Current Issues in Molecular Biology最新文献

Environmental exposures are widely recognized as major risk factors for human health. According to projections by the World Health Organization, climate change is expected to cause a significant increase in mortality within the next few decades. Environmental factors, including diet, weather, occupational exposures, and pollutants play a key role in human diseases affecting different systems, such as cardiovascular, pulmonary, gastrointestinal, and neurological. This narrative review explores the relationship between environmental stressors and neuropathological mechanisms, such as microglial and astrocytic activation, oxidative stress, and neuronal injury, involved in neuroinflammation and the associated neurodegeneration. The pathogenesis and progression of Alzheimer's disease is discussed in detail, establishing a link between environmental stressors and neuroinflammation. A deeper understanding of these neuropathological mechanisms may guide the development of preventive and therapeutic strategies to safeguard brain health in the context of global environmental change.

Cancer is one of the leading causes of morbidity and mortality worldwide, and it poses a persistent challenge to modern medicine [...].

Cryptotanshinone (CTS), an antiplatelet compound from Salvia miltiorrhiza, exhibits in vitro potency comparable to aspirin. This study integrated network pharmacology and metabolomics to elucidate its underlying mechanisms. An acute blood stasis model was induced in Sprague-Dawley rats using epinephrine and ice-water immersion. Animals were assigned to seven groups. Platelet aggregation was measured turbidimetrically using arachidonic acid (AA) and adenosine diphosphate (ADP) as agonists. Core targets were predicted by network pharmacology, differential metabolites were screened, and pathways were enriched using untargeted metabolomics. Integrated analysis identified shared pathways and key targets, validated by molecular docking. AA- and ADP-induced aggregation was significantly increased in model rats versus the blank group. CTS at all doses markedly inhibited aggregation in a dose-dependent manner. Network pharmacology identified 15 core targets. Metabolomics identified 51 differential metabolites enriched in seven pathways, including glycerophospholipid and butanoate metabolism. Integrated analysis revealed five common pathways: linoleic acid metabolism, arginine biosynthesis, AA metabolism, glutathione metabolism, and drug metabolism-and four key targets (CYP3A4, NOS3, PTGS2, and GSTP1). Molecular docking showed strong binding energies (<-9 kcal/mol) between CTS and these targets. CTS inhibits platelet aggregation by regulating CYP3A4, NOS3, PTGS2, and GSTP1 and intervening in five metabolic pathways, supporting its potential as an anti-platelet agent.

Serine protease inhibitor A3 (SERPINA3), also called α-1-antichymotrypsin, is a serine protease involved in placental dysfunction. This study examines SERPINA3 polymorphisms and haplotypes for associations with maternal hypertensive disorders of pregnancy (HDPs) and preeclampsia with severe features (sPE) or Hemolysis, Elevated Liver Enzymes, and Low Platelet (HELLP) syndrome in mother-baby dyads (HDP) and mother-father-baby triads (sPE/HELLP). This retrospective case-control study examined two patient cohorts, HDPs and severe PE/HELLP syndrome. The HDP population included cases (n = 142) and controls (n = 168) of mother-baby dyads recruited from a large, urban, safety-net hospital in Los Angeles. The sPE/HELLP syndrome population included cases (n = 189) and controls (n = 28) of mother-father-baby triads recruited through HELLP syndrome research websites. Cases were verified by medical chart abstraction when possible. Two SERPINA3 SNPs, rs4934 and rs1884082, were genotyped from saliva samples, mouthwash, or buccal swabs. The Haplin package in R was used to perform genetic association analyses. No evidence of increased risk related to individual SERPINA3 SNPs or haplotypes for the developing HDPs or sPE/HELLP was found in individual nor combined cohorts. In the HDP cohort, the g-a haplotype (relative to T-G haplotype) was borderline significant for increased risk of HDPs when carried by the child (double dose: RR = 1.58, 95% CI: (1.00, 2.52), p = 0.05). We observed significant parent-of-origin (PoO) effects in the combined cohort: specifically, an increased risk of HDPs/sPE/HELLP if the mother carries a double copy for both rs4934 (RR = 3.03, 95% CI (1.50, 6.09), p < 0.01) and rs1884082 (RR = 2.38, 95% CI (1.22, 4.71), p = 0.01). A reduced risk of HDPs/sPE/HELLP was observed for rs4934 (RR = 0.54, 95% CI (0.31, 0.98), p = 0.04) and rs1884082 (RR = 0.52, 95% CI (0.30, 0.91), p = 0.02) with child carriage of the maternally inherited allele. In contrast, child carriage of a paternally inherited copy of the variant allele for rs4934 increased risk of HDPs/sPE/HELLP (RR = 1.54, 95% CI (1.09, 2.20), p = 0.02). There was no evidence that SERPINA3 gene polymorphisms and haplotypes were associated with risk of HDPs or sPE/HELLP. However, significant PoO effects were observed in the combined cohort analysis, with child carriage of rs4934 that is maternally inherited decreasing HDPs/sPE/HELLP risk while a paternally inherited copy increases risk, suggesting a role for maternal-fetal genomic incompatibility.

