Changes and significance of Treg and Th17 in adult patients with primary membranous nephropathy.

OBJECTIVE: To investigate the changes in Treg and Th17 cells and explore the significance of Treg/Th17 balance in adult primary membranous nephropathy (PMN) patients. MATERIALS AND METHODS: A total of 60 PMN patients and 50 healthy adults from June 2013 to October 2016 were enrolled in this study. The levels of Treg, Th17, and related cytokines were assessed. Pearson correlation was used for conducting correlation analysis. RESULTS: There was a significant increase in Th17 frequencies and IL-17 (Th17-related cytokines) in the peripheral blood mononuclear cells (PBMCs), as well as a significant decrease in Treg frequencies and IL-10 (Treg-related cytokines). The IL-17 concentrations in the peripheral blood of PMN patients were positively correlated with urinary protein, while IL-10 levels were negatively correlated with urinary protein. Protein expression of Treg transcription factor (Foxp3) was significantly low in the renal tissues of PMN patients, while the expression of IL-17 was much higher. Th17/Treg imbalance was reversed to normal after effective treatment with tacrolimus in 15 PMN patients. CONCLUSION: These results suggested the existence of Treg/Th17 imbalance in PMN patients, showing the importance of Treg/Th17 imbalance in PMN pathogenesis.

MiR-802 Suppresses Colorectal Cancer Cell Viability, Migration and Invasion by Targeting RAN.

PURPOSE: Colorectal cancer is one of the most malignant tumors in the world, and the incidence is increasing every year. MicroRNAs (miRNA) are small non-coding RNAs that are involved in a variety of physiological or pathological processes. Abnormal expression of microRNA-802 (miR-802) has been demonstrated in various types of cancer. However, the expression and biological role of miR-802 in human colorectal cancer remain largely unknown. METHODS: Here, we used quantitative real-time PCR (qRT-PCR) to measure miR-802 expression levels in colorectal cancer tissues and cell lines. Cell Counting Kit-8 (CCK-8) was used to assess the effect of miR-802 on colorectal cancer cell viability. Migration and invasion assays were performed to determine the effect of miR-802 on metastasis of colon tumor cells by transwell analysis. Luciferase activity assays were used to confirm the target of miR-802. RESULTS: The results show that miR-802 is significantly downregulated in colorectal cancer tissues and cell lines. Overexpression of miR-802 profoundly inhibited viability, migration and invasion of colorectal cancer cells. In addition, we have newly discovered that the Ras-associated nucleus (RAN) is a direct target of miR-802 which could reverse the effects induced by miR-802 overexpression in colorectal cancer cells. CONCLUSION: In conclusion, our study shows that miR-802 is downregulated in colorectal cancer, and overexpression of miR-802 inhibits colorectal cancer cell viability, migration and invasion by directly targeting RAN.

Protective Effects of Evodiamine against LPS-Induced Acute Kidney Injury through Regulation of ROS-NF-κB-Mediated Inflammation.

Acute kidney injury (AKI) is a critical care syndrome, which is usually associated with sepsis-related endotoxemia. Evodiamine (EVO) is an active ingredient of many traditional medicinal formulations that possess a battery of biological activities. In the study, we aimed to evaluate the potential protective effect of EVO against lipopolysaccharide- (LPS-) induced AKI and cytotoxicity. LPS-resulted pathological injuries were significantly ameliorated by the administration of EVO. EVO reduced the levels of blood urea nitrogen (BUN) and creatinine in LPS-treated rats. EVO also inhibited LPS-induced reduction of cell viability in NRK-52E cells. LPS-resulting increase of TNFα and IL-1ß in both serum and kidney of rats and NRK-52E cells was inhibited by EVO. LPS-induced increase of P65 NF-κB expression was markedly inhibited by EVO. EVO-induced reduction of TNFα and IL-1ß expression in LPS-treated cells was blocked by overexpression of P65 NF-κB. Moreover, the increase of cell viability in LPS-treated cells induced by EVO was remarkably suppressed by overexpression of P65 NF-κB. LPS-resulting increase of reactive oxygen species (ROS) production was suppressed by EVO. H2O2 suppressed EVO-induced decrease of P65 NF-κB expression and increase of cell viability in LPS-treated NRK-52E cells. Moreover, the antioxidant NAC significantly promoted EVO-induced decrease of P65 NF-κB expression and increase of cell viability in LPS-treated NRK-52E cells. In conclusion, EVO had crucial protective effects against LPS-induced AKI and cytotoxicity through the antioxidant activities and thus the inhibition of inflammation. Our data highlight EVO as a potential candidate for the development of new strategies for the treatment of AKI.

