OBJECTIVETo observe the signal transducers and activator of transcriptions (STATs) protein expression changes and investigate the functional role of STATs pathway in case of high glucose-induced cardiac fibroblasts (CFs) proliferation and collagen deposition in vitro.

METHODSRat cardiac fibroblasts were isolated from 1- to 3-day-old SD rats, cells from the second to fourth passages were used for the experiment. CFs were cultured in Dulbecco's modified Eagle's medium, supplemented with 5.5 mmol/L glucose (NG), 5.5 mmol/L glucose plus 19.4 mmol/L mannose (OC) or 25 mmol/L glucose (HG) in the presence of absence of STAT1 inhibitor (fludarabine, FLU) and STAT3 inhibitor (S3I-201). After 24 h and 48 h culture in vitro, the proliferation of CFs was measured by 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. After 12 h and 24 h culture in vitro, the production of type I and III collagen was evaluated using real-time quantitative PCR and ELISA. After 0, 30, 60 and 120 min culture in vitro, the phosphorylated expression of STAT1 and STAT3 was analyzed by Western blot.

RESULTSCFs proliferation was significantly enhanced post 24 h and 48 h HG stimulation, and procollagen I and III mRNA expression was significantly upregulated post 12 h and 24 h HG stimulation. Deposition of collagen I and III was also significantly increased post 24 h and 72 h HG stimulation. STAT1 phosphorylation in CFs was increased after 120 min HG stimulation and STAT3 phosphorylation in CFs was increased post 60 min and 120 min HG stimulation. FLU and S3I-201 could inhibit HG-induced CFs proliferation and suppress of which was stimulated by FLU and S3I-201 could both suppress upregulated procollagen I and III mRNA expression and the deposition of collagen types I and III post HG stimulation. STAT1 phosphorylation inhibition resulted in less mRNA downregulation of procollagen type III than that of procollagen type I post 12 h HG stimulation. The STAT3 phosphorylation inhibition resulted in more significantly upregulated procollagen type III mRNA expression than procollagen type I mRNA expression at 12 h post HG stimulation.

CONCLUSIONHG could enhance the protein expression of phosphorylated STAT1 and STAT3 in CFs, which are responsible for HG-induced increased CFs proliferation and collagen deposition in vitro.

Aminosalicylic Acids ; pharmacology ; Animals ; Benzenesulfonates ; pharmacology ; Cell Proliferation ; Cells, Cultured ; Collagen Type I ; metabolism ; Collagen Type III ; metabolism ; Fibroblasts ; cytology ; drug effects ; Glucose ; adverse effects ; Myocardium ; cytology ; Phosphorylation ; RNA, Messenger ; metabolism ; Rats ; Rats, Sprague-Dawley ; STAT1 Transcription Factor ; metabolism ; STAT3 Transcription Factor ; metabolism ; Signal Transduction ; Up-Regulation ; Vidarabine ; analogs & derivatives ; pharmacology

Objective To determine the prevalence of penicillinase-producing Neisseria gonorrhoeae(PPNG) and the distribution of blaTEM-135 gene variants in PPNG at several gonococcal antimicrobial surveillance sites in China, to compare N. gonorrhoeae multi-antigen sequence typing(NG-MAST)types of PPNG and its blaTEM-135 gene variants, and to assess the difference and association in NG-MAST types of blaTEM-135 gene variants among different regions. Methods A total of 572 N. gonorrhoeae isolates were collected at 6 gonococcal antimicrobial surveillance sites from Jiangsu, Shanghai, Zhejiang, Tianjin, Guangdong and Guangxi in 2012. After isolation, purification, and identification, cefalotin paper discs were used for detection of PPNG. DNA was extracted by QIAxtractor DX kits after cultivation of the PPNG strains. Then, mismatch amplification mutation assay (MAMA) PCR was performed to identify blaTEM-135 variants, and NG-MAST analysis to determine N. gonorrhoeae genotypes. Results Among the 572 N. gonorrhoeae strains, 38.1%(218/572) were identified as PPNG, and of the PPNG strains, 52.3% (114/218) were blaTEM-135 variants. The detection rate of PPNG at these surveillance sites from high to low was as follows: 51.7% (45/87, Zhejiang), 45.6%(36/79, Shanghai), 38.0% (78/205, Guangdong), 37.5% (12/32, Guangxi), 31.2% (24/77, Jiangsu) and 25.0%(23/92, Tianjin), and that of blaTEM-135 variants was as follows: 68.9%(31/45, Zhejiang), 58.3%(14/24, Jiangsu), 50.0%(39/78, Guangdong), 47.2%(17/36, Shanghai), 39.1%(9/23, Tianjin)and 33.3%(4/12, Guangxi). NG-MAST analysis showed that the ST2318, ST1768, ST1866, ST1053 and ST8726 types predominated among these bla TEM-135 variants, and a strong correlation was found between blaTEM-135 variants and some NG-MAