Search Results (69,110)

Background: Clear cell renal cell carcinoma (ccRCC) is a prevalent urological malignancy, accounting for approximately 1.6% of all cancer-related deaths in 2022. While endocrine-disrupting chemicals (EDCs) have been implicated as risk factors for ccRCC, the toxicological profiles and immune mechanisms underlying Bisphenol A (BPA) exposure in ccRCC progression remain inadequately understood. Materials and Methods: Protein–protein interaction (PPI) analysis and visualization were performed on overlapping genes between ccRCC and BPA exposure. This was followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to elucidate potential underlying mechanisms. Subsequently, 108 distinct machine learning algorithm combinations were evaluated to identify the optimal predictive model. An integrated CoxBoost and Ridge regression model was constructed to develop a prognostic signature, the performance of which was rigorously validated across two independent external datasets. Finally, molecular docking analyses were employed to investigate interactions between key genes and BPA. Results: A total of 114 overlapping targets associated with both ccRCC and BPA were identified. GO and KEGG analyses revealed enrichment in cancer-related pathways, including pathways in cancer, endocrine resistance, PD-L1 expression and PD-1 checkpoint signaling, T-cell receptor signaling, endocrine function, and immune responses. Machine learning algorithm selection identified the combined CoxBoost-Ridge approach as the optimal predictive model (achieving a training set concordance index (C-index) of 0.77). This model identified eight key genes (CHRM3, GABBR1, CCR4, KCNN4, PRKCE, CYP2C9, HPGD, FASN), which were the top-ranked by coefficient magnitude in the prognostic model. The prognostic signature demonstrated robust predictive performance in two independent external validation cohorts (C-index = 0.74 in cBioPortal; C-index = 0.81 in E-MTAB-1980). Furthermore, molecular docking analyses predicted strong binding affinities between BPA and these key targets (Vina scores all <−6.5 kcal/mol), suggesting a potential mechanism through which BPA may modulate their activity to promote renal carcinogenesis. Collectively, These findings suggested potential molecular mechanisms that may underpin BPA-induced ccRCC progression, generating hypotheses for future experimental validation. Conclusions: These findings enhance our understanding of the molecular mechanisms by which BPA induces ccRCC and highlight potential targets for therapeutic intervention, particularly in endocrine and immune-related pathways. This underscores the need for collaborative efforts to mitigate the impact of environmental toxins like BPA on public health. Full article

Gynogenesis is a reproductive mode where offspring inherit exclusively maternal chromosomes. Gynogenetic development in fish may be induced intentionally by activating eggs with the UV-irradiated, inactive spermatozoa. In the meiotic variant of gynogenesis, the resultant haploid gynogenetic zygote is then exposed to a physical shock to inhibit the release of the 2nd polar body and to reconstitute the diploid state of the embryo. Here, meiotic gynogenesis was induced in the rainbow trout eggs from different clutches to find any differences in terms of gene expression and antioxidant enzyme activity between eggs with high and low ability for gynogenetic development. The survival rates of the gynogenotes after hatching from the eggs originating from five females varied from 16.6 ± 4.3% to 53.8 ± 9.8%. Biochemical and molecular examination revealed that eggs with higher developmental potential for meiotic gynogenesis exhibited significantly greater glutathione peroxidase (GPx) activity than eggs with lower efficiency of gynogenesis. Moreover, eggs exhibiting the highest ability for gynogenetic development showed increased transcription of the keratin 8 gene and decreased abundance of keratin 18 and tubulin β mRNA transcripts. Since keratins protect oocytes from physical stress after ovulation, the high abundance of keratin 8 in the rainbow trout eggs may increase their resilience to the physical shock applied for the zygote diploidization during gynogenesis. On the other hand, a low level of tubulin-building microtubules may increase the efficiency of high hydrostatic pressure (HHP) shock used for diploidization of the gynogenetic zygotes. Full article

Oral cancer, the most common head and neck malignancy, has a high recurrence rate and poor prognosis largely owing to chemotherapy resistance. The adverse effects of conventional therapies have prompted investigations into safer and more effective alternative therapies. Chloroquine (CQ) and hydroxychloroquine (HCQ) have shown potential owing to their roles in autophagy modulation and immune regulation. This study clarifies the selective efficacy of hydroxychloroquine (HCQ) and chloroquine (CQ) in oral squamous cell carcinoma models, emphasizing distinct responses in gingival (Ca9-22) and tongue (SCC-9) carcinoma cells. Non-oncogenic oral epithelial cells (GMSM-K) and oral carcinoma cell lines from the tongue (SCC-9, Cal-27) and gingiva (Ca9-22) were used. Cell viability, cytotoxicity, and colony formation were assessed via MTT, LDH, and crystal violet assays. Flow cytometry was used to measure apoptosis, autophagy, oxidative stress, mitochondrial membrane potential, and DNA damage. The transcriptomic profiles of apoptosis and autophagy-related genes were assessed by qPCR arrays. Bioinformatics analysis allowed estimation of the main gene interaction networks. Pre-screening showed that GMSM-K and Cal-27 cells were non-responsive or exhibited non-specific toxicity at high doses; therefore, subsequent analyses focused on Ca9-22 (GC) and SCC-9 (TC). HCQ significantly reduced viability and colony formation in Ca9-22 cells while moderately affecting SCC-9 cells. Autophagy inhibition was accompanied by compensatory up-regulation of autophagy-related genes, consistent with feedback activation of TFEB and FOXO3a pathways. Gene expression profiling and flow-cytometry analyses revealed cell-type-specific differences in apoptosis, mitochondrial potential, and DNA damage, suggesting HCQ’s selective anti-tumor potential in gingival carcinoma. These findings highlight HCQ as a repurposed adjuvant therapy that modulates autophagy and apoptosis to enhance chemosensitivity in oral cancer. Full article

Killer-cell immunoglobulin-like receptors (KIRs) play a crucial role in the cytotoxic activity of natural killer (NK) cells, encompassing both inhibitory and activating types. A higher ratio of cytotoxic to inhibitory receptors may harm successful pregnancies by disrupting the uterine environment. Ongoing debates surround the impact of KIR gene variations on recurrent pregnancy loss (RPL) and infertility across populations. This study aimed to explore KIR gene polymorphisms in RPL and infertility among the Venezuelan admixed population. The Venezuelan population exhibits a genetic mix of Caucasian, African, and local Amerindian ancestry, distinguishing it from other Latin American admixed populations. This study included 100 controls and 86 patients: 73 women with idiopathic RPL (53 primary and 20 secondary) and 13 infertile patients (4 primary and 9 secondary). The frequency of activating receptors KIR2DS2 and KIR2DS3 was significantly lower (p < 0.05) in the whole patient group compared to controls. However, when analyzing the haplotypes and genotypes, the significance between patients and controls was lost. When comparing RPL and infertile patients, KIR2DS2, KIR2DL3, 2DL5, and 3DL1 were significantly less frequent in infertile women. In infertile women, KIR2DS3 frequency was increased compared to controls and RPL. The results suggest that the frequency of inhibitory receptors may differentiate patients with RPL and infertility. Further studies should ascertain the expression and function of KIRs in uterine NK cells in patients with RPL and infertility. Full article

The nucleoid-associated protein Fis functions as a global regulator that influences various cellular processes in Gram-negative bacteria. In this study, we examined the role of Fis in the transcriptional regulation of type 3 fimbriae in Klebsiella pneumoniae, a notable opportunistic pathogen associated with hospital-acquired infections. Our transcriptional analyses revealed that deleting the fis gene caused a significant upregulation of mrkA and mrkH, the genes responsible for the structure and regulation of type 3 fimbriae, respectively. Additionally, phenotypic assays demonstrated that the Δfis mutant exhibited enhanced biofilm formation and greater adherence to A549 lung epithelial cells compared to the wild-type strain. These effects were restored to wild-type levels in the cis-complemented strain. Electrophoretic mobility shift assays confirmed that Fis directly binds to the regulatory regions upstream of both mrkA and mrkH, indicating that repression occurs through direct interaction with the promoter. In summary, our findings show that Fis acts as a transcriptional repressor of mrkA and mrkH, thereby negatively regulating the expression of type 3 fimbriae, biofilm formation, and adherence. This study highlights Fis as a direct regulator of fimbrial expression and biofilm development in K. pneumoniae, deepening our understanding of its virulence regulatory network. Full article

