Protective effect of salidroside on streptozotocin-induced diabetic nephropathy by inhibiting oxidative stress and inflammation in rats via the Akt/GSK-3ß signalling pathway.

CONTEXT: Salidroside (SAL), one of the major glycosides isolated from the roots of Rhodiola rosea L. (Crassulaceae), has anti-inflammatory, antioxidant, and antidiabetic properties. OBJECTIVE: Our study assessed whether SAL exerts a protective effect on streptozotocin (STZ)-induced diabetic nephropathy (DN) in rats via the Akt/GSK-3ß signalling pathway. MATERIALS AND METHODS: Adult male Wistar rats were divided into three groups (n = 8): normal control, DN + vehicle, and DN + SAL. SAL (50 mg/kg/day, oral) was administered for 8 weeks. Biochemical and histopathologic examinations were performed to evaluate the therapeutic effects of SAL on oxidative stress, inflammation, renal function, and apoptosis. RESULTS: SAL induced rats demonstrated ameliorated levels of FBG (20.53 ± 0.72 mmol/L vs. 26.02 ± 1.44 mmol/L), urine albumin excretion (27.00 ± 1.46 mmol/L vs. 41.00 ± 1.59 mmol/L), blood urea nitrogen (14.42 ± 0.70 mmol/L vs. 17.77 ± 0.72 mmol/L), and serum creatinine (112.80 ± 6.98 mmol/L vs. 159.00 ± 3.81 mmol/L) compared to normal control rats, along with the alleviation of renal pathologic changes by improving the irregular shape of glomeruli tissues. Biochemical analysis showed that SAL-treated animals displayed suppressed levels of serum inflammatory cytokines and kidney oxidative stress markers and attenuated apoptotic characteristics. Moreover, it increased the phosphorylation levels of Akt and GSK-3ß in kidneys. DISCUSSION AND CONCLUSION: The present study validated the involvement of the Akt/GSK-3ß signalling pathway in renal improvement. These findings can form the basis to investigate the protective effect of SAL in DN in clinical trials.

Clinical implication of prognostic and predictive biomarkers for castration-resistant prostate cancer: a systematic review.

BACKGROUND: Diagnosis of metastatic castrate resistant prostate cancer (mCRPC) with current biomarkers is difficult and often results in unnecessary invasive procedures as well as over-diagnosis and over-treatment. There are a number of prognostic biomarkers for CRPC, but there are no validated predictive biomarkers to guide in clinical decision-making. Specific biomarkers are needed that enable to understand the natural history and complex biology of this heterogeneous malignancy, identify early response to treatment outcomes and to identify the population of men most likely to benefit from the treatment. In this systematic review, we discuss the existing literature for the role of biomarkers in CRPC and how they aid in the prognosis, treatment selection and survival outcomes. METHODS: We performed a literature search on PubMed and EMBASE databases from January 2015 through February 2020 in accordance to Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Articles were assessed to identify relevant observational studies and randomized controlled trials regarding biomarkers which aid in identifying progression to mCRPC as well as predictive biomarkers which help in treatment selection. RESULTS: We identified 3640 number of hits of which 58 articles were found to be relevant. Here we addressed biomarkers in the context of prognosis, prediction and patient selection of therapy. These biomarkers were found to be effective as prognostic or predictive factors under variety of conditions. The higher levels for all these biomarkers were associated with shorter median OS and sometimes PFS. Lower amounts of biomarkers in serum or urine were associated with prolonged survival outcomes, longer time to CRPC development or CRPC progression and longer median follow-up irrespective of any therapy. CONCLUSION: We observed that the biomarkers included in our study predicted clinically relevant survival outcomes and treatment exposure. Though the current biomarkers are prognostic when measured prior to initiating treatment, not all are validated as predictive markers in post treatment setting. A greater understanding of biomarkers in CRPC is need of the hour for development of more personalized approach to maximize benefit and minimize harm in men with CRPC.

Prognostic value of maximum standard uptake value, metabolic tumor volume, and total lesion glycolysis of 18F-FDG PET/CT in patients with renal carcinoma: A protocol for systematic review and meta analysis.

PURPOSE: We present a comprehensive systematic review of the documented literature on parameters derived from F-fluorodeoxyglucose positron emission tomography (F-FDG PET) and meta-analysis of the prognostic value of maximal standard uptake value (SUVmax), metabolic tumor volume (MTV) and total lesional glycolysis (TLG) in patients with renal carcinoma (RCC). PATIENTS AND METHODS: Relevant articles in English from PubMed, EMBASE, and the Cochrane Library were retrieved. Pooled hazard ratio (HR) values were used to assess the prognostic value of SUVmax, MTV, and TLG. RESULTS: A total of 10 primary studies involving 780 patients with RCC were included. The combined HRs for event-free survival were 1.32 (95% CI 1.10-1.58) for SUVmax, 2.40 (95% CI 1.20-4.79) for MTV, and 3.31 (95% CI 1.68-6.50) for TLG. Pooled HRs for overall survival were 1.264 (95% CI 1.124-1.421) for SUVmax, 3.52 (95% CI 1.451-8.536) for MTV, and 6.33 (95% CI 1.32-30.30) for TLG. Subgroup analysis revealed SUVmax as an independent risk factor for patients with recurrence or metastasis. CONCLUSION: The present meta-analysis confirmed that despite the clinical heterogeneity of RCC and adoption of various methods between studies, high SUVmax is a significant prognostic factor, especially in patients with recurrence or metastasis. MTV and TLG were associated with prediction of higher risk of adverse events or death in patients with RCC.