Obesity, metabolic syndrome and diabetic retinopathy: Beyond hyperglycemia

Diabetic retinopathy(DR) is the most feared ocular manifestation of diabetes. DR is characterized by progressive retinal damage that may eventually result in blindness. Clinically, this blindness is caused by progressive damage to the retinal microvasculature, which leads to ischemia, retinal swelling, and neovascularization. Retinopathy is associated with both type 1 and type 2 diabetes, with DR being the leading cause of new onset blindness in United States adults. Despite this strong association with diabetes, it must be noted that the development of retinopathy lesions is multifactorial and may occur in individuals without an established history of diabetes. Metabolic syndrome is a multifactorial condition of central obesity, hypertriglyceridemia, dyslipidemia, hypertension, fasting hyperglycemia, and insulin resistance. Although several studies examined the individual components observed in the metabolic syndrome in relation to the development of DR, there is conflicting data as to the association of the metabolic syndrome with the development of retinopathy lesions in nondiabetic subjects. This review will summarize the current literature on the evidence of the metabolic syndrome on retinopathy in subjects with and without an established history of diabetes. This review will also discuss some of the mechanisms through which metabolic syndrome can contribute to the development of retinopathy.

High fat diet dysregulates microRNA-17-5p and triggers retinal inflammation:Role of endoplasmic-reticulum-stress

AIM To elucidate how high diet-induced endoplasmic reticulum-stress upregulates thioredoxin interacting protein expression in Müller cells leading to retinal inflammation. METHODS Male C57Bl/J mice were fed either normal diet or 60% high fat diet for 4-8 wk. During the 4 wk study, mice received phenyl-butyric acid(PBA); endoplasmic reticulum-stress inhibitor; for 2 wk. Insulin resistance was assessed by oral glucose tolerance. Effects of palmitate-bovine serum albumin(BSA)(400 μmol/L) were examined in retinal Müller glial cell line and primary Müller cells isolated from wild type and thioredoxin interacting protein knock-out mice. Expression of thioredoxin interacting protein, endoplasmic reticulum-stress markers, mi R-17-5p m RNA, as well as nucleotide-binding oligomerization domain-like receptor protein(NLRP3) and IL1β protein was determined.RESULTS High fat diet for 8 wk induced obesity and insulin resistance evident by increases in body weight and impaired glucose tolerance. By performing quantitative real-time polymerase chain reaction, we found that high fat diet triggered the expression of retinal endoplasmic reticulum-stress markers(P < 0.05). These effects were associated with increased thioredoxin interacting protein and decreased mi R-17-5p expression, whichwere restored by inhibiting endoplasmic reticulumstress with PBA(P < 0.05). In vitro, palmitate-BSA triggered endoplasmic reticulum-stress markers, which was accompanied with reduced mi R-17-5p and induced thioredoxin interacting protein m RNA in retinal Müller glial cell line(P < 0.05). Palmitate upregulated NLRP3 and IL1β expression in primary Müller cells isolated from wild type. However, using primary Müller cells isolated from thioredoxin interacting protein knock-out mice abolished palmitate-mediated increase in NLRP3 and IL1β.CONCLUSION Our work suggests that targeting endoplasmic reticulumstress or thioredoxin interacting protein are potential therapeutic strategies for early intervention of obesityinduced retinal inflammation.

TIMP-1 and its potential diagnostic and prognostic value in pulmonary diseases

Tissue inhibitors of metalloproteases(TIMPs)have caught the attention of many scientists due to their role in various physiological and pathological processes.TIMP-1,2,3,and 4 are known members of the TIMPs family.TIMPs exert their biological effects by,but are not limited to,inhibiting the activity of metalloproteases(MMPs).The balance between MMPs and TIMPs is critical for maintaining homeostasis of the extracellular matrix(ECM),while the imbalance between MMPs and TIMPs can lead to pathological changes,such as cancer.In this re-view,we summarized the current knowledge of TIMP-1 in several pulmonary diseases namely,acute lung injury(ALI)/acute respiratory distress syndrome(ARDS),pneumonia,asthma,chronic obstructive pulmonary disease(COPD),cystic fibrosis,and pulmonary fibrosis.Considering the potential of TIMP-1 serving as a non-invasive di-agnostic and/or prognostic biomarker,we also reviewed the circulating TIMP-1 levels in translational and clinical studies.

尼古丁与手术后镇痛

1931年，Davis等在研究动物猫时，发现注射尼古丁可以消除胆囊扩张引起的呼吸反应，而这种反应可作为一种内脏痛的模型。1974年，Daly等发现从三纹毒镖蛙皮肤提取的一种生物碱，能够产生类似于阿片类药物导致的Straub样鼠尾反应（一种竖立的、僵硬的、s形的尾巴）。这种生物碱的活性成分最初被称为毒镖蛙素，后来证实是一种烟碱样胆碱受体（nAChR）激动剂，其镇痛效应是吗啡的100倍。