Biochemical Genetics最新文献

This study evaluates the C-reactive protein-albumin-lymphocyte (CALLY) index for predicting multiple organ failure syndrome (MOFS) in elderly with sepsis (SP) through a retrospective analysis of 209 cases stratified by severity into SP, severe SP (SSP), and septic shock (SPS) groups. Patients were further categorized into MOFS and N-MOFS groups according to 30-day ICU outcomes. Correlations of CALLY index with APACHE II and SOFA scores were assessed using Spearman's correlation analysis, while predictive utility was evaluated via ROC and Kaplan-Meier curves and Cox regression. Results demonstrated a progressive decline in CALLY index with worsening severity (SPS < SSP < SP; P < 0.001), alongside negative correlations with APACHE II and SOFA scores (P < 0.001). Patients who developed MOFS exhibited a significantly lower CALLY index than their N-MOFS counterparts (P < 0.05). The index achieved superior MOFS prediction (AUC = 0.892) compared to APACHE II (AUC = 0.772; P < 0.001) and SOFA (AUC = 0.815; P = 0.042), with low-CALLY patients showing higher cumulative MOFS incidence (P < 0.001). Multivariate analysis confirmed elevated SOFA as an independent risk factor for MOFS, while higher CALLY index conferred protective effects, establishing this novel index as a robust predictor of MOFS that inversely correlates with SP severity in elderly.

Insects rely heavily on their olfactory system for crucial behaviours like finding mates, locating food, and avoiding predators. Odorant binding proteins (OBPs) bind to odorant molecules, facilitating their transport to olfactory receptors. Understanding OBP diversity and the genomic landscape is vital for elucidating insect olfaction. Bemisia tabaci, a global invasive pest with significant economic impact, has limited OBP diversity studies across its genetic groups. This research investigates OBPs in B. tabaci Asiatic groups, a major invasive genetic group in Asia, to enhance our knowledge of their olfactory mechanisms and inform targeted pest control strategies. A computational pipeline identified OBPs in B. tabaci Asiatic groups using TBLASTN analysis of annotated genomes and whole-genome data. Unique OBP sequences were verified with BLASTX. Bioinformatics tools analysed gene structure, domain prediction, chromosomal localization, scaffold-wise arrangement, and protein structure. Phylogenetic analyses characterised OBPs and explored evolutionary relationships. We identified 9-10 OBPs in B. tabaci Asiatic groups, expanding our knowledge beyond previously studied genetic groups. Comparative analyses with other Hemipteran species showed similarities and differences in OBP diversity. Functional domain analysis highlighted conserved domains associated with odorant binding and membrane interactions. Variations in signal peptide presence suggested differences in protein stability and ligand-binding capabilities. Genomic organisation analysis revealed non-random OBP gene clustering on specific chromosomes, indicating potential co-regulation and functional relationships. The findings enhance understanding of B. tabaci olfaction and provide insights for targeted pest control strategies.

Prostate cancer (PCa) is highly aggressive and poses significant threats to health. Investigating the molecular regulatory mechanisms that potentially inhibit tumor progression is essential to identifying valuable target genes for therapeutic intervention. Bioinformatics techniques were employed to explore potential key target genes. siRNA interference was used to construct gene knockdown cell models. Dot blot and MeRIP-qPCR techniques are utilized to investigate the overall N6-methyladenosine (m6A) methylation levels of the target gene. qRT-PCR was used to evaluate the mRNA expression levels of the genes, while Western blotting analysis was performed to detect the protein expression levels of the target genes. The results from bioinformatics, Western blotting and qRT-PCR demonstrate that EphA10 is significantly overexpressed in PCa, highlighting its potential as a target gene for PCa. Mechanistically, EphA10 mRNA undergoes m6A modification mediated by RBM15B, which enhances its stability and expression. YTHDF1 has been identified as an m6A reader for EphA10, promoting its stability and expression in an m6A-dependent manner. Furthermore, the study reveals that m6A-modified EphA10 accelerates PCa cell proliferation, invasion, and migration by activating the ERK/AKT signaling pathway. Our findings suggest that PCa stabilizes the m6A methylation of EphA10, thereby sustaining the activation of the ERK/AKT signaling pathway and accelerating cancer progression. Targeting EphA10, or the m6A methylation "writer" and "reader" proteins involved in its regulation, to inhibit this methylation process could represent a promising therapeutic strategy for PCa.

