PLK1 as one novel target for the poor prognosis of bladder cancer: An observational study.

Bladder cancer (BC) is one of the most common male malignant tumors and the most common urological tumor. However, the molecular mechanism and role of PLK1 on bladder cancer were unclear. Therefore, the study aims to explore the potential part of the overall survival of bladder cancer through bioinformatics analysis. GSE121711 and GSE130598, from the Gene Expression Omnibus database. The GEO2R screened differently expressed genes, and DAVID and Metascape were used for functional annotation. The cytoHubba made hub genes identification and expression. A total of 50 BC participants were recruited. After surgery, 50 BC tumor samples from BC patients and 50 adjacent standard bladder tissue samples were obtained. The RT-qPCR assay was performed to verify the expression of hub genes. The Kaplan-Meier Plotter analyzed the effect of hub gene expression for overall survival of BC. The compulsory module of Molecular Complex Detection tool analysis was shown, which included CDK1, TTK, AURKB, MELK, PLK1, and BUB1. And the six hub genes were up-regulated in the BC compared with the normal tissues. The relative expression levels of CDK1, TTK, AURKB, MELK, PLK1, and BUB1 were significantly higher in BC samples compared with the regular kidney tissue groups. The result demonstrated that CDK1, TTK, AURKB, MELK, PLK1, and BUB1 might be considered biomarkers for BC. Overall survival analysis showed that BC patients with high expression level of PLK1 had poorer overall survival times than those with low expression level (P < .05). The expression levels of CDK1, TTK, AURKB, MELK, and BUB1 was not related to the overall survival of BC patients (P > .05). The PLK1 gene might provide new ideas and evidence for bladder cancer research.

Identification and Verification of Biomarker in Clear Cell Renal Cell Carcinoma via Bioinformatics and Neural Network Model.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is the most common subtype of kidney cancer, which represents the 9th most frequently diagnosed cancer. However, the molecular mechanism of occurrence and development of ccRCC is indistinct. Therefore, the research aims to identify the hub biomarkers of ccRCC using numerous bioinformatics tools and functional experiments. METHODS: The public data was downloaded from the Gene Expression Omnibus (GEO) database, and the differently expressed genes (DEGs) between ccRCC and normal renal tissues were identified with GEO2R. Protein-protein interaction (PPI) network of the DEGs was constructed, and hub genes were screened with cytoHubba. Then, ten ccRCC tumor samples and ten normal kidney tissues were obtained to verify the expression of hub genes with the RT-qPCR. Finally, the neural network model was constructed to verify the relationship among the genes. RESULTS: A total of 251 DEGs and ten hub genes were identified. AURKB, CCNA2, TPX2, and NCAPG were highly expressed in ccRCC compared with renal tissue. With the increasing expression of AURKB, CCNA2, TPX2, and NCAPG, the pathological stage of ccRCC increased gradually (P < 0.05). Patients with high expression of AURKB, CCNA2, TPX2, and NCAPG have a poor overall survival. After the verification of RT-qPCR, the expression of hub genes was same as the public data. And there were strong correlations between the AURKB, CCNA2, TPX2, and NCAPG with the verification of the neural network model. CONCLUSION: After the identification and verification, AURKB, CCNA2, TPX2, and NCAPG might be related to the occurrence and malignant progression of ccRCC.

Hydrogen sulfide improves endothelial dysfunction in hypertension by activating peroxisome proliferator-activated receptor delta/endothelial nitric oxide synthase signaling.

