Melatonin alleviates alcoholic liver disease via EGFR-BRG1-TERT axis regulation

Chronic alcohol consumption causes liver steatosis, cell death, and inflammation. Melatonin (MLT) is reported to alleviate alcoholic liver disease (ALD)-induced injury. However, its direct regulating targets in hepatocytes are not fully understood. In the current study, a cell-based screening model and a chronic ethanol-fed mice ALD model were used to test the protective mechanisms of MLT. MLT ameliorated ethanol-induced hepatocyte injury in both cell and animal models (optimal doses of 10 μmol/L and 5 mg/kg, respectively), including lowered liver steatosis, cell death, and inflammation. RNA-seq analysis and loss-of-function studies in AML-12 cells revealed that telomerase reverse transcriptase (TERT) was a key downstream effector of MLT. Biophysical assay found that epidermal growth factor receptor (EGFR) on the hepatocyte surface was a direct binding and regulating target of MLT. Liver specific knock-down of Tert or Egfr in the ALD mice model impaired MLT-mediated liver protection, partly through the regulation of nuclear brahma-related gene-1 (BRG1). Long-term administration (90 days) of MLT in healthy mice did not cause evident adverse effect. In conclusion, MLT is an efficacious and safe agent for ALD alleviation. Its direct regulating target in hepatocytes is EGFR and downstream BRG1-TERT axis. MLT might be used as a complimentary agent for alcoholics.

Hepatic COX1 loss leads to impaired autophagic flux and exacerbates nonalcoholic steatohepatitis

The mechanisms underlying autophagic defects in nonalcoholic steatohepatitis (NASH) remain largely unknown. We aimed to elucidate the roles of hepatic cyclooxygenase 1 (COX1) in autophagy and the pathogenesis of diet-induced steatohepatitis in mice. Human nonalcoholic fatty liver disease (NAFLD) liver samples were used to examine the protein expression of COX1 and the level of autophagy. Cox1Δhepa mice and their wildtype littermates were generated and fed with 3 different NASH models. We found that hepatic COX1 expression was increased in patients with NASH and diet-induced NASH mice models accompanied by impaired autophagy. COX1 was required for basal autophagy in hepatocytes and liver specific COX1 deletion exacerbated steatohepatitis by inhibiting autophagy. Mechanistically, COX1 directly interacted with WD repeat domain, phosphoinositide interacting 2 (WIPI2), which was crucial for autophagosome maturation. Adeno-associated virus (AAV)-mediated rescue of WIPI2 reversed the impaired autophagic flux and improved NASH phenotypes in Cox1Δhepa mice, indicating that COX1 deletion-mediated steatohepatitis was partially dependent on WIPI2-mediated autophagy. In conclusion, we demonstrated a novel role of COX1 in hepatic autophagy that protected against NASH by interacting with WIPI2. Targeting the COX1-WIPI2 axis may be a novel therapeutic strategy for NASH.

The role of group 3 innate lymphoid cells(ILC3) in the evolution of the immune system: An update / 细胞与分子免疫学杂志

Group 3 innate lymphoid cells (ILC3) are an ILC subset that is characterized by the expression of retinoic acid-related orphan nuclear receptor γt (RORγt) and interleukin 22 (IL-22). This review summarizes the role of ILC3 in coordinating innate immunity and adaptive immunity based on current research and elaborate the significance of ILC3 from the perspective of immune system evolution. In addition, based on immune-related functions, we propose a possible time when ILC3 appears in the evolution of the immune system. And then, the research limitations and prospects are discussed.

