Biochemical Genetics最新文献

The chloroplast (Cp) genome offers valuable perceptions into plant evolution, systematics, and phylogenetics. Here we are reporting complete chloroplast genome of Stellaria media (L.) Vill. collected from Dokdo Island, South Korea. The genome, assembled at 6340 × coverage, is 147,329 bp with a typical quadripartite structure, covering two inverted repeat (IR) regions of 25,600 bp and one single copy of large (79,366 bp) and small region (16,763 bp) each. Genome annotation identified 129 genes, including 84 protein-coding genes, 8 rRNA and 37 tRNA genes. In the IR region, ycf3 and clpP1 each contain two introns, while 17 genes, including rpl2, trnL-CAA, ycf2, and ndhB are present in duplicate, whereas rps19 is present as a single copy, reflecting structural conservation and evolutionary mechanisms such as intron retention and gene duplication. Comparative genomic analysis revealed substantial variations both among Stellaria species and in the formerly classified Stellaria dichotoma var. lanceolata. Codon usage showed a biasness toward codons ending with A/U, with leucine being most frequently encoded amino acid. Phylogenetic reconstruction based on complete chloroplast genomes positioned S. media within the Alsineae tribe and highlighted monophyletic relationships in the genus. Sliding window analysis identified hypervariable regions, including ycf1, ndhF-rpl32, and trnK-rps16 as potential molecular markers. This study provides crucial perceptions into chloroplast genome evolution, comparative genomics, and phylogeny within Caryophyllaceae, contributing essential data for taxonomic and conservation research. Additionally, multiple lines of evidence, including comparative chloroplast genomics, analyses of long and short repeat sequences, codon usage patterns, and phylogenetic relationships, support the taxonomic revision of inclusion of the genus Myosoton within Stellaria, and the exclusion of Stellaria dichotoma var. lanceolata from the genus Stellaria.

This study aimed to identify diagnostic marker genes for myocardial infarction (MI) and analyzed the key genes pertaining to immune cell infiltration. The MI expression microarrays GSE48060 and GSE66360 were retrieved and downloaded from the GEO database. The merged expression data were subjected to Weighted Gene Co-expression Network Analysis (WGCNA). Subsequently, differentially expressed genes (DEGs) were analyzed in MI. Primary rat cardiomyocytes (NRVMs) were isolated for an oxygen-glucose deprivation/reoxygenation (OGD/R) model, in which the effect of ICAM1, NFIL3, TULP2, and ZFP36 on cell phenotype experiments was detected. Gene differential expression analysis identified 96 significant DEGs, and the intersection of these genes with the module genes obtained from WGCNA analysis yielded 81 candidate genes. LASSO regression and Support Vector Machine-Recursive Feature Elimination (SVM-RFE) algorithms identified 7 candidate diagnostic genes. ICAM1, NFIL3, TULP2, and ZFP36 exhibited good diagnostic potential in both experimental and validation datasets, showing significant correlations with immune cells, including Neutrophils. ICAM1, NFIL3, TULP2, and ZFP36 were markedly up-regulated in OGD/R-treated NRVMs, while ICAM1 knockdown suppressed NRVM damage triggered by OGD/R. ICAM1, NFIL3, TULP2, and ZFP36 can serve as candidate diagnostic genes for MI, and ICAM1 silencing can ameliorate OGD/R-elicited myocardial cell damage.

