High Dose Vitamin E Attenuates Diabetic Nephropathy via Alleviation of Autophagic Stress

It has been reported that autophagic stress, which is involved in many diseases, plays a key role in the development of diabetic nephropathy (DN). In this study, we investigated the effects of high dose vitamin E on renal tubular epithelial cells and autophagic stress-related mechanisms in diabetes condition. In diabetic rats, high dose vitamin E treatment significantly decreased the serum creatinine, urea nitrogen, urinary albumin and urinary protein, reduced the levels of LCN2, HAVCR1, LDH and 8-OHdG in urine, and attenuated the cellular apoptosis and interstitial fibrosis in renal cortex. In vitro, vitamin E could reduce the release of LCN2 and HAVCR1 and the protein levels of caspase 3 and TGF-β1, as well as improve the growth inhibition in cultured HK-2 cells after exposure to advanced glycation end products (AGEs). Also, LC3-II and SQSTM1-positive dots were significantly increased in the renal tubular epithelial cells of DN patients and diabetic rats, and in HK-2 cells after exposure to AGEs, which were markedly declined by vitamin E. In addition, we found that the autophagosome formation was not affected by AGEs, as assessed by the mRNA levels of LC3B, Beclin-1, and ATG7. However, AGEs blocked the lysosomal degradation of autophagosome, which was characterized by a decrease in the enzymatic activity of cathepsin B/cathepsin L and DQ-ovalbumin degradation in HK-2 cells, indicating that AGEs-induced accumulation of autophagic vacuoles was a sign of autophagic stress. Interestingly, vitamin E exerted a protective effect on lysosomes to reduce the autophagic stress. Taken together, we conclude that autophagic stress may play an important part in the progression of DN, and alleviation of autophagic stress though improvement of lysosomal function provides a promising novel approach for treating DN

Assessment of radiation exposure and public health before and after the operation of Sanmen nuclear power plant

IntroductionSanmen nuclear power plant (SNPP) operates the first advanced passive (AP1000) nuclear power unit in China.MethodsTo assess the radiological impacts of SNPP operation on the surrounding environment and the public health, annual effective dose (AED) and excess risk (ER) were estimated based on continuous radioactivity monitoring in drinking water and ambient dose before and after its operation during 2014–2021. In addition, the residents' cancer incidence was further analyzed through authorized health data collection.ResultsThe results showed that the gross α and gross β radioactivity in all types of drinking water were ranged from 0.008 to 0.017 Bq/L and 0.032 to 0.112 Bq/L, respectively. The cumulative ambient dose in Sanmen county ranged from 0.254 to 0.460 mSv/y, with an average of 0.354 ± 0.075 mSv/y. There is no statistical difference in drinking water radioactivity and ambient dose before and after the operation of SNPP according to Mann–Whitney U test. The Mann-Kendall test also indicates there is neither increasing nor decreasing trend during the period from 2014 to 2021. The age-dependent annual effective doses due to the ingestion of drinking water or exposure to the outdoor ambient environment are lower than the recommended threshold of 0.1 mSv/y. The incidence of cancer (include leukemia and thyroid cancer) in the population around SNPP is slightly higher than that in other areas, while it is still in a stable state characterized by annual percentage changes.DiscussionThe current comprehensive results show that the operation of SNPP has so far no evident radiological impact on the surrounding environment and public health, but continued monitoring is still needed in the future

Additional file 1: of Comparison of the effect of high versus low mean arterial pressure levels on clinical outcomes and complications in elderly patients during non-cardiothoracic surgery under general anesthesia: study protocol for a randomized controlled trial

SPIRIT checklist. Completed SPIRIT checklist. (PDF 97 kb