Efficacy and safety of tacrolimus in Osserman grade III and Osserman grade IV Myasthenia Gravis.

OBJECTIVE: A retrospective observational cohort study was conducted to evaluate the efficacy and safety of tacrolimus in Osserman grade III and Osserman grade IV myasthenia gravis (MG) patients. PATIENTS AND METHODS: MG patients admitted to the First Affiliated Hospital of Guangzhou University of Chinese Medicine between June 2011 and January 2017 with grade III and grade IV according to the modified Osserman scale were recruited and received a telephone follow-up in September 2017. Patients treated with tacrolimus plus prednisone were compared with those treated without tacrolimus. The efficacy of tacrolimus was assessed using MG-activities of daily living (MG-ADL) score, Osserman classification, Myasthenia Gravis Foundation of America (MGFA) post intervention status (PIS), the number of hospitalizations, the number of myasthenic crises and deaths. The adverse drug effects of tacrolimus were monitored. RESULTS: A total of 124 patients were included. The tacrolimus group had a significantly lower MG-ADL score than the control group at follow-up (1.90 ± 2.27vs 2.97 ± 2.78, p = 0.029). The difference of MG-ADL score between baseline and after follow-up was significantly greater in the tacrolimus group than the control group (-7.20 ± 2.95 vs -5.52 ± 2.91, p = 0.003). Fewer patients were hospitalized in the tacrolimus group (p = 0.011). The Osserman classification, MGFA PIS, the number of myasthenic crises and deaths did not differ significantly between the two groups. Nineteen patients in the tacrolimus group had adverse drug reactions, but no severe adverse effects appeared. CONCLUSION: Our study suggested that tacrolimus could be an effective and safe treatment for Osserman grade III and Osserman grade IV MG patients.

Role of miR-19a targeting TNF-α in mediating ulcerative colitis.

OBJECTIVE: Ulcerative colitis (UC) is a widely studied inflammatory disease associated with differential expression of genes involved in immune function, wound healing, and tissue remodeling. MicroRNAs have been reported to play a role in various cancer types. However, the mechanism of how microRNAs regulate UC remains unclear. METHODS: In the present study, we investigated the role of miR-19a and tumor necrosis factor (TNF)-α in human colon tissues with UC and dextran sodium sulfate (DSS)-induced experimental colitis. RESULTS: We identified that the expression of miR-19a was significantly reduced and TNF-α was remarkably increased in human colon tissue with UC. Moreover, this observation of miR-19a and TNF-α was also occurred in DSS-treated mice colitis. Further, we observed that miR-19a directly regulated TNF-α expression because miR-19a can suppress the expression of wild-type TNF-α reporter, but not the mutant form. The expression of inflammatory factors TNF-α, IL-8, and GM-GSF were significantly elevated upon application of miR-19a inhibitor. CONCLUSION: Taken together, this study determines the levels of miR-19a and TNF-α in both DSS-induced experimental murine colitis and human UC and further demonstrates that miR-19a might directly regulate TNF-α. The findings may provide a new insight in the clinical treatment of UC.

Resveratrol down-regulates Myosin light chain kinase, induces apoptosis and inhibits diethylnitrosamine-induced liver tumorigenesis in rats.

Hepatocellular carcinoma (HCC) is a serious healthcare problem worldwide because of its increasing morbidity and high mortality rates. However, our understanding of the mechanism of liver tumorigenesis remains incomplete. We report the expression of myosin light chain kinase (MLCK) in the livers of rats with diethylnitrosamine (DENA)-induced HCC and investigated the correlation between MLCK and liver tumorigenesis by observing the expression of MLCK in a rat model of HCC. HCC was induced in rats by an intraperitoneal injection of DENA, and resveratrol-treated rats were orally administered resveratrol with 50 mg/kg body weight/day. The livers of rats were excised after 20 weeks and immersed in 10% formaldehyde prior to immunohistochemical and Western blot analyses for determining the level of MLCK expression. These analyses indicated that the MLCK expression was higher in the livers of HCC rats than in normal and resveratrol-treated rats. High level of MLCK expression was responsible for proliferation and anti-apoptotic effects. However, resveratrol down-regulated the expression of MLCK, which induced cell apoptosis and inhibited liver tumorigenesis in rats with DENA-induced HCC. Our results suggest that the over expression of MLCK may be related to the development of liver tumorigenesis.

