inhibitor

摘要： Normal tension glaucoma(NTG)is a multifactorial optic neuropathy characterized by normal intraocular pressure,progressive retinal ganglion cell(RGC)death,and glaucomatous visual field loss.Recent studies have described the mechanisms underlying the pathogenesis of NTG.In addition to controlling intraocular pressure,neuroprotection and reduction of RGC degeneration may be beneficial therapies for NTG.In this review,we summarized the main regulatory mechanisms of RGC death in NTG,including autophagy,glutamate neurotoxicity,oxidative stress,neuroinflammation,immunity,and vasoconstriction.Autophagy can be induced by retinal hypoxia and axonal damage.In this process,ischemia can cause mutations of optineurin and activate the nuclear factor-kappa B pathway.Glutamate neurotoxicity is induced by the over-stimulation of N-methyl-D-aspartate membrane receptors by glutamate,which occurs in RGCs and induces progressive glaucomatous optic neuropathy.Oxidative stress also participates in NTG-related glaucomatous optic neuropathy.It impairs the mitochondrial and DNA function of RGCs through the apoptosis signal-regulating kinase-JUN N-terminal kinase pathway.Moreover,it increases inflammation and the immune response of RGCs.Endothelin 1 causes endothelial dysfunction and impairment of ocular blood flow,promoting vasospasm and glaucomatous optic neuropathy,as a result of NTG.In conclusion,we discussed research progress on potential options for the protection of RGCs,including TANK binding kinase 1 inhibitors regulating autophagy,N-methyl-D-aspartate receptor antagonists inhibiting glutamate toxicity,ASK1 inhibitors regulating mitochondrial function,and antioxidants inhibiting oxidative stress.In NTG,RGC death is regulated by a network of mechanisms,while various potential targets protect RGCs.Collectively,these findings provide insight into the pathogenesis of NTG and potential therapeutic strategies.

摘要： 背景:已有证据表明,LncRNA-HOTAIR能调节骨髓间充质干细胞中成骨相关基因的表达,但其对脂肪间充质干细胞成骨分化的影响尚未见报道.目的:探讨LncRNA-HOTAIR对脂肪间充质干细胞成骨分化的影响.方法:体外培养Lewis大鼠脂肪间充质干细胞,转染lncRNA-NC、lncRNA-HOTAIR mimics、lncRNA-HOTAIR inhibitor并进行成骨诱导,成骨诱导第7天检测碱性磷酸酶活性,成骨诱导第14天进行茜素红染色.成骨诱导第6天,通过RT-PCR及Western blot检测成骨相关基因碱性磷酸酶、Runt相关转录因子2、骨钙素、骨桥蛋白mRNA和蛋白的表达.结果 与结论:①转染LncRNA-HOTAIR mimic后,脂肪间充质干细胞中碱性磷酸酶活性及钙化程度显著降低,而转染LncRNA-HOTAIR inhibitor后则显著增加(P<0.05);②转染LncRNA-HOTAIR mimic后,脂肪间充质干细胞中碱性磷酸酶、Runt相关转录因子2、骨钙素和骨桥蛋白的表达显著降低(P<0.05),而转染LncRNA-HOTAIR inhibitor后则显著增加(P<0.05);③上述结果表明,LncRNA-HOTAIR能负向调控脂肪间充质干细胞的成骨分化.

摘要： Matrixmetalloproteinase-2 (MMP-2), also called gelatinase-A, is a 72 Kd protein present in chromosome 16 in human. It is a zinc binding protein, responsible for the degradation of Extra Cellular Matrix (ECM) in normal physiological as well as disease processes like arthritis and cancer. It has a specific role in the cancer development and angiogenesis. MMP-2 contributes to cell migration. MMPs are the key to normal development as well as in the pathology of cancer and other inflammatory diseases. The inhibitors of MMP-2 activity are very important in maintaining the normal activity of MMP-2 and have an important role in the management of cancer. Regulation of MMP-2 activity is done by inhibitors like, TIMPs. In this report, we are discussing about a possible inhibitor(s) present in the PBS extract of guava leaves, inhibiting the active MMP-2 present in the saliva of breast cancer patients.

