Effects of grape seed-derived proanthocyanidin B2 pretreatment on oxidative stress, endoplasmic reticulum stress and apoptosis of renal tubular epithelial cells in renal ischemia-reperfusion injury model of mice.

PURPOSE: To investigate the effect of grape seed-derived proanthocyanidin B2 (GSPB2) pretreatment on acute renal ischemia-reperfusion injury model of mice. METHODS: 50 mice were divided into 5 groups: Sham group: mice were treated with right nephrectomy. GSPB2 group: GSPB2 was injected intraperitoneally 45 min before right nephrectomy. IRI group: right kidney was resected and the left renal arteriovenous vessel was blocked for 45 min. GSPB2 + IRI group: GSPB2 was intraperitoneally injected 45 min before IRI established. GSPB2 + BRU + IRI group: GSPB2 and brusatol (BRU) were injected intraperitoneally 45 min before IRI established. Creatinine and urea nitrogen of mice were detected, and the kidney morphology and pathological changes of each group were detected by HE staining, PAS staining and transmission electron microscopy. Expressions of Nrf2, HO-1, GRP78, CHOP, and cleaved-caspase3 were detected by immunofluorescence staining and western blotting. RESULTS: Morphology and mitochondrial damages of kidney in GSPB2 + IRI group were significantly alleviated than those in IRI group. Expression levels of Nrf2 and HO-1 were significantly higher in GSPB2 + IRI group than those in IRI group. Expression levels of GRP78, CHOP and cleaved-caspase3 were significantly lower in GSPB2 + IRI group than those in IRI group. However, compared to GSPB2 + IRI group, protective effects of GSPB2 pretreatment were weakened in GSPB2 + BRU + IRI group. CONCLUSIONS: GSPB2 pretreatment could alleviate oxidative stress damage and reduce apoptosis of renal tubular epithelial cells, which might be related to activating the antioxidant system, up-regulating the expression of Nrf2 and HO-1, inhibiting the expressions of GRP78, CHOP and cleaved-caspase3. However, the protective effect could be reversed by brusatol.

Construction of Glycolytic Regulator Gene Signature to Predict the Prognosis and Tumor Immune Cell Infiltration Levels for Prostate Cancer.

Prostate cancer (PCa) is the commonly generated noncutaneous neoplasm among men worldwide. Glycolysis had been validated to promote cancer progression. However, the clinical significance of glycolytic regulators in PCa was not well understood. Here, we discovered that glycolytic regulators were dysregulated in PCa samples using GSE8511, GSE6919, and GEPIA. By detecting the expression of these regulators in PCa samples, we found that SLC2A1, SLC2A3, HK2, PFKFB2, TPI1, PKM2, and LDHA had higher expression in PCa compared with normal tissues. Moreover, both higher expression of TPI1, ALDOA, ENO1, LDHA, and PKM and lower expression of LDHB and HK2 were significantly related to shorter progression-free survival time in PCa. Of note, an 8 gene-based risk score was further constructed and confirmed to have a good performance in predicting progression-free survival (PFS) time in PCa. The signature risk score significantly correlated with NK cell, neutrophil cell, macrophage M2 cell, and myeloid dendritic cell infiltration levels in PCa. After bioinformatics analysis, our data suggested glycolytic regulators participated in the regulation of multiple nonmetabolic biological processes, such as RNA transport, biosynthesis of antibiotics, and cell cycle. We recapitulate that the glycolytic regulator signature was a prospective indicator for prognosis and immune cell infiltration levels in PCa.

High Expression of SLC16A1 as a Biomarker to Predict Poor Prognosis of Urological Cancers.

