Gene最新文献

The aging population has led to a significant increase in neurodegenerative diseases, particularly Alzheimer's disease (AD), which adversely affects the quality of life and longevity of the elderly. Abnormal plasmalogen metabolism plays a crucial role in the pathogenesis of AD. This study focused ontmem189, a key gene involved in plasmalogen synthesis. We successfully cloned and characterized the open reading frame (ORF) oftmem189, revealing that it encodes a protein consisting of 275 amino acids. Notably,tmem189expression was found to be highest in liver tissues compared to other tissues. We transfected a GFP-fused eukaryotic expression vector into 293 T cells, confirming successful expression oftmem189with increased relative levels. Additionally, liquid chromatography-mass spectrometry (LC-MS) analysis demonstrated thattmem189promotes plasmalogen synthesis in the transfected 293 T cells. Our findings suggest thattmem189could serve as a potential target for the treatment of neurodegenerative diseases, providing new insights into the promotion of plasmalogen synthesis.

Background: Kidney stone disease (KSD) is a common disorder of the urinary system and is closely related to genetic polymorphisms. However, the relationship between OSBPL8 polymorphisms and kidney stones has not been thoroughly investigated.

Methods: Six OSBPL8 polymorphisms (rs17042391,rs17042409,rs4761431,rs7303892,rs4761434, and rs17042390) were analyzed in a Chinese case-control cohort containing 923 nephrolithiasis patients and 945 healthy controls.The association of these OSBPL8 gene polymorphisms with KSD susceptibility was analyzed using logistic regression, and examined by calculating the odds ratios (ORs) and 95% confidence intervals (CIs).

Results: The OSBPL8 polymorphisms (GG for rs17042391, rs17042409, rs4761431, rs7303892; AA for rs4761434; and G for rs17042390) were significantly associated with a decreased risk of KSD in females.The protected alleles (G allele of rs17042391, G allele of rs17042409, G allele of rs4761431, A allele of rs4761434, and G allele of rs17042390) were related to decreased BMI levels in KSD patients; female patients with these alleles also exhibited lower BMI, HDL, and LDL levels,the G allele of rs7303892 was linked to reduced serum cholesterol levels in these females.Additionally, the haplotype ACAAGA was associated with decreased KSD risk in females, but haplotype GGGGAG presented an opposing effect.

Conclusion: Our research shows that the OSBPL8 gene polymorphisms reduced the risk of KSD in females, and were also associated with lipid-related metabolic traits.

Emerging evidence suggests that circular RNAs (circRNAs), a class of non-coding RNAs, play a critical role in the progression of several cancers, including osteosarcoma (OS). In this study, we focused on a specific circRNA, hsa_circ_0002005, derived from the mesoderm-induced early response 1 family member 2 (MIER2) gene. We determined the expression levels of hsa_circ_0002005 in OS samples through the use of real-time quantitative polymerase chain reaction (RT-qPCR). To assess the effect of hsa_circ_0002005, we used lentiviral analysis and performed several assays including transwell migration, cell invasion, 5-ethynyl-2'-deoxyuridine assay (EdU), cell counting kit-8 (CCK-8), proliferation, colony formation, and western blotting. In addition, we investigated the delivery mechanism of hsa_circ_0002005 in nude mice and predicted the interaction network involving hsa_circ_0002005, microRNA (miRNA), and mRNAs through bioinformatics analysis. The results showed that hsa_circ_0002005 is overexpressed in OS tissues and cells and is derived from exons 2 to 7 of the MIER2 gene. Knockdown of hsa_circ_0002005 markedly reduced the proliferation, migration, and invasive capabilities of cells, as well as their metastatic potential. We discovered miRNAs that may engage with hsa_circ_0002005. Further mechanistic studies indicated that the suppression of hsa_circ_0002005 influenced the expression levels of proteins associated with the epithelial-mesenchymal transition (EMT), suggesting its regulatory role in EMT progression through modulation of cell proliferation, migration, and invasion.

The alternative splicing of a gene results in distinct transcript isoforms that can result in proteins that differ in function. Alternative splicing processes are prevalent in the brain, have varying incidence across brain regions, and can present sexual dimorphism. Exposure to opiates and other substances of abuse can also alter the type and incidence of the splicing process and the relative abundance of the isoforms produced. The disruption of alternative splicing patterns associated with sex differences and morphine exposure in the prefrontal cortex of a pig model was studied. The numbers of genes presenting one or more significant (FDR-adjusted p-value < 0.05) alternative splicing events were 933 and 1,368 genes when comparing females relative to males and morphine- relative to saline-treated animals, respectively. The sex-dependent opioid effect was most extreme in the contrast between morphine- versus saline-treated males with 1,934 significantly differentially spliced genes. The most frequent and significant alternative splicing type was skipped exon (∼56 % event), followed by retained intron (∼15 % events). The pathways encompassing a significant number of differentially spliced genes included axon guidance, glutamatergic synapses, circadian rhythm, and lysine degradation. Genes in these pathways included ROBO1, SEMA6C, GRIN3A, GRM2, ARNTL, CLOCK, HYKK, and DOT1L. Transcription factors ETV7 and DMAP1 presented a significant number of differentially spliced target genes. The distribution of the genes presenting differential alternative splicing in the axon guidance and circadian rhythm pathways indicates that this regulatory mechanism impacts hubs and peripheral genes. The identification of sexual dimorphism in the effect of morphine across multiple pathways confirms the necessity to explore the effects of drugs of abuse within sex. Altogether, our findings advance the understanding of the response to factors that can impact the activity of excitatory synapses by modulating transcriptional mechanisms that support the plasticity of the prefrontal cortex.