摘要： Type 2 diabetes mellitus(T2DM)and other metabolic disorders are often silent and go unnoticed in patients because of the lack of suitable prognostic and diagnostic markers.The current therapeutic regimens available for managing T2DM do not reverse diabetes;instead,they delay the progression of diabetes.Their efficacy(in principle)may be significantly improved if implemented at earlier stages.The misfolding and aggregation of human islet amyloid polypeptide(hIAPP)or amylin has been associated with a gradual decrease in pancreatic b-cell function and mass in patients with T2DM.Hence,hIAPP has been recognized as a therapeutic target for managing T2DM.This review summarizes hIAPP's role in mediating dysfunction and apoptosis in pancreatic b-cells via induction of endoplasmic reticulum stress,oxidative stress,mitochondrial dysfunction,inflammatory cytokine secretion,autophagy blockade,etc.Furthermore,it explores the possibility of using intermediates of the hIAPP aggregation pathway as potential drug targets for T2DM management.Finally,the effects of common antidiabetic molecules and repurposed drugs;other hIAPP mimetics and peptides;small organic molecules and natural compounds;nanoparticles,nanobodies,and quantum dots;metals and metal complexes;and chaperones that have demonstrated potential to inhibit and/or reverse hIAPP aggregation and can,therefore,be further developed for managing T2DM have been discussed.

摘要： The modulation of protein aggregation is involved not only in biochemical engineering processes,but also in in vivo biological events such as Alzheimer's disease(AD)that features amyloid-βprotein(Aβ)deposits.Inspired by the different pharmacological efficacy of enantiomers,taking heptapeptide LVFFARK(LK7)as an example,herein the chiral influence of peptide inhibitors on Aβfibrillogenesis and cytotoxicity was investigated by extensive biophysical and biological analyses.It was intriguing to find that although both LLK7 and D-LK7 could inhibit Aβaggregation in a concentration-dependent manner,it was the D-enan-tiomer that exhibited chirality preference and selectivity for modulation of Aβself-assembly.As com-pared with L-LK7 at the same conditions,D-LK7 showed significantly enhanced potency on suppressing cross-βsheet formation,fibrillar Aβaggregates deposition,Aβconformational transition,and Aβ-triggered neurotoxicity on cultured cells.For instance,L.LK7 and D-LK7 rescued cells by increasing cell via-bility from 60%to 62%and 84%at 100μmolL^(-1),respectively.The chiral discrimination of L-LK7 and D-LK7 was further validated by the different elimination efficiency on amyloid accumulation in AD model nematodes.It is considered that the higher binding affinity of D-LK7 to Aβmonomers than that of L LK7 resulted in the stronger inhibition effect.This work provided new insights into understanding chiral-ity in the interaction with Aβand the consequent inhibitory effect,and would contribute to the design of anti-amyloid agents.

摘要： ASTM A182 F51 duplex stainless steel with a 50:50 ratio of austenite to ferrite microstructure is a material used in mechanical engineering.Its uses include the manufacturing of equipment and components subject to acidification or acid stimulation for oil and gas industries.During acid stimulation or acidification,hydrochloric acid(HCl)solution with concentrations ranging from 5%to 28%(by volume)is injected into the limestone(CaCO3)and dolomite(CaCO3·MgCO3)reservoir rock to restore permeability and consequently increase oil well productivity.Therefore,it is important to use a corrosion inhibitor,such as propargyl alcohol,to prevent or inhibit the aggressive attack of HCl on duplex stainless steel.The present study evaluates the corrosion resistance of ASTM A182 F51 stainless steel using gravimetric(mass loss)and electrochemical(polarization)tests.Studies were completed with and without the addition of 500 and 1,000 mg/L propargyl alcohol in HCl solutions with concentrations of 10%and 15%(by volume)at temperatures of 25,40 and 55°C.The good protection by propargyl alcohol of duplex steel immersed in HCl is observed.

