Salvianolic acid B (SAB) is one the major phytocomponents of Radix Salvia miltiorrhiza and exhibit numerous health promoting properties. The objective of the current study was to examine whether SAB exerts a renoprotective effect by attenuating oxidative stress and inflammatory response through activating phosphatidylinositol 3-kinase/serine-threonine kinase B (PI3K/ Akt) signaling pathway in a renal ischemic reperfusion rat model. Forty Sprague-Dawley male rats (250-300 g) were obtained and split into four groups with ten rats in each group. The right kidney of all rats was removed (nephrectomy). The rats of the Control group received only saline (occlusion) and served as a sham control group, whereas rats subjected to ischemic reperfusion (IR) insult by clamping the left renal artery served as a postitive control group. The other 2 groups of rats were pretreated with SAB (20 and 40 mg Á kg -1 Á day -1 ) for 7 days prior IR induction and served as treatment groups (SAB 20+IR; SAB 40+IR). Renal markers creatinine (Cr) and blood urea nitrogen (BUN) were significantly lower in the groups that received SAB. Pretreatment with SAB appears to attenuate oxidative stress by suppressing the production of lipid peroxidation products like malondialdehyde as well as elevating antioxidant activity. The concentration of inflammatory markers and neutrophil infiltration (myeloperoxidase) were significantly decreased. Meanwhile, PI3K protein expression and pAkt/Akt ratio were significantly upregulated upon supplementation with SAB, indicating its renoprotective activity. Taken together, these results indicate that SAB can therapeutically alleviate oxidative stress and inflammatory process via modulating PI3K/Akt signaling pathway and probably ameliorate renal function and thus act as a renoprotective agent.

BackgroundFor coronary artery disease, percutaneous coronary intervention (PCI) is the preferred treatment. Reperfusion injury is a common and serious complication of PCI. Studies showed that early statin therapy has a favorable prognostic impact for patients undergoing PCI. However, the effects of statins on improving post-PCI myocardial perfusion are still unclear. In this study we evaluated the potential effect of high-dose statin pretreatment on postprocedure myocardial perfusion and MACE rate in patients receiving PCI.Material/MethodsWe searched randomized controlled trials that evaluated the effect of high-dose statin pretreatment on post-PCI TIMI flow grade and MACE in patients undergoing PCI from the databases of PubMed, Embase, and Cochrane Library. All data were pooled for analysis and were stratified by type of statin, clinical presentation, and current statin therapy status in subgroup.ResultsFifteen RCTs with 4240 individuals were selected. The pooled analysis showed that high-dose statin pretreatment before PCI significantly improved the final TIMI flow grade compared with the control group (OR=0.61, 95% CI: 0.46 to 0.80, p=0.0005), and showed reduced incidence of MACE (OR=0.53, 95%CI: 0.39 to 0.71, p<0.0001). In subgroup analysis, the beneficial effect of high-dose statin was significant in statin-naive treatment patients, ACS patients, and patients on atorvastatin therapy, but no difference occurred in rosuvastatin, previous statin therapy, and stable angina patients.ConclusionsHigh-dose statin pretreatment has an important effect on postprocedure myocardial perfusion by improving the TIMI flow in patients undergoing PCI, and high-dose statin preloading also reduces the incidence of MACE.

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ObjectiveTo evaluate the effect of GSTA3 within the PI3K–Keap1/Nrf2 pathway in renal interstitial fibrosis (RIF).MethodsAn in vitro RIF model with TGF-β1 stimulation in NRK-52E cells was established to identify potential signaling pathways that modulate GSTA3. Changes in GSTA3 expression were observed in the RIF model after silencing or enhancing Nrf2 expression. Changes in GSTA3, Keap1, and Nrf2 expression were detected after blocking the upstream of the Keap1/Nrf2 signaling pathway (including MAPK and PI3K/Akt). The effect of Nrf2 on GSTA3 expression was evaluated by overexpressing Nrf2.ResultsProtein and mRNA levels of GSTA3, FN, Nrf2, and Keap1 were significantly increased after TGF-β1 stimulation. GSTA3 was also upregulated following overexpression of Nrf2. TGF-β1 activated the PI3K/Akt signaling pathway, leading to RIF. After blocking this pathway, the production of superoxide dismutase, reactive oxygen species, and fibronectin were reduced. The MAPK pathway was not involved in the development of RIF via regulating GSTA3 expression.ConclusionsThe PI3K–KEAP1/Nrf2–GSTA3 signaling pathway is a possible mechanism of resisting external stimulation of renal fibrosis factors, regulating oxidative stress, and preventing RIF.

ObjectiveWhether uric acid (UA) has an effect on renal function remains controversial. We aimed to investigate the association between serum UA with the decline in estimated glomerular filtration rate (eGFR) in middle-aged and elderly populations in the China Health and Retirement Longitudinal Study (CHARLS).DesignLongitudinal cohort study.SettingThis was a second analysis of a public dataset (CHARLS).ParticipantsIn this study, 4538 middle-aged and elderly individuals were screened after removing individuals younger than 45 years old, with kidney disease, malignant tumour and missing values.Outcome measuresBlood tests were performed both in 2011 and 2015. Decline in eGFR was defined as an eGFR decrease of more than 25% or deterioration of the eGFR stage during the 4-year follow-up period. Logistic models corrected for multiple covariables were used to analyse the association of UA with the decline in eGFR.ResultsThe median (IQR) concentrations of serum UA grouped by quartiles were 3.1 (0.6), 3.9 (0.3), 4.6 (0.4) and 5.7 (1.0) mg/dL, respectively. After multivariable adjustment, the OR of the decline in eGFR was higher for quartile 2 (3.5–<4.2 mg/dL: OR 1.44; 95% CI 1.07 to 1.64; p<0.01), quartile 3 (4.2–<5.0 mg/dL: OR 1.72; 95% CI 1.36 to 2.18; p<0.001) and quartile 4 (≥5.0 mg/dL: OR 2.04; 95% CI 1.58 to 2.63; p<0.001) when compared with quartile 1 (<3.5 mg/dL), and the p value for the trend was <0.001.ConclusionsOver a 4-year follow-up period, we found that elevated UA was associated with a decline in eGFR in the middle-aged and elderly individuals with normal renal function.