Breast cancer (BC) remains one of the leading causes of cancer-related mortality among women worldwide, with distant metastasis being the primary contributor to poor prognosis. However, the molecular mechanisms driving BC metastasis are not yet fully understood. We integrated three public microarray datasets (GSE14776, GSE103357, and GSE32489) to identify the differentially expressed genes (DEGs) associated with breast cancer metastasis. Functional enrichment analysis, protein-protein interaction (PPI) network construction, and hub gene identification were performed using bioinformatics tools including DAVID, STRING, Cytoscape, and R. The prognostic significance of hub genes was assessed using Kaplan-Meier plotter and GEPIA. Expression validation was conducted through UALCAN, immunohistochemistry (IHC), and single-cell RNA sequencing (scRNA-seq) analysis from the GSE180286 dataset. A total of 295 co-DEGs were identified across the three datasets, enriched in pathways such as MAPK signaling, Rap1 signaling, and cell adhesion molecules. Twenty hub genes were identified from the PPI network, with eight showing strong prognostic value. Among them, PRC1 and POLR3H emerged as potential novel biomarkers. IHC confirmed the differential protein expression of PRC1, CDCA8, KIF14, and POLR3H. scRNA-seq analysis revealed that these hub genes were predominantly expressed in malignant epithelial and EMT (epithelial-mesenchymal transition) cells, particularly those from metastatic lymph node sites. This integrative analysis combining bulk and single-cell transcriptomic data identified key metastasis-associated genes in breast cancer. PRC1 and POLR3H, in particular, may serve as novel prognostic biomarkers and potential therapeutic targets.

This study aimed to explore thrombin-related prognostic biomarkers for hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT). Bioinformatics analyses were conducted using TCGA-LIHC and GEO datasets. LASSO Cox regression screened thrombin-related genes (TRGs). Differential expression analysis, GSEA, and protein-protein interaction (PPI) network analysis were performed to identify key pathways and hub genes. Clinical validation included immunohistochemistry (IHC) on 78 post-LT HCC tissues. In vitro assays (CCK-8, Transwell, Colony formation) assessed MMP1/SPP1 roles in HCC cell proliferation and migration. Nine TRGs were prognostic in HCC, with MMP1 and SPP1 emerging as core regulators linked to EMT. Both genes were significantly upregulated in recurrent HCC tissues (1-year recurrence group vs. non-recurrence, P < 0.05) and correlated with reduced overall survival (OS) and recurrence-free survival (RFS). GSEA revealed EMT as a key enriched pathway. PPI network analysis highlighted MMP1/SPP1 centrality in ECM remodeling and cell adhesion. Clinical samples confirmed MMP1 association with vascular invasion (P = 0.023) and poor differentiation. In vitro, MMP1/SPP1 overexpression enhanced HCC cell proliferation, migration, and colony formation. Multivariate analysis identified MMP1 expression and tumor differentiation as independent recurrence risk factors. MMP1 and SPP1 are potential biomarkers for predicting post-LT HCC recurrence, likely driving metastasis via EMT activation. Their overexpression correlates with aggressive tumor behavior and adverse outcomes, offering prognostic utility and therapeutic targets to improve transplant outcomes.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by abnormal social interactions, verbal communication difficulties, and restricted repetitive behaviors. Identifying the underlying genetic factors is crucial because of the complex genetic and environmental etiology. In this study, we performed whole-exome sequencing (WES), whole-genome sequencing (WGS), and array comparative genomic hybridization (aCGH) of four Iranian families with ASD-related conditions to identify novel genomic alterations. Five previously undescribed mutations were identified in these families. Family 1: A homozygous 290.7 kb deletion CNV (chr8:103,652,204-103942926; hg38) encompassing exons 2-16 of RIMS2 (NM_001348484), confirmed in a 7-year-old male proband with developmental delay and cone-rod synaptic disorder. Family 2: A heterozygous nonsense mutation in FOXG1 (NM_005249.5:c.839C > A; p.Ser280Ter) in a 6-year-old female with Rett-like features, resulting in a truncated protein lacking corepressor domains. Family 3: A splice donor site mutation in AUTS2 (NM_015570.4:c.742 + 1G > C) in a 10-year-old female with ASD and Attention-deficit/hyperactivity disorder, generating a frameshift and premature stop codon affecting mRNA-binding functionality. Family 4: A heterozygous nonsense mutation in ZCCHC17 (NM_016505.4:c.220C > T; p.Arg74Ter) and a splicing variant in SPTBN5 (NM_016642.4:c.3470 + 2T > A) in two male siblings with ASD were predicted to result in truncated proteins and aberrant splicing. Pathogenicity was supported through in silico analyses and structural modeling using I-TASSER, and segregation was confirmed using Sanger sequencing. This study highlights the genetic diversity of ASD and underscores the importance of advanced sequencing technologies in identifying novel mutations. Our findings contribute to the growing body of knowledge regarding the genetic basis of ASD, paving the way for personalized treatment strategies and early diagnosis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease with high disability rates, necessitating early diagnosis. This study investigated the potential of circRNAs, specifically CircRNA_0001412 and CircRNA_0001566, as diagnostic biomarkers for RA. High-throughput transcriptome sequencing was performed on peripheral blood mononuclear cells (PBMCs) from RA patients and healthy controls to identify differentially expressed circRNAs. Reverse transcription quantitative PCR (RT-qPCR) was used to validate circRNA expression in an independent cohort of 78 RA patients and 82 healthy controls. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic value of the selected circRNAs. Correlation analyses with clinical markers such as CRP, ESR, CCP, RF, WBC, lymphocyte count, and monocyte count were also conducted. Bioinformatics analyses, including GO and KEGG pathway enrichment, were conducted to explore the functional roles of the identified circRNAs and associated miRNAs. A total of 54 circRNAs were identified as differentially expressed in RA, with 21 circRNAs upregulated and 33 downregulated. Among these, CircRNA_0001412 and CircRNA_0001566 were highly expressed in RA PBMCs and demonstrated good sensitivity and specificity as diagnostic biomarkers (AUC = 0.751 (95%CI 0.673, 0.830) and 0.605(95%CI 0.516, 0.694)). Combined analysis of these circRNAs further improved diagnostic performance (AUC = 0.776 (95%CI 0.702, 0.851)). Notably, CircRNA_0001412 showed a significant correlation with CRP, suggesting its potential as a biomarker for RA disease severity. Bioinformatics analysis predicted that CircRNA_0001412 and CircRNA_0001566 could promote T-cell activation via the PI3K-Akt signaling pathway, contributing to RA pathogenesis. CircRNA_0001412 and CircRNA_0001566 are promising diagnostic biomarkers for RA, with CircRNA_0001412 additionally serving as a potential indicator of inflammatory activity. These findings provide a basis for further research into the diagnostic and prognostic utility of circRNAs in RA.

