Network pharmacology­based investigation of potential targets of triptonodiol acting on non-small-cell lung cancer.

BACKGROUND: Triptonodiol is a very promising antitumor drug candidate extracted from the Chinese herbal remedy Tripterygium wilfordii Hook. F., and related studies are underway. METHODS: To explore the mechanism of triptonodiol for lung cancer treatment, we used network pharmacology, molecular docking, and ultimately protein validation. Gene ontology (GO) analysis and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis were performed through the David database. Molecular docking was performed using PyMoL2.3.0 and AutoDock Vina software. After screening, the major targets of triptonodiol were identified for the treatment of lung cancer. Target networks were established, Protein-protein interaction (PPI) network topology was analyzed, then KEGG pathway enrichment analysis was performed. Useful proteins were screened by survival analysis, and Western blot analysis was performed. RESULTS: Triptonodiol may regulate cell proliferation, drug resistance, metastasis, anti-apoptosis, etc., by acting on glycogen synthase kinase 3 beta (GSK3B), protein kinase C (PKC), p21-activated kinase (PAK), and other processes. KEGG pathway enrichment analysis showed that these targets were associated with tumor, erythroblastic oncogene B (ErbB) signaling, protein phosphorylation, kinase activity, etc. Molecular docking showed that the target protein GSK has good binding activity to the main active component of triptonodiol. The protein abundance of GSK3B was significantly downregulated in non-small-cell lung cancer cells H1299 and A549 treated with triptonodiol for 24 h. CONCLUSION: The cellular-level studies combined with network pharmacology and molecular docking approaches provide new ideas for the development and therapeutic application of triptonodiol, and identify it as a potential GSK inhibitor.

SEL1L3 as a link molecular between renal cell carcinoma and atherosclerosis based on bioinformatics analysis and experimental verification.

BACKGROUND: Renal cancer, the most common type of kidney cancer, develops in the renal tubular epithelium. Atherosclerosis of the aorta is the primary cause of atherosclerosis. However, the underlying mechanisms remain unclear. METHODS: The renal clear cell carcinoma RNA sequence profile was obtained from The Cancer Genome Atlas (TCGA) database, and the atherosclerosis datasets GSE28829 and GSE43292 based on GPL570 and GPL6244 was obtained from the Gene Expression Omnibus (GEO) database. The difference and hub genes were identified by the Limma protein-protein interaction (PPI) network in R software. Functional enrichment, survival, and immunoinfiltration analyses were performed. The role of SEL1L3 in the ErbB/PI3K/mTOR signaling pathway, apoptosis, invasion, cell cycle, and inflammation was analyzed using western blotting. RESULTS: 764 DEGs were identified from TCGA Kidney Renal Clear Cell Carcinoma (KIRC) dataset. A total of 344 and 117 DEGs were screened from the GSE14762 and GSE53757 datasets, respectively. Functional enrichment analysis results primarily indicated enrichment in the transporter complex, DNA-binding transcription activator activity, morphogenesis of the embryonic epithelium, stem cell proliferation, adrenal overactivity and so on. Fifteen common DEGs overlapped among the three datasets. The PPI network revealed that SEL1L3 was the core gene. Survival analysis showed that lower SEL1L3 expression levels led to a worse prognosis. Immune cell infiltration analysis showed that SEL1L3 expression was significantly correlated with antibody-drug conjugates (aDC), B cells, eosinophils, interstitial dendritic cells (iDC), macrophages, and more. CONCLUSIONS: SEL1L3 plays an important role in renal clear cell carcinoma and atherosclerosis and may be a potential link between them.

Pretreatment dual-energy CT for predicting early response to induction chemotherapy and survival in nasopharyngeal carcinoma.