Bisphenol A (BPA) is a widely used industrial compound commonly found in various everyday plastic products. Known for its endocrine-disrupting properties, BPA can enter the human body through multiple pathways. Prenatal exposure to BPA not only disrupts placental structure and function but also interferes with normal steroid metabolism. This study investigates the epigenetic regulatory mechanisms by which BPA influences steroid metabolism in the placenta. Using BPA-treated JEG3 cells, we analyzed hormone levels, gene promoter DNA methylation, and gene expression, further validating our findings in placental samples. Additionally, we explored the role of epigenetic modifications in regulating steroid metabolism at the cellular level and assessed related phenotypes in cohort samples. The results demonstrated that BPA significantly reduced the levels of progesterone, estradiol, and testosterone, and notably affected the promoter methylation and expression levels of 63 genes. Enrichment analysis highlighted PLA2G4F, JUN, MRAS, ERBB4, DUSP1, and GADD45G as being primarily enriched in the MAPK signaling pathway. Further studies revealed that the methylation level of the JUN promoter regulates its expression, impacting hormone levels by modulating downstream signaling pathways. In placental samples, male offspring in the hypermethylated JUN promoter group had shorter anogenital distance (AGD) compared to those in the hypomethylated group. These findings suggest that BPA reduces the expression of steroid metabolism genes via the epigenetic regulation of the JUN gene, thereby decreasing progesterone, estradiol, and testosterone levels and leading to shortened AGD in offspring.

Background/aim: Autosomal-recessive carnitine-acylcarnitine translocase deficiency (CACTD) is a rare disorder of long-chain fatty acid oxidation caused by variants in the SLC25A20 gene, leading to energy deficiency and the toxic accumulation of long-chain acylcarnitines. Under fasting conditions, most newborns with severe CACTD experience sudden cardiac arrest and hypotonia, often leading to premature death due to rapid disease progression. The genetic factors and pathogenic mechanisms in CACTD are essential for its diagnosis, treatment, and prevention.

Methods: Whole-exome sequencing was carried out on the CACTD patients. Bioinformatics analysis predicted the pathogenicity and three-dimensional structure of SLC25A20. Quantitative PCR was employed to detect changes in SLC25A20, CPT1A and CPT2 mRNA levels. The expression and stability of the variant protein were assessed via Western blot. Additionally, the subcellular localization of the variant protein was observed using immunofluorescence.

Results: We identified compound heterozygous pathogenic variants of SLC25A20 (c.476 T > C and c.199-10 T > G) in CACTD families, with patients exhibiting an abnormal carnitine spectrum. In vitro functional studies demonstrated that the c.476 T > C and c.199-10 T > G variants decreased the protein stability of SLC25A20, reduced CPT1A and CPT2 mRNA expression, and caused protein aggregation of SLC25A20.

Conclusions: We propose that the decreased stability of the SLC25A20 variants c.476 T > C and c.199-10 T > G has the potential to lead to the development of CACTD by affecting the mitochondrial shuttle of acylcarnitine and carnitine, thereby inhibiting the β-oxidation pathway. Therefore, we believe these compound heterozygous variants (c.199-10 T > G and c.476 T > C) are loss-of-function variants. Our findings provide valuable data on CACTD pathogenesis and genotype-phenotype correlations.

Purpose: This study aimed to identify a lactylation-related gene signature for predicting prognosis and guiding therapies in colon adenocarcinoma (COAD). We seek to address the challenges in COAD prognostication due to tumor heterogeneity and variable treatment responses.

Methods: The study employed integrative bioinformatics analyses on multi-omics data from public databases, including gene expression profiles, clinical data, and lactylation-related genes (LRGs). The least absolute shrinkage and selection operator (LASSO) regression analysis and Cox risk model were applied to develop a prognostic signature. The predictive capabilities of the signature were assessed in four independent COAD cohorts (GSE39582, GSE71187, GSE75500, and GSE17536). Functional enrichment, immune infiltrations, and scRNA-seq analysis were performed to investigate biological processes and the tumor microenvironment (TME). Additionally, functional assays were performed to assess the impact of gene knockdown on COAD cell behavior.