Protective effect of Sijunzi decoction on neuromuscular junction ultrastructure in autoimmune myasthenia gravis rats.

OBJECTIVE: To investigate the protective role of Sijunzi decoction in neuromuscular junction (NMJ) and muscle cell mitochondria ultrastructure; as well as its effects on the amount of adenosine triphosphate (ATP) and the activities of mitochondrial respiratory chain complexes I, II, III, and IV in autoimmune myasthenia gravis rats. METHODS: An experimental autoimmune myasthenia gravis (EAMG) rat model was established by inoculating rats with acetylcholine receptors extracted from Torpedo. Rats were divided into three groups: model, prednisone, and Sijunzi decoction, and were fed physiological saline, prednisone, or Sijunzi decoction, respectively. NMJ and muscle cell mitochondria ultrastructure were observed by transmission electron microscope. The amount of ATP was assessed by high performance liquid chromatography. The activities of mitochondrial respiratory chain complexes I, II, III, and IV was determined using the Clark oxygen electrode method. RESULTS: In the model group, there were sparse muscle fibers, with decreased mitochondria, and sparse, diffluent, or absent NMJ folds. After intervention with Sijunzi decoction, the above pathology changes were improved: muscle fiber structure was clear and complete; the mitochondria count was higher; and the NMJ structure was close to normal. Gastrocnemius muscle mitochondria in the model group produced significantly less ATP than those in the prednisone group (P < 0.01). Conversely, the ATP of Sijunzi decoction group was significantly higher than prednisone group (P < 0.01). The activities of gastrocnemius muscle mitochondrial respiratory chain complexes I, II, III, and IV in both the prednisone and Sijunzi decoction groups was dramatically higher compared with the model group (P < 0.05). The activities of complexes I and III in the Sijunzi decoction group were significantly higher than those in the prednisone group (P < 0.05), but there was no obvious difference in complex II or IV activities between the two groups (P > 0.05). CONCLUSION: Sijunzi decoction improved pathological changes in muscle mitochondria and NMJ, enhanced the amount of ATP in gastrocnemius muscle mitochondria, and improved the activities of respiratory chain complexes I, II, III, and IV (especially I and III) of the EAMG rats.

[Clinical study on treatment of liver fibrosis by different dosages of Salvia injection].

OBJECTIVE: To find the optimal dosage of Salvia injection in treating chronic hepatitis B caused liver fibrosis. METHODS: Sixty-four patients, whose diagnosis was confirmed as chronic hepatitis B caused liver fibrosis and differentiated by TCM typing as blood stasis blocking Collaterals type, were selected and randomly divided by lottery method into the large, middle and small dose of SI treated groups and the control group. All the patients were treated with modified Gexia Zhuyu Decoction, to the patients in the SI groups, 24 ml, 16 ml and 8 ml of SI were additionally administered by intravenous dripping respectively. The therapeutic course was 45 days. The clinical symptoms and signs; liver functional indexes as alanine transaminase (ALT), aspartate aminotransferase (AST) and albumin (ALB); and liver fibrosis indexes as procollagen type III (PC-III), collagen type IV (C-IV) and hyaluronic acid (HA), were measured before and after treatment. RESULTS: Different dosages of SI all could improve the clinical symptoms, and lower levels of ALT, AST, HA, PC-III and C-IV. Treatment of large dosage SI showed the best efficacy, superior to that of middle and small dosage SI, but no significant difference was found between the efficacy of the latter two. CONCLUSION: Anti-liver fibrosis effect of large dosage SI is better than that of middle or small dosage SI.