OBJECTIVES: To evaluate the predictive performance of pretreatment dual-energy CT (DECT) for early response to induction chemotherapy and survival in nasopharyngeal carcinoma (NPC). METHODS: In this retrospective study, 56 NPC patients who underwent pretreatment DECT scans with posttreatment follow-up were enrolled. The DECT-derived normalised iodine concentration (nIC), effective atomic number (Zeff), 40-180 keV (20 keV interval), and Mix-0.3 value of the tumour lesions were measured to predict the early response to induction chemotherapy and survival in nasopharyngeal carcinoma. The Mann‒Whitney U test, ROC analysis, Kaplan‒Meier method with log-rank test, and Cox proportional hazards model were performed to evaluate the predictive performance of DECT parameters, respectively. RESULTS: Among all DECT-derived parameters, ROC analysis showed the predictive performances of nIC and Zeff values for early objective response to induction chemotherapy (AUCs of 0.803 and 0.826), locoregional failure-free survival (AUCs of 0.786 and 0.767), progression-free survival (AUCs of 0.856 and 0.731) and overall survival (AUCs of 0.765 and 0.799) in NPC patients, respectively (all p < 0.05). Moreover, multivariate analysis showed that a high nIC value was an independent predictor of poor survival in NPC. In addition, survival analysis indicated that NPC patients with higher nIC values in primary tumours tend to have lower 5-year locoregional failure-free survival, progression-free survival and overall survival rates than those with lower nIC values. CONCLUSIONS: DECT-derived nIC and Zeff values can predict early response to induction chemotherapy and survival in NPC; in particular, a high nIC value is an independent predictive factor of poor survival in NPC. CLINICAL RELEVANCE STATEMENT: Preoperative dual-energy computed tomography may provide predictive value for early response and survival outcomes in patients with nasopharyngeal carcinoma, and facilitate their clinical management. KEY POINTS: • Pretreatment dual-energy computed tomography helps to predict early response to therapy and survival in NPC. • NIC and Zeff values derived from dual-energy computed tomography can predict early objective response to induction chemotherapy and survival in NPC. • A high nIC value is an independent predictive factor of poor survival in NPC.

Metal artifacts reduction in kV-CT images with polymetallic dentures and complex metals based on MV-CBCT images in radiotherapy.

This paper proposes a metal artifact reduction method of using MV-CBCT images to correct metal artifacts in kV-CT images, especially for the complex metal artifacts caused by multi-metal interaction of patients with head and neck tumors. The different tissue regions are segmented in the MV-CBCT images to obtain template images and the metal region is segmented in the kV-CT images. Forward projection is performed to get sinogram of the template images, kV-CT images and metal region images. Artifact images can be reconstructed through those sonograms. Corrected images is generated by subtracting the artifact images from the original kV-CT images. After the first correction, the template images are generated again and brought into the previous step for iteration to get better correction result. CT data set of 7 patients are used in this study, compared with linear interpolation metal artifact (LIMAR) and normalized metal artifact reduction method, mean relative error of CT value is reduced by 50.5% and 63.3%, noise is reduced by 56.2% and 58.9%. The Identifiability Score of the tooth, upper/lower jaw, tongue, lips, masseter muscle and cavity in the corrected images by the proposed method have significantly improved (P < 0.05) than original images. The artifacts correction method proposed in this paper can effectively remove the metal artifacts in the images and greatly improve the CT value accuracy, especially in the case of multi-metal and complex metal implantation.

KIF20A as a potential biomarker of renal and bladder cancers based on bioinformatics and experimental verification.

BACKGROUND: Bladder cancer (BC) is a malignant tumor that occurs in the bladder wall and often appears in elderly individuals. Renal cancer (RC) arises from the renal tubular epithelium, but its molecular mechanism remains unclear. METHODS: We downloaded RC datasets (GSE14762 and GSE53757) and a BC dataset (GSE121711) to screen differentially expressed genes (DEGs). We also performed weighted gene coexpression network analysis (WGCNA). We created a protein-protein interaction (PPI) network and performed functional enrichment analysis, such as gene set enrichment analysis (GSEA). Heatmaps were made for gene expression. Survival analysis and immunoinfiltration analysis were performed. Comparative toxicogenomics database (CTD) analysis was performed to find the relationship between disease and hub genes. Western blotting was performed to verify the role of KIF20A in apoptosis. RESULTS: A total of 764 DEGs were identified. The GSEA showed that the DEGs were mainly enriched in organic acid metabolism, drug metabolism, mitochondria, and metabolism of cysteine and methionine. The PPI network in GSE121711 showed that KIF20A was a hub gene of renal clear cell carcinoma. Where the expression level of KIF20A was higher, the prognosis of patients was worse. CTD analysis showed that KIF20A was associated with inflammation, proliferation, and apoptosis. KIF20A expression in the RC group was upregulated, as shown by western blotting. The core proteins (including pRB Ser 780, CyclinA, E2F1, CCNE1, and CCNE2) in the pRB Ser 780/CyclinA signaling pathway were also upregulated in the RC group. CONCLUSIONS: KIF20A might be a novel biomarker for researching renal and bladder cancers.