OBJECTIVE: Tumor metabolism has always been the focus of cancer research. SLC16A1, as a key factor in catalysis of monocarboxylate transport across the plasma membrane, has been found to be associated with the occurrence and metastasis of a variety of cancers, but its prognostic significance and mechanism in different tumors are still unclear. METHODS: Based on the gene expression matrix and clinical information of human cancer tissues acquired from TCGA and GTEX databases, the differential expression of SLC16A1 in different tumors and normal tissues was analyzed. To confirm the association between its expression, the mutation of MMRS gene, and the expression level of DNMTs. Univariate Cox regression was applied to analyze the association between SLC16A1 expression and patient prognosis. The effect of SLC16A1 expression on patient survival was examined by Kaplan Meier analysis. GSEA was used to identify related signaling pathways. RESULTS: The expression of SLC16A1 was differentially expressed in most tumors, especially in the urinary tract where it is commonly highly expressed, and differential expression of SLC16A1 in different clinical stages. SLC16A1 expression was significantly positively correlated with MMRS gene mutation and DNMTS expression. Moreover, high SLC16A1 expression was associated with poorer overall survival (OS) and progression-free survival (PFS) in urological cancers. In particular, the results of the enrichment analysis showed that SLC16A1 was associated with processes such as cell adhesion and many signaling pathways affecting cell cycle were significantly enriched in the group with high-expressed SLC16A1. CONCLUSION: SLC16A1 expression was upregulated in urological cancer. SLC16A1 may promote tumor development by regulating the epigenetic process of urological cancer and demonstrated a great potential as a prognostic biomarker of urological cancer patients.

Effects of grape seed proanthocyanidin B2 pretreatment on oxidative stress and renal tubular epithelial cell apoptosis after renal ischemia reperfusion in mice.

PURPOSE: To investigate the effects of grape seed proanthocyanidin B2 (GSPB2) preconditioning on oxidative stress and apoptosis of renal tubular epithelial cells in mice after renal ischemia-reperfusion (RIR). METHODS: Forty male ICR mice were randomly divided into 4 groups: Group A: mice were treated with right nephrectomy. Group B: right kidney was resected and the left renal vessel was clamped for 45 minutes. Group C: mice were intraperitoneally injected with GSPB2 before RIR established. Group D: mice were intraperitoneally injected with GSPB2 plus brusatol before RIR established. Creatinine and urea nitrogen of mice were determined. Pathological and morphological changes of kidney were checked. Expressions of Nrf-2, HO-1, cleaved-caspase3 were detected by Western-blot. RESULTS: Compared to Group B, morphology and pathological damages of renal tissue were less serious in Group C. Western-blot showed that expressions of Nrf-2 and HO-1 in Group C were obviously higher than those in Group B. The expression of cleaved-caspase3 in Group C was significantly lower than that in Group B. CONCLUSION: GSPB2 preconditioning could attenuate renal oxidative stress injury and renal tubular epithelial cell apoptosis by up-regulating expressions of Nrf-2 and HO-1 and down-regulating the expression of cleaved-caspase-3, but the protective effect could be reversed by brusatol.

Primary prostate cancer synchronous with renal cell carcinoma: clinical experience and literature review.

The objective of this study was to report the diagnosis and treatment results of primary prostate adenocarcinoma (PRAD) concurrent in a patient with renal cell carcinoma (RCC), and to review the relative literature. A 62-year-old man was admitted to our hospital with chief complaint of a painless, incidentally found renal mass for one year. RCC was initially found by computed tomography (CT) scan, but prostate cancer was incidentally found by abnormal prostate-specific antigen (PSA) level results. The post-nephrectomy pathology assay reported clear RCC with positive staining of vimentin, cluster of differentiation 10 (CD10), carbonic anhydrase IX (CA-IX), paired box 8 (Pax-8), epithelial membrane antigen (EMA), and Ki67 labeling index (Ki67 LI). Magnetic resonance imaging (MRI) revealed uneven signals in the right peripheral zone of the prostate. Both prostate biopsy and post-prostatectomy pathology examination revealed prostate acinar adenocarcinoma with positive staining of P504S and Ki67 LI. The patient has been in periodic follow-up and has remained in good general condition without any evidence of recurrence to date. To the best of our knowledge, the present report is the only case of systematically described pre- and post-therapy laboratory, pathology, and imaging examination results. Our report together with published studies suggest that increased awareness of synchronous PRAD risk will enable early detection and prompt therapies in patients with RCC.