Lung cancer is a common and highly lethal malignancy globally, predominantly comprising non-small cell lung cancer (NSCLC), accounting for 80-85% of lung cancer cases. Lung adenocarcinoma (LUAD) represents the predominant subtype of NSCLC and is characterized by challenging early diagnosis and poor prognosis. Studies have implicated CBFA2T3 expression in treatment outcomes and prognosis across various cancers, yet its specific mechanisms remain under investigation. Analysis of TCGA data revealed a negative correlation between CBFA2T3 expression and tumor growth, suggesting that lower CBFA2T3 levels are associated with poorer outcomes in patients with LUAD. Our research identifies CBFA2T3 as a therapeutic target and potential prognostic indicator in LUAD, closely linked to immune cell infiltration and key immune regulatory markers. A model integrating CBFA2T3-regulated immune-related genes was constructed to predict the prognosis and immunotherapy response of patients with LUAD. Our findings were validated using GSE31210 and IMvigor210 datasets. qPCR and WB experiments on clinically collected samples confirmed reduced CBFA2T3 expression in LUAD. Online analysis using the Kaplan‒Meier plotter website confirmed a correlation between reduced CBFA2T3 expression and poorer prognosis in patients with lung cancer. Ultimately, our study identifies CBFA2T3 as a pivotal prognostic biomarker and potential therapeutic target for managing LUAD.

Hepatocarcinogenesis is associated with various factors, including oxidative stress. Alterations in selenoprotein genes could impair redox balance and influence cancer development. In this study, we aimed to evaluate the association of single nucleotide variants (SNVs) from selenoproteins with hepatocellular carcinoma risk. The case and healthy groups were genotyped using quantitative polymerase chain reaction (qPCR), and the analyzed SNVs were rs1050450 and rs3448 GPX1, rs713041 GPX4, rs5845 and rs5859 SEP15, and rs7579 and rs3877899 SELENOP. Significant differences in genotype frequencies were observed between the case and healthy groups (p < 0.05) for all studied SNVs, except for GPX1 rs3448. Furthermore, G/G rs1050450 GPX1 (OR = 1.975; 95% CI 1.075-3.628; p = 0.028) and homozygous C/C rs7579 SELENOP (OR = 3.088; 95% CI 1.667-5.722; p < 0.001) were associated with an increased risk of hepatocellular carcinoma. Comparisons with 1000 Genomes Project data revealed genotype frequencies similar to those of European descendants. These results could suggest a role of genetic alterations of selenoproteins in hepatocellular carcinoma risk.

