Global trends in diabetic eye disease research from 2012 to 2021

Diabetic eye disease refers to a group of eye complications that occur in diabetic patients and include diabetic retinopathy, diabetic macular edema, diabetic cataracts, and diabetic glaucoma. However, the global epidemiology of these conditions has not been well characterized. In this study, we collected information on diabetic eye disease-related research grants from seven representative countries––the United States, China, Japan, the United Kingdom, Spain, Germany, and France––by searching for all global diabetic eye disease journal articles in the Web of Science and Pub Med databases, all global registered clinical trials in the Clinical Trials database, and new drugs approved by the United States, China, Japan, and EU agencies from 2012 to 2021. During this time period, diabetic retinopathy accounted for the vast majority(89.53%) of the 2288 government research grants that were funded to investigate diabetic eye disease, followed by diabetic macular edema(9.27%). The United States granted the most research funding for diabetic eye disease out of the seven countries assessed. The research objectives of grants focusing on diabetic retinopathy and diabetic macular edema differed by country. Additionally, the United States was dominant in terms of research output, publishing 17.53% of global papers about diabetic eye disease and receiving 22.58% of total citations. The United States and the United Kingdom led international collaborations in research into diabetic eye disease. Of the 415 clinical trials that we identified, diabetic macular edema was the major disease that was targeted for drug development(58.19%). Approximately half of the trials(49.13%) pertained to angiogenesis. However, few drugs were approved for ophthalmic(40 out of 1830;2.19%) and diabetic eye disease(3 out of 1830;0.02%) applications. Our findings show that basic and translational research related to diabetic eye disease in the past decade has not been highly active, and has yielded few new treatment methods and newly approved drugs.

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 10μmol/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.Cox1^(Δhepa)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 Cox1^(Δhepa)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.

宁夏枸杞子治疗肝脏疾病的作用机制

枸杞子作为药食同源的植物,具有滋补肝肾、益精明目等诸多药理作用,是中国传统的中草药和食品补品,但直到近年来其分子机制研究才被重视.枸杞子含有丰富的生物活性成分,如枸杞多糖、枸杞色素和枸杞亚精胺等组分,能够改善多种疾病的病症.研究表明,枸杞子具有显著的抗炎、抗氧化、抗凋亡、抗纤维化和抗肿瘤等作用.枸杞子性平味甘,对于大部分肝脏疾病具有显著的修复功能,并且在防治相关并发症等方面取得良好效果.但由于枸杞子的活性物质复杂多样,研究人员难以厘清发挥这些有益功效的主要单体和具体的分子机制,从而限制其在保健食品和药物方面的应用.本文总结了枸杞子提取物在肝病治疗中的作用和机制,梳理了现有枸杞子护肝研究的优势和不足,以期为肝脏疾病的研究提供新的给药方案,对促进枸杞子活性成分的药物开发进程提供参考和借鉴.