Gene Reports最新文献

Preeclampsia is a pregnancy-associated hypertensive pathology that affects maternal and fetal quality of life. It was linked to several environmental and genetic factors including genetic polymorphisms. This study aimed to study the association, SNP-SNP interactions and haplotypes associations of thrombophilia, folate cycle and hypertension maternal genetic variations with preeclampsia risk in Russian women from Rostov region. 53 pregnant women diagnosed with preeclampsia were compared with 3108 women with relatively healthy pregnancy. DNA was extracted from blood samples and real time allele specific PCR was used for genotyping. MDR analysis was used for SNP-SNP interactions study. According to our data, F5(G1691A) and ITGB3(T1565C) mutant homozygotes were associated with higher risk of preeclampsia. MTRR (A66G) mutant allele (G) was shown as significant preeclampsia risk factor. ADD1 (G1378T) showed significantly higher frequency of mutant allele (T) and mutant homozygote genotype (TT) in preeclampsia patients comparing to control group. MDR showed that this polymorphism has the higher entropy among targeted variations which was confirmed by binary haplotypes association study. We have also examined linkage disequilibrium showing two haploblocks in between the studied genetic variations included MTHFR (C677T) and MTHFR (A1298C) block and AGT (T704C) with AGT (C521T) block. Results suggest several genetic variations and haplotypes as perspective maternal marker for preeclampsia which will contribute to improve prognosis tools and accordingly treatment and prevention possibilities.

Background

Ohdo syndrome (OMIM≠ 249,620) is a clinically heterogeneous group of genetic disorders mainly characterized by intellectual disability, blepharophimosis and specific facial features. It comprises five distinct subtypes, each exhibiting unique clinical characteristics. Herein, we report a novel case of the Maat-Kievit-Brunner (OSMKB; X-linked recessive) subtype caused by a novel pathogenic MED12 nonsense variant, classically associated with missense variants of the MED12 gene (Xq13.1). Moreover, we conduct a comparative analysis of reported MED12 pathogenic variants in the literature.

Case presentation

Our patient is a five-year-old girl demonstrating a complete OSMKB phenotype. She exhibits all the characteristic features associated to this latter including intellectual disability, developmental delay, indicative dysmorphia featured by blepharophemosis and a triangular face, and hypotonia.

Conclusions

clinical and molecular data of this rare case expands the clinical and genetic landscapes of MED12 gene which is considered important for establishing strong genotype-phenotype correlations as much as for genetic counselling.

Type 2 Diabetes (T2D) as a global health challenge is characterized by insulin resistance and impaired glucose regulation. This condition has a significant impact on both human health and the global economy. Insulin plays a crucial role as a peptide hormone in regulating glucose metabolism throughout the body. Insulin resistance (IR) as one of the common implications of type 2 diabetes occurs when the body's response to insulin is disrupted, leading to dysfunction in various molecular pathways within tissues targeted by insulin. Identifying the genetic factors involved in T2D is a crucial focus of diabetes research to better comprehend its mechanisms and complications, for treatment, and prevention. Progress in genetic research during the 1980s allowed researchers to identify genetic markers associated with this hereditary trait. Genome Wide Association Studies (GWAS) have been instrumental in pinpointing genetic loci associated with various complications of diabetes. Over 300 loci have been linked to T2D, accounting for more than 19 % of the risk.

The present review manuscript aims to examine the complex interplay between genetic factors and T2D development. We review the current knowledge regarding the genetic basis, examining predisposing genetic variants, epigenetic modifications, and gene-environment interactions implicated in the disease pathogenesis. Understanding the underlying genetic mechanisms of T2D opens new avenues for personalized therapies and preventive strategies.

Introduction

Increasing temperature and elevated atmospheric carbon dioxide levels could impact the survival of stress-adapted bacteria.

Method and results

In this study, RNA sequencing was performed to quantify Escherichia coli BL21 (DE3) gene expression in culture media under environmental temperature (27 °C and 42 °C) and carbon dioxide (0.2 % and 6 % v/v) conditions. Differential gene expression analysis between low temperature and different carbon dioxide conditions revealed up-regulated genes such as ldtC and bioA, optimising cell wall integrity and nutrient uptake. While, the downregulation of genes such as malK suggested a metabolic adaptation. Low temperature and high carbon dioxide levels enhanced bacterial tolerance to environmental stress. Under optimal temperatures, Escherichia coli adapts through various metabolic pathways while engaging in different processes at low temperatures and carbon dioxide levels, with temperature having a greater impact on gene expression than carbon dioxide levels. This study shows that complex metabolic activities are activated when both temperatures and carbon dioxide levels are combinsed, affecting antimicrobial resistance, nutrient acquisition, and adaptation strategies.

Conclusion

Each condition exhibited mechanisms to enhance cellular resilience and adaptation to stress, focusing on cellular integrity, optimising energy utilisation, and activating stress response pathways.

