Shenshuaifu Granule Attenuates Acute Kidney Injury by Inhibiting Ferroptosis Mediated by p53/SLC7A11/GPX4 Pathway.

Background: Acute kidney injury (AKI) is a common clinical condition resulting in a rapid decline in renal function, and requires improvement in effective preventive measures. Ferroptosis, a novel form of cell death, is closely related to AKI. Shenshuaifu granule (SSF) has been demonstrated to prevent AKI through suppressing inflammation and apoptosis. Objective: This study aimed to explore whether SSF can inhibit ferroptosis in AKI. Methods: Active ingredients in SSF were detected through HPLC-MS/MS, and their binding abilities with ferroptosis were evaluated by molecular docking. Then, male C57/BL/6J mice were randomly divided into control, cisplatin, and cisplatin+SSF groups. In the latter two groups, mice were intraperitoneally injected with 20 mg/kg of cisplatin. For five consecutive days prior to cisplatin injection, mice in the cisplatin+SSF group were gavaged with 5.2 g/kg of SSF per day.72 h after cisplatin injection, the mice were sacrificed. Serum creatinine (SCr) and blood urea nitrogen (BUN) were measured to evaluate renal function. H&E and PAS staining were used to observe pathological damage of kidney. Cell death was observed by TUNEL staining, and iron accumulation in kidneys of mice was detected by Prussian blue staining. Western blotting, immunohistochemistry, and immunofluorescence were used to investigate the presence of inflammation, oxidative stress, mitochondrial dysfunction, iron deposition, and lipid peroxidation in mouse kidneys. Results: Active ingredients in SSF had strong affinities with ferroptosis. SSF reduced SCr (p<0.01) and BUN (p<0.0001) levels, pathological damage (p<0.0001), dead cells in the tubular epithelium (p<0.0001) and iron deposition (p<0.01) in mice with cisplatin induced AKI. And SSF downregulated macrophage infiltration (p<0.01), the expressions of high mobility group box 1 (HMGB1, p<0.05) and interleukin (IL)-17 (p<0.05), upregulated superoxide dismutase (SOD) 1 and 2 (p<0.01), and catalase (CAT, p<0.05), and alleviated mitochondrial dysfunction (p<0.05). More importantly, SSF regulated iron transport and intracellular iron overload and reduced the expression of ferritin (p<0.05). Moreover, it downregulated the expressions of cyclo-oxygenase-2 (Cox-2, p<0.001), acid CoA ligase 4 (ACSL4, p<0.05), and solute carrier family 7, member 11 (SLC7A11, p<001), upregulated glutathione peroxidase 4 (GPX4, p<0.01) and p53 (p<0.01), and decreased 4-hydroxynonenal (4-HNE) level (p<0.001). Conclusion: SSF attenuates AKI by inhibiting ferroptosis mediated by p53/SLC7A11/GPX4 pathway.

Effectiveness and safety of warm needle acupuncture on chronic renal failure: Protocol for a systematic review and meta-analysis.

BACKGROUND: Warm needle acupuncture (WNA) is an integral part of the acupuncture therapy. Chronic renal failure (CRF) is a common disease, which is a type of kidney disease characterized by a slow and progressive decline in renal function. The clinical practice indicates that WNA has a therapeutic effect on CRF. Therefore, we will provide a protocol to explore the effectiveness and safety of WNA for CRF. METHODS: We will search the randomized controlled trials literatures of WNA for CRF in 5 English databases (PubMed, Web of Science, EMBASE, the Cochrane Central Register of Controlled Trials [Cochrane Library], and World Health Organization International Clinical Trials Registry Platform) and 4 Chinese databases (Chinese national knowledge infrastructure, Chinese Scientific Journal Database Information, Wanfang Database, and Chinese biomedical literature database). The renal function will be considered as the primary outcome and the secondary outcome will include curative effect, security, syndrome according to standards for assessing traditional Chinese medicine, adverse events caused by WNA, such as dizziness, nausea, vomiting, weariness, and so on. We will use EndnoteX7 software to perform the selection of the studies. And all analyses will be conducted by using RevMan software V5.3. RESULT: This study will provide a rational synthesis of current evidences for WNM on CRF. CONCLUSION: The conclusion of this study will provide evidence to judge the effectiveness and safety of WNA on CRF.Registration: PROS-PERO CRD42019144530.

Effectiveness and safety of fire needle on periarthritis of shoulder: Protocol for a systematic review and meta-analysis.

BACKGROUND: Fire needle which is an integral part of the acupuncture therapy. Periarthritis of shoulder (PAS) is a common disease, which brings lots of pain for patients. The clinical practice indicates that fire needle has a therapeutic effect on the PAS. Here, we will provide a protocol to explore the effectiveness and safety of fire needle for the PAS. METHODS: We will search the randomized controlled trails (RCT) literatures of fire needle for the PAS in 9 electronic databases, including 5 English databases (PubMed, Web of Science, EMBASE, the Cochrane Central Register of Controlled Trials [Cochrane Library], and WHO International Clinical Trials Registry Platform [TCTRP]) and 4 Chinese databases (Chinese National Knowledge Infrastructure [CNKI], Chinese VIP Information, Wanfang Database, and Chinese Biomedical Literature Database [CBM]). We will consider the Ability assessment of daily living activities (ADL) as the primary outcome and the secondary outcome will include visual analogue scale (VAS), shoulder range of motion (ROM) and adverse events incidence caused by fire needle, such as dizziness, nausea, vomiting, weariness, etc. The selection of the studies will be performed by EndnoteX7 software. All analyses will be conducted by using RevMan software V5.3. RESULT: This study will provide a rational synthesis of current evidences for fire needle on PAS. CONCLUSION: The conclusion of this study will provide evidence to judge the effectiveness and safety of fire needle on PAS. REGISTRATION: PROS-PERO CRD42019119686.