Fluoxetine-induced hepatic lipid accumulation is mediated by prostaglandin endoperoxide synthase 1 and is linked to elevated 15-deoxy-Δ12,14PGJ2

Major depressive disorder and other neuropsychiatric disorders are often managed with long-term use of antidepressant medication. Fluoxetine, an SSRI antidepressant, is widely used as a first-line treatment for neuropsychiatric disorders. However, fluoxetine has also been shown to increase the risk of metabolic diseases such as non-alcoholic fatty liver disease. Fluoxetine has been shown to increase hepatic lipid accumulation in vivo and in vitro. In addition, fluoxetine has been shown to alter the production of prostaglandins which have also been implicated in the development of non-alcoholic fatty liver disease. The goal of this study was to assess the effect of fluoxetine exposure on the prostaglandin biosynthetic pathway and lipid accumulation in a hepatic cell line (H4-II-E-C3 cells). Fluoxetine treatment increased mRNA expression of prostaglandin biosynthetic enzymes (Ptgs1, Ptgs2, and Ptgds), PPAR gamma (Pparg), and PPAR gamma downstream targets involved in fatty acid uptake (Cd36, Fatp2, and Fatp5) as well as production of 15-deoxy-Δ^12,14PGJ₂ a PPAR gamma ligand. The effects of fluoxetine to induce lipid accumulation were attenuated with a PTGS1 specific inhibitor (SC-560), whereas inhibition of PTGS2 had no effect. Moreover, SC-560 attenuated 15-deoxy-Δ^12,14PGJ₂ production and expression of PPAR gamma downstream target genes. Taken together these results suggest that fluoxetine-induced lipid abnormalities appear to be mediated via PTGS1 and its downstream product 15d-PGJ₂ and suggest a novel therapeutic target to prevent some of the adverse effects of fluoxetine treatment.     

间歇性禁食法在糖尿病前期及糖尿病病人中的应用进展

对间歇性禁食法的概念、方法及形式、历史发展以及在糖尿病前期及糖尿病病人中的应用效果等进行介绍,阐述间歇性禁食法研究现状,总结间歇性禁食法对糖尿病前期和糖尿病病人的有益影响。     

Gestational alloimmune liver disease treated with exchange transfusion and intravenous immunoglobulin: A case study

Gestational alloimmune liver disease (GALD) is a materno-fetal alloimmune disorder that targets the fetal liver and often causes neonatal liver failure. GALD most commonly presents as neonatal hemochromatosis (NH), which is a severe neonatal liver injury confirmed by extra-hepatic iron accumulation at various sites. With the discovery of the alloimmune mechanism of GALD, exchange transfusion and intravenous immunoglobulin (IVIG) administration are being used as novel treatments. Here, we present a rare case of an 11-day-old female infant who presented with marked hyperbilirubinemia. Laboratory findings showed significantly elevated direct and indirect bilirubin, high ferritin and alpha fetoprotein levels, high transferrin saturation, and severe coagulopathy. Abdominal magnetic resonance imaging revealed markedly reduced T2 signal intensity in the liver and pancreas compared to the spleen, suggesting iron deposition. The infant was diagnosed with NH and successfully treated with exchange transfusion and four doses of IVIG.     

The Risk of Alzheimer's Disease After Acute Appendicitis With or Without Appendectomy

ObjectivePrevious epidemiologic studies have suggested an association between appendectomy and Parkinson's disease. The aim of the current study was to examine the risk of Alzheimer's disease (AD) and other types of dementia following appendicitis or appendectomy for appendicitis.DesignPopulation-based cohort study.Setting and participantsWe used claims data from the Taiwan National Health Insurance Research Database. Participants aged ≥45 years with acute appendicitis or who received appendectomy for appendicitis were enrolled and followed up for more than 15 years. Cases and controls underwent 1:1 matching by age, sex, index date, and dementia-related comorbidities.MethodsThe primary outcome was AD, and secondary outcomes included other dementia types. Adjusted hazard ratios (aHRs) were calculated, and a competing risk regression model was created. The E value for causality of evidence was calculated.ResultsPatients developing appendicitis (0.6% vs 0.1%, P = .005) and those receiving appendectomy for appendicitis (0.4% vs 0.1%, P = .003) had higher incidences of AD than the controls during the follow-up period. A Cox regression analysis with adjustment for potential confounders showed that patients with appendicitis [aHR 6.68, 95% confidence interval (CI) 1.84-24.48] and those receiving appendectomy for appendicitis (aHR 5.01, 95% CI 1.33-18.85) were more likely to develop AD than the controls. These 2 groups also had higher risks for unspecified dementia and all types of dementia but not for vascular dementia than the controls. The age at dementia diagnosis was 88.51 years in the controls; however, among people who developed dementia following appendicitis, the mean age at diagnosis was 70.18 years, and dementia occurred 5.84 years after appendicitis. The competing risk regression models and the E values support the study findings.Conclusions and implicationsAfter recovery from appendicitis, these patients should be followed up for signs of AD.     