Effects of grape seed proanthocyanidin B2 pretreatment on oxidative stress and renal tubular epithelial cell apoptosis after renal ischemia reperfusion in mice

Abstract Purpose To investigate the effects of grape seed proanthocyanidin B2 (GSPB2) preconditioning on oxidative stress and apoptosis of renal tubular epithelial cells in mice after renal ischemia-reperfusion (RIR). Methods Forty male ICR mice were randomly divided into 4 groups: Group A: mice were treated with right nephrectomy. Group B: right kidney was resected and the left renal vessel was clamped for 45 minutes. Group C: mice were intraperitoneally injected with GSPB2 before RIR established. Group D: mice were intraperitoneally injected with GSPB2 plus brusatol before RIR established. Creatinine and urea nitrogen of mice were determined. Pathological and morphological changes of kidney were checked. Expressions of Nrf-2, HO-1, cleaved-caspase3 were detected by Western-blot. Results Compared to Group B, morphology and pathological damages of renal tissue were less serious in Group C. Western-blot showed that expressions of Nrf-2 and HO-1 in Group C were obviously higher than those in Group B. The expression of cleaved-caspase3 in Group C was significantly lower than that in Group B. Conclusion GSPB2 preconditioning could attenuate renal oxidative stress injury and renal tubular epithelial cell apoptosis by up-regulating expressions of Nrf-2 and HO-1 and down-regulating the expression of cleaved-caspase-3, but the protective effect could be reversed by brusatol.

Hydrogen sulfide treatment protects against renal ischemia-reperfusion injury via induction of heat shock proteins in rats.

OBJECTIVES: Hydrogen sulfide (H2S) attenuates ischemia-reperfusion injury (IRI) in different organs. However, its mechanism of action in renal IRI remains unclear. The present study investigated the hypothesis that H2S attenuates renal IRI via the induction of heat shock proteins (HSPs). MATERIALS AND METHODS: Adult Wistar rats were subjected to unilateral renal ischemia for 45 min followed by reperfusion for 6 hr. One group of rats underwent I/R without treatment, one group was administered 150 µmol/l sodium hydrosulfide (NaHS) prior to I/R, one group was injected with 100 mg/kg quercetin (an HSP inhibitor) intraperitoneally prior to I/R, and another group received quercetin prior to I/R and treatment with NaHS following I/R. Two other groups underwent a sham operation and one of them received 150 µmol/l NaHS following the sham operation whereas the other received no treatment. Renal function and histological changes were compared and relevant indices of oxidative stress, apoptosis, and inflammation were examined. RESULTS: IRI increased serum creatinine and blood urea nitrogen concentrations, promoted lipid peroxidation by elevating malondialdehyde levels, suppressed superoxide dismutase activity, stimulated inflammation by inducing NF-kB, IL-2, and TLR-4 expression, and increased renal apoptosis. Levels of HSP 70, heme-oxygenase-1 (HO-1) and HSP 27 were increased following IRI and reversed following H2S treatment. H2S attenuated changes observed in pathology, lipid peroxidation, inflammation, and apoptosis following IRI. The administration of quercetin reversed all protective effects of H2S. CONCLUSION: The present study indicated that H2S protected renal tissue against IRI induced lipid peroxidation, inflammation, and apoptosis, which may be attributed to the upregulation of HSP 70, HO-1, and HSP 27.

Effect of ozone oxidative preconditioning on oxidative stress injury in a rat model of kidney transplantation.

