miR-200b-3p accelerates progression of pituitary adenomas by negatively regulating expression of RECK

MicroRNA(miR)-200b-3p has been associated with many tumors,but its involvement in pituitary adenoma is unclear.This study investigated the molecular mechanism underlying miR-200b-3p regulation in pituitary adenomas to provide a theoretical basis for treatment.Bioinformatics was used to analyze pituitary adenoma-related genes and screen new targets related to RECK and miRNA.As well,the relationship between miR-200b-3p and RECK protein was verified using a double-luciferase reporter gene assay.The expression of miR-200b-3p in clinical samples was analyzed by in situ hybridization.Transfection of the miR-200b-3p inhibitor and small interfering-RECK(si-RECK)was verified by qPCR.GH3 cell viability and proliferation were detected using CCK8 and EdU assays.Apoptosis was detected by flow cytometry and western blotting.Wound healing and Transwell assays were used to detect cell migration and invasion.The effects of miR-200b-3p and RECK on GH3 cells were verified using salvage experiments.miR-200b-3p was highly expressed in pituitary tumor tissue.Inhibitors of miR-200b-3p inhibited cell proliferation promoted cell apoptosis,inhibited invasion and migration,and inhibited the expression of matrix metalloproteinases.Interestingly,miR-200b-3p negatively regulated RECK.The expression of RECK in pituitary adenoma tissues was lower than that in neighboring tissues.Si-RECK rescued the function of miR-200b-3p inhibitors in the above cellular behaviors,and miR-200b-3p accelerated the development of pituitary adenoma by negatively regulating RECK expression.In summary,this study investigated the molecular mechanism by which miR-200b-3p regulates the progression of pituitary adenoma through the negative regulation of RECK.The findings provide a new target for the treatment of pituitary adenoma.

Evaluation of teplizumab's efficacy and safety in treatment of type 1 diabetes mellitus:A systematic review and meta-analysis

BACKGROUND Islets of Langerhans beta cells diminish in autoimmune type 1 diabetes mellitus(T1DM).Teplizumab,a humanized anti-CD3 monoclonal antibody,may help T1DM.Its long-term implications on clinical T1DM development,safety,and efficacy are unknown.AIM To assess the effectiveness and safety of teplizumab as a therapeutic intervention for individuals with T1DM.METHODS A systematic search was conducted using four electronic databases(PubMed,Embase,Scopus,and Cochrane Library)to select publications published in peerreviewed journals written in English.The odds ratio(OR)and risk ratio(RR)were calculated,along with their 95%CI.We assessed heterogeneity using Cochrane Q and I2 statistics and the appropriate P value.RESULTS There were 8 randomized controlled trials(RCTs)in the current meta-analysis with a total of 1908 T1DM patients from diverse age cohorts,with 1361 patients receiving Teplizumab and 547 patients receiving a placebo.Teplizumab was found to have a substantial link with a decrease in insulin consumption,with an OR of 4.13(95%CI:1.72 to 9.90).Teplizumab is associated with an improved Cpeptide response(OR 2.49;95%CI:1.62 to 3.81)and a significant change in Glycated haemoglobin A1c(HbA1c)levels in people with type 1 diabetes[OR 1.75(95%CI:1.03 to 2.98)],and it has a RR of 0.71(95%CI:0.53 to 0.95).CONCLUSION In type 1 diabetics,teplizumab decreased insulin consumption,improved C-peptide response,and significantly changed HbA1c levels with negligible side effects.Teplizumab appears to improve glycaemic control and diabetes management with good safety and efficacy.

Treatment of chronic prostatitis in Chinese men

The aim of this study is to assess the status of treatment of chronic prostatitis(CP)in Chinese men.A population-based cross-sectional survey was performed,in which 15000 men aged between 15 and 60 years were randomly selected to receive a questionnaire designed to assess National Institutes of Health Chronic Prostatitis Symptoms Index(NIH-CPSI)status,therapeutic efficacy and 28 other items.A total of 12743 men(84.95%)completed the questionnaire,of whom 1071(8.4%)were identified as having prostatitis-like symptoms and 517(4.5%)were diagnosed with CP according to NIH-CPSI criteria and prostatitis-like symptomatology.Of the CP patients,372(65%)underwent long-term routine treatment 12 times per year.Additionally,217(72.8%)patients received antibiotic therapy and 215(79.3%)men showed therapeutic effects.The treatment cost USD 1151(8059 yuan)per person per year on average.Most CP patients received routine treatment,in most cases with antibiotics.Treatment was costly and most CP patients were not satisfied with its effectiveness.Antibacterial treatment might have been effective primarily in patients with bacterial disease.

