Human Gene最新文献

Background

The global burden of Diabetic nephropathy is rising and eventually leads to chronic kidney disease. Methylglyoxal (MGO) is an antecedent to advanced glycation end products (AGEs), implicated in diabetes mellitus microvascular complications. Glyoxalase I (GLO1), is the primary enzyme responsible for metabolizing methylglyoxal (MG). Any genetic variants of GLO1 may have a significant impact on the development of diabetic microvascular complications.

Objectives

To determine the association of rs1049346 and rs4746 (rs2736654) of Glyoxalase I gene polymorphism in type 2 Diabetes patients (T2DM) with nephropathy risk.

Materials and methods

The case-control study included a hundred T2DM with nephropathy and a hundred healthy controls. The TaqMan single nucleotide polymorphism genotyping assays were performed using Real-Time PCR to assess the genotype frequencies. The circulating levels of GLO-1 activity, MGO, CML and CEL were estimated using Enzyme-linked immunosorbent assay (ELISA).

Results and discussion

We observed increased serum levels of MGO, AGEs and decreased GLO-1 activity in diabetic nephropathy when compared to control. The patients carrying the CC genotypes (CC) and allele frequency of GLO-1 (rs1049346) were associated with nephropathy risk in T2DM patients (p < 0.024). We found no association of rs4746 with nephropathy risk in patients with T2DM. The patients with the CC + CT genotype showed lower GLO-1 activity and increased MGO levels when compared to homozygous wild-type. The CA haplotype significantly increased the risk of T2DM nephropathy.

Conclusion

Patients with T2DM who carry the variant CC genotype of rs1049346 (A > C) are at increased risk for developing nephropathy. The patients carrying the CC + CT genotype was associated with lower GLO-1 activity and increased MGO levels.

HepatoCellular Carcinoma (HCC) is one of the most deadly and prevalent neoplasia, accounting for nearly 830,180 mortalities and 905,677 fresh occurrences worldwide annually. Aggressive malignancy with multifaceted etiologies increases in occurrence due to inadequate early diagnosis and ineffective treatment outcomes. Hence the present study aims to identify novel HCC associated biomarkers and inhibit the plausible genes through phytocompounds. Herein, we have implemented the meta-analysis of GSE36376, GSE57957 and GSE84598 micro-array profiles by utilizing GEO2R which resulted in identification of 1683 aberrantly expressed genes. The predicted DEGs were further subjected to Functional annotation and pathway enrichment analysis by using Blast2GO and ExpressAnalyst respectively. Successively, Protein-Protein Interaction analysis was performed by Cytoscape software, and the top 11 most significant hub nodes were identified. The most frequently occurring hub gene Aurora Kinase A (AURKA) was considered as plausible target for subsequent identification of inhibitors. The plant-derived small molecules retrieved from NPACT database were subjected to molecular docking, Molecular dynamic simulations and MMGBSA analysis against AURKA. Conclusively, findings from our study postulates Garcinone C and Silymarin targeting elevated AURKA levels which may contribute as potential inhibitors for HCC patients. However, these outcomes provide only computational insights for targeted HCC-therapeutics but for clinical application of Garcinone C and Silymarin in vitro and in vivo molecular validations are still warranted.

MFSD1 (Major facilitator superfamily domain containing 1) protein is a lysosomal multiple transmembrane-spanning protein responsible for the active transport of various compounds. Due to its potential role in maintaining liver homeostasis, any mutation might lead to altered protein expression, thus affecting the functionality. In this study, we explored the impact of deleterious nsSNPs (Nonsynonymous single nucleotide polymorphisms) on the stability, conformation, and functionality of the MFSD1 protein. SNP data and MFSD1 protein sequences were retrieved from NCBI dbSNP and Uniprot respectively. In total, five highly conserved nsSNPs were predicted to be deleterious based on their negative impact on the stability of the protein. Furthermore, the simulation analysis on the 3D structures of both native and mutant proteins revealed a notable impact on the physiological conformation of the protein. The identified variants not only affect the native conformation but also impact the association of MFSD1 with GLMP (Glycosylated Lysosomal Membrane Protein). In conclusion, the analysis revealed that the mutant protein's structural stability was inferior to that of the native protein. This research provides crucial insights for identifying and assessing MFSD1 mutations as potential diagnostic markers for liver-related diseases.

Background and objective

Cancer biomarkers serve as measurable indicators for the early detection of cancer, as they can be detected in sample tissues. They play a crucial role in optimizing decision-making in clinical practice. To advanve in this field, it is necessary to identify of markers with higher sensitivity, specificity, and positive predictive value. Therfore, wer have chosen to investigate the expression of multiple biomarkers simultaneously in oral squamous cell carcinoma.

Materials and methods

In this experimental study, we investigated the expression levels of miRNA-214, circ-0005407, and ZFAND3 genes using the quantitative RealTime PCR method. The samples examined included 30 samples of fresh cancerous tissue and adjacent normal tissue obtained from the Cancer Institute of Imam Khomeini Hospital. The data were analyzed using the dependent samples t-test and ANOVA test.

