production of extracellular lysophosphatidic acid in the regulation of adipocyte functions and liver fibrosis

Lysophosphatidic acid(LPA), a glycerophospholipid, consists of a glycerol backbone connected to a phosphate head group and an acyl chain linked to sn-1 or sn-2 position. In the circulation, LPA is in submillimolar range and mainly derived from hydrolysis of lysophosphatidylcholine, a process mediated by lysophospholipase D activity in proteins such as autotaxin(ATX). Intracellular and extracellular LPAs act as bioactive lipid mediators with diverse functions in almost every mammalian cell type. The binding of LPA to its receptors LPA1-6 activates multiple cellular processes such as migration, proliferation and survival. The production of LPA and activation of LPA receptor signaling pathways in the events of physiology and pathophysiology have attracted the interest of researchers. Results from studies using transgenic and gene knockout animals with alterations of ATX and LPA receptors genes, have revealed the roles of LPA signaling pathways in metabolic active tissues and organs. The present review was aimed to summarize recent progresses in the studies of extracellular and intracellular LPA production pathways. This includes the functional, structural and biochemical properties of ATX and LPA receptors. The potential roles of LPA production and LPA receptor signaling pathways in obesity, insulin resistance and liver fibrosis are also discussed.

Case report and review of the literature of primary gastrointestinal amyloidosis diagnosed with enteroscopy and endoscopic ultrasonography

Here, we report a rare case of primary gastrointestinal amyloidosis in a stable condition after being followed up for three years. The patient was admitted to the hospital in 2014. Tests showed decreased levels of hemoglobin and ferritin. Transoral and transanal enteroscopy showed multiple nodular protuberances in the esophagus, ileum, colon and rectum. Endoscopic ultrasonography indicated the nodular protuberances stemmed from the submucosa and partially invaded the intrinsic myometrium. Pathological examinations found multiple small nodules in the submucosa and dyed structures, which were positive for special Congo red dyeing. After treatment with oral iron supplements, the levels of hemoglobin and ferritin became normal. It is concluded that the patient represents a case of primary gastrointestinal amyloidosis with multiple nodular protuberances in the digestive tract with controllable moderate abdominal discomfort and anemia and a benign course. Enteroscopy and endoscopic ultrasonography play an important role in the diagnosis of primary gastrointestinal amyloidosis.

Current understanding of glucose transporter 4 expression and functional mechanisms

Glucose is used aerobically and anaerobically to generate energy for cells.Glucose transporters(GLUTs)are transmembrane proteins that transport glucose across the cell membrane.Insulin promotes glucose utilization in part through promoting glucose entry into the skeletal and adipose tissues.This has been thought to be achieved through insulin-induced GLUT4 translocation from intracellular compartments to the cell membrane,which increases the overall rate of glucose flux into a cell.The insulin-induced GLUT4 translocation has been investigated extensively.Recently,significant progress has been made in our understanding of GLUT4 expression and translocation.Here,we summarized the methods and reagents used to determine the expression levels of Slc2a4 mRNA and GLUT4 protein,and GLUT4 translocation in the skeletal muscle,adipose tissues,heart and brain.Overall,a variety of methods such real-time polymerase chain reaction,immunohistochemistry,fluorescence microscopy,fusion proteins,stable cell line and transgenic animals have been used to answer particular questions related to GLUT4 system and insulin action.It seems that insulininduced GLUT4 translocation can be observed in the heart and brain in addition to the skeletal muscle and adipocytes.Hormones other than insulin can induce GLUT4 translocation.Clearly,more studies of GLUT4 are warranted in the future to advance of our understanding of glucose homeostasis.

Roles of vitamin A in the regulation of fatty acid synthesis

Dietary macronutrients and micronutrients play important roles in human health.On the other hand,the excessive energy derived from food is stored in the form of triacylglycerol.A variety of dietary and hormonal factors affect this process through the regulation of the activities and expression levels of those key player enzymes involved in fatty acid biosynthesis such as acetyl-CoA carboxylase,fatty acid synthase,fatty acid elongases,and desaturases.As a micronutrient,vitamin A is essential for the health of humans.Recently,vitamin A has been shown to play a role in the regulation of glucose and lipid metabolism.This review summarizes recent research progresses about the roles of vitamin A in fatty acid synthesis.It focuses on the effects of vitamin A on the activities and expression levels of mRNA and proteins of key enzymes for fatty acid synthesis in vitro and in vivo.It appears that vitamin A status and its signaling pathway regulate the expression levels of enzymes involved in fatty acid synthesis.Future research directions are also discussed.