Endometriosis impairs fertility by interfering with ovarian function, embryonic development, and endometrial receptivity. Extracellular vesicles (EVs) are recognised as non-invasive biomarkers that may indicate biological processes based on their lipid, protein, and microRNA composition. This narrative review synthesises current data on extracellular vesicle (EV) signatures in serum/plasma, menstrual blood, follicular fluid, and uterine fluid in endometriosis patients using assisted reproductive technology (ART). We highlight critical EV-mediated processes, such as progesterone signalling, fibrosis, angiogenesis, inflammation, and metabolism, and their associations with oocyte competence, embryo development, and implantation. Certain EV-miRNA profiles, including miR-22-3p, miR-320a, the miR-200 family, and miR-145-5p, have shown use for diagnostic and prognostic purposes in various investigations. These characteristics are associated with live birth, implantation, and blastocyst quality. We propose a clinical framework that incorporates (i) menstrual-blood EVs for non-invasive endotyping, (ii) serum/plasma EV profiling for baseline risk stratification, and (iii) pre-transfer uterine-fluid EV evaluation to inform embryo-transfer decisions. Translation requires standardisation, cycle phase control, and prior validation. EVs may serve as a beneficial instrument for personalised in vitro fertilisation operations for ladies experiencing infertility due to endometriosis.

Canine hepatocellular carcinoma (HCC), the most common primary liver malignancy in dogs, shares many clinicopathological and molecular similarities with human HCC. However, its molecular characteristics remain insufficiently defined, and reliable diagnostic biomarkers are lacking. Elucidating dysregulated microRNAs (miRNAs) may aid in both disease characterization and comparative oncology research. Small RNA sequencing datasets from canine HCC were analyzed to identify significantly dysregulated miRNAs with high expression and biomarker potential. The top candidate was validated in clinical tissues, cell lines, patient's plasma and plasma exosomes using RT-qPCR. Comparative analyses were conducted using human HCC datasets (TCGA and GEO), followed by target prediction and functional enrichment to identify conserved molecular pathways. Among the 59 differentially expressed miRNAs, cfa-miR-10a showed the highest average expression level and yet was significantly downregulated in canine HCC tissues. RT-qPCR confirmed reduced expression of cfa-miR-10a in canine HCC tissues, whereas plasma exosomes showed significant enrichment, demonstrating excellent diagnostic performance (AUC = 0.94). The mature sequence of cfa-miR-10a is highly conserved with hsa-miR-10a-5p. TCGA datasets confirmed downregulation of hsa-miR-10a-5p in HCC tissues, whereas a GEO dataset showed no significant change in serum exosome levels. Target prediction and functional annotation identified 59 overlapping genes, with the Proteoglycans in cancer pathways being conserved in both species, mediated by ACTG1, SDC1, FRS2, and WNT9B. Collectively, these findings demonstrate distinct intra-tumoral and exosomal expression pattern of miR-10a in canine HCC and support its potential as a non-invasive biomarker with translational relevance.

