Indoleamine 2,3-dioxygenase 1 (IDO1) is an extrahepatic enzyme that catalyzes the first and rate-limiting step in the catabolism of the essential amino acid tryptophan (Trp) along the kynurenine pathway (KP).The overexpression or overactivation of IDO1 leads to the accumulation of downstream neurotoxic metabolite,quinolinic acid (QUIN),which is the main reason of nervous disorder and neurodegenerative disease.As an immunotolerant enzyme,IDO1 is regarded as a new immune checkpoint due to vital role in both the induction of maternal-fetal immune tolerance and tumor immune escape.Furthermore,the correlation between IDO1 and the pathogenesis of Alzheimer′s disease (AD),age-related cataracts and cancer has been confirmed,which brings IDO1 inhibitors increasingly widespread attention as promising drugs.This paper reviews the biological activity and development of IDO1 inhibitors.
Objective To study high glucose induced expressiont of endothelial adhesion molecule inhibited by propofol in umbilical vein endothelial cells,and to investigate its mechanism.Methods Human peripheral mononuclear cells were prepared with Histopaque-1077 solution.Nitric oxide (NO) production was measured with an assay kit.Vascular cell adhesion molecule 1 (VCAM-1) expression,endothelial nitric oxide synthase (eNOS) total protein,dimer and monomer expression,eNOS phosphorylation and caveolin-1 were measured by Western blot.Results High glucose induced VCAM-1 expression,increased mononuclear-endothelial adhesion and reduced NO production.Propofol improved NO level,and inhibited VCAM-1 expression and mononuclear-endothelial adhesion.The protective effect of propofol would be blocked by an eNOS inhibitor of L-NAME.Propofol increased high glucose-mediated eNOS-Ser1177phosphrylation and dimmer/monomer ratio,and attenuated high glucose-induced eNOS-Thr495 phosphrylation and caveolin-1 expression.Conclusions Propofol improved high glucose mediated eNOS phosphrylation,dimer/monomer ratio and caveolin-1 expression,so that NO production was improved and VCAM-1 expression and mononuclear-endothelial interaction were inhibited.
Skeletal muscles are the body′s agent of motion and important sites for the control of metabolism.The respiratory muscles are unique among skeletal muscles,since they must work without sustained rest throughout life.The diaphragm is the principal inspiratory pump muscle,it is more resistant to developing fatigue than limb muscles.The blood flow and the oxidative capacity of the diaphragm exceed those of limb muscles.Muscle atrophy and contractile dysfunction can be found in a variety of diseases.The reductions in muscle mass is tilted toward reduced protein synthesis and enhanced protein degradation.During pathologic conditions,enhanced protein breakdown is the main reason resulting in myofiber atrophy.Recent studies have underlined a critical role for the autophagy-lysosome (AL) system in regulating muscle mass.The main function of AL system involves the delivery of cytoplasmic cargo sequestered inside double-membrane vesicles to the lysosome which can eliminate the cell of superfluous or damaged organelles and proteins.Basal autophagy is necessary to muscle homeostasis,since it is responsible for the removal of intracellular metabolites.But excessive activation of autophagy can aggravate catabolism and contribute to muscle loss.This review focuses on the AL system and discusses its beneficial or detrimental role in skeletal and diaphragm atrophy.
Physiopathological effects of cardiac lymphatics have been neglected for many years.Recently research on cardiac lymphatics increases greatly following discovering of specific markers of lymphatic endothelial cells such as vascular endothelial growth factor receptor 3 (VEGFR-3),lymphatic vessel endothelial hyaluronan recepotor 1 (LYVE-1),prospero homeobox protein 1 (Prox-1) and podoplanin.Cardiac lymphatics drain lymph and balance the fluid metabolism.Dysfunction of the lymphatic vessels contributes to lymphedema,atherosclerosis,arrhythmia and fibrosis.It is significant to explore physiopathological effects of cardiac lymphatics for treatment of myocardial infarction,improvement of cardiovascular functions and prevention of complication after heart surgery.This review summarizes development and distribution of cardiac lymphatics and their relation to prognosis of cardiovascular diseases.
MicroRNA(miRNA) is a class of 19-25-nucleotide non-coding RNAs that plays an important role in cellular proliferation,differentiation,development as well as cell death.The miRNA that can be detected in the plasma is known as circulating miRNA,and it can exist stable in the circulation of the blood.Recently,circulating miRNA has been increasingly suggested as novel potential biomarkers of a series of myocardial lesions.This review article summarized the progress of clinical and experimental studies of circulating miRNA as early diagnosis index for cardiopathologic conditions,including acute myocardial infarction,heart failure along with drug-induced cardiotoxicity.
Patients with femoral head necrosis are common in young adults.There are plenty of reasons causing femoral head necrosis in young adults,such as the application history of high-dose corticosteroid,femoral neck fracture aroused by trauma,alcoholism,etc.Otherwise,there are still some unknown etiologies of femoral head necrosis.For young patients,the preferred treatment of femoral head necrosis is taking a variety of methods to avoid further collapse of the femoral head and going into the late stage of osteoarthritis.Other than utilizing the simple core decompression of the femoral head,orthopaedic surgeons often combine with some implants,hoping to improve the blood supply of femoral head and give mighty mechanical assistance to prevent further collapse of the femoral head,thus can delay the replacement of artificial hip joint.In this Review,we summarize the joint-preserving procedures for femoral head necrosis,and analyze the advantages and disadvantages of each method.
Clinical researchers have begun to recognize the importance of long-term preservation and sharing of data because of the emergency of numerous medical data in clinical studies,so the concept and methods of research data management emerged.Data management in clinical researches can accelerate the accuracy and efficiency of clinical research and meet the expectations and requirements of researchers,institutions and research sponsors.This paper discussed the key points of clinical data management through two aspects,data management in individual clinical research and data management in organizational clinical researches.It will help clinical researchers and scientific research governors to understand the process of data management in clinical researches and promote standardized clinical research activities.