Clinical characteristics and current management of hepatitis B and C in China

AIM: To describe a population of outpatients in Chinainfected by hepatitis B virus(HBV) and/or hepatitis C virus(HCV), and assess their current management status.METHODS: A multicenter, cross-sectional study of HBV- and/or HCV-infected patients was conducted from August to November, 2011 in western China. Patients ≥ 18 years of age with HBV and/or HCV infections who visited outpatient departments at 10 hospitals were evaluated, whether treated or not. Data were collected on the day of visit from medical records and patient interviews.RESULTS: A total 4010 outpatients were analyzed, including 2562 HBV-infected and 1406 HCV-infected and 42 HBV/HCV co-infected patients. The median duration of documented infection was 7.5 years in HBV-infected and 1.8 years in HCV-infected patients. Cirrhosis was the most frequent hepatic complication(12.2%), appearing in one-third of patients within 3 years prior to or at diagnosis. The HCV genotype was determined in only 10% of HCV-infected patients. Biopsy data were only available for 54 patients(1.3%). Antiviral medications had been received by 58.2% of patients with HBV infection and 66.6% with HCV infection. Nucleos(t)ide analogs were the major antiviral medications prescribed for HBV-infected patients(most commonly adefovir dipivoxil and lamivudine). Ribavirin + pegylated interferon was prescribed for two-thirds of HCV-infected patients. In the previous 12 mo, around one-fifth patients had been hospitalized due to HBV or HCV infection.CONCLUSION: This observational, real-life study has identified some gaps between clinical practice and guideline recommendations in China. To achieve better health outcomes, several improvements, such as disease monitoring and optimizing antiviral regimens, should be made to improve disease management.

Transcriptomic analysis:the protection of over-expression thioredoxin reductase 1 in Parkinson’s disease

Background Parkinson’s disease(PD)is the second most common neurodegenerative disease.The pathologic characteristic feature is the loss of dopaminergic neurons in the substantia nigra(SN).However,the biochemical mechanisms are unclear.A large number of studies have shown that oxidative damage is the primary cause of PD.Hence,antioxidants could become a suitable option to treat PD.The thioredoxin(Trx)system represents a useful,potentially disease-relevant oxidation-reduction system.Thioredoxin reductase 1(TR1)is a significant component of the Trx system.Methods The overexpression lentivirus(LV)or LV-TR1 in the TR1-A53T model of PD by the stereotactic brain,and successful overexpression of LV or LV-TR1 in the MPP^(+)-induced cellular model by LV or LV-TR1 transfection.Results We confirmed that interleukin-7 mRNA levels increased in MPP^(+)compared to that in the control and MPP^(+)-TR1 groups using quantitative polymerase chain reaction.Theγ-H_(2)AX level was increased in the Tg-A53T group compared to that in the TR1-A53T group by western blotting.The expression of Na^(+)-K^(+)-ATP was decreased in the MPP^(+)group compared to that in the control and MPP^(+)-TR1 groups by high content screening.Tg-A53T(the C57BL/6 mice transferred with mutant human a-syn);TR1-A53T(A53T mice which were injected TR1-LV 2µl in SNc on two sides with minipump).The mice were fed for 10 months.control(the N2a cells cultivated with DMEM);MPP^(+)(the N2a cells dealt with MPP^(+)(1 mM)48 h),MPP^(+)-LV(the N2a cells over-expressed LV for 24 h then dealt with MPP^(+)(1 mM)48 h).MPP^(+)-TR1(the N2a cell over-expressed TR1-LV for 24 h then dealt with MPP^(+)(1 mM)48 h).From the Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis,we confirmed that the overexpression of TR1 in SN pars compacta cells decreased oxidative stress,apoptosis,DNA damage,and inflammatory response and increased NADPH,Na^(+)-K^(+)-ATP,and immune response in this PD model.Conclusions Our study shows that overexpressed TR1 can be developed as a neuroprotective agent for PD.Therefore,our findings demonstrate a new targeted protein for the treatment of PD.

Insulin-like growth factor(IGF)signaling in tumorigenesis and the development of cancer drug resistance

One of the greatest obstacles to current cancer treatment efforts is the development of drug resistance by tumors.Despite recent advances in diagnostic practices and surgical interventions,many neoplasms demonstrate poor response to adjuvant or neoadjuvant radiation and chemotherapy.As a result,the prognosis for many patients afflicted with these aggressive cancers remains bleak.The insulin-like growth factor(IGF)signaling axis has been shown to play critical role in the development and progression of various tumors.Many basic science and translational studies have shown that IGF pathway modulators can have promising effects when used to treat various malignancies.There also exists a substantial body of recent evidence implicating IGF signaling dysregulation in the dwindling response of tumors to current standard-of-care therapy.By better understanding both the IGF-dependent and-independent mechanisms by which pathway members can influence drug sensitivity,we can eventually aim to use modulators of IGF signaling to augment the effects of current therapy.This review summarizes and synthesizes numerous recent investigations looking at the role of the IGF pathway in drug resistance.We offer a brief overview of IGF signaling and its general role in neoplasia,and then delve into detail about the many types of human cancer that have been shown to have IGF pathway involvement in resistance and/or sensitization to therapy.Ultimately,our hope is that such a compilation of evidence will compel investigators to carry out much needed studies looking at combination treatment with IGF signaling modulators to overcome current therapy resistance.

Zinc bis-Schiff base complexes： Synthesis, structure, and application in ring-opening polymerization of rac-lactide

A series of bis-ligated zinc complexes supported by Schitt base ligands were successfully synthesized and characterized by 1 H, 13C NMR, elemental analysis, and X-ray crystallography. These zinc complexes can be used as catalysts for the polymerization of rac-lactide in solution as well as in molten lactide. The results show that all catalysts exhibited high catalytic activity and obtained moderate heterotactic PLAs with the expected molecular weight. Complex 1 can catalyze the polymerization of rac-lactide under controllable conditions with living and immortal character in toluene solution. In addition, the steric hindrance and electronic effects has a great influence on the catalytic activity and selectivity of catalysts.