Celastrol induces lipophagy via the LXRα/ABCA1 pathway in clear cell renal cell carcinoma.

Celastrol is a triterpene derived from the traditional Chinese medicine Tripterygium wilfordii Hook f, which displays potential anticancer activity. In the present study, we investigated the anticancer effects of celastrol against clear cell renal cell carcinoma (ccRCC) and the underlying mechanisms. Using Cancer Genome Atlas (TCGA) database and genotype-tissue expression (GTEx) database we conducted a bioinformatics analysis, which showed that the mRNA levels of liver-X receptors α (LXRα) and ATP-binding cassette transporter A1 (ABCA1) in ccRCC tissues were significantly lower than those in adjacent normal tissues. This result was confirmed by immunoblotting analysis of 4 ccRCC clinical specimens, which showed that the protein expression of LXRα and ABCA1 was downregulated. Similar results were obtained in a panel of ccRCC cell lines (786-O, A498, SN12C, and OS-RC-2). In 786-O and SN12C cells, treatment with celastrol (0.25-2.0 µM) concentration-dependently inhibited the cell proliferation, migration, and invasion as well as the epithelial-mesenchymal transition (EMT) process. Furthermore, we demonstrated that celastrol inhibited the invasion of 786-O cells through reducing lipid accumulation; celastrol concentration-dependently promoted autophagy to reduce lipid storage. Moreover, we revealed that celastrol dramatically activated LXRα signaling, and degraded lipid droplets by inducing lipophagy in 786-O cells. Finally, celastrol promoted cholesterol efflux from 786-O cells via ABCA1. In high-fat diet-promoted ccRCC cell line 786-O xenograft model, administration of celastrol (0.25, 0.5, 1.0 mg·kg-1·d-1, for 4 weeks, i.p.) dose-dependently inhibited the tumor growth with upregulated LXRα and ABCA1 protein in tumor tissue. In conclusion, this study reveals that celastrol triggers lipophagy in ccRCC by activating LXRα, promotes ABCA1-mediated cholesterol efflux, suppresses EMT progress, and ultimately inhibits cell proliferation, migration, and invasion as well as tumor growth. Thus, our study provides evidence that celastrol can be used as a lipid metabolism-based anticancer therapeutic approach.

External therapy of Chinese medicine for postherpetic neuralgia: A protocol for systematic review and meta-analysis.

BACKGROUND: Postherpetic neuralgia (PHN), the most common complication of herpes zoster, brings about a health-care burden at both the individual and societal levels. External therapy of Chinese medicine (ETCM) is an effective treatment of PHN generally available in China, yet there is incomplete evidence to evaluate the efficacy and safety of it. METHODS: This protocol is based on the previous reporting items. We will search 3 English databases (PubMed, EMBASE, and the Cochrane Library) and 3 Chinese databases (CNKI, CBM, and Wan Fang Database) until January 2020. RCTs to evaluate the efficacy and safety of external therapy of Chinese medicine for postherpetic neuralgia will be included. The primary outcome will be assessed by VAS or NRS. We will use the criteria provided by Cochrane Handbook 5.3.0 for quality evaluation and risk assessment, and use the Revman 5.3 software for meta-analysis. ETHICS AND DISSEMINATION: Ethical approval is not required for systematic review and meta- analysis. The results of this review will be disseminated in a peer-review journal. PROSPERO REGISTRATION NUMBER: CRD42020163511.

The efficacy and safety of Health Qigong for ankylosing spondylitis: Protocol for a systematic review and meta-analysis.