Chanos chanos (Milkfish) is an ecologically and economically important aquaculture species in the Indo-Pacific, valued for its rapid growth, broad salinity tolerance, and high market demand. Sustainable utilization of this resource requires a clear understanding of its population genetic structure. In this study, we used 20 microsatellite loci to assess genetic variation across five Indian locations. These markers exhibited high resolution, with a mean polymorphic information content (PIC) value of 0.841, making them highly suitable for population genetic analyses. Analyses revealed high levels of genetic diversity w.r.to parameter like observed and exected heterozygosity (mean H_O = 0.897; H_E = 0.867), with an average of 14 alleles per locus. The global F_ST was low but significant (0.008; P = 0.000), indicating weak genetic differentiation. Hierarchical AMOVA, grouping Chilika separately from other populations, showed a slight but significant difference between groups (F_CT = 0.034; P = 0.023), while most genetic variation occurred within populations. These findings highlighted the importance of conserving natural genetic resources while enabling stock-specific management and selective crossbreeding strategies to enhance heterosis, improve aquaculture resilience, and ensure the long-term sustainability of Milkfish farming.

Colorectal cancer (CRC) is a critical global health challenge and ranks third among commonly diagnosed malignancies worldwide. As a cancer related long-noncoding RNA (lncRNA), Jumonji C domain containing histone demethylase 1 homolog D antisense 1 (JHDM1D-AS1) is analyzed to be differentially expressed in CRC samples according to bioinformatics analysis. This study aimed to further explore its effects on CRC cellular process and tumor growth as well as the related mechanisms. Quantitative polymerase chain reaction (RT-qPCR) was utilized to assess expression levels of JHDM1D-AS1 and its downstream molecules in CRC tissues and cells. Functional assays, including colony formation, wound healing, and Transwell assays, were performed to evaluate cellular processes such as proliferation, migration, and invasion. In vivo xenograft and metastasis models were established to examine tumor growth and liver metastasis. The subcellular distribution of JHDM1D-AS1 in CRC cells was measured using fluorescence in situ hybridization (FISH). RNA pulldown and luciferase reporter assays were conducted to confirm molecular interactions. HPRT1 protein expression was quantified using Western blotting. JHDM1D-AS1 is significantly upregulated in CRC cells. Knockdown of JHDM1D-AS1 suppresses CRC cell proliferation, migration, and invasion as well as xenograft tumor growth. JHDM1D-AS1 interacts with miR-193b-3p to regulate HPRT1 expression. MiR-193b-3p targets and downregulates HPRT1. Overexpression of HPRT1 reverses the suppressive effects caused by JHDM1D-AS1 depletion on CRC cell malignancy. In conclusion, JHDM1D-AS1 promotes CRC cell proliferation, metastasis, invasion and tumor development by upregulating HPRT1 expression via miR-193b-3p.

