Biochemical Genetics最新文献

Acute coronary syndrome (ACS) is a significant contributor to cardiovascular mortality. Research has indicated that CA125 levels are linked to cardiovascular disease. This study aimed to explore the role of CA125 in ACS and its underlying mechanism. A retrospective study was conducted involving 34 healthy volunteers and 46 patients diagnosed with ACS. Clinical characteristics and CA125 expression were recorded and detected. Bioinformatics analysis was performed to identify miRNAs that regulate CA125. HL-1 cardiac muscle cells were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) to investigate the role of CA125 in myocardial injury. An ACS mice model was constructed to further explore the role of CA125 on ACS. The levels of serum creatinine, blood urea nitrogen, uric acid, high-sensitivity C-reactive protein, cystatin C, and white blood cells in ACS were markedly higher than those in healthy volunteers. CA125 was up-regulated in ACS and was a target of miR-203. Injection of miR-203 agomir reduced plaque deposition and vascular thrombosis in the coronary lumen, alleviating myocardial damage. Additionally, miR-203 inhibited myocardial apoptosis and inflammation responses induced by OGD/R and ACS. miR-203 can reduce the inflammatory response by inhibiting CA125 expression, thereby improving ACS symptoms and mitigating ACS-induced myocardial injury.

Lens Epithelial Cells (LECs) apoptosis is a critical driving factor of age-related cataract (ARC), but the specific molecular mechanisms remain undefined. Herein, a novel target of ROR1 regulation was identified, the mechanism was elucidated by which ROR1 and its associated pathway proteins influence hydrogen peroxide (H₂O₂)-induced apoptosis of LECs in ARC. We found decreased ROR1 expression in human cataract lens capsules compared to normal ones, the trend was also observed in young and old mice. Experiments including CCK8, Hoechst 33,342 staining, and Western blot analysis confirmed that reduced ROR1 levels were linked to H₂O₂-induced apoptosis in HLEB3 cells. To investigate its effects on cell viability and apoptosis, we created a ROR1 interference plasmid and an overexpression plasmid. The overexpression of ROR1 effectively inhibited H₂O₂-induced apoptosis of HLEB3 cells while ROR1 knockdown lowered the viability and increased the apoptosis of HLEB3 cells. Additionally, increased P38 phosphorylation was identified as a contributor to lens epithelial cell apoptosis and ARC, with ROR1 influencing this through the phosphorylation of the P38. Similarly, the relationships between P300 and STAT3, upstream of ROR1, in apoptosis of LECs and ARC were explored, and it was found that P300 and STAT3 were negatively correlated with apoptosis of LECs and ARC. In addition, the double luciferase report showed that P300 and STAT3 synergistically up-regulated the expression of ROR1. Overall, this study demonstrates that the STAT3/ROR1/P38 pathway mitigates apoptosis of LECs in ARC progression, offering a novel strategy for ARC prevention and treatment in clinical settings.

Ideonella and Thermobifida were the most promising bacterial candidates for degrading plastic polymers. A comparative pan- and phylogenomic analysis of 33 Ideonella and Thermobifida strains was done to determine their plastic degradation potential, niche adaptation and speciation. Our study disclosed that more accessory genes in the strains showed phenotypic plasticity, according to the BPGA data. Pan and core genes were employed for the phylogenetic reconstruction. Pathway enrichment analyses scrutinized the functional roles of the core and adaptive-associated genes. KEGG annotation revealed that most genes were associated with the metabolism of amino acids and carbohydrates. The detailed COG analysis disclosed that approximately 40% of the pan genes performed metabolic functions. The unique gene pool consisted of genes chiefly involved in "general function prediction" and "amino acid transport and metabolism". Our in silico study revealed that these strains could assist in agronomic applications in the future since they devour nitrogen compounds and their central metabolic pathways are involved in amino acid metabolism. The rational selection of strains of Ideonella is far more effective at depolymerising plastics than Thermobifida. A greater number of unique genes, 1701 and 692, were identified for Ideonella sakaiensis 201-F6 and Thermobifida alba DSM-43795, respectively. Furthermore, we examined the singletons involved in xenobiotic catabolism. The unique singleton data were used to construct a supertree. To characterize the conserved patterns, we used SMART and MEME to identify domain and transmembrane regions in the unique protein sequences. Therefore, our study unraveled the genomic insights into the ecology-driven speciation of Ideonella and Thermobifida.

Red algae are widely used as a source of health-promoting bioactive compounds and dietary fibers in health foods. The identification and classification of red algal species based on morphological and molecular characteristics is challenging because of the similarity of the thallus and its high degree of plasticity and because complete mitochondrial genomes have only been reported for a few species. In this study, the complete mitochondrial genome sequencing of the red macroalga Chondracanthus tenellus (Harvey) (Hommersand et al., Hydrobiologia 260:105-120, 1993)) (Rhodophyta, Gigartinales) was performed for the first time. Additionally, we aimed to reconstruct the phylogenetic relationships of the species within the order Gigartinales using complete mitochondrial genome sequences. Genomic DNA was extracted, analyzed by whole-genome sequencing (WGS), and assembled using NOVOPlasty. The mitochondrial genome sequence was annotated, and both a genome map and a phylogenetic tree were constructed using maximum likelihood analysis. The mitochondrial genome was 25,928 bp in length, had strongly biased [AT] content (72.08%), and comprised 3 rRNAs, 23 tRNAs, and 24 protein-coding genes (PCGs). In comparison with the mitochondrial genome of other red algae, that of C. tenellus lacks rpl5 and rpl20. Based on a phylogenetic study of the complete mitochondrial genome, C. tenellus belongs to the family Gigartinaceae and is monophyletic with other species of the order Gigartinales. This is the first report of C. tenellus complete mitochondrial genome; its characteristics are consistent with those of other red algae. The study of genomic data will be beneficial for future comparative genomics, phylogenetics, and evolutionary studies.

Maladaptive changes in gene expression at transcriptional level in dorsal root ganglia (DRGs) after nerve injury are critical for neuropathic pain genesis. Emerging evidence reveals the important role of non-coding RNAs (ncRNAs) in regulating gene transcription. Recent studies also have showed the contribution of ncRNAs to neuropathic pain. However, the expression profile of ncRNAs in the DRGs and potential regulatory mechanism in peripheral nerve injury-induced neuropathic pain are not fully clear. We used bCCI neuropathic pain model induced by chronic constriction injury of bilateral sciatic nerves to study the expression profile and potential functional mechanism of micro RNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs) and messenger RNA (mRNA) in the DRGs by RNA sequencing and bioinformatics analysis. A total of 47 miRNAs, 337 lncRNAs, 32 circRNAs, and 2269 mRNAs were differentially expressed (DE) in the DRGs of CCI mice 14 days after surgery. KEGG analysis demonstrated nociception-related signaling pathways were significantly enriched for DEncRNAs, including Rap1, Ras, and Hippo signaling pathway. GO analysis showed neuron related biological process, membrane related cell components, and binding related molecular functions were significantly enriched. The competing endogenous RNA (ceRNA) regulatory network of DEmiRNA-DEmRNA, DElncRNA-DEmRNA, and DEcircRNA-DEmiRNA existed in the DRGs of mice with neuropathic pain induced by peripheral nerve injury. In addition, 81 pain-related DE genes had protein-protein interactions (PPI) with each other. Our findings indicated that ncRNAs are involved in the development of peripheral nerve injury-induced neuropathic pain. DEncRNAs may provide us with a new perspective in chronic neuropathic pain research and may become a potential target for pain treatment.

This study employs a comprehensive multi-omics approach to investigate the regulatory roles of specific microRNAs (miRNAs) in Congenital Tooth Agenesis (CTA). A total of 58 miRNAs associated with tooth diseases, cancer, and bone development were initially identified through a literature review and analyzed using bioinformatics. Based on target prediction and network analysis, eight miRNAs with strong connectivity and common target genes were shortlisted for further investigation. Blood samples from 10 CTA patients and 5 healthy controls were analyzed for miRNA expression using stem-loop RT-PCR. Four miRNAs-hsa-miR-218-5p, hsa-miR-15b-5p, hsa-miR-200b-3p, and hsa-let-7a-3p-were identified as significantly differentially expressed, marking their first reported involvement in CTA. Notably, hsa-miR-218-5p and hsa-let-7a-3p emerged as novel regulators with no prior associations with CTA or tooth development. To address the limitations of a small sample size, a multi-omics strategy was employed to validate these findings, integrating miRNA expression data with whole exome sequencing (WES), gene expression panels, and metabolomic profiling. The analysis confirmed the association of these four miRNAs with CTA and highlighted their involvement in critical biological pathways such as Wnt signaling, FGF signaling, and PI3 kinase pathways, which are essential for cellular proliferation, differentiation, and tissue morphogenesis. Importantly, the identification of these miRNAs in blood samples, rather than traditional dental tissues, highlights a minimally invasive approach that could aid in the early detection, therapeutic targeting, and personalized management of dental anomalies.

This study evaluated talin1 expression in platelets and platelet-derived microvesicles (PMVs) from nonvalvular atrial fibrillation (NVAF) patients. Meanwhile, this study analyzed the impacts of talin1 expression in PMVs on platelet activation. Twelve healthy controls and 38 NVAF patients were recruited in this study. The levels of talin1 and RAP1B activation were observed in the platelets and PMVs from the participants, and their levels were significantly increased in the NVAF patients compared to the healthy controls (P < 0.01). Talin1 silence in MEG-01 cells was obtained by transfecting talin1 siRNA, and the cells were stimulated by thrombin receptor-activating peptide 6 (TRAP-6) to induce platelet-dense granule secretion. TRAP-6 stimulation increased the talin1 expression and RAP1B activation in the platelet-like particles from MEG-01 cells, but talin1 silence suppressed the TRAP-6-stimulated RAP1B activation and CD62p expression in the platelet-like particle. Moreover, the platelets from healthy donors were activated by the PMVs from the TRAP-6-stimulated MEG-01 cells. However, the decreased talin1 level in the PMVs from MEG-01 cells weakened the platelet activation. This study suggested that talin1 expression in the PMVs affected platelet activation in patients with NVAF.