Alzheimer’s disease (AD) is the leading cause of dementia and is often prefaced by mild cognitive impairment (MCI). Detection of AD-related changes via blood-based biomarkers would enable critical therapeutic interventions early in disease progression. Neuronal enriched extracellular vesicle (NEEV) miRNAs regulate peripheral genes as a response to early AD brain changes and hence may have biomarker potential. Plasma NEEVs were captured from plasma samples of Mexican Americans (MAs) and Non-Hispanic Whites (NHWs) using an antibody against the neuronal surface marker CD171. miRNAs isolated from NEEVs were sequenced and analyzed using miRDeep2/DEseq2 and QIAGEN RNA-seq portal for differential expression between cognitively impaired (CI) and cognitively unimpaired controls. hsa-miR-122-5p was significantly underrepresented in the CI group in both MAs and NHWs compared to the healthy control. Other population-specific miRNAs (MAs: hsa-miR-26a-5p, hsa-let-7f-5p, and hsa-miR-139-5p, NHWs: hsa-miR-133a-3p, hsa-miR-125b-5p, and hsa-miR-100-5p) identified may have biomarker potential in AD precision medicine. Some of these differentially expressed miRNAs were associated with key AD-related comorbidities such as APOE genotype, age, and metabolic burden and were predicted to target genes within NF-κB -regulated inflammatory pathways. Together, these findings suggest that dysregulated miRNA networks may serve as a mechanistic link between comorbidity burden and AD-related neuroinflammation and neurodegeneration. Full article

Gene expression-based tumor classification aims to distinguish tumor types based on gene expression profiles. This task is difficult due to the high dimensionality of gene expression data and limited sample sizes. Most datasets contain tens of thousands of genes but only a small number of samples. As a result, selecting informative genes is necessary to improve classification performance and model interpretability. Many existing gene selection methods fail to produce stable and consistent results, especially when training data are limited. To address this, we propose a multi-task ensemble strategy that combines repeated sampling with joint feature selection and classification. The method generates multiple training subsets and applies multi-task logistic regression with ${\ell }_{2,1}$ group sparsity regularization to select a subset of genes that appears consistently across tasks. This promotes stability and reduces redundancy. The framework supports integration with standard classifiers such as logistic regression and support vector machines. It performs both gene selection and classification in a single process. We evaluate the method on simulated and real gene expression datasets. The results show that it outperforms several baseline methods in classification accuracy and the consistency of selected genes. Full article

Endometriosis represents a prevalent gynaecological disorder, impacting around 10% of the female population and affecting as many as 50% of women who are facing challenges with infertility. The pathogenesis of the disease encompasses intricate processes such as the formation of adhesions, degradation of the extracellular matrix, angiogenesis, increased cell proliferation, impaired apoptosis, and dysregulation of the immune response. Although endometriosis is common, its precise etiology remains unidentified, despite various hypotheses being suggested. Recent findings underscore the significance of non-coding RNAs, specifically long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), which have been identified as important regulators in the development of endometriosis. This literature review integrates findings from various transcriptomic and molecular studies to distinguish between lncRNAs and miRNAs that are associated with direct pathogenic roles and those that simply represent altered gene expression profiles in endometriosis. Particular long non-coding RNAs, such as H19, MALAT1, and LINC01116, are associated with chromatin remodeling, functioning as competitive endogenous RNAs, and influencing critical signaling pathways. Concurrently, specific microRNAs, including the miR-200 family, miR-145, and let-7b, seem to govern processes like epithelial-to-mesenchymal transition, angiogenesis, and cell adhesion. The findings highlight the significant potential of non-coding RNAs to serve as biomarkers for diagnostic purposes and as innovative therapeutic targets. Subsequent research endeavours ought to focus on corroborating these findings and elucidating the specific pathogenic roles of these non-coding RNAs in the context of endometriosis. Full article

AINTEGUMENTA-LIKE6 (AIL6) is a transcription factor specifically expressed in embryos. It is a key to improving peony regeneration through tissue culture. Based on transcriptomic data from our previous research and the published genome data of Paeonia ostii, we identified the PoAIL6 gene associated with somatic embryogenesis (SE) in Paeonia ostii ‘Fengdan’. Structural and phylogenetic analyses were conducted on the PoAIL6-encoded protein, and its expression pattern across tissues and embryo developmental stages were explored using real-time quantitative PCR. Our results revealed that PoAIL6 contained two AP2 conserved domains and the characteristic motif of AIL6 genes. Phylogenetic analysis revealed that the PoAIL6 gene has similarity to grape (Vitis vinifera) and cocoa (Theobroma cacao). PoAIL6 exhibited the highest expression during early embryonic development, with expression levels gradually decreasing throughout SE progression. It was most highly expressed in peony seeds and showed relatively high expression in callus tissue. This study underscores the pivotal role of PoAIL6 in the early SE and lays a playground for elucidating its molecular mechanisms, supporting the development of efficient and stable regeneration and transformation systems in peony. Full article