The aim of the present study was to investigate the protective effect of ozone oxidative preconditioning (OOP) on renal oxidative stress injury in a rat model of kidney transplantation. Thirty-six male Sprague Dawley (SD) rats were randomly divided into three groups: A sham (S) group, a kidney transplantation (KT) group and an OOP and kidney transplantation (OOP+KT) group. In the S group, the rats' abdomens were opened and closed without transplantation. In the KT group, the rats received a left kidney from donor SD rats. In the OOP+KT group, donor SD rats received 15 OOP treatments by transrectal insufflations (1 mg/kg), once a day, at an ozone concentration of 50 µg/ml, before the kidney transplantation. Twenty-four hours after transplantation, the parameters of renal function of the recipients were measured. The morphology and pathological effects of renal allograft were examined using hematoxylin and eosin staining, periodic acid-Schiff staining, a terminal deoxynucleotidyl transferase dUTP nick end labeling assay and immunohistochemistry. Markers of oxidative stress were also detected using the thiobarbituric acid method, and expression levels of Nrf-2 and HO-1 were determined by western blot analysis. Blood urea nitrogen and creatinine levels were significantly decreased in the OOP+KT group compared with the KT group, and the morphology and pathological changes of renal allograft were also less severe. Meanwhile, the renal allograft cell apoptosis index was significantly higher in the KT group compared to the OOP+KT group (P<0.05). Levels of superoxide dismutase, glutathione and catalase in the renal allografts were significantly higher in the OOP+KT group compared to those in the KT group (P<0.05), while malondialdehyde levels were significantly lower in the OOP+KT group compared to those in the KT group (P<0.05). Western blot analysis indicated that the expression levels of nuclear factor erythroid 2-related factor 2 (Nrf-2) and heme oxygenase 1 (HO-1) were significantly higher in the OOP+KT compared to the KT group (P<0.05). In conclusion, the mechanism by which OOP alleviates oxidative stress injury in renal transplantation may be related to the activation of the signaling pathways of Nrf-2/HO-1 and inhibition of renal tubular epithelial cell apoptosis.

Allopurinol preconditioning attenuates renal ischemia/reperfusion injury by inhibiting HMGB1 expression in a rat model.

PURPOSE: To investigate the potential effects of pretreatment with allopurinol on renal ischemia/reperfusion injury (IRI) in a rat model. METHODS: Twenty four rats were subjected to right kidney uninephrectomy were randomly distributed into the following three groups (n=8): Group A (sham-operated group); Group B (ischemic group) with 30 min of renal ischemia after surgery; and Group C (allopurinol + ischemia group) pretreated with allopurinol at 50 mg/kg for 14 days. At 72 h after renal reperfusion, the kidney was harvested to assess inflammation and apoptosis. RESULTS: Pretreatment with allopurinol significantly improved renal functional and histological grade scores following I/R injury (p<0.05). Compared with Group B, the expression levels of caspase-3 and Bax were markedly reduced in Group C, meanwhile, whereas expression of bcl-2 was clearly increased (p<0.05). A newly described marker of inflammation, High Mobility Group Box 1(HMGB1), showed reduced expression in Group C (p<0.05). CONCLUSION: Pretreatment with allopurinol had a protective effect on kidney ischemia/reperfusion injury, which might be related to the inhibition of HMGB1 expression.

Allopurinol preconditioning attenuates renal ischemia/reperfusion injury by inhibiting HMGB1 expression in a rat model

ABSTRACT PURPOSE: To investigate the potential effects of pretreatment with allopurinol on renal ischemia/reperfusion injury (IRI) in a rat model. METHODS: Twenty four rats were subjected to right kidney uninephrectomy were randomly distributed into the following three groups (n=8): Group A (sham-operated group); Group B (ischemic group) with 30 min of renal ischemia after surgery; and Group C (allopurinol + ischemia group) pretreated with allopurinol at 50 mg/kg for 14 days. At 72 h after renal reperfusion, the kidney was harvested to assess inflammation and apoptosis. RESULTS: Pretreatment with allopurinol significantly improved renal functional and histological grade scores following I/R injury (p<0.05). Compared with Group B, the expression levels of caspase-3 and Bax were markedly reduced in Group C, meanwhile, whereas expression of bcl-2 was clearly increased (p<0.05). A newly described marker of inflammation, High Mobility Group Box 1(HMGB1), showed reduced expression in Group C (p<0.05). CONCLUSION: Pretreatment with allopurinol had a protective effect on kidney ischemia/reperfusion injury, which might be related to the inhibition of HMGB1 expression.

Tripterysium glycosides preconditioning attenuates renal ischemia/reperfusion injury in a rat model.