Triptonodiol, a Diterpenoid Extracted from Tripterygium wilfordii, Inhibits the Migration and Invasion of Non-Small-Cell Lung Cancer.

Lung cancer is the most prevalent oncological disease worldwide, with non-small-cell lung cancer accounting for approximately 85% of lung cancer cases. Tripterygium wilfordii is a traditional Chinese herb that is widely used to treat rheumatism, pain, inflammation, tumors, and other diseases. In this study, we found that Triptonodiol extracted from Tripterygium wilfordii inhibited the migration and invasion of non-small-cell lung cancer and inhibited cytoskeletal remodeling, which has not been previously reported. Triptonodiol significantly inhibited the motility activity of NSCLC at low toxic concentrations and suppressed the migration and invasion of NSCLC. These results can be confirmed by wound healing, cell trajectory tracking, and Transwell assays. We found that cytoskeletal remodeling was inhibited in Triptonodiol-treated NSCLC, as evidenced by the reduced aggregation of actin and altered pseudopod morphology. Additionally, this study found that Triptonodiol induced an increase in complete autophagic flux in NSCLC. This study suggests that Triptonodiol reduces the aggressive phenotype of NSCLC by inhibiting cytoskeletal remodeling and is a promising anti-tumor compound.

Prognostic value of circWWC3 as a novel survival­related biomarker for clear cell renal cell carcinoma.

The aim of the present study was to assess the prognostic value of circular RNA WW and C2 domain-containing protein 3 (circWWC3) in patients with clear cell renal cell carcinoma (ccRCC). The clinicopathological data were collected for patients with ccRCC treated between January 1, 2012, and February 31, 2014, at The Fourth Hospital of Hebei Medical University Hospital (Shijiazhuang, China). A total of 150 patients who underwent nephrectomy were included in the study. Analysis of stored tissues and long-term follow-up data was performed. Fluorescence in situ hybridization was used to detect the relative circWWC3 expression in fresh-frozen cancerous and adjacent para-cancerous tissue samples from patients with ccRCC. A χ2 test was used to analyze the association between circWWC3 expression levels and the clinicopathological parameters of the patients. A Cox proportional risk regression model was used to analyze the clinical factors affecting patient prognosis. The survival curve was plotted using the Kaplan-Meier method, and the association between circWWC3 expression levels and patient survival status was tested using the log-rank test. circWWC3 expression in cancerous tissues was higher than that in the adjacent normal tissues. Additionally, circWWC3 expression was significantly associated with T stage (P=0.005) and pathological grade (P=0.033). Univariate Cox regression analysis showed that overall survival (OS) was associated with T stage, pathological Fuhrman grade and circWWC3 expression levels (all P<0.05). Multivariate Cox regression analysis also yielded similar results in patients with ccRCC (P<0.05). Moreover, the OS time of patients with high circWWC3 expression was significantly shorter than that of patients with low circWWC3 expression. In conclusion, high circWWC3 expression is an independent risk factor affecting patient prognosis, and is expected to be an important prognostic biomarker and novel therapeutic target for patients with ccRCC.

The Ethyl acetate extract from Celastrus orbiculatus suppresses non-small-cell lung cancer by activating Hippo signaling and inhibiting YAP nuclear translocation.