Salt stress is a major environmental constraint that severely limits cotton seed germination. However, the regulatory mechanisms governing salt stress responses during the post-germination stage remain largely unclear. Here, we employed an integrated transcriptomic and metabolomic approach to investigate salt-responsive mechanisms in the salt-tolerant cotton cultivar ST022-1056m5 (ST) following exposure to 150 mM NaCl. Our analysis identified 4368 differentially expressed genes (DEGs) and 441 differentially accumulated metabolites (DAMs) under salt stress conditions. Multi-omics integration revealed that alpha-linolenic acid and linoleic acid metabolic pathways were particularly responsive to salt stress. In the α-linolenic acid pathway, salt stress triggered substantial accumulation of jasmonic acid (JA) precursors and concurrent upregulation of key JA biosynthetic genes. Simultaneously, the linoleic acid metabolism pathway exhibited increased metabolite levels and enhanced the relative gene expression. These findings provide compelling evidence that alpha-linolenic acid and linoleic acid metabolism pathways collectively modulate post-germination salt stress responses in cotton, offering new insights into the molecular mechanisms underlying salt tolerance and presenting potential targets for breeding resilient cotton varieties.

Oral infections caused by Candida spp. represent a major health concern due to the increasing resistance of these fungi to conventional antifungal agents. Photodynamic therapy (PDT) is a treatment based on the use of light at a specific wavelength that activates a photosensitizer (PS) in the presence of oxygen. The activated PS selectively binds to infected cells and induces apoptosis through the generation of reactive oxygen species (ROS). Previous biomolecular studies on Candida albicans have demonstrated that its infection triggers characteristic molecular signals, such as miRNA-146a and miRNA-155, which serve as inflammatory markers. This in vitro study aimed to evaluate the impact of PDT on the expression of their primary transcripts (pri-miRNAs) in a cell culture model of C. albicans infection. Human embryonic kidney (HEK-293) cells were infected with a multidrug-resistant strain of C. albicans (CA97) and subsequently exposed to curcumin-based PDT activated by blue light (470 nm). The expression of pri-miRNAs 146a and 155 was assessed before and after PDT treatment for each experimental group. The expression levels of pri-miRNAs increased approximately 2- to 3.5-fold following C. albicans infection but returned to baseline values after PDT treatment. The evaluation of pri-miRNAs 146a/155 may serve as a valuable research tool for monitoring early inflammatory responses induced by Candida infection, as well as a sensitive biomarker for assessing the effectiveness of photodynamic therapy in an in vitro cell culture model.

Ewing sarcoma is a pediatric malignant cancer that usually develops in bones and soft tissues. The current study investigates the function of hsa-let-7a as a target molecule in the pathophysiology of Ewing sarcoma using computational approaches. To anticipate complementary sites, miRNA and mRNA sequences were retrieved from the miRBase and NCBI databases. The three-dimensional structures of both hsa-let-7a and mRNA_EWSR1 were predicted through MC-Fold and RNAComposer, respectively. Furthermore, online HNADOCK and PatchDock docking servers were utilized to check the docking energy values and interactive behavior between miRNA and mRNA. The generated docked results showed good binding score values and interaction profiles between nucleotides of hsa-let-7a and mRNA of EWSR1. Moreover, both docking complexes were also studied using anisotropic network model analysis, which involved plotting correlation, inter-nucleotide distance fluctuations, and deformation energy graphs. The predicted heatmap graph also highlighted the significance of hsa-let-7a in various cellular signaling pathways, which may be interconnected with Ewing sarcoma, making it a potential therapeutic target. Together, this study offers computational insights that highlight hsa-let-7a as a promising therapeutic candidate for Ewing sarcoma, based on miRNA-driven predictive modeling.