Mechanism of action of Orthosiphon stamineus against non-alcoholic fatty liver disease: Insights from systems pharmacology and molecular docking approaches

Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of a metabolic syndrome caused by excessive accumulation of fat in the liver. Orthosiphon stamineus also known as Orthosiphon aristatus is a medicinal plant with possible potential beneficial effects on various metabolic disorders. This study aims to investigate the in vitro inhibitory effects of O. stamineus on hepatic fat accumulation and to further use the computational systems pharmacology approach to identify the pharmacokinetic properties of the bioactive compounds of O. stamineus and to predict their molecular mechanisms against NAFLD. Methods: The effects of an ethanolic extract of O. stamineus leaves on cytotoxicity, fat accumulation and antioxidant activity were assessed using HepG2 cells. The bioactive compounds of O. stamineus were identified using LC/MS and two bioinformatics databases, namely the Traditional Chinese Medicine Integrated Database (TCMID) and the Bioinformatics Analysis Tool for the Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Pathway enrichment analysis was performed on the predicted targets of the bioactive compounds to provide a systematic overview of the molecular mechanism of action, while molecular docking was used to validate the predicted targets. Results: A total of 27 bioactive compounds corresponding to 50 potential NAFLD-related targets were identified. O. stamineus exerts its anti-NAFLD effects by modulating a variety of cellular processes, including oxidative stress, mitochondrial β-oxidation, inflammatory signalling pathways, insulin signalling, and fatty acid homeostasis pathways. O. stamineus is significantly targeting many oxidative stress regulators, including JNK, mammalian target of rapamycin (mTOR), NFKB1, PPAR, and AKT1. Molecular docking analysis confirmed the expected high affinity for the potential targets, while the in vitro assay indicates the ability of O. stamineus to inhibit hepatic fat accumulation. Conclusion: Using the computational systems pharmacology approach, the potentially beneficial effect of O. stamineus in NAFLD was indicated through the combination of multiple compounds, multiple targets, and multicellular components.     

腹腔镜食管裂孔疝修补术联合改良DOR胃底折叠术治疗食管裂孔疝合并胃食管反流病的临床疗效

目的探讨腹腔镜食管裂孔疝修补术联合改良DOR胃底折叠术治疗食管裂孔疝（HH）合并胃食管反流病患者的临床疗效。 方法选择2016年1月至2019年1月河北北方学院附属第二医院收治的108例食管裂孔疝合并胃食管反流病患者开展回顾性研究，按照不同手术方式将患者分为2组，每组患者54例。对照组行常规开腹手术，联合组行腹腔镜食管裂孔疝修补术联合改良DOR胃底折叠术，比较2组患者术前及术后6个月反流时间、反流次数、DeMeester评分、食管下括约肌压力及Gerd Q量表评分。 结果2组术前反流时间、反流次数、DeMeester评分、食管下括约肌压力及Gerd Q量表评分比较，差异无统计学意义（P>0.05）；2组患者术后6个月反流症状与术前比较，均得到明显改善，差异有统计学意义（P<0.05）；2组术后反流时间、反流次数、DeMeester评分、食管下括约肌压力及Gerd Q量表评分比较，差异有统计学意义（P<0.05）。联合组患者的手术时间、术中出血量及术后住院时长均明显优于对照组，差异有统计学意义（P<0.05）。 结论腹腔镜食管裂孔疝修补术联合改良DOR胃底折叠术对HH合并胃食管反流病患者效果显著，有利于患者身体快速恢复，微创、安全且近期疗效满意。