Arthrospira platensis polysaccharide component 1 (PAP-1), a purified polysaccharide monomer isolated from Arthrospira platensis, exhibits pronounced antioxidant activity. To investigate the in vivo and in vitro regulatory effects of PAP-1 on antioxidant enzyme activities and inflammatory mediators in mice and RAW264.7 cells, the mice were administered PAP-1 by gavage, and the cells were cultured with PAP-1. Subsequently, serum, lung, spleen, and thymus tissues from mice, as well as the cultured RAW264.7 cells, were collected for analysis using RNA sequencing, commercial assay kits, immunohistochemistry, RT-qPCR, and Western blotting. The results demonstrated that PAP-1 significantly reduced the levels of oxidative stress-related indicators (NO, iNOS, MDA, MPO, and XOD), while markedly enhancing the activities of antioxidant enzymes (SOD, CAT, and GSH-Px) (p < 0.05), a trend consistently observed in both in vivo and in vitro experiments. Furthermore, PAP-1 upregulated the expression of key antioxidant genes and proteins, including HO-1, NQO1, GCLM, p62, Prdx1, and SLC7A11. Collectively, these findings indicate that PAP-1 exerts regulatory antioxidant effects in mice and RAW264.7 cells by enhancing antioxidant enzyme activity and suppressing oxidative stress responses, underscoring its potential as a natural antioxidant agent. Full article

Internal reference genes are a prerequisite for ensuring the accuracy of gene verification experiments, but few relevant studies on Lyophyllum decastes have investigated the growth cycle and different environmental conditions. In this study, the qPCR results of 22 house-keeping genes were analyzed using GeNorm, BestKeeper, NormFinder and RefFinder. The results revealed that the most stable gene differed under different conditions. Across all developmental stages and under hot, cold, acidic, alkaline, and salt conditions, UBCE gene displays the greatest expression stability. However, EF1b, β-ACT, HSD17B3, and Cyb presented the greatest stability under cold, heat, and acidic conditions, and heavy metal exposure, respectively. To screen for genes suitable for all conditions, RefFinder’s ranking results revealed that UBCE and EF1b ranked in the top 2, demonstrating the highest gene expression stability. In contrast, Cyb was positioned at the bottom of the comprehensive ranking table. This study not only revealed potential factors affecting the suitability of reference genes but also identified optimal reference genes from a set of candidate genes across diverse conditions. Full article

Dissolved oxygen (DO) is a crucial determinant of aquatic organism health. This study demonstrates that hypoxia (at MH, 2.0 mg/L; SH, 0.5 mg/L) disrupts intestinal homeostasis in the blood clam, Anadara granosa. Exposure to hypoxia induced severe histopathological damage, including villus loss, inflammatory cell infiltration, and epithelial cell vacuolization. Immune-related gene expression analysis revealed coordinated regulation, with TLR4 and NF-κB significantly up-regulated by 4.5-fold and 5-fold, respectively, in the SH14 group, while HSP70 showed a remarkable 13-fold increase in the MH14 group. In contrast, TAK1 and TRAF6 exhibited substantial downregulation. High-throughput sequencing of the 16S rRNA gene revealed a significant reduction in gut microbiota diversity under hypoxic conditions, as evidenced by notable decreases of approximately 30% in the Chao1 index and 35% in the Shannon index in the SH group compared to the normoxic control (N group). Functional pathway analysis indicated alterations in pathways associated with xenobiotic biodegradation, lipid metabolism, and energy metabolism. These findings highlight a strong association between hypoxia and adverse intestinal health outcomes in A. granosa, underscoring the critical importance of maintaining adequate dissolved oxygen levels to support bivalve health. Future research should aim to develop strategies to mitigate hypoxia-induced stress and further elucidate the molecular mechanisms underlying hypoxia adaptation in bivalves. Full article