Withania somnifera (L.) Dunal, commonly known as ashwagandha, belongs to the family Solanaceae is a significant medicinal plant in Ayurveda, valued for its high-quality roots and usage to treat an extensive physiological disorder. To enhance sustainable production and genetic gains, mutagenic treatment was applied to generate genetic variation. This study focused on investigating probit, genetic parameters, correlation associations, and path analysis in an M₁ population of two cultivars, NMITLI-118 (NM-118) and CIM-Pushti (CIM-P), exposed to Ethyl Methane Sulphonate (EMS). A total of fifteen morphological traits and seven biochemical markers were assessed across five different EMS doses: 02%, 0.4%, 0.6%, 0.8%, and 1%, with a control. The experiment was conducted at Mahatma Gandhi Central University, Motihari, Bihar. Significant genetic improvement along with high heritability were observed for traits like no. of leaves, seeds per plant, and berries per plant in NM-118 while, in CIM-P no. of leaves, seeds per plant, and main root length exhibited high genetic gain. Strong positive correlations were found between root dry wt. and root fresh wt. (0.852✷✷/0.894✷✷), no. of branches (0.721✷✷/0.816✷✷), and plant height (0.743✷✷/0.809✷✷) in NM-118, while CIM-P showed strong correlations with root width (0.864✷✷/1.076✷✷), root fresh wt. (0.983✷✷/0.998✷✷), and main root length (0.979✷✷/0.987✷✷). Path coefficient analysis revealed that the no. of seeds per berry, 1000-seed wt., and total seeds per plant had a strong positive direct effect on root dry wt. in NM-118, while in CIM-P, total seeds per plant, main root length, and root fresh wt. had the highest direct effects. In conclusion, the root dry yield of NM-118 is higher with a 1% EMS dose compared to all other treatments and cultivar. Additionally, the study found that CIM-P, treated with a 0.8% EMS dose, has the highest concentration of steroidal lactones/withanolides among the selected cultivars and doses, making it the most effective source for extracting withanolide A from the Withania mutant population. These traits are promising for breeding programs targeting improved root dry production in Withania cultivars.

The relationship between low back pain (LBP) and diabetes mellitus (DM) remains inconclusive, with no prior meta-analysis specifically evaluating risk factors for DM in patients with LBP. A comprehensive search of PubMed, Web of Science, Embase, and Cochrane Library databases was conducted. Eligible studies explicitly reported risk factors for LBP and DM. Demographic data were extracted, and meta-analyses were performed using random- or fixed-effects models, with statistical analyses conducted in Review Manager (RevMan) 5.4 software. A total of 21 studies involving 346,380 patients were included. The prevalence of DM in patients with LBP was 27%. Sixteen risk factors were identified, with six quantitatively investigated. Substantial evidence supported the association of LBP with age (mean difference [MD] = 4.27; 95% confidence interval [CI]: 2.98 - 5.56; p < 0.00001), male gender (OR = 1.18; 95% CI: 1.08 - 1.29; p < 0.0002), body mass index (BMI) (MD = 1.02; 95% CI: 0.15 - 1.89; p = 0.02), hypertension (OR = 2.63; 95% CI: 2.29 - 3.01; p < 0.00001), and educational level (OR = 0.76; 95% CI: 0.46 - 0.91; p = 0.003). No significant association was found between smoking and DM in those with LBP. This meta-analysis highlights a significant correlation between LBP and DM, identifying age, male gender, BMI, hypertension, and lower educational level as key risk factors for DM in patients with LBP.