Findings

The mean CT values of circ-0005407, miRNA-214, and ZFAND3 in the cancerous and normal groups were (15.48 ± 1.62 & 13.23 ± 1.63), (16.64 ± 1.51 & 13.21 ± 1.29), and (14.41 ± 1.07 & 16.72 ± 1.28), respectively. There was a statistically significant difference in the expression levels of all markers in the two investigated groups (P˂0.05). The fold change levels in circ-0005407, miRNA-214, and ZFAND3 gene markers were (0.51,0.22,6.34) respectively, indicating an increase in gene expression in cancerous tissue compared to normal. However, the other two markers showed decreased expression in cancerous tissue compared to normal tissue.

Conclusion

Based on the data obtained regarding the change in expression levels of these markers in cancerous tissue compared to normal tissue, it seems that these biomarkers can be used in the early diagnosis of oral cancer.

Background: The HOXA9 gene is an essential gene during the developmental stages of the embryo, and its mutations can result in different phenotypes in both fetal and adult life. Additionally, this gene encodes a transcription factor that plays a crucial role in hematopoietic processes. Deregulation of these pathways has been reported in some leukemia cases. This in-silico analysis aims to evaluate the pathogenic effect of missense mutations in the HOXA9 gene by utilizing various bioinformatics tools.

Methods: From dbSNP NCBI, 288 non-synonymous/missense mutations of the HOXA9 gene have been obtained. These missense mutations' functional impact was analyzed using various bioinformatics tools, including SIFT, Polyphen-2, PROVEAN, I-Mutant, PHD-SNP, and SNP&GO. Additionally, their structural impacts were investigated using Netsurf P-2.0, HOPE, ConSurf, and PyMOL. Furthermore, the analysis of protein hydrophobicity changes was examined using PEPTIDE 2.0 and ExPASy web tools.

Results: Out of the 288 non-synonymous mutations, 45 mutations have been identified as functional genetic variants that affect the structure and stability of the HOXA9 protein. According to the analysis, 10 out of the 45 missense mutations were more likely to be involved in changing the characteristics of the protein. These changes include absolute and relative solvent accessibility (ASA, RSA), classification secondary structure, surface accessibility, noncovalent interactions, and protein conformation.

Conclusion: Based on the results of this in-silico study, high-risk deleterious missense mutations have been predicted in the HOXA9 gene. These mutations may be potential candidates for future experimental investigations in various hematologic malignancy conditions.

The phosphatase and tensin homolog gene (PTEN) is a key tumor suppressor gene, which signals down the phosphoinositol-3-kinase/Akt pathway and affects cell cycle arrest and apoptosis. Alteration and mutation of the PTEN gene have been found in several types of tumors, including prostate cancer. Germline mutations of this gene are associated with the PTEN Hereditary Tumor Syndromes (PHTS), a hereditary overgrowth and cancer predisposition disorder. The present study aimed to determine whether germline alterations in exon 5 of the PTEN gene could be detected in the blood of men known to have prostate cancer, in order to uncover any aberrations that affect this key gene, which is likely involved in the cancer process.

Forty-eight blood samples from men diagnosed with prostate cancer were analyzed for germline mutations in the PTEN and confirmed by Sanger sequencing. The Sanger sequencing results revealed that 69% of the population carries mutations, including several new mutations and known mutations. The Frameshift mutations: c.459delT variant was detected with a frequency of 12.5%, and four frameshift variants were observed with frequencies of 8% each: c.304delA, c.338delG, c.439_440insG, c.457delG. For the missense mutations, the most frequent variant was c.473 T > C (p.Val158Ala), recorded in four patients (8%), while the variants c.361G > C (p.Ala121Pro) was detected in 6% of the population. There was no significant difference between mutation carriers and non-carriers regarding clinicopathological features. Our results provide insight into novel mutations identified in the PTEN gene in prostate cancer. This presents a new opportunity to focus on and highlight key genes for clinical exploration as potential biomarkers in the diagnosis and management of prostate cancer.

The scientific evidences suggest that the common polymorphism in vitamin D receptors (VDR) such as ApaI (rs7975232), BsmI (rs1544410), TaqI (rs731236), and FokI (rs2228570) may influence the risk of chronic periodontitis (CP) however the existing studies have inconclusive results. The present current aim to perform a meta – analysis of the published studies to determine the association of VDR polymorphism with CP susceptibility. An extensive literature search was conducted on various database to find the relevant studies and the crude odds ratio (OR) with 95% confidence interval was calculated. Twenty-two case control studies were included in the study with 2083 cases and 2013 control for TaqI, 989 cases and 722 control for FokI, 1240 cases and 1026 control for BsmI and 972 cases and 961 control for ApaI polymorphism. The overall analysis reported an increased association of CP with the FokI only under dominant model [1.42 (1.12–1.79); 0.002]. The other polymorphism - ApaI, BsmI, and TaqI did not report any significant association in the overall analysis however BsmI and TaqI was associated with CP risk in subgroup analysis. The TaqI polymorphism showed an increased risk of developing CP in African population under allelic [2.00(1.09–3.65)0.024], recessive [10.21 (1.25–82.8)0.029], homozygous [13.75 (1.54–122.0)0.018] and heterozygous [8.80 (1.06–73.0) 0.04] model however the association cannot be concluded as there were fewer studies. The presence of mutant allele of BsmI polymorphism demonstrated a reduced risk of developing CP among Asian under recessive [0.54 (0.29–0.99)0.047] and homozygous [0.49 (0.25–0.94) 0.034] model. The meta – analysis indicate the association of major VDR polymorphism with the development of CP is population specific.