BACKGROUND: Celastrus orbiculatus Thunb. is a medicinal plant that has been widely used for thousands of years in China, and the ethyl acetate extract (Celastrus orbiculatus Thunb. Extract, COE) from its stem was reported to exert antitumor and anti-inflammatory effects in various preclinical studies. However, the anti-non-small-cell lung cancer activity of COE and its potential mechanism are not yet fully understood. PURPOSE: To investigate the antitumor effects of COE on non-small-cell lung cancer (NSCLC) cells and explore its molecular mechanism from the perspective of Hippo signaling, YAP nuclear translocation, and reactive oxygen species (ROS) generation. METHODS: The effects of COE on proliferation, cell cycle arrest, apoptosis, stemness, and senescence in NSCLC cell lines were determined by CCK-8, clone formation, flow cytometry, and ß-galactosidase staining assays. The effects of COE on Hippo signaling were investigated by Western blotting. The intracellular expression and distribution of YAP were analyzed by immunofluorescence assay. DCFH-DA probe combined with flow cytometry was used to detect intracellular total ROS levels in NSCLC cells after COE treatment. Xenograft tumor model was established, and the animal living image system was employed to analyze the effects of COE on the Hippo-YAP signaling in vivo. RESULT: COE significantly inhibited NSCLC activity in vitro and in vivo, mainly by proliferation inhibition, cycle arrest, apoptosis promotion, senescence promotion, and stemness downregulation. COE strongly activated Hippo signaling and inhibited YAP expression and nuclear retention. Activation of Hippo signaling induced by COE was associated with ROS-mediated phosphorylation of MOB1. CONCLUSION: This study demonstrated that COE inhibited NSCLC through activating Hippo signaling and suppressing YAP nuclear translocation, in which ROS may play a role in the phosphorylation of the MOB1 protein.

Role of CCT4/ErbB signaling in nephroblastoma: Implications for a biomarker of Wilms tumor.

Wilms tumor is a common abdominal malignant tumor in children. However, the molecular mechanism of Wilms tumor is unclear. GSE66405 and GSE197047 were obtained from the Gene Expression Omnibus database. To identify differentially expressed genes (DEGs) in Wilms tumor, the R package "limma" was used. Weighted gene co-expression network analysis was performed to identify the significant module. The list of DEGs was input into the Search Tool for the Retrieval of Interacting Genes database to construct a protein-protein interaction network for predicting core genes. Gene Ontology analysis and the Kyoto Encyclopedia of Genes and Genomes analysis are computational methods for assessing gene function and biological pathways. The genome was analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes and developed by gene set enrichment analysis. Comparative Toxicogenomics Database analysis was performed to find the diseases most related to the core genes. TargetScan was used to screen for miRNAs that regulate hub genes. A total of 925 DEGs were identified. The differently expressed genes were mainly enriched in the metabolic pathway, AMPK signaling pathway, ErbB signaling pathway, mRNA detection pathway, and folded protein binding. A total of 16 core genes (HNRNPK, PABPC1, HNRNPD, NCL, YBX1, EIF4G1, KHDRBS1, HNRNPAB, HSPA4, EEF2, HSP90AA1, EEF1A1, A TP5A1, SDHA, CCT4, CCT5) were obtained. chaperonin containing TCP-1 subunit 4 (CCT4) was downregulated in tumor tissue samples, which may have reverse regulatory significance for Wilms tumor. CCT4, HSP90AA1, NCL, PABPC1, and YBX1 were found to be associated with kidney disease, acute kidney injury, edema, tumor metastasis, transitional cell carcinoma, necrosis, and inflammation. The research found that the related miRNA of the CCT4 gene was hsamiR-7-5p. CCT4 might play an essential role in the occurrence and development of Wilms tumor, and they may participate in the occurrence and development of Wilms tumor through the ERBB signal pathway. CCT4 may be a promising biomarker of Wilms tumor.

High expression of KIF20A in bladder cancer as a potential prognostic target for poor survival of renal cell carcinoma.

Urinary system tumors are malignant tumors, including renal cancer and bladder cancer. however, molecular target of them remains unclear. GSE14762 and GSE53757 were downloaded from GEO database to screen differentially expressed genes (DEGs). Weighted gene co-expression network analysis was performed. Gene Ontology (GO) and Kyoto encyclopedia of genes and genomes were used for enrichment analysis. Gene ontology and Kyoto encyclopedia of genes and genomes analyses were performed on whole genome, as formulated by gene set enrichment analysis. Survival analysis was also performed. Comparative toxicogenomics database was used to identify diseases most associated with hub genes. A total of 1517 DEGs were identified. DEGs were mainly enriched in cancer pathway, HIF-1 signaling pathway, organic acid metabolism, glyoxylate and dicarboxylate metabolism, and protein homodimerization activity. Ten hub genes (TPX2, ASPM, NUSAP1, RAD51AP1, CCNA2, TTK, PBK, MELK, DTL, kinesin family member 20A [KIF20A]) were obtained, which were up-regulated in tumor tissue. The expression of KIF20A was related with the overall survival of renal and bladder cancer. KIF20A was up-regulated in the tumor tissue, and might worsen the overall survival of bladder and kidney cancer. KIF20A could be a novel biomarker of bladder and kidney cancer.

