Biochemical Genetics最新文献

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.

LIM homeobox transcription factor 4 (LHX4) is one of the genes involved in sheep reproduction. Consequently, this study investigated whether the LHX4 gene affects the litter size of ewes. Genomic DNA extraction was performed on 123 ewes with singleton lambs and 109 ewes with twins. Using polymerase chain reaction (PCR), fragments of 207, 256, 257, 325, and 377 bp were amplified from exons 1, 2, 3, 5, and 6 of the LHX4 gene. Genetic analysis of the amplified locus of 207 bp revealed three genotypes. An analysis of the sequence revealed a novel mutation in exon 1: p.17Pro = SNP. Statistical analysis showed that the p.17Pro = SNP was associated with reproductive characteristics (P ≤ 0.01). Ewes carrying the GG genotype had significantly lower live body weight, litter sizes, twinning rates, lambing rates, and more lambing days than ewes with AG and AA genotypes. Lambs produced by GG genotype ewes were fewer than those produced by AA and AG genotype ewes. These results indicate that the p.17Pro = SNP negatively affects Awassi sheep's reproductive traits. Ewes carrying the GG genotype are less prolific and have lower litter sizes than those without the SNP.

This research was purposed to explore the role and mechanism of Erzhi pills (EZP) in age-related macular degeneration (AMD). TCSMP, PubChem, SwissTargetPrediction, and TargetNet databases were utilized to identify the active ingredients and targets of EZP, while disease targets were obtained from the DISEASES and DisGeNET databases. All identified targets were standardized using the UniProt platform. Overlapping targets between the drug and disease were determined using the Jvenn tool, and these targets were subsequently imported into the STRING database for network analysis. Enrichment analyses were conducted using the gProfiler web tool. The hub gene network was constructed utilizing Cytoscape software. Molecular docking studies were performed to assess the interactions between key components and their respective targets. A total of 16 active ingredients and 310 targets of EZP were identified, with 46 targets overlapping with disease-related targets, which implicated pathways involving inflammatory response, angiogenesis, and HIF-1α signaling. The top five hub genes identified were KDR, STAT3, mTOR, ESR1, and HIF1A. In vitro experiments, the CCK-8 assay, DCFH-DA staining, ELISA, tube formation assay, RT-qPCR, and Western blot analysis were conducted to evaluate the cellular biological behaviors and protein expression levels. The results showed that EZP could reduce H₂O₂-induced ROS accumulation, proinflammatory cytokine release, and promote angiogenesis. EZP inactivated HIF-1α pathway. EZP might target HIF-1α pathway to suppress oxidative stress, inflammation, and angiogenesis in H₂O₂-exposed ARPE-19 cells.

Preeclampsia (PE) is a serious pregnancy complication characterized by impaired trophoblast function. Insulin-like growth factor-1 (IGF1) is a peptide hormone that exhibits metabolic effects similar to insulin, modulating diverse physiological processes such as cellular proliferation, differentiation, motility, survival, and gene expression regulation. The objective of this study was to investigate the expression level and biological function of IGF1 in PE. The expression level of the IGF1 was quantified by quantitative real-time polymerase chain reaction (RT-qPCR). Functional phenotypes in IGF1-regulated HTR8/SVneo cells were assessed; cell proliferation, migration, invasion, cell cycle, and apoptosis were determined by CCK8 assays, wound healing assays, Transwell assays, and flow cytometry, respectively. Compared to normal pregnancy, preeclamptic placental tissues exhibited significantly downregulated IGF1 expression levels. Functional analyses revealed that IGF1 knockdown suppressed proliferation, migration, and invasion in HTR-8/SVneo cells, whereas IGF1 upregulation enhanced these functions. Both IGF1 knockdown and overexpression were performed without influencing the cell cycle or inducing apoptosis. These findings indicate that IGF1 serves as a critical mediator of trophoblast proliferation, migration, and invasion, contributing to preeclampsia development, providing novel insights of PE pathogenesis.