Impact statement

The findings stress the importance of continued research to understand the implications of climate change on microbial transcriptomes comprehensively.

Background

Coronary artery disease (CAD) is a group of diseases caused by plaque formation in the wall of arteries supplying blood to the heart. Adiponectin (ADIPOQ) is an adipocytokine that controls carbohydrate and lipid metabolism, has anti-diabetic properties, and correlates well with cardio-metabolic risk. ADIPOQ gene polymorphism is reported to be associated with CAD in numerous populations.

Objective

To explore the impact of adiponectin gene polymorphism, rs2241766 T > G, rs1501299 G > T, rs17300539 G > A, rs266729 G > A, and rs822395 A > C SNPs, on the CAD in the Iraqi population.

Methods

A case-control study of 317 healthy individuals and 302 CAD patients was conducted. Standard protocols for measuring serum lipid profile levels were followed. ADIPOQ and insulin levels were estimated using the ELISA method. Genotyping of ADIPOQ gene was carried out using the RFLP technique.

Results

Genotype assessment of rs2241766, rs1501299, rs266729, and rs17300539 SNPs under several inheritance models pointed out significant (P = 0.012–10⁻⁴) elevations of the variant alleles in CAD patients in comparison to the control group. The haplotype analysis of the five analyzed SNPs exhibited five disease-susceptible haplotypes; they were GTCGA (OR: 7.6, 95 % CI: 2.55–21.76), TGCAA (P = 0.013), TGGGA (P = 0.046), TGGAA (P = 0.017), and GGGGA (P = 0.032). The linkage disequilibrium (LD) analysis of the five SNPs in the control versus the patient groups revealed significant LD. The variant genotype of the rs2241766 SNP was found to significantly increase the atherogenic lipids and HOMA values and decrease the ADIPOQ and high-density cholesterol (HDL-c) levels. Those of the rs1501299, rs17300539, and rs266729 SNPs were indicated to increase the metabolic parameter values except ADIPOQ and HDL-c magnitudes, which are reduced in the variant carriers.

Conclusion

The rs2241766, rs1501299, rs266729, and rs17300539 SNPs of the ADIPOQ gene are risk factors for CAD in Iraqi individuals. Both single nucleotide and haplotype analyses suggested the implication of the ADIPOQ gene in the pathogenesis of the disease. This implication has occurred through lowering ADIPOQ levels and increasing atherogenic lipids.

Dysfunction of T cells is a causative factor in Immune Thrombocytopenia (ITP), an autoimmune disorder. Circular RNAs (circRNAs), which have been associated with the pathophysiology of various immunological conditions, are of particular interest. Our study aimed to identify pivotal regulatory circRNAs within the peripheral T cells of ITP patients. We utilized circRNA sequencing to discern differences in circRNA expression between the ITP cohort and healthy controls. We identified 606 upregulated and 719 downregulated circRNAs. Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted to scrutinize the parent genes of these differentially expressed circRNAs, revealing their significant involvement in metabolic processes and T cell receptor signaling pathways. Following a rigorous selection process that included DEG analysis, KEGG, and GO pathways analysis, along with an assessment of the potential roles of their parent genes, five top differentially expressed circRNAs were subjected to further validation via quantitative Polymerase Chain Reaction (RT-qPCR). Specifically, in the peripheral T cells of ITP patients, hsa_circ_0008866 (TAOK1), hsa_circ_0006856 (MAP3K5), and hsa_circ_0007444 (RHOBTB3) emerged as key regulatory circRNAs. The potential miRNA targets of these circRNAs were predicted employing miRanda, RNAhybrid, and TargetScan algorithms.

Constitutional methylation of the MLH1 promoter is implicated in colorectal cancer (CRC) susceptibility by silencing the expression of the MLH1 protein. While MLH1 promoter methylation has been identified in variable frequencies among various populations, no data exist for CRC patients from Pakistan. In this study, we investigated constitutional MLH1 promoter methylation in Pakistani CRC patients. We screened 210 CRC patients belonging to HNPCC/suspected-HNPCC (n = 27) and non-HNPCC (n = 183) groups and 100 healthy controls for constitutional MLH1 promoter methylation using a methylation-sensitive high-resolution melting (MS-HRM) assay with methylated and unmethylated standards. Of the 210 CRC patients, 12.9 % (n = 27) had a family history of HNPCC-associated cancers, and 87.1 % (n = 183) had CRC with no family history (non-HNPCC group). The mean age at disease onset was 43.1 years (range 14–77), while controls had a mean age at enrollment of 40.0 years (range 19–74.4). Constitutional MLH1 promoter methylation was not identified in 210 CRC patients and 100 healthy controls. Constitutional MLH1 promoter methylation does not appear to be associated with CRC susceptibility in Pakistani patients.