Potato virus Y (PVY) is a major threat to global potato production, causing yield losses of nearly 90%. This emphasizes the urgent need to explore the genetic factors underlying resistance mechanisms. Developments in transcriptomics and plant genomes have shed significant light on the genetic underpinnings of PVY resistance. This review summarizes current knowledge on PVY biology and structure, its impacts, key hypersensitive resistance (HR) and extreme resistance (ER) genes and their associated molecular markers, genomic strategies for discovering resistance genes and improving resistance breeding, and challenges. Genetic resistance is a key strategy for controlling PVY, primarily through HR and ER, which are governed by specific genes: the Ny gene for HR and the Ry gene for ER. Our understanding of the molecular mechanisms underlying this resistance has increased significantly due to the advancement of high-throughput sequencing methods, including RNA and whole-genome sequencing. More than 10 PVY resistance genes have been identified in potato, including well-characterized ER genes such as Ry_sto, Ry-f_sto, Ry_adg, Ry_chc, and Ry(o)_phu, as well as HR genes such as Ny-1, Ny-2, and Ny-Smira, which are discussed in this review. Transcriptomic analyses have revealed the involvement of small RNAs and other regulatory molecules in modulating resistance responses. Transcriptomic studies have also identified 6071 differentially expressed genes (DEGs) in potato cultivars infected with PVY, highlighting strong defense responses influenced by strain, cultivar, and environmental conditions. The identification of these resistance genes facilitates the development of PVY-resistant cultivars through marker-assisted selection and gene pyramiding, offering significant opportunities to enhance PVY management and promote sustainable potato production under the challenges posed by climate change. Full article

Background/Objectives: Galectins contribute to the pathogenesis of osteoarthritis (OA) by amplifying inflammatory and catabolic signaling, yet targeted therapeutic approaches remain limited. Three Dimensional (3D) models offer a promising platform to study human OA pathophysiology and evaluate novel interventions. Methods: We established 3D pellet cultures derived from human OA chondrocytes to investigate galectin-induced extracellular matrix (ECM) remodeling and the chondroprotective potential of phytochemicals. OA pellets were stimulated with individual galectins (Gal-1, -3, -4, -8) or a Gal-1/-3/-8 mixture, followed by co-treatment with Brazilin, Diacerein, Quercetin, Resveratrol, or Avocado-Soybean Unsaponifiables (ASU). Morphological, histological, biochemical, and gene expression analyses were performed to assess tissue integrity and molecular responses. Results: Galectin treatment induced pronounced pellet shrinkage, matrix depletion, and upregulation of matrix-degrading enzymes (MMP-1, MMP-3, MMP-13, ADAMTS-4), while suppressing matrix synthesis markers (COL2A1, COL1A1), highlighting their cooperative catabolic effects. Co-treatment with phytochemicals conferred differential protection: Brazilin and Diacerein most consistently preserved pellet size, reduced matrix-degrading gene expression, and attenuated pro-MMP-13 secretion. Resveratrol restored histological matrix density but failed to suppress pro-MMP-13 secretion. Notably, no phytochemical fully restored COL2A1 expression under galectin-induced stress. Conclusions: Our study identifies Brazilin, Diacerein, and Resveratrol as promising modulators of galectin-driven cartilage degeneration and demonstrates the translational potential of patient-derived chondrogenic pellets as a human-relevant platform for preclinical drug evaluation in OA. The 3D culture effectively recapitulates key aspects of OA pathophysiology and offers a robust system to advance therapeutic discovery targeting ECM remodeling. Full article

Milk-production is one of the most important economic traits in dairy goats. Fundamentally, increasing milk-production at the genetic level can provide potential genetic markers for improving milk-production in dairy goats. Previous studies have shown that milk-production traits in dairy goats are highly polygenic and can be influenced by multiple genes. We therefore performed high-throughput sequencing on 350 Saanen dairy goats and conducted a genome-wide association study (GWAS) on the sequencing and production data. A total of 9,667,930 valid SNPs were identified, among which approximately 51% of the mutations were synonymous changes, and apart from unknown mutations, only a few changes affected gene expression. Finally, 318 SNP loci and 244 candidate genes were selected. We selected 10 loci most likely to influence these traits for large-scale population-based identification. Finally, four candidate genes, CDC14A, F11, RBPJL and ZFAND2A, were identified as the most likely to affect milk-production traits in dairy goats. To prevent spurious association analyses, we conducted subsequent experiments. Further results showed that the four candidate genes could regulate the proliferation and secretion of dairy goat mammary epithelial cells by regulating MAPK, mTOR and other pathways. These findings provide more valuable genetic markers and a theoretical basis for better understanding the intrinsic mechanisms of dairy goat mammary glands. Full article