Micro-RNAs (miRNAs) become a promising biomarker for diagnosis due to their stability and reproducibility and could be help to find a new effective treatment. This study is designed to evaluate the diagnostic utility and clinical significance of circulating micro-RNAs (miR-21-5p and miR-142-3p (and tumor necrosis factor-α (TNF-α) for patient with RA and to assess their correlation with disease activity. This case control study involved sixty patients and 30 apparently healthy subjects as control group. The diagnosis was done depending on the classification criteria of American college of rheumatology-European league against rheumatism (ACR- EULAR). Expression levels of circulating miRNA were determined by two step reversed transcription polymerase chain reactions (RT- PCR). The concentrations of TNF-α, anti-citrullinated protein antibodies(ACPA) and C- reactive protein(CRP) were estimated by Enzyme linked immune-sorbent assay technique (ELISA). The expression level of circulating miRNA- 21- 5p and miRNA - 142- 3p was significantly elevated (P <0.01) in patients group as well as the levels of blood ESR, serum CRP, ACPA, and TNF-α compared to controls. There are significant differences (P < 0.01) in miRNA- 21- 5p levels between different patients groups, while the expression of miR-142-3p show non-significant difference (p>0.05). It is found that miRNA- 21-5p expression levels are significantly correlated with RA activity. Both miR-21-5p and miR-142-3p have significant positive correlation with levels of CRP, ACPA, and TNF-α. The level of TNF-α have significant positive correlation with both of CRP and ACPA also with the DAS-28 and CDAI. In conclusion, circulating miR-21- 5p and miRNA - 142- 3p may be associated to RA pathogenesis due to their positive correlation with inflammatory cytokine TNF-α, CRP and ACPA, therefore these miRNAs might be considered new targets for RA treatment, and alterations in their expression could be used for diagnosis and monitoring the disease activity and treatment response.

Objectives

To study the role of microRNA 130a-3p and microRNA 301a-3p in urinary bladder carcinoma.

Background

Despite the discovery of several clinical and molecular indicators for predicting outcomes in bladder cancer, it is unclear how to use these indicators in clinical practice. A recent study revealed that the miR-130 family may play a vital role in the occurrence and development of BC by regulating signal pathways through various target genes. We intend to apply them as novel, nonintrusive, and easily detectable bladder cancer indicators.

Subjects and methods

The current study involved one hundred subjects. Fifty subjects had bladder cancer diagnosed by cystoscope biopsy and histopathological examination, and the other fifty were age- and gender-matched healthy adults serving as a control group. All participants were subjected to complete history taking through medical examination and estimation of expression levels of plasma miRNA 130a-3p by reverse transcriptase – polymerase chain reaction (RT-PCR) through quantitative real-time technique.

Results

miRNA 130a-3p and miRNA 301a-3p were expressed at higher levels in the plasma of bladder cancer patients than in the controls. The points for the diagnostic capacities of miR 130a-3p and miR 301a-3p for bladder cancer were > 0.921 and > 1.32, respectively, indicating that they are potential clinical diagnostic biomarkers for bladder cancer with good sensitivity and specificity. Moreover, stage IIIA versus stage IIIB can be discriminated as >0.96 (miR 130a-3p) and > 2.48 (miR 301a-3p), which can be utilized for estimating the clinical prognosis of bladder cancer.

Conclusion

miRNA 130a-3p and miRNA 301a-3p expression levels in plasma can differentiate bladder cancer patients from healthy controls and discriminate between stage IIIA and stage IIIB. This finding may facilitate the clinical diagnosis of bladder cancer.

Background

The rabies virus (RABV) continues to be the deadly cause of rabies and to be a hazard to international health. The specific epigenetic modifications in the host response to RABV vaccination have not been fully elucidated. While long noncoding RNAs (lncRNAs) are known to play crucial roles in viral infection control, their specific expression profiles in humans vaccinated against RABV have not been clearly defined.

Methods

This study investigated the lncRNAs and mRNAs expression profiles in four volunteers vaccinated with the RABV vaccine using high-throughput RNA sequencing.

Results

We have discovered 33 lncRNAs and 427 mRNAs that exhibited differential expression after RABV vaccination. The functional annotation, utilizing gene ontology and Kyoto Encyclopedia of Genes and Genomes pathways, revealed that these lncRNAs are involved in signaling pathways that enhance host immune response to RABV vaccination.

Conclusions

Our findings indicate that these lncRNAs, via influencing host immune response, could be explored as potential therapeutic targets in treatments against RABV infection. To the best of our knowledge, it is the first time to report the transcriptome landscape of lncRNAs in human immunized with RABV vaccine.