Effect of SGLT in Type 2 Diabetes and Gastric Bypass Surgery - A Narrative Review

Body fat is regulated by a complex neuroendocrine system,making it difficult to maintain weight loss achieved via caloricrestriction. Bariatric surgery produces greater weight lossand weight loss that is more durable than caloric restriction,and therefore is currently the most effective therapy forobesity. Sodium-glucose-co-transporter inhibitors areglucose lowering drugs that reduces plasma glucose levelsby inhibiting glucose and sodium reabsorption in the kidneys,resulting in glycosuria.Sleeve gastrectomy is one such bariatric surgical procedurethat involves the creation of a reduced stomach lumen alongthe lesser curvature of the stomach through the removal ofgastric tissues along the greater curvature from the fundusto the antrum. Stomach capacity is typically reduced 80%or more, and the intestine remains intact. This procedureproduces dramatic weight loss in humans and in rodents. Infact, recent reports indicate that its efficacy is close to that ofthe more common Roux-en Y gastric bypass.There are many diverse factors on which operative mortalityof bariatric surgery depends such as facility related, surgeonrelated, followed by patient and procedure-related. Tominimize operative mortality, specific factors were consideredfor the specific patients. As a result, to treat type 2 diabetes inassociation with obesity, slightly obese patients or overweightpatients were treated with conventional bariatric proceduresworldwide. For the management of morbidity obese diabeticpatients, there is no single or standard procedure

Combined use of interleukin-6 receptor monoclonal antibody and bone marrow mesenchymal stem cells reduces neuronal apoptosis after acute spine cord injury / 中国组织工程研究

BACKGROUND:Studies have suggested that interleukin-6 is crucial for inducing cel apoptosis after acute spinal cord injury. OBJECTIVE:To observe the effect of interleukin-6 receptor monoclonal antibody combined with bone marrow mesenchymal stem cel s to treat acute spinal cord injury in rats. METHODS:Thirty Sprague-Dawley rats were randomly divided into sham group, model group (spinal cord injury group), treatment group 1 (interleukin-6 receptor monoclonal antibody transplantation group), treatment group 2 (bone marrow mesenchymal stem cel transplantation group), treatment group 3 (bone marrow mesenchymal stem cel+interleukin-6 receptor monoclonal antibody group), with six rats in each group. In the sham group, the spinal cord was only exposed with no injury, and in the other four groups, rat models of acute spinal cord injury were made using modified Al en’s method. Local injection treatment was performed in al the groups at 28 days after modeling. Basso, Beattie and Bresnahan (BBB) scoring and improved Tarlov scoring were used at 1 day before treatment and 1, 3, 7, 14, 28 days after treatment to test the hindlimb function. At 28 days after treatment, TUNEL method was used to detect cel apoptosis in the spinal cord. RESULTS AND CONCLUSION:Compared with the sham group, BBB scores and improved Tarlov scores were decreased significantly in the other four groups (P<0.05). At 7 days after treatment, the BBB scores and improved Tarlov scores in the treatment group 3 were significantly higher than those in the model group (P<0.05). At 14 days after treatment, the BBB scores and improved Tarlov scores in the treatment groups 1 and 2 were significantly higher than those in the model group (P<0.05);compared with the treatment group 2, the BBB score and improved Tarlov score were significantly increased in the treatment group 3 (P<0.05). Compared with the sham group, the number of apoptotic cel s was significantly increased in the other four groups (P<0.05);compared with the model group, the number of apoptotic cel s was significantly decreased in the three treatment groups (P<0.05);compared with the treatment group 2, the number of apoptotic cel s was significantly lower in the treatment group 3 (P<0.05). These findings indicate that the combined use of interleukin-6 receptor monoclonal antibody and bone marrow mesenchymal stem cel transplantation is better than bone marrow mesenchymal stem cel transplantation alone in the treatment of spinal cord injury, and interleukin-6 receptor monoclonal antibody reduces cel apoptosis in spinal cord injury, which is of positive significance for preventing against acute spinal cord injury.