BACKGROUND: Ischemia-reperfusion (I/R) injury to the kidney occurs commonly in organ transplantation from donation after cardiac death, involving many pathologic processes. In this study, we used rat model to assess whether tripterysium glycosides (TG) preconditioning could exert protective effects in renal I/R injury. MATERIALS AND METHODS: All male SD rats were randomly divided into four groups (6 each): sham group, TG group, I/R group and TG + I/R group. Groups TG and TG + I/R were pretreated with TG at 0.1 mg/kg for 14 days; groups sham and I/R were administered with the same dosage of normal saline. Groups TG + I/R and I/R underwent 45 min of renal ischemia of left kidney after right nephrectomy, and then, they were subjected to 72-h reperfusion. Groups sham and TG were only received right nephrectomy. The indicators of apoptosis, fibrosis and inflammation were analyzed to evaluate the effect of tripterysium glycosides preconditioning on renal I/R injury. RESULTS: Pretreatment with TG significantly inhibited the levels of serum creatine and blood urea nitrogen and improved histologic lesions induced by I/R injury. Moreover, for the apoptosis signal pathway, pretreatment with TG markedly decreased the expression of caspase-3 and Bax and increased the level of Bcl-2. HMGB1, which was regarded as one of inflammation marker molecule, it was inhibited in the TG + I/R group. For the fibrosis signal pathway, the pretreatment with TG before I/R could down-regulate the expression level of typical molecules of fibrosis (TGF-ß1, Smad3, p-Smad3). CONCLUSIONS: Pretreatment with tripterysium glycosides exhibited protective effect on kidney ischemia/reperfusion injury, which might be related to the alleviation of inflammation, fibrosis and the reduction in apoptosis.

Metformin attenuated the inflammation after renal ischemia/reperfusion and suppressed apoptosis of renal tubular epithelial cell in rats.

PURPOSE: To investigate the effect of metformin on renal tubular epithelial cell apoptosis and inflammation after kidney ischemia/ reperfusion in rats. METHODS: Eighteen SD rats were randomly divided into three groups: Sham (S), Ischemia/reperfusion (I/R), and Metformin (E). Before establishing the I/R model, group E was administered metformin for three days, while groups S and I/R were administered equal volumes of saline. After three days, a right nephrectomy was performed on all groups, after which the left kidneys of groups E and I/R rats were subjected to 45 min renal ischemia. Renal function, histology, and cell apoptosis were assessed. AMPK, pAMPK, COX-2, and Caspase 3 were also detected. RESULTS: Compared to I/R group, Caspase 3 and COX-2 levels were decreased in group E. COX-2, Caspase3 and pAMPK levels were higher in groups E and I/R than in group S. The pAMPK level of group E was higher than that of I/R group, while COX-2 and caspase 3 were lower in group E than they were in the other groups. There was no significant difference between E and I/R groups in AMPK levels. CONCLUSION: Metformin preconditioning attenuated the inflammation caused by ischemia/reperfusion and inhibited the apoptosis of renal tubular epithelial cells.

Metformin attenuated the inflammation after renal ischemia/reperfusion and suppressed apoptosis of renal tubular epithelial cell in rats

PURPOSE:To investigate the effect of metformin on renal tubular epithelial cell apoptosis and inflammation after kidney ischemia/ reperfusion in rats.METHODS:Eighteen SD rats were randomly divided into three groups: Sham (S), Ischemia/reperfusion (I/R), and Metformin (E). Before establishing the I/R model, group E was administered metformin for three days, while groups S and I/R were administered equal volumes of saline. After three days, a right nephrectomy was performed on all groups, after which the left kidneys of groups E and I/R rats were subjected to 45 min renal ischemia. Renal function, histology, and cell apoptosis were assessed. AMPK, pAMPK, COX-2, and Caspase 3 were also detected.RESULTS:Compared to I/R group, Caspase 3 and COX-2 levels were decreased in group E. COX-2, Caspase3 and pAMPK levels were higher in groups E and I/R than in group S. The pAMPK level of group E was higher than that of I/R group, while COX-2 and caspase 3 were lower in group E than they were in the other groups. There was no significant difference between E and I/R groups in AMPK levels.CONCLUSION:Metformin preconditioning attenuated the inflammation caused by ischemia/reperfusion and inhibited the apoptosis of renal tubular epithelial cells.