The objective of this research was to explore the impact of HOXC13-AS on the prognosis of NSCLC patients and the mechanism underlying disease progression. The study included 124 NSCLC patients. The expression levels of HOXC13-AS and miR-218-1-3p in NSCLC tissues and cells were assessed by RT-qPCR. The cumulative survival of NSCLC patients was examined by the Kaplan-Meier method. Cell viability was determined by MTT. Transwell was adopted to evaluate the migration and invasion capabilities of the cells. The interaction between HOXC13-AS and miR-218-1-3p was verified by luciferase reporter assay and RIP assay. Pearson correlation coefficient was utilized to assess the relationship between HOXC13-AS and miR-218-1-3p. HOXC13-AS was elevated in NSCLC tissues and cells, and patients with high HOXC13-AS expression had poorer cumulative survival than the low expression group. Silencing of HOXC13-AS led to a decrease in HOXC13-AS expression and inhibition of cell proliferation, migration and invasion in cells. Experiments confirmed that HOXC13-AS targets miR-218-1-3p. miR-218-1-3p was downregulated in NSCLC tissues and cells, and HOXC13-AS was negatively correlated with miR-218-1-3p. After silencing HOXC13-AS, further inhibition of miR-218-1-3p led to a decrease in its levels and enhanced cell proliferation, migration, and invasion. In NSCLC patients, HOXC13-AS is aberrant expression and closely associated with poor prognosis. Inhibition of miR-218-1-3p expression partially reverses the inhibitory effects of HOXC13-AS silencing on NSCLC cells. This suggests that HOXC13-AS could serve as a promising biomarker for NSCLC, providing new insights into NSCLC progression.

Prostate-specific antigen (PSA) testing lacks specificity due to benign conditions. This study assessed whether integrating DNA methylation signatures with PSA metrics improves discrimination of prostate cancer (PCa) from non-PCa cases. Targeted bisulfite sequencing of 74 CpG sites in 9 genes was performed on urine sediment from 194 patients (89 PCa, 105 non-PCa). Patients were stratified by total PSA (tPSA) and free-to-total PSA ratio (%fPSA) into risk groups. Random forest identified discriminatory methylation markers, and support vector machine (SVM), k-nearest neighbor (KNN), and Bayesian models were constructed and validated. PSA-based stratification alone could not reliably distinguish PCa from non-PCa, with 26.80% of patients falling into a diagnostic "gray zone". Twenty CpG sites showed significant differential methylation (p < 0.01). In addition, several CpG loci exhibited methylation differences across PSA risk groups. Models based on random forest-selected markers achieved strong diagnostic performance, with KNN yielding the highest accuracy (AUC > 0.95, 100% specificity), and consistently high sensitivity (> 80%), maintaining strong discriminative power even in PSA "gray-zone" cases. Urine-based DNA methylation profiling enhances the diagnostic accuracy of PCa beyond PSA testing, particularly in cases within the PSA gray zone. Validation in larger independent cohorts is warranted to establish its clinical utility.

Pain following endodontic treatment is a common complication potentially linked with genetic polymorphisms that modulate pain biomarkers. Hence, this study aimed to explore the association between pain experienced after endodontic treatment and genetic polymorphisms in the genes encoding inducible nitric oxide synthase (NOS2), and suppressor of cytokine signaling (SOCS1). The study involved 108 participants with single-rooted teeth, single canals, and necrotic pulp related to asymptomatic apical periodontitis. All endodontic treatments were executed in a single session. Pain and tenderness levels were measured using a visual analog scale (VAS) on the 1st, 2nd, 3rd, 4th, 5th, 6th, 7th, 14th, and 30th day post-treatment. Genomic deoxyribonucleic acid (DNA) was extracted from saliva cells and the genetic polymorphisms rs2779249, rs2297518, rs243327 and rs33977706 were genotyped using real-time polymerase chain reaction. Genotype distribution was assessed using univariate and multivariate Poisson regressions through generalized estimating equations (GEE) and categorized based on the presence or absence of pain and tenderness, and the significance threshold was set at p < 0.05. The genetic polymorphism rs2297518 in the NOS2 gene was associated with pain in the recessive model (p = 0.019) and to tenderness in both the codominant (p = 0.008) and recessive (p < 0.001) models. The genetic polymorphisms rs2779249 in NOS2 and rs243327 and rs33977706 in SOCS1 showed no association with pain or tenderness (p > 0.05). In conclusion, the genetic polymorphism rs2297518 in the NOS2 gene was associated with pain after root canal treatment. These findings contribute to a better understanding of the genetic factors influencing postoperative pain in endodontics, which may help in developing personalized pain management strategies and improving patient care.