Background

Airway remodeling caused by smoking is an important pathological change in chronic obstructive pulmonary disease (COPD), and epithelial-mesenchymal transition (EMT) is one of the core mechanisms involved in airway remodeling. However, the exact molecules and pathway mechanisms involved in the induction of EMT in COPD remain largely unknown. Numerous previous studies have elucidated that overexpression of PIK3CA promotes the proliferation and metastasis in various types of tumors by inducing EMT, while inhibition of PIK3CA can inhibit the invasion and proliferation of tumors. However, the relationship between PIK3CA and EMT has not been reported in COPD.

Methods

Fresh pulmonary specimens were collected away from the tumor site from the smoker with COPD (n = 9) and non-smokers without COPD control group (n = 9) who underwent lung tissue resection, and conducted deep sequencing of lung tissue mRNA. It was found that the PIK3CA and EMT pathways play a significant role in the development of COPD using bioinformatics. Therefore a mouse model of emphysema exposed to cigarette smoke(CS) was constructed which demonstrated increased PIK3CA expression and EMT activation in bronchial epithelial cells with increased apoptosis by immunohistochemical and immunofluorescence. In vitro, it was further confirmed the expression of PIK3CA and the activation of EMT by cigarette smoke extract (CSE)-incubated BEAS-2B cells. By PIK3CA knockout, it was proved that PIK3CA plays an important role in the EMT process.

Results

Through the analysis of mRNA sequencing data of fresh pulmonary specimens from smokers with COPD and non-smokers without COPD, we found that EMT plays a core role in COPD. Through analysis of GSEA and PPI, we found that PIK3CA is a key gene in COPD. By studying the established mouse model of COPD and BEAS-2B cells incubated with CSE, we found that CS exposure increased PIK3CA expression and associated EMT activation. CSE can induce EMT in vitro by increasing PIK3CA expression, and knockout PIK3CA can reverse CSE-induced EMT.

Conclusion

Cigarette smoke induces EMT in bronchial epithelial cells by up-regulating PIK3CA expression. PIK3CA knockdown reversed CSE-induced EMT. EMT and PIK3CA may be potential new targets for the treatment of COPD in the future.

Introduction

Acute lymphoblastic leukemia (ALL) is a rare form of blood cancer that can quickly advance if left untreated. Research has suggested that progesterone (P4) may be effective in treating certain types of tumors. Specifically, the membrane progesterone receptors may play a role in either enhancing or inhibiting cell growth in various tumors. This study aimed to investigate the impact of P4 on inhibition of NALM6 cells.

Methods

NALM6 cells were exposed to different concentrations of P4 (ranging from 10 to 50 μM) at 24,48 and 72 h intervals. The cell survival rate was then evaluated using an MTT assay. Additionally, the study assessed the rate of mPR expression in the cells using flow cytometry at 48 and 72 h after P4 administration (at concentrations of 20 and 10 μM, respectively). Furthermore, the level of ROS was evaluated using the dichlorofluorescein diacetate (DCFDA) flow cytometry technique.

Results

The study found that mPR-β was expressed in NALM6 cells and that P4 had a significant inhibitory effect on the growth of tumor cells in a time and concentration-dependent manner. Furthermore, P4 was found to reduce mPR-β expression at 48 and 72 h. The treatment also resulted in a decrease in ROS levels compared to untreated cells (P ≤ 0.05).

Conclusion

The study suggests that p4 may be effective in growth-inhibiting NALM6 cells by decreasing cell viability and reducing ROS levels. However, further research is needed to understand the mechanism of action and interactions with various receptors and to confirm its effectiveness in treating NALM6 leukemia.

Dried fruit beetle, Carpophilus hemipterus, (Linnaeus, 1758) (Coleoptera: Nitidulidae) is a serious pest of ripened fresh fruit in the orchard and dried fruit in post-processing storage. Despite the economic significance and widespread distribution of C. hemipterus, there is a lack of functional genomics research seeking to elucidate features of developmental biology and molecular physiology for improved pest management. Performing such functional genomics studies requires validated, stably expressed reference genes for accurate normalization of real-time quantitative reverse transcription-PCR (qRT-PCR) data. Here, we identified and validated 12 common insect reference genes (RPL6, RPL4, RPL9, RPS13, RPS18, RPSA, TUB, UBE3A, RPS23, GLU, EF1A, and RBP) for expression stability in C. hemipterus. These genes were assessed across developmental stages and sexes (egg, three larval instars, prepupa, pupa, adult male, and adult female) as well as thermal stress conditions. Stability of candidate genes was estimated using software algorithms geNorm, NormFinder, BestKeeper, comparative delta-Ct, and RefFinder. Two genes UBE3A and RPL9 showed the highest stability across the treatments, and thus were proposed for normalizing the qRT-PCR raw data. Results of this study will strengthen the application of genomics to reveal the fundamental and applied biological aspects in this important beetle species.