OBJECTIVE: We aimed to elucidate the ameliorative effect of hydrogen sulfide (H2S) on endothelium-dependent relaxation disturbances via peroxisome proliferator-activated receptor delta/endothelial nitric oxide synthase (PPARδ/eNOS) pathway activation in hypertensive patients and rats. METHODS: Renal arteries were collected from normotensive and hypertensive patients who underwent nephron-sparing surgery. Renal arteries from 37 patients were cultured with or without sodium H2S (NaHS) 50 µmol/l. The rats were randomly divided into four groups: Sham; Sham + NaHS, two kidneys; one clipped (2K1C); and 2K1C + NaHS. Mean arterial pressure was measured by tail-cuff plethysmography. A microvessel recording technique was used to observe the effect of NaHS on endothelium-dependent relaxation. Plasma H2S concentrations were detected using the monobromobimane method. Real-time PCR and western blotting were used to assess mRNA and protein levels of AT1, cystathionine γ-lyase, PPARδ, and phosphor-eNOS. Laser confocal scanning microscopy measured intracellular NO production in human umbilical vein endothelial cells. RESULTS: NaHS improved endothelial function in hypertensive humans and rats. The 20-week administration of NaHS to 2K1C rats lowered the mean arterial pressure. In human umbilical vein endothelial cells, NaHS improved the AngII-induced production of NO. NaHS upregulated PPARδ expression, increased protein kinase B (Akt) or adenosine monophosphate kinase-activated protein kinase (AMPK) phosphorylation, and enhanced eNOS phosphorylation. A PPARδ agonist could mimic the ameliorative effect of NaHS that was suppressed by PPARδ, AMPK, or Akt inhibition. CONCLUSION: H2S plays a protective function in renal arterial endothelium in hypertension by activating the PPARδ/PI3K/Akt/eNOS or PPARδ/AMPK/eNOS pathway. H2S may serve as an effective strategy against hypertension.

Association of the rs3077 and rs9277535 polymorphisms in HLA-DP with hepatitis B virus infection and spontaneous clearance: a meta-analysis.

PURPOSE: Owing to inconsistent observations in the literature of an association between HLA-DP polymorphisms (rs3077 and rs9277535) and hepatitis B virus (HBV) infection and spontaneous clearance, there is an urgent need for a comprehensive and reliable understanding of this subject. This meta-analysis was performed to quantitatively summarise the evidence for the relevance of these HLA-DP polymorphisms to HBV infection and spontaneous clearance. METHODS: A meta-analysis was conducted with the data from eight relevant papers published from April 2009 to March 2012, following strict selection. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for alleles, co-dominant, dominant and recessive genotype models of the rs3077 and rs9277535 loci. RESULTS: Our analysis indicated a significant association of rs3077 and rs9277535 in HLA-DP with HBV infection, suggesting that these HLA-DP polymorphisms act beneficially against HBV infection (for rs3077, AG vs. GG: OR = 0.522, 95% CI = 0.485-0.561; AA vs. GG: OR = 0.350, 95% CI = 0.311-0.393; for rs9277535, AG vs. GG: OR = 0.542, 95% CI = 0.506-0.579; AA vs. GG: OR = 0.371, 95% CI = 0.336-0.409). Additionally, these HLA-DP polymorphisms served as protective factors in the spontaneous clearance of HBV (for rs3077, AG vs. GG: OR = 0.600, 95% CI = 0.464-0.775; AA vs. GG: OR = 0.420, 95% CI = 0.299-0.590; for rs9277535, AG vs. GG: OR = 0.623, 95% CI = 0.570-0.681 and AA vs. GG: OR = 0.464, 95% CI = 0.386-0.556) with similar results for both dominant and recessive genotype models. CONCLUSIONS: Our results demonstrated that the rs3077 and rs9277535 HLA-DP polymorphisms reduced HBV infection and increased the likelihood of spontaneous viral clearance in some Asian populations.

A study of middle ear function in the treatment of nasopharyngeal carcinoma with IMRT technique.

PURPOSE: This study evaluates the difference in damage to middle ear function with CRT and IMRT techniques in the treatment of nasopharyngeal carcinoma (NPC). We explore the isthmus of the Eustachian tube (ET) as the key anatomic site for the prevention of radiation-induced otitis media with effusion. METHODS AND MATERIALS: Eighty-two patients with NPC were divided into two groups: 40 patients treated with CRT and 42 patients treated with IMRT. The difference between dosage over the middle ear cavity and the isthmus of the ET was evaluated in both CRT group and IMRT group. All patients underwent hearing tests including pure tone audiometry and impedance audiometry before and after RT. RESULTS: The dosage difference to the middle ear cavity and isthmus between these two groups was statistically significant (p<0.05). The difference in hearing test results between these two groups was also statistically significant (p<0.05). If we limited the dose to the middle ear cavity under 34 Gy and the dose to the isthmus under 53 Gy with IMRT, we may decrease radiation-induced OME even with the larger 2.25 Gy fraction size. CONCLUSIONS: IMRT may have better protected the middle ear function compared with the CRT technique, even with larger fraction sizes than for the conventional CRT technique.