Hypertriglyceridemia is mostly associated with secondary conditions in children but can also result from monogenic disorders. The most prevalent genes identified as the underlying reason for impaired clearance of triglycerides from plasma by genome-wide association studies are the LPL, APOC2, APOA5, LMF1, APOE and GPIHBP1 genes. In this study, 26 pediatric patients with primary hypertriglyceridemia, 12 of whom were severe, were screened for monogenic causes via a next-generation sequencing panel that included 25 genes, namely, ABCA1, ABCG5, ABCG8, ANGPTL3, APOA1, APOA5, APOB, APOC2, APOC3, APOE, CETP, GPD1, GPIHBP1, LCAT, LDLR, LDLRAP1, LIPA, LIPC, LMF1, LPL, MTTP, NPC1L1, OSBPL5, PCSK9 and SAR1B. Additional findings, such as positive family history, hepatomegaly, splenomegaly, history of acute pancreatitis, hepatosteatosis, and atherosclerotic cardiovascular disease, were recorded. Twenty different variants, 16 of which were novel, were detected. Among these, six of the eight clinically significant mutations detected in the LPL, GPD1, GPIHBP1, APOC2, and LIPC genes were novel mutations. At least one variant was identified in 17 of 26 patients (65.4%), whereas no variants were detected in 9 patients (34.6%). Clinically significant variants that could explain the clinical findings were detected in 7 (58.3%) of the 12 patients with severe hypertriglyceridemia. In 4 out of the 6 patients with a familial history of hypertriglyceridemia, we identified pathogenic variants in the GPD1, LIPC, LPL and APOC2 genes, which are associated with hypertriglyceridemia. Targeting gene panels for suspected monogenic hypertriglyceridemia is a promising way to identify the underlying etiology, which enables genetic counseling and family screening to identify new patients and provides a personalized treatment approach.

Circular RNAs (circRNAs) are emerging as major regulatory factors in gastric cancer progression. Here, in addition to the regulatory role of hsa_circ_0013729, we also evaluated its biomarker potential in gastric cancer. RNA-Seq profiles were obtained from GSE194384 and GSE184882. 116 gastric cancer specimens and adjacent para- tumor gastric tissues were analyzed for the expression of hsa_circ_0013729. The functional (proliferative, migratory, and invasive) significance of hsa_circ_0013729 was evaluated by cell experiments. The competing theories of endogenous RNAs and RNA-binding proteins were used to explore the underlying mechanism. Analyses of GSE194384 and GSE184882 identified hsa_circ_0013729 as a dysregulated circRNA in gastric cancer. The quantification of hsa_circ_0013729 in our patient cohort revealed its upregulation, diagnostic significance (ROC-AUC = 0.94, 95% confidence interval: 0.9149 to 0.9718; p < 0.0001), and prognostic value with a hazard ratio of 2.65 in gastric cancer. Hsa_circ_0013729 was identified as a potential driver in gastric cancer cell proliferation, migration, and invasion. Hsa_circ_0013729 acted as a ceRNA for miR-361-3p and interfered with the binding between miR-361-3p and MEF2D. Hsa_circ_0013729 interacted with HNRNPIL1 to stabilize MEF2D mRNA.Hsa_circ_0013729 may promote gastric cancer via the miR-361-3p/MEF2D axis and HNRNPUL1/MEF2D axis, showing potential as a biomarker and therapeutic target.

Labyrinthine aplasia, type I microtia and microdontia (LAMM) syndrome, a rare autosomal recessive disease, is characterized by labyrinthine aplasia, microtia, and microdontia initially described in 2007 by Tekin. It is evident that the syndrome is associated with FGF3, and several mutations within the FGF3 gene have been reported in individuals with LAMM syndrome. We have identified a novel mutation (c.155C>G,p.Thr52Arg) which has never been reported. Furthermore, the pathogenicity of the new mutation has not yet been tested in human or zebrafish models. We present a case of LAMM syndrome with cholesteatoma in a 5-year-old male with compound heterozygosity for FGF3 mutations, born to non-consanguineous parents. This report describes a novel mutation (c.155C>G,p.Thr52Arg) that has never been previously reported and (c.310C>T,p.Arg104Ter) that have been reported several times. We tested its pathogenicity by (1) detecting the stable inheritance of gene mutations of FGF3 (c.155C>G,p.Thr52Arg) in DNA, 3D domain, and species conservation and (2) injecting mRNA into zebrafish to observe potential anomalies. The novel case showed the presence of cholesteatoma that may expand the manifestation of LAMM syndrome. There were no mutation-related bands observed in PCR analysis for the inheritance of the mutation sites. The residue (Thr52) is evolutionarily conserved across species. Analysis of the 3D structure indicated variations in FGF3's structural surface, possibly associated with illness etiology. Injection of constructed mutant plasmid into zebrafish resulted in evident malformation. The present case is the first documented report of LAMM syndrome accompanied by cholesteatoma, unveiling a novel possible pathogenic mutation of FGF3. The presence of otitis media and cholesteatoma will expand the manifestations of LAMM syndrome. The novel mutation FGF3 (c.155C>G,p.Thr52Arg) may be pathogenic by disturbing the connection of ligand of FGF3 and receptor of FGFR3 in the ear during fetal.