BACKGROUND: Non-pharmacological treatments (education, exercise, and physical therapy) are remain basic approaches to long-term management of ankylosing spondylitis (AS) patients. As an important part of non-pharmacological treatments, Health Qigong is widely used for AS treatment. We will perform the systematic review to confirm the safety and efficacy of Health Qigong for AS. METHODS: Systematical search of 6 electronic databases will be done, including English and Chinese, until December 2019. All randomized controlled trials (RCTs) involving Health Qigong in combination with conventional therapy for AS will be included. Study selection, data extraction, and validation were performed independently by 2 reviewers. RevMan (V.5.3) will be used for mata-analysis. RESULTS: This systematic review will identify the safety and efficacy of Health Qigong in the treatment of AS and update evidence summaries of Health Qigong. At the end of the treatment, the primary outcome is Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) with a range of 0 to 10,and the secondary outcomes will include functional ability that measured by Bath Ankylosing Spondylitis Functional Index (BASFI), mobility measured by Bath Ankylosing Spondylitis Metrology Index (BASMI), chest expansion, night spinal pain, adverse reactions, laboratory measures such as erythrocyte sedimentation rate (ESR) and C protein response (CRP). CONCLUSION: This study will provide evidence that whether Health Qigong can benefit patients with ankylosing spondylitis by reducing disease activity, alleviating pain to support the application of Health Qigong in the AS treatment. REGISTRATION NUMBER: CRD42019159126.

The effectiveness and safety of acupuncture therapy for Guillain-Barré syndrome: A systematic review and meta-analysis protocol.

BACKGROUND: Guillain-Barré syndrome (GBS) is the most common acute paralytic neuropathy. Many clinical trials indicate acupuncture provides a good effect as a complementary therapy of Western medicine for GBS. The objective of this systematic review protocol is to provide the evidence to evaluate the effectiveness and safety of acupuncture on the treatment of GBS. METHODS: We will search relevant randomized controlled trials investigating the effect of acupuncture for GBS in following databases from start to October 2019: PubMed, Embase, the Cochrane Library, CINAHL Complete, National Digital Science Library, China National Knowledge Infrastructure, and Wanfang Database without language restriction. For articles that meet our inclusion criteria, 2 researchers will extract the data information independently, and assess the risk of bias and trial quality by the Cochrane collaboration's tool. All data will be analyzed by RevMan V.5.3.3 statistical software. RESULTS: According to the Barthel index of Activities of Daily Living (ADL) and the Medical Research Council (MRC) muscle scale, the efficacy and safety of acupuncture for GBS will be determined in this study. CONCLUSION: This systemic review will provide high quality evidence to judging whether acupuncture provides benefits to treat GBS.Prospero registration number: CRD42019158710.

Changes in gonadal function at different stages of chronic restraint stress-induced depression animals.

The aim of this study was to determine the time-dependent changes in adolescent male gonadal function due to chronic restraint stress (CRS)-induced depression in a rat model and to elucidate the underlying mechanism. CRS was established in adolescence male Wistar rats by placing the animals in a cylinder for 3 h every day for 28 days, during which time the general behavior and serum hormonal levels were routinely monitored. The CRS model rats showed anxiety-like behavior in the open field test (OFT) and sucrose consumption test, and their body weights also decreased significantly on the 14th, 21st and 28th days. The CRS rats showed a significant decrease in serum 5-hydroxytryptamine (5-HT) after 14 days of restraint and an increase in the CORT and NE levels after 21 days of restraint, while the serum GnRH levels increased significantly on the 14th and 21st days and decreased significantly over the last 7 days. In contrast, the FSH and LH levels decreased significantly from the 14th day to the 28th day, while the PRL and E2 levels were significantly higher during the same time period compared to those of the controls. The serum T levels also decreased significantly in the CRS group on the 21st and the 28th days, with the lowest levels occurring on day 28. Histopathological examination showed that testicular damage was aggravated during CRS. In addition, the levels of MDA, CytC and 8-OHDG increased significantly, while those of SOD decreased significantly in the CRS rats testicular mitochondrial. These results indicate that the gonadal function is altered at different stages of CRS, which can be attributed to changes in neurotransmitters and PRL that affect GnRH levels in the hypothalamus and subsequently regulate the serum T levels. In addition, excessive production of CORT impairs the testicle in adolescent period via enhanced oxidative damage, which eventually leads to gonadal dysfunction.