Learning curve of Roux-en-Y gastric bypass on rats by single operator / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To analyze the learning curve of gastric bypass procedure on rats model by a single operator.</p><p><b>METHODS</b>From June 2013 to September 2013, two groups (group A and group B) of rats model were performed gastric bypass surgery, 60 rats for each group. Each group was divided into 3 stages according to sequence. The operative time and postoperative survival rate were compared between A group and B group at first, then among stages of each group.</p><p><b>RESULTS</b>There were no significant differences between A and B group in operative time and postoperative survival rate. However, the operative time significantly decreased in group AII( and AIII( compared with AI(, [(78.5±2.5) and (73.3±1.4) with (127.3±3.2) min, P<0.01]. The postoperative survival rate was increased in group AII( and AIII( than in the group AI(, [75%(15/20) and 85%(17/20) with 30%(6/20), P<0.05]. All results of 3 stages in group B was similar to group A.</p><p><b>CONCLUSION</b>For an efficient and stable rate of successful model establishment, the researcher needs to operate about 20 rats to pass the learning curve of gastric bypass procedure.</p>

Normalizing TSH level prevents postoperative recurrence of common bile duct stone / 中华普通外科杂志

Objective To investigate the impact of thyrotropic hormone (TSH) on recurrence rate of common bile duct stone (CBDS).Methods The clinical data of 268 cases of primary or recurrent CBDS undergoing surgery was analyzed.According to whether screening preoperative TSH level routinely,we assigned the patients into two groups,unchecked group with 171 cases and screened group with 97 cases.The postoperative recurrence rates in 36 months between two groups were compared.Results The recurrence rates of unchecked group and screened group were 3.5％,12.9％,16.9％ and 0.0％,5.2％,8.2％ respectively in 12-,24-,36-months,there was statistically significant difference between two groups (x2 =4.029,P ＜ 0.05).In unchecked group,patients ≥ 60 years had a significant higher recurrence rate than ＜ 60 years patients (x2 =6.485,P ＜ 0.05).In screened group,there was no statistically significant difference between ≥60 and ＜ 60 patients (x2 =0.142,P ＞ 0.05).In those 34 patients with a high TSH level in the screened group,normalizing the level from (6.23 ± 1.44) μIU/ml to (2.91 ±0.74) μIU/ml by oral intake of thyroid hormone postoperatively,led to the recurrence rates of 0％,5.9％,8.8％ in 12-,24-,36-months,which was not significantly different from those with normal TSH (x2 =0.022,P ＞ 0.05).And that,there was not statistically different between the young and elder patients in those 34 cases for the 12-,24-,36-month recurrence rates (x2 =0.086,P ＞ 0.05).Conclusions Some CBDS patients may be with high level of TSH.Normalizing TSH level may be conducive to a reduced postoperative recurrence rate of CBDS.

Early intervention of acute pancreatitis accompanying choledocholithiasis by laparoscopic choledochotomy and choledochoscopy / 中华内分泌外科杂志

Objective To explore the feasibility and validity of laparoscopic choledochotomy and choledochoscopy for treament of patients with acute pancreatitis accompanying commom bile duct stones. Methods A total of 102 patients acute pancreatitis accompanying common bile duct gall stones were treated in our institution between January 2007 and November 2009. Among them, 43 patients underwent laparoscopic choledochotomy and choledochoscopy within 72h after admission entered our study group. They all had a laparscopic cholecystectomy and choleldochotomy and choledochoscopy to retrieve common bile duct stones. Of these, 13 patients undergoing pancreatic capsule incision and peritoneal lavage. Fifty-nine patients undergoing traditional conservative treatment firstly were used as a control group. Of these, 46 were performed laparscopic surgery and choledochotomy after smoothly recovery from pancreatitis. 13 underwent emergency open operation due to complications of pancreatitis. Results In the gastrointestinal function recovery time, amylase recovery time, length of stay and hospitalization cost, there was a significant difference between study group and the control group (P<0.05). Conclusions Our study provides evidence for the good clinical efficacy of early implementation of laparoscopic choledochotomy and choledochoscope for treatment of choledocholithiasis and acute pancreatitis.