Breast cancer is one of the most prevalent cancers globally and remains a significant cause of cancer-related mortality among women despite advancements in early detection and treatment. The heterogeneity of breast cancer arises from a complex interplay of genetic and environmental factors. Early-stage breast cancer is often asymptomatic, with initial signs including subtle changes in breast morphology and localized swelling, emphasizing the need for reliable diagnostic tools for early detection. Recent research has highlighted the potential of molecular biomarkers, particularly non-coding RNAs such as circular RNAs (circRNAs), in cancer diagnosis. CircRNAs, a unique subset of non-coding RNAs, are characterized by their covalently closed-loop structure, which confers exceptional stability and resistance to exonuclease degradation. They are present in various body fluids and have demonstrated regulatory roles in transcription, translation, and as microRNA sponges, making them promising candidates for cancer diagnostics and prognostics. This study focuses on evaluating the diagnostic potential of two circRNAs, hsa_circ_0001666 and hsa_circ_0003227, by examining their expression in normal, tumor, and metastatic breast cancer cell lines. Breast cancer cell lines representing normal (MCF-10A), tumor (MCF-7), and metastatic (BT-20) stages were cultured for analysis. Total RNA was extracted using a column-based RNA extraction kit, and RNA quality was assessed through NanoDrop spectrophotometry and agarose gel electrophoresis. Complementary DNA (cDNA) synthesis was performed using random hexamers, and the expression levels of hsa_circ_0001666 and hsa_circ_0003227 were quantified using Real-Time Quantitative Reverse Transcription PCR (RT-qPCR), with beta-actin serving as the internal control. Statistical analyses were conducted using SPSS software to evaluate differences in expression levels across cell lines. A significant downregulation of hsa_circ_0001666 and hsa_circ_0003227 was observed in tumor and metastatic cell lines compared to normal breast cell lines (P < 0.05). These results suggest that the expression of these circRNAs correlates with the progression of breast cancer, with decreased levels observed as cells transition from normal to tumorigenic and metastatic stages. The findings of this study indicate that hsa_circ_0001666 and hsa_circ_0003227 have potential utility as diagnostic biomarkers for breast cancer. Their significant expression changes across different stages of breast cancer highlight their relevance in early detection and disease monitoring. This study reinforces the potential of RNA-based biomarkers, particularly circRNAs, in cancer diagnosis and treatment. However, in vitro findings require validation in clinical samples and larger cohorts. Future research should explore their roles in breast cancer progression and integration into non-invasive diagnostics.

The genus Babylonia, classified under Mollusca, Gastropoda, Neogastropoda, has been a subject of controversy concerning the phylogenetic relationships within Neogastropoda, a highly intricate group of predatory marine snails. In this study, we sequenced complete mitogenomes of Babylonia spirata and Babylonia zeylanica. Both mitogenomes consist of 37 genes, including 13 PCGs, 22 tRNAs, and 2 rRNAs, which is consistent with the gene numbers observed in most neogastropod snails. We analyzed base content, codon usage preference, and tRNA structure to describe the basic structural features. Additionally, phylogenetic trees were constructed using Maximum Likelihood and Bayesian Inference based on the complete mitogenomes of 43 Neogastropoda species. This analysis revealed that all 19 families formed monophyletic groups, collectively constituting seven monophyletic superfamilies. Moreover, by analyzing the gene arrangement characteristics of these 43 Neogastropoda species, we identified four distinct types of mitochondrial genome arrangements. This study strongly supports the monophyly of Neogastropoda families, contradicting previous molecular studies and providing fundamental insights for further phylogenetic studies in Neogastropoda.

Nephrotic Syndrome (NS), especially in the Chronic Kidney Disease (CKD) stage, poses significant challenges in pediatric nephrology. Urine-derived stem cells (USCs) show promise for renal repair and regeneration. While benazepril is commonly used to treat CKD, its impact on USCs from children with NS during the CKD stage is unclear. USCs were isolated from the urine of 6 healthy children and 6 with NS (CKD stage), cultured through passages, and their morphology and cell surface markers were assessed microscopically and by flow cytometry, respectively. USCs were treated with benazepril at concentrations of 1, 10, 20, 40 μmol/L, and proliferation was evaluated using the CCK-8 assay. ROS levels were measured using DCFH-DA probe, and the expression levels of IL-1β, Connexin 43, AEC, ACE2, Ang2, AQP-1 and E-cadherin were analyzed by Western Blot. Tubular epithelial cell differentiation was also examined. USCs could be cultured from both healthy and NS (CKD stage) children, but USCs from NS children only reached passage 5 and exhibited weaker proliferation and differentiation abilities compared to those from healthy children. IL-1β, Connexin 43, ROS,ACE and Ang2 levels were higher in USCs from NS children than in those from healthy children, while ACE2 showed the opposite trend. Treatment with 1 μmol/L benazepril enhanced the proliferation and differentiation ability of USCs from NS children, inhibiting the level of inflammation factors, ROS, ACE and Ang2 while promoting ACE2 expression in these cells. This study offers valuable insights for future USCs applications.