Gene Reports最新文献

Genetic diversity existing between the chicken breeds can be used as a means to unravel the biological mechanisms affecting traits of commercial prominence. The present study attempted to compare the biological pathways enriched in pectoralis major muscles in five diverse chicken breeds. RNA sequencing data was generated from four biological replicates of pectoralis major muscles from Ankleshwar, Aseel, Kadaknath, Punjab Brown and Nicobari chicken. A total of 40 genes each for Nicobari and Aseel, 46 for Punjab Brown, 65 for Kadaknath and 86 for Ankaleshwar were found to be unique. The Neuroactive ligand-receptor interaction pathway was enriched in Ankaleshwar, Aseel and Kadaknath. However, the set of genes identified in this pathway were associated with different ligand receptors in each of the three breeds. The Wnt signaling pathway showed significant enrichment in Nicobari chicken while the Steroid biosynthesis pathway showed prominent expression in Punjab Brown chicken. The significant pathways pinpoint to genetic characteristics associated with each breed suggesting a transcriptome footprint. Our study is a first step toward determining the genetic basis of phenotypic diversity in chicken.

This study aimed to determine the impact of genetic variation in FKBP prolyl isomerase 5 (FKBP5) on mRNA and protein expression levels, on glucocorticoids (GC) responsiveness and its clinical association in systemic lupus erythematosus (SLE). The genotyping of the FKBP5-rs1360780 was performed using TaqMan SNP genotyping technology. The mRNA expression level in peripheral blood mononuclear cells was evaluated using realtime-PCR. The immunohistochemistry staining was used to analyze FKBP5 protein expression level in renal biopsies. A risk association was revealed between rs1360780 > C allele and SLE pathogenesis. We found an up-regulation in the FKBP5 mRNA expression level in SLE patients with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score ≤ 6 compared to patients with SLEDAI score > 6. Our results revealed an altered renal cell expression of FKBP5 protein in patients with lupus nephritis compared to control samples. However, no association was observed between the FKBP5 and the response to GC treatment. Our study is the first to demonstrate a link between SLE and FKBP5 gene, in terms of mRNA and protein expression levels, and the variant of the SNP rs1360780 in SLE, suggesting a susceptibility role of rs1360780 > C.

Background

Insulin resistance is a common manifestation among patients with chronic hepatitis C. The aim of this study was to investigate the effect of haplotypes in the microsomal triglyceride transfer protein (MTTP) gene on insulin resistance in Brazilian patients with chronic hepatitis C.

Methods

Genetic variants in the MTTP gene were genotyped by PCR-RFLP.

Results: Of the 232 patients with chronic hepatitis C, 34.5 % had insulin resistance (HOMA-IR ≥3) and the majority were ≥50 years old. The minor allele frequencies for the -400A/T (rs1800803), -164T/C (rs1800804), H297Q (rs2306985), I128T (rs3816873), Q95H (rs61733139), Q244E (rs17599091) and -493G/T (rs1800591) variants in the MTTP gene were 0.41, 0.30, 0.49, 0.30, 0.08, 0.06 and 0.32. In multivariate analysis, elevated levels of gamma-glutamyl transpeptidase (GGT) was associated with insulin resistance (p = 0.006). Haplotype-based association testing presented that the haplotype ATCTGGG of the -400A/T, -164T/C, H297Q, I128T, Q95H, Q244E and -493G/T variants was associated with the presence of insulin resistance (p = 0.028) and the haplotype TTGTGCG may be a protective factor (p = 0.012).

Conclusion

The combination of alleles in the -400A/T, -164T/C, H297Q, I128T, Q95H, Q244E and -493G/T genetic variants in the MTTP gene may play a relevant role in insulin resistance among patients with chronic hepatitis C.

Objectives

The aim of this study was to characterize the co-occurrence of the blaSHV-182, blaKPC-2, blaCTX-M-65, and blaTEM-1B genes in a multi-resistant carbapenem carbapenem-resistant K. pneumoniae (CRKP) strain.

Methods

The multi-resistant CRKP strain was isolated from the bronchoalveolar lavage fluid (BAL) of a patient with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), after cultured in lysogeny broth, the colonies with apparent phenotypic differences (size, shape, color, and surface states) were picked out for species identification by sequencing their 16S rDNA and BLASTN in the NCBI database, antimicrobial susceptibility was determined, Genomic DNA of overnight cultured K. pneumoniae D1a was extracted by using the Bacterial DNA Isolation Kit, the library was constructed by using NEBNext®UltraTM DNA Library Prep Kit for Illumina, and the whole-genome sequencing was performed on the Illumina HiSeq PE150 platform. The pair-end reads were assembled by SOAP denovo v2.04, SPAdes, and ABySS. Genome characteristics were analyzed by using bioinformatics methods.

