Prevalence of Adverse Effects Associated With Transcranial Magnetic Stimulation for Autism Spectrum Disorder: A Systematic Review and Meta-Analysis.

Background: A growing number of studies have suggested that transcranial magnetic stimulation (TMS) may represent a novel technique with both investigative and therapeutic potential for autism spectrum disorder (ASD). However, a full spectrum of the adverse effects (AEs) of TMS used in ASD has not been specifically and systematically evaluated. Objective: This systematic review and meta-analysis was to assess the prevalence of AEs related to TMS in ASD and to further explore the potentially related factors on the AEs. Methods: A systematic literature research of articles published before 31 December 2020 was conducted in the databases of PubMed, Embase, Cochrane Library, Ovid, PsycINFO, Chinese National Knowledge Infrastructure (CNKI), Chongqing VIP, and WANFANG DATA. AEs reported in the studies were carefully examined and synthesized to understand the safety and tolerability of TMS among ASD. Then, subgroup and sensitivity analyses were performed to examine the potentially related factors on the AEs. PROSPERO registration number: CRD42021239827. Results: Eleven studies were included in the meta-analysis. The pooled prevalence with 95% confidence interval (CI) of AEs was calculated (overall AEs: 25%, 95% CI 18-33%; headache: 10%, 95% CI 3-19%; facial discomfort: 15%, 95% CI 4-29%; irritability 21%, 95% CI 8-37%; pain at the application site: 6%, 95% CI 0-19%; headedness or dizziness: 8%, 95% CI 0-23%). All reported AEs were mild and transient with relatively few serious AEs and can be resolved after having a rest or medication. In addition, the following variables showed no significant change in overall prevalence of AEs: the purpose of using TMS, mean age of participants, whether the stimulation site was dorsolateral pre-frontal cortex (DLPFC), intensity of TMS, and the number of stimulation sessions. Conclusion: The overall prevalence of reported AEs of TMS among ASD was 25%. No identified ASD-specific risk factors for TMS-induced AEs were found. Further studies are needed to clarify the variation in the prevalence. Systematic Review Registration: www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=239827, PROSPERO, identifier: CRD42021239827.

Coumarin glycosides from Hydrangea paniculata slow down the progression of diabetic nephropathy by targeting Nrf2 anti-oxidation and smad2/3-mediated profibrosis.

BACKGROUND: Water extract of Hydrangea paniculata (HP) stem, rich in coumarin glycosides, has been demonstrated to have renal protective effect in several experimental kidney injury animal models. Currently, it is under pre-clinical development as a class 5 herbal drug against membranous nephropathy. However, whether it also benefits diabetic nephropathy (DN) is not clear. PURPOSE: This study was performed to investigate the protective effect of HP on streptozotocin-induced experimental DN, and further understand its molecular mechanisms. METHODS: In the present study, type 1 diabetes rat model was established by the intraperitoneal injection of streptozotocin. HP was orally administered every day for three months. Biochemical analysis and histopathological staining were conducted to evaluate the renal functions. In vivo pharmacokinetic study was conducted to analyse the metabolites of HP with high blood drug concentration. In vitro assay using these metabolites was performed to analyse their ability to reduce reactive oxygen species (ROS) production induced under high glucose (HG) condition by flow cytometry. Reverse transcription-polymerase chain reaction was conducted to analyse the mRNA level of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and IL6 and western blot was performed to analyse the phosphorylation status of smad 2/3 in HK2 cells under TGFß1 stimulation. RESULTS: The treatment with HP significantly reduced the blood urea nitrogen and serum creatinine content, and urine albumin excretion in diabetic rats, and increased the creatinine clearance rate. Periodic acid-schiff and methenamine staining and immunohistochemistry revealed that HP also ameliorated glomerulosclerosis and tubular vacuolar degeneration, as well as the deposition of fibronectin and collagen IV in the glomeruli. Pharmacokinetic study results revealed that the major coumarin compounds from HP were metabolised into umbelliferone and esculetin. By in vitro assay, umbelliferone and esculetin were found to significantly decrease ROS production induced by HG content, as well as increase the mRNA level of Nrf2. HP and its metabolites also can down-regulate fibronectin secretion in HK2 cells stimulated by TGFß1 and inhibit smad2/3 phosphorylation. CONCLUSION: HP has beneficial effect on DN by increasing Nrf2 expression and inhibiting TGF-smad signal activation. Further, it can be a novel herbal drug against DN.

Total Coumarins from Hydrangea paniculata Protect against Cisplatin-Induced Acute Kidney Damage in Mice by Suppressing Renal Inflammation and Apoptosis.

Aim. Hydrangea paniculata (HP) Sieb. is a medical herb which is widely distributed in southern China, and current study is to evaluate renal protective effect of aqueous extract of HP by cisplatin-induced acute kidney injury (AKI) in animal model and its underlying mechanisms. Materials and Methods. HP extract was prepared and the major ingredients were coumarin glycosides. AKI mouse models were established by single i.p. injection of 20 mg/kg cisplatin, and HP was orally administrated for total five times. The renal biochemical functions, pathological staining, kidney oxidative stress, and inflammatory status were measured. Apoptosis of tubular cells and infiltration of macrophages and neutrophils were also tested. Results. HP administration could improve the renal function by decreasing concentration of blood urea nitrogen (BUN) and creatinine and attenuates renal oxidative stress and tubular pathological injury and apoptosis; further research demonstrated that HP could inhibit the overproduction of proinflammatory cytokines and regulate caspase and BCL-2 family proteins. HP also reduced renal infiltration of macrophages and neutrophils, and its effect might be by downregulating phosphorylation of ERK1/2 and stat3 signaling pathway. Conclusions. This present study suggests that HP could ameliorate cisplatin induced kidney damage by antioxidation and suppressing renal inflammation and tubular cell apoptosis.