摘要： 为了揭示miR-199a-5p在鹅卵泡颗粒细胞凋亡中的作用及调控机制,本研究分离培养鹅等级卵泡颗粒细胞并转染miR-199a-5p相似物(mimic)和抑制物(inhibitor),采用qPCR法检测细胞凋亡相关基因的mRNA表达量;为进一步探究其作用机制,结合RNAhybrid和Targetscan 7.0预测miR-199a-5p靶基因,然后在中国仓鼠卵巢细胞系(CHO)中采用双荧光素酶报告系统检测miR-199a-5p对血管生成因子A(vascular endothelial growth factor A,VEGFA)3′UTR荧光素酶活性的影响,最后采用qPCR检测miR-199a-5p对鹅颗粒细胞VEGFA表达量的影响.结果显示,过表达miR-199a-5p能显著升高BCL2/BAX比值(P0.05).双荧光素酶报告载体系统发现,miR-199a-5p能极显著抑制VEGFA-WT报告载体荧光素酶活性(P0.05).上述试验结果表明,miR-199a-5p可能通过抑制BAX和Caspase3表达量来抑制鹅颗粒细胞凋亡,但在鹅颗粒细胞中miR-199a-5p是否通过VEGFA调控细胞凋亡需要进一步研究.

摘要： Chitosanases EAG1 is a classical glycoside hydrolase from Bacillus ehimensis. The previous researches showed that this Chitosanases can not only hydrolyze the b1,4-glycosidic bonds of chitosan to COS in different sizes but also keep a high catalytic activity in organic, which was useful for producing chitooligosaccharides and GlcN for use in the food and pharmacological industries. While it is instable in the liquid state. This shortcoming seriously restricts its industrial application. Here we used the modeled structure of EAG1 and the molecular modeling software package to screen the free chemical database ZINC. Moreover, the strategies including “initial filter” and consensus scoring were applied to accelerate the process and improve the success rate of virtual screening. Finally, five compounds were screened and they were purchased or synthetized to test their binding affinity against EAG1. The test results showed that one of them could inhibit the enzyme with an apparent Ki of 1.5 μM. The result may take the foundation for further inhibitor screening and design against EAG1 and the screened compound may also help to improve the liquid stability of EAG1 and expand its industrial application.

摘要： BACKGROUND Mammalian target of rapamycin(mTOR)inhibitors have been shown to reduce the risk of tumour recurrence after liver transplantation for hepatocellular carcinoma(HCC).However,their role in established post-transplant HCC recurrence is uncertain.AIM To investigate whether mTOR inhibitor offers a survival benefit in posttransplant HCC recurrence.METHODS A retrospective study of 143 patients who developed HCC recurrence after liver transplantation was performed.They were divided into 2 groups based on whether they had received mTOR inhibitor-based immunosuppression.The primary endpoint was post-recurrence survival.RESULTS Seventy-nine(55%)patients received an mTOR inhibitor-based immunosuppressive regime,while 64(45%)patients did not.The mTOR inhibitor group had a lower number of recurrent tumours(2 vs 5,P=0.02)and received more active treatments including radiotherapy(39 vs 22%,P=0.03)and targeted therapy(59 vs 23%,P<0.001).The median post-recurrence survival was 21.0±4.1 mo in the mTOR inhibitor group and 11.2±2.5 mo in the control group.Multivariate Cox regression analysis confirmed that mTOR inhibitor therapy was independently associated with improved post-recurrence survival(P=0.04,OR=0.482,95%CI:0.241-0.966).The number of recurrent tumours and use of other treatment modalities did not affect survival.No survival difference was observed between mTOR inhibitor monotherapy and combination therapy with calcineurin inhibitor.CONCLUSION mTOR inhibitors prolonged survival after post-transplant HCC recurrence.