Results

The WGS of the multi-resistant CRKP strain D1a (CRKP D1a) yielded 84 scaffolds of genomic DNA (5, 492, 035 bp) and two circular plasmids, pD1a1 (173, 413 bp) and pD1a2 (57, 686 bp). CRKP D1a was classified as the sequence type 11, and harbored 16 antibiotic resistance genes and 30 multidrug efflux pump-encoding genes associated with the resistance to almost all kinds of commonly used antibiotics. The plasmid pD1a1 belonged to the IncFII/IncR hybrid plasmid family with blaSHV-182, blaKPC-2, blaCTX-M-65, and blaTEM-1B genes flanked by the IS6-like element. The plasmid pD1a2 was comprised of 95 phage-related genes but had no lysis activity on the tested K. pneumoniae strains.

Conclusion

This study reports the isolation of a multidrug-resistant CRKP strain co-carrying IncFII/IncR-KPC2 plasmid and phage-like plasmid, the findings hold significant implications for further investigating the resistance mechanism and molecular diversity of CRKP.

Breast cancer is the most common cancer in women worldwide. The high-temperature requirement A (HTRA) protein family is a highly conserved serine protease family that plays a critical role in the regulation of several important physiological processes such as cell growth, apoptosis, and senescence. It has also been implicated in the pathogenesis, diagnosis, progression, and prognosis of several types of cancer. HTRA1 is the first and most extensively studied member of the HTRA family, which plays a pivotal role in the pathogenesis and progression of various cancers. In breast cancer, HTRA1 is involved in the regulation of tumor cell, proliferation, migration, and invasion. Clinically, it may also be involved in chemotherapy resistance. A thorough investigation of the mechanism of HTRA1 in breast cancer progression is crucial for the implementation of disease diagnosis and individualized medicine. This review provides a comprehensive overview of the current progress of HTRA1 in breast cancer research, focusing on its molecular characteristics, tissue distribution, potential substrates, involved signaling pathways, and interactions with upstream and downstream molecules.

Bacterial biofilms cause serious problems in the industrial sector and human healthcare. Nucleases are characterized as biofilm-degrading enzymes. In this work, the extracellular nuclease nucB gene from a new isolate Bacillus paralicheniformis str. PMp/10 was isolated and cloned successfully into the cloning vector pET 29a⁺, then transformed into E. coli DH5α. The nucB gene has a molecular weight of 429 bp, its sequence was uploaded to the NCBI GenBank database under the accession number OP712506 which is the first report for B. paralicheniformis. The gene encoded a nuclease B enzyme consisting of 142 amino acids with an estimated molecular weight of 13 kDa. The 3D and 2D structure of nuclease B was predicted and the NucB enzyme's secondary structure prediction showed that it has five β-strands and three α-helices. Finally, the Molecular docking interaction between NucB and deoxyribonucleic acid was performed successfully with a high binding affinity (−7.1 kcal/mol).

In recent times, the SARS-CoV-2 virus has been observed to cause a serious threat to the world through its high permissive mutations by adapting itself to the host environment, which is a time to design an effective vaccine that could be able to produce immune response to fight against the virus. An Immunoinformatics approach was employed to conduct a high-throughput analysis aimed at developing a multi-epitope-based vaccine that specifically targets the BF.7 Omicron variant, which is currently a variant of concern. The essential aspect for the successful development of a vaccine lies in identifying B-cell and T-cell epitopes that exhibit both antigenic features, capable of eliciting a defensive immune response, while also possessing non-allergenic characteristics to prevent any harmful allergic reactions. These epitopes are essential for the development of vaccines because they aid in the immune system's ability to identify and attack certain infections without inducing unfavorable allergic reactions. The Docking and MD simulation studies have shown structural stability and Toll-like receptors with chosen vaccine architecture interact strongly. The in-silico immune simulation boosted the research study confirming the efficiency of the vaccination that has the potential to stimulate immunological responses by producing antibodies to not only targeting the specific VOC, BF.7 Omicron variant but also other omicron sublineages. Overall, the computational study have provided strong evidences to the designed vaccine construct which needs to be confirmed through the experiemental study.

Background

Bladder urothelial carcinoma (BLCA) is one of the most common malignant tumors in urinary system worldwide. High possibility of recurrence and progression leads to poor prognosis, revealing the significant role of long-term postoperative monitoring to the patients. However, effective noninvasive diagnosis is currently limited.

Materials and methods

Differentially expressed genes (DEGs) were analyzed using R-packages. Functional enrichment analyses were performed on Metascape. The prognostic model was established by multi-step cox regression and evaluated by survival plots and receiver operating characteristic (ROC) curves. The nomogram was then constructed based on three identified prognostic factors. C-index and calibration curves were calculated to testify the capacity for predicting survival possibility of BLCA patients. The transcription levels of model genes were further verified in a gemcitabine-resistant bladder cancer cell line T24 (TGR) by quantitative real-time PCR (qRT-PCR).