Uses of knockout,knockdown,and transgenic models in the studies of glucose transporter 4

Currently,glucose transporter 4(GLUT4)has been considered as the key player for the insulin-stimulated glucose transport in the muscle and adipose tissues.The development of recombinant DNA techniques allows the creations of genetically knockout,knockdown and transgenic animals and cells for the study of GLUT4’s physiological functions.Here,we have used key words to search the PubMed and summarized the methods used in Slc2a4 gene knockout,GLUT4 knockdown and overexpression in the whole body and tissue specific manner.The whole body GLUT4-null mice have growth retardation,but normal glucose tolerance and basal glucose turnover rates.Compared with whole body Slc2a4 knockout mice,adipose and muscle double knockout mice have impaired insulin tolerance and glucose intolerance.The results of GLUT4 knockdown in 3T3-L1 adipocytes have shown that its expression is needed for lipogenesis after,but not during,differentiation.Transgenic mice with the whole body GLUT4 overexpression have normal body weight and lowered blood glucose level.The adipose tissue specific overexpression of GLUT4 leads to increases in mouse body weight and adipose tissue weight.The insulin-stimulated GLUT4 translocation in the skeletal muscle contributes to the regulation of glucose homeostasis.Data from both transgenic overexpression and tissue specific Slc2a4 knockout indicate that GLUT4 probably plays a role in the glucose uptake in the fasting state.More studies are warranted to use advanced molecular biology tools to decipher the roles of GLUT4 in the control of glucose homeostasis.

Clinical use of low-dose aspirin for elders and sensitive subjects

The use of low-dose aspirin(LDA)has been a common preventive measure to reduce the risk of cardiovascular events.This is attributed to aspirin’s ability to inhibit platelet activation.On the other hand,the use of LDA in human subjects has been associated with the development of gastrointestinal injuries like ulcer and bleeding,especially for those sensitive subjects such as elder human subjects.This opinion review will summarize the recent clinical reports regarding the use of LDA and the development of gastrointestinal conditions in China.Based on these reports,it seems that the use of LDA is commonly associated with gastrointestinal injuries,and stopping its use leads to recovery in elderly subjects.Therefore,we would like to suggest that gastroduodenal health and conditions should be seriously taken into consideration when LDA is recommended to the elderly,or other alternative means to reduce the risk of cardiovascular events such as nutritional interventions should be suggested.

Urotensin Ⅱ level is elevated in inflammatory bowel disease patients

It was reported that the urotensin Ⅱ(U-Ⅱ) level in inflammatory bowel disease(IBD) patients are significantly higher than in controls. To provide future guidance for the management of cardiovascular risk factors in IBD patients, the sample size of the current study appears to be limited, and more clinical samples to compare U-Ⅱ levels in IBD patients and controls are needed. This will clarify the possible roles of inflammation factors and related signaling pathways(like EPK1/2, NF-κB and Rho/ROCK) in the pathophysiology of IBD. Therefore, large multicenter studies should be done to confirm the findings and underlying mechanisms in the future.

The Distribution,Uses,and Characteristic Components of Gentianaceae Plants in China

Extracts of Gentianaceae herbs have been widely used as food additives,teas,or medicinal remedies for various human diseases and disorders.Iridoids,secoiridoids,and analogs glycosides,mainly include gentiopicroside,sweroside,swertiamarin,and loganic acid,are the characteristic compounds found in the Gentianaceae plants.The uses of the medicinal herbs containing these secoiridoids have been described in Chinese Materia Medica.Herbal extracts containing iridoids,secoiridoids,and analogs could exert protective effects in multiple human tissues and cells.Some of these medicinal herbs have been studied using modern pharmacological means.The results indicate that they have analgesic,liver protective,anti-inflammatory,antiallergic,anti-pathogeny,and anti-bacterial functions.This review was aimed to summarize the use of Gentianaceae herbs for disease treatments and pharmacokinetic characteristics of the active compounds.In so doing,we hope to demonstrate that Gentianaceae herbs and bioactive compounds in them may have abilities to affect inflammation,hepatic metabolism and cell signaling.In addition,we would like to bring this to the attention of the field about the use and study of compounds derived from Gentianaceae herbs.