摘要： BACKGROUND Liver cirrhosis is the late stage of hepatic fibrosis and is characterized by portal hypertension that can clinically lead to decompensation in the form of ascites,esophageal/gastric varices or encephalopathy.The most common sequelae associated with liver cirrhosis are neurologic and neuropsychiatric impairments labeled as hepatic encephalopathy(HE).Well established triggers for HE include infection,gastrointestinal bleeding,constipation,and medications.Alterations to the gut microbiome is one of the leading ammonia producers in the body,and therefore may make patients more susceptible to HE.AIM To investigate the relationship between the use of proton pump inhibitors(PPIs)and HE in patients with cirrhosis.METHODS This is a single center,retrospective analysis.Patients were included in the study with an admitting diagnosis of HE.The degree of HE was determined from subjective and objective portions of hospital admission notes using the West Haven Criteria.The primary outcome of the study was to evaluate the grade of HE in PPI users versus non-users at admission to the hospital and throughout their hospital course.Secondary outcomes included rate of infection,gastrointestinal bleeding within the last 12 mo,mean ammonia level,and model for end-stage liver disease scores at admission.RESULTS The HE grade at admission using the West Haven Criteria was 2.3 in the PPI group compared to 1.7 in the PPI nonuser group(P=0.001).The average length of hospital stay in PPI group was 8.3 d compared to 6.5 d in PPI nonusers(P=0.046).Twenty-seven(31.8%)patients in the PPI user group required an Intensive Care Unit admission during their hospital course compared to 6 in the PPI nonuser group(16.7%)(P=0.138).Finally,10(11.8%)patients in the PPI group expired during their hospital stay compared to 1 in the PPI nonuser group(2.8%)(P=0.220).CONCLUSION Chronic PPI use in cirrhotic patients is associated with significantly higher average West Haven Criteria for HE compared to patients that do not use PPIs.

摘要： 本发明提出一种miR‑29a‑3p inhibitor在体外诱导人体mBreg细胞的用途及方法，采用miR‑29a‑3p inhibitor在体外诱导人体mBreg细胞，进一步的，miR‑29a‑3p inhibitor诱导CD19+B细胞向mBreg细胞转化，mBreg细胞为CD19+CD24hiCD27+Breg细胞亚群；本发明利用miR‑29a‑3p inhibitor体外诱导人体mBreg细胞的方法，纯度高、细胞活性损伤小，转化效率高，细胞活性高，来源广，污染可能性小，能够弥补目前mBreg基础和临床研究上数量不足的缺陷。

摘要： 本发明公开了大豆提取物Bowman‑Birk inhibitor切割DNA的方法，属于医药技术领域。本发明提供了大豆Bowman‑Birk胰蛋白酶抑制剂BBI‑A的一种新应用，将BBI‑A应用于DNA的切割中，通过条件的优化，使得切割效率可达100％，可有效切割DNA。为制备DNA结构探针、并且为潜在制备抗肿瘤药物提供了新的可能。

摘要： 本发明公开了一种耐热小鼠RNase inhibitor突变体，其氨基酸序列如SEQ ID NO：3所示。本发明还公开了一种上述所述的耐热小鼠RNase inhibitor突变体在PCR反应中的应用。采用本发明的耐热小鼠RNase inhibitor突变体能够耐受70°C高温反应30min；同时，能够在高温下保护RNA免受RNase降解。

摘要： 本发明提出一种miR‑29a‑3p inhibitor在体外诱导人体mBreg细胞的用途，以及利用miR‑29a‑3p inhibitor体外诱导人体mBreg细胞的方法，采用miR‑29a‑3p inhibitor在体外诱导人体mBreg细胞，以及miR‑29a‑3p inhibitor诱导CD19+B细胞向mBreg细胞转化的效果中，采用miR‑29a‑3p inhibitor诱导Breg细胞诱导纯度高，诱导后mBreg细胞促炎性细胞因子分泌减少，诱导后mBreg细胞抑制炎症细胞因子分泌增多，免疫抑制功能增强。采用本发明利用miR‑29a‑3p inhibitor体外诱导人体mBreg细胞的方法，纯度高、细胞活性损伤小，转化效率高，细胞活性高，来源广，污染可能性小，能够弥补目前mBreg基础和临床研究上数量不足的缺陷，为mBreg细胞的体外扩增以及进一步的功能研究和过继回输提供了一种新的实验方法。