Results

360 genes were differentially expressed between BLCA and normal bladder mucosae simultaneously in three GEO datasets, of which 59 were up-regulated and 301 were down-regulated. 159 prognostic genes were obtained from DEGs. Lasso and multivariate cox regression were conducted in sequence and the prognostic model was eventually optimized to four genes (EHBP1, RHOJ, FASN, STXBP6). Survival analyses demonstrated that the overall survival (OS) of patients in high-risk group was significantly shorter than that in low-risk group. The area under the curve (AUC) values of 3–5 years survival were basically above 0.7. Moreover, cox regression analyses showed that age, T stage and risk score were independent indicators for BLCA prognosis. For further clinical application, a nomogram was then constructed by integrating these factors. The C-index (0.72, CI 95 %, 0.669–0.775) and calibration curves demonstrated the good performance of nomogram. Importantly, the mRNA level of model genes was significantly up-regulated in TGR compared to T24, indicating a better prediction for chemotherapy-resistant BLCA patients.

Conclusion

Collectively, our findings suggest a novel four-gene predictive model for BLCA prognosis. It is expected to provide a valuable reference for prognostic evaluation and treatment in BLCA patients.

Background

Head and neck squamous cell carcinoma (HNSCC) is prevalent and highly aggressive. HNSCC pathogenesis is characterized by the presence of long non-coding RNAs (lncRNAs) that lead to abnormal cellular functions such as proliferation, migration, and invasion.

Methods

This study examined the expression levels of lncRNAs TMPO-AS1, DDX11-AS1, and the POLE gene in 100 HNSCC tumors and normal adjacent tumors (NATs). The analysis was performed using quantitative reverse transcription polymerase chain reaction (RT-qPCR) on fresh-frozen samples.

Results

In HNSCC samples, tumor tissue exhibited markedly elevated levels of POLE expression compared to NATs (p < .001, 95 % CI: 2.410–3.170 vs. 0.9834–1.549). DDX11-AS1 expression was also significantly higher in HNSCC samples than in NATs (p < .001, 95 % CI: 1.879–3.250 vs. 1.029–1.731). Similarly, TMPO-AS1 levels were significantly elevated in HNSCC samples compared to NATs (p < .001, 95 % CI: 1.903–2.639 vs. 0.894–1.329). ROC curve diagnostic analyses revealed AUC values of 0.838 (95 % CI: 0.761–0.915) for POLE, 0.689 (95 % CI: 0.585–0.793) for DDX11-AS1, and 0.808 (95 % CI: 0.724–0.893) for TMPO-AS1. Notably, a substantial association was found between tumor grade and human papillomavirus levels with POLE and TMPO-AS1. Additionally, significant associations were observed between tumor stage and metastasis with DDX11-AS1 and TMPO-AS1 levels. Our findings further investigate a remarkable association between the combined effect of smoking and HPV positive infections and expression levels of POLE, DDX11-AS1, and TMPO-AS1. Our final results align with those from The Cancer Genome Atlas (TCGA), which included 520 HNSCC cases and 44 controls.

Conclusions

Our data emphasize the potential significance of DDX11-AS1, TMPO-AS1, and POLE in the poor prognosis of HNSCC, indicating their contribution to tumor growth and progression.

Aim

We investigated the role of magnesium sulfate (MgSO4) and insulin administration on improved autophagy and apoptosis to prevent diabetes in high-fat diet (HFD)-diabetic parents and their offspring.

Methods

A HFD and a low dose of streptozotocin (STZ) were used to induce diabetes. Animals were assigned to four groups: non-diabetic control (NDC), diabetic control (DC), the diabetic group received insulin (INS), and the diabetic group received magnesium (MG). The duration of the research was 6 months, and offspring were fed a normal diet for 4 months. Blood glucose was determined weekly in rats (parents and offspring). The gene expression of adenosine monophosphate-activated protein kinase (AMPKα1), Bcl-2-interacting myosin-like coiled-coil protein (Becline-1), P62, Microtubule-associated protein 1 light chain 3 (LC3-II), and caspase-9 of liver tissues were assessed using Real-time PCR.

Result

The analysis of maternal gene expression data showed that treatment with MG and INS considerably augmented the AMPKα1 and LC3-II genes expression and diminished P62 and caspase-9 expression. Also, a significant decrease in the expression of AMPKα1, LC3-II, P62, and Becline-1 was observed in the female offspring in the MG and INS groups. Significant alterations in levels of AMPKα1, Beclin-1, P62, and caspase-9 mRNA were not observed between groups in male offspring, but the expression of LC3-II considerably diminished in the groups compared with the DC group.

Discussion

Our data demonstrated that MG supplementation strengthened the mother's autophagy and reduced the transmission of damage to the female offspring. In the male offspring, the transmission of damage was generally less, and MG improved the autophagy condition in the male offspring. Our findings support the presence of a link between autophagy induction and MG-modified biomaterials and determine a potential mechanism of MG-mediated diabetes and autophagy.