Results: A 3-gene signature (SUSD5, FABP4, CALB2) was identified, demonstrating robust predictive performance for clinical outcomes in COAD patients across multiple cohorts. The signature revealed involvement in critical cancer-related biological processes and showed potential in guiding therapeutic decisions. The bulk RNA-seq and scRNA-seq analysis suggested that LRGs modulates the TME, particularly immune cell populations like mast cells. Knockdown of CALB2 significantly suppressed COAD cell proliferation, invasion, and migration.

Conclusion: This comprehensive analysis identified a lactylation-related signature with significant prognostic and therapeutic implications for COAD. The findings highlight the importance of lactylation in COAD biology and offer novel insights for developing personalized treatment strategies, potentially improving patient outcomes in this prevalent malignancy.

Santalum album is an economically important plant in the craft, spices and medicine industries. The main chemical constituents found in sandalwood essential oils are sesquiterpenes. 3-Hydroxy-3-methylglutaryl monoacyl-coenzyme A reductase (HMGR) is one of the rate-limiting enzymes required for the synthesis of sandal sesquiterpenes, but there are no studies on the HMGR gene in S. album. In this study, the full-length ORFs of the upper rate-limiting enzyme genes SaHMGR1 and SaHMGR2, which lie upstream of the MVA metabolic pathway of sandal sesquiterpenes, were cloned for the first time. Bioinformatics and phylogenetic analyses were conducted. The results showed that SaHMGR1 and SaHMGR2 had typical domains of HMGR class I enzymes in the HMGR superfamily, including four catalytic sites, six NADPH-binding sites, five substrate binding regions, four inhibitor binding sites, and several dimer interface regions. A phylogenetic analysis showed that SaHMGR1 and SaHMGR2 were highly conserved relative to corresponding genes in other plants. An analysis of subcellular localization showed that these SaHMGR genes were located in the endoplasmic reticulum. SaHMGR1 and SaHMGR2 were detected by real-time PCR in roots, sapwood, heartwood, young leaves, mature leaves and twigs. Highest expression was in roots. SaHMGR1 expression was higher in mature leaves than in heartwood while SaHMGR2 expression was lower in mature leaves than in heartwood. Expression in Escherichia coli strain DH5α with plasmid pET-32a (+) was also used to verify the functionality of both HMGR proteins, which catalyzed the formation of MVA from HMG-CoA. In E. coli, the enzymatic activity of SaHMGR1 was higher than that of SaHMGR2. These findings provide a basis for further studies on the function of SaHMGR genes and the regulation of sesquiterpene biosynthesis in S. album.

The development of lung adenocarcinoma (LUAD) is intricately linked with cell cycle regulation and epithelial-mesenchymal transition (EMT). Our study, leveraging bioinformatics and database analysis, identified FUCA2 as a key gene influencing the prognosis and progression of LUAD. We observed that FUCA2 is highly expressed in LUAD and correlates with poor outcomes. Functionally, we assessed the role of this gene through cell cloning, scratch assays, transwell migration, and western blotting, revealing that FUCA2 knockdown significantly inhibits tumor cell proliferation and migration, downregulates the expression of cell cycle and EMT-related proteins, and markedly reduces tumor burden. Mechanistically, pathway enrichment analysis identified GGH as a downstream target of FUCA2. Knockdown of GGH similarly inhibits the proliferation, migration, and cell cycle progression of LUAD cells. FUCA2 upregulates GGH to modulate cell cycle and EMT in LUAD. Collectively, our findings indicate that the FUCA2/GGH axis promotes LUAD progression by regulating cell cycle and EMT.

Global reporting of antibiotic resistant bacteria (ARB) bearing antibiotic resistance genes (ARGs) have increased in the past decade. Sewage systems act as breeding grounds for these pathogens. Dumping of untreated sewage effluent in river water systems have aided in their dissemination and spread. The molecular pathways circumventing antibiotics through ARGs is rising owing to overuse of these drugs. Use of aminoglycoside spectrum drugs has been increased exponentially. The genes providing resistance to these antibiotics are transferred through extra-chromosomal circular DNA elements. Polluted water bodies are ground zero for exchange of these genetic factors. Through literature survey, we shortlisted some clinically relevant genes which provide resistance against aminoglycosides and hold immense importance in present scenario. Initial screening for these genes was done on water samples collected from Swarna Rekha River channel in Gwalior District of Madhya Pradesh, India. A total of five identified genes were sequence verified using conventional PCR followed by targeted sequencing. Further, diagnostic platforms were designed for two reoccurring genes npmA & sat4^A and their presence evaluated from wastewater samples collected from urban establishments of the district. Prevalence of these genes in sewage samples validated the broad impact of urban waste burden in polluting local water bodies. We were able to identify some indispensable and high risk aminoglycoside resistance providing genes, unreported in Indian context. This approach towards ARG screening could support risk assessment of future antibiotic resistance associated public health hazards.