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.

KIF11: A potential prognostic biomarker for predicting bone metastasis-free survival of prostate cancer.

Most prostate cancer (PCa) cases remain indolent with a relatively good prognosis. However, bone metastasis of PCa can quickly worsen prognoses and lead to mortality. Metastasis-free survival (MFS), a strong surrogate for overall survival, is widely used in PCa prognosis research. The present study identified molecules that affect bone MFS in PCa, with clinical validation. Three datasets (GSE32269, GSE74367 and GSE77930) were downloaded from the Gene Expression Omnibus database. Hub genes most relevant to clinical traits (bone metastasis-associated morbidity) were identified by weighted gene co-expression network analysis (WGCNA) and subjected to logistic regression analysis. Patient samples were obtained between January 2014 and December 2016, with a clinically annotated follow-up in December 2021. Clinical data and follow-up information for 60 patients with PCa were used in MFS analysis. Tumor samples were retrieved, and immunohistochemistry was performed to detect vascular endothelial growth factor (VEGF). The prognostic potential of the two molecules was assessed using Cox proportional hazards regression analysis. A total of 16 gene modules were obtained via WGCNA, and the tan module, containing 147 genes, was most closely linked to bone metastasis. In total, 877 differentially expressed genes (DEGs) were detected. The DEG-tan module intersection yielded seven hub genes [BUB1, kinesin family member (KIF)2C, RACGAP1, CENPE, KIF11, TTK and KIF20A]. Using univariate and multivariate logistic regression analyses for independent risk factors of bone metastasis, KIF11 and VEGF were found to be significantly associated with a higher T stage, prostate-specific antigen level and Gleason score. In addition, KIF11 and VEGF expression levels were positively correlated (P<0.001). Using univariate Cox analysis, KIF11 and VEGF were found to exhibit a significant association with poor MFS (P<0.05). However, only KIF11 was significantly associated with MFS upon multivariate analysis (P=0.007; hazard ratio, 2.776; 95% confidence interval, 1.315-5.859). Markers of bone metastasis in PCa were identified. Overall, KIF11 is an independent indicator that can predict bone metastasis for patients with PCa, which could be used to guide clinical practice.

Mucosa-associated lymphoid tissue of nasopharynx: A case report and literature review.

Nasopharyngeal MALT lymphoma is a rare disease, with limited cases reported in the literature. To the best of our knowledge, there is no research detailing the treatment of nasopharyngeal MALT lymphoma. In this present paper, we report an unusual case of a 70-year-old female patient with nasopharyngeal MALT lymphoma. The patient was treated with radiotherapy alone. The detailed radiation therapy of the treatment was demonstrated. The patient is free of locally recurrent or distant disease at two years. Radiotherapy alone can be a helpful treatment for MALT lymphoma confined to the nasopharyngeal cavity.

The role of 18F-FDG PET/CT in diagnosis and treatment evaluation for ocular adnexal mucosa-associated lymphoid tissue lymphoma.

