identified 196 upregulated DEGs (such as GPAT2, MST1R, ACAN, SLCO4A1, and CHRNA3) and 887 downregulated DEGs (such as KLHDC7B, TRIM58, CST1, FBLL1, INHBE, and TMEM132D) shared between FB-E6/E7-HPV80 and FB-E6/E7-HPV16. Enriched pathways included p53, TNF, IL-17, apoptosis, cell cycle, etc. These findings suggest that E6/E7-HPV80 exhibits transforming capabilities that could play an important role in cervical carcinogenesis. Full article

Sleep deprivation is a prevalent issue that disrupts the circadian rhythm of estrogen, particularly estradiol, thereby significantly affecting women’s skin health and appearance. These disruptions can impair skin barrier functionality and decrease dermal collagen synthesis. In this study, our results demonstrate that topical taurine supplementation promotes the expression of tight junction (TJ)-related proteins and enhances collagen production, effectively restoring skin homeostasis in sleep-deprived female mice. Mechanistically, taurine upregulates the expression of TMEM38B, a gene encoding the TRIC-B trimeric cation channel, resulting in increased intracellular calcium ion levels. This, in turn, promotes the upregulation of TJ-related proteins, such as ZO-1, occludin, and claudin-11 in epidermal cells, while also enhancing the expression of type III collagen in fibroblasts, thus restoring skin homeostasis. These findings suggest that taurine may serve as an alternative to estradiol, effectively improving skin homeostasis disrupted by sleep deprivation while mitigating the potential risks associated with exogenous estrogen supplementation. Collectively, these results provide preliminary insights into the protective mechanisms of taurine against sleep deprivation-induced skin impairments and establish a foundation for its potential application in treating skin conditions related to estrogen imbalances, such as skin aging in menopausal women. Full article

Research indicates that fine particulate matter (PM2.5) exposure is associated with the onset of non-alcoholic fatty liver disease (NAFLD), the most prevalent chronic liver disorder. However, the underlying pathogenesis mechanisms remain to be fully understood. Our study investigated the hub long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) associated with hepatic steatosis caused by PM2.5 exposure and their pathological mechanisms. The analysis of gene profiles in the GSE186900 dataset from the Gene Expression Omnibus (GEO) enabled the identification of 38 differentially expressed lncRNAs and 1945 mRNAs. To explore further, a co-expression network was established utilizing weighted gene co-expression network analysis (WGCNA). Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were utilized for functional enrichment analysis. Our analysis identified specific modules, particularly the blue and turquoise modules, which showed a strong correlation with NAFLD. Through functional enrichment analysis, we identified several lncRNAs (including Gm15446, Tmem181b-ps, Adh6-ps1, Gm5848, Zfp141, Rmrp, and Rb1) which may be involved in modulating NAFLD, multiple metabolic pathways, inflammation, cell senescence, apoptosis, oxidative stress, and various signaling pathways. The hub lncRNAs identified in our study provide novel biomarkers and potential targets for the diagnosis and treatment of NAFLD. Full article