Protective effect of a polysaccharide from Dipsacus asper Wall on streptozotocin (STZ)-induced diabetic nephropathy in rat.

The effects of a polysaccharide (DAP) from the roots of Dipsacus asper on renal complication in streptozotocin (STZ)-induced diabetic rats were investigated in the present study. Administration of DAP (100 and 300 mg/kg) for 4 weeks significantly decreased the fasting blood glucose (FBG) and glycosylated hemoglobin (HbA1c) levels, but increase the body weight of STZ-induced diabetic rats. Increased kidney weight index, serum creatinine (Scr), blood urea nitrogen (BUN), urine protein, and urinary albumin excretion (UAE) levels along with decreased creatinine clearance (Ccr) were nearly reversed to the normal levels by DAP. Moreover, DAP was able to normalize hyperlipidemia, improve oxidative stress, and down-regulate the formation of advanced glycation end products-receptor for advanced glycation end products (AGE-RAGE). In conclusion, our work demonstrates the preventive effect of DAP was achieved via antihyperglycemic, hypolipidemic, and antioxidant activity along with inhibition of AGE accumulation and RAGE expression in STZ-treated diabetic rats.

Aspirin resistance predicts unfavorable functional outcome in acute ischemic stroke patients.

OBJECTIVE: To investigate the prognostic value of aspirin reaction units (ARU) in a 3-month follow-up study in a cohort of Chinese patients with first-ever ischemic stroke. METHODS: Prospective single-center survey of acute ischemic stroke patients receiving aspirin therapy. Two hundred and seventy-five Chinese patients with first-ever ischemic stroke who previously received aspirin therapy were enrolled. ARU was measured using the VerifyNow system. A cutoff of 550 ARU was used to determine the presence of aspirin resistance (AR). RESULTS: Median age at study entry was 67 years (IQR: 59-75) and 142(51.6%) were male. A total of 52 of 275 enrolled patients (18.9%) were AR. Median regression estimated a statistically significant increase in NIHSS score of 0.033 point for every 1-point increase in ARU (95% CI, 0.024 to 0.068; P < 0.001). The unfavorable outcomes distribution across the ARU quartiles ranged between 11.8% (first quartile) to 64.8% (fourth quartile). After adjusting for other established risk factors, in multivariate models comparing the third and fourth quartiles against the first quartile of the ARU, levels of ARU were associated with unfavorable outcome, and the adjusted risk of unfavorable outcome increased by 145% (OR = 2.45 [95% CI 1.46-3.87], P = 0.011) and 317% (4.17[2.76-6.15], P < 0.001), respectively. Similarly, the adjusted risk of mortality increased by 215% (OR = 3.15 [95% CI 1.98-4.73], P = 0.008) and 429% (5.29[4.02-8.17], P < 0.001), respectively. CONCLUSIONS: The results suggest that AR is a meaningful and independent marker to predict short-term functional outcome in patients with ischemic stroke.

Zingerone attenuates diabetic nephropathy through inhibition of nicotinamide adenine dinucleotide phosphate oxidase 4.

Diabetes affects a large proportion of population wide across the world and kidney is a main target organ of diabetic complications. Zingerone is a stable active component derived from dry ginger rhizome. We investigated the effect of zingerone on diabetic nephropathy and explored the possible mechanisms. We showed that zingerone decreased the levels of serum insulin, C-peptide and glycosylated hemoglobin A1c. The levels of blood urea nitrogen (BUN), serum creatinine, urinary albumin content and albumin/creatinine ratio (ACR) were reduced by zingerone. Moreover, zingerone attenuated the pathological injuries of kidneys, reduced the surface area of Bowman's capsule, Bowman's space, glomerular tuft, and decreased the expression of collagen IV and fibronectin in kidneys in db/db mice. The high levels of triglyceride and cholesterol, and high expression of TNFɑ and IL-6 were decreased by zingerone. Furthermore, zingerone decreased the level of MDA and increased the content of glutathione (GSH). NADPH oxidase 4 (NOX4) expression was significantly increased in kidneys of db/db mice and in HK-2 cells after exposure to high glucose. Zingerone significantly decreased the expression of NOX4 in vivo and in vitro. Upregualtion of NOX4 significantly inhibited zingerone-induced protective effects against the cytotoxicity of high glucose. Downregulation of NOX4 was responsible for zingerone-exhibited pharmacological activities and reduction of diabetic nephropathy. Overall, zingerone is a promising therapeutic treatment to attenuate diabetic nephropathy.