OBJECTIVE: The purpose of this study is to evaluate the value of fluorine-18-fludeoxyglucose positron emission tomography (18F-FDG PET)/CT in the diagnosis and treatment evaluation of ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma. METHODS: 70 patients with OAML who received radiotherapy were recruited in our study. All the patients had the 18F-FDG PET/CT examination before the treatment. We retrospectively reviewed the medical records, pathological reports, laboratory results, and imaging features of all patients. The associations between 18F-FDG PET/CT parameters and Epstein-Barr virus antibodies, treatment response, MRI data, and Ki-67 expression were investigated. RESULTS: The PET/CT scan indicated that 80% (56/70) of the patients showed orbital FDG avidity. The median level of maximum standardized uptake value (SUVmax) of the lesions was 4.65 ± 3.00 (range:1.2-13.5). 92.0% (46/50) of the mass-forming lesions showed 18F-FDG avidity, while only 50.0% (10/20) of the non-massive lesions had 18F-FDG avidity (χ2 = 13.23, p=0.01). The SUVmax in orbit, conjunctiva, and lacrimal gland lymphoma were 5.6, 2.9, and 3.7, respectively. A significant difference was identified of SUVmax among the three locations' lymphoma using one-way ANOVA analysis (F = 5.039, p = 0.01). After completion of radiotherapy, the complete remission rate was achieved in 30.8% (4/13) of the patients without 18F-FDG avidity, and 70.4% (38/54) in cases with 18F-FDG avidity (χ2 = 5.43, p = 0.02). The correlation between high Ki-67 score and 18F-FDG avidity was confirmed (χ2 = 3.916, p = 0.048); however, no significant correlation was found between the SUVmax and Ki-67 score of the lesions (p = 0.971). Three patients (3/70, 4.3%) were upregulated the stage via PET/CT. CONCLUSION: 18F-FDG PET/CT had some potential values in the diagnosis and assessment of treatment response in patients with OAML. ADVANCES IN KNOWLEDGE: The value of 18F-FDG PET/CT for patients with OAML.

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.

Calcitriol restores renovascular function in estrogen-deficient rats through downregulation of cyclooxygenase-2 and the thromboxane-prostanoid receptor.

Cardiovascular risks increase in postmenopausal women. While vitamin D is supplemented for osteoporosis, it is not known whether it protects renal arterial function during estrogen deficiency. Here we measured changes in renovascular reactivity induced by ovariectomy in rats and examined whether calcitriol, the most active form of vitamin D, was able to correct such changes. The impairment of endothelium-dependent relaxation in renal arteries from ovariectomized rats was effectively reversed by long-term calcitriol treatment. It was also corrected by acute exposure to cyclooxygenase-2 (COX-2) inhibitors and a thromboxane-prostanoid receptor antagonist, respectively. Calcitriol normalized the overexpression of COX-2 and thromboxane-prostanoid receptors in intralobal renal artery segments and aortic endothelial cells isolated from ovariectomized rats. In vitro exposure of the arterial segments to calcitriol for 12 h improved relaxation and downregulated thromboxane-prostanoid receptors. The attenuated nitric oxide production in ovariectomized rat aortic endothelial cells was restored following a 12-h treatment with calcitriol, COX-2 inhibition, or thromboxane-prostanoid receptor antagonism. Thus, impaired endothelium-dependent renal artery relaxation in ovariectomized rats is mediated largely through increased activity and expression of COX-2 and the thromboxane-prostanoid receptor. Calcitriol restores endothelial function through downregulating both signaling proteins during estrogen deficiency.

Demethoxycurcumin inhibits cell proliferation, migration and invasion in prostate cancer cells.

Curcumin (CUR) is a natural agent that has been demonstrated to effectively inhibit prostate cancer growth. However, natural CUR is relatively unstable and can be easily degraded in vivo. Therefore, it is essential to develop other stable curcuminoids. Demethoxycurcumin (DMC) is a candidate that has been verified in several tumor types and has potential for the treatment of prostate cancer. In the present study, we investigated the effects of DMC on proliferation, apoptosis and migration of PC-3 cells. MTT assay results indicated that DMC inhibited PC-3 cell viability in a dose- and time-dependent manner, and DMC induced G2/M phase arrest. Furthermore, PC-3 cells in DMC-treated groups had a higher apoptotic rate compared with DMSO-treated control. This effect may be due to the activation of the caspase-3 pathway. In DMC-treated groups, migrating and invasive cells were dramatically reduced (P<0.05). The activity of MMP-2, which is correlated with migration and invasion was also suppressed by DMC. These results indicated that DMC may inhibit PC-3 cell migration and invasion partially by affecting MMP-2 activity. In conclusion, DMC significantly inhibits proliferation, migration and invasion of cultured PC-3 cells, and this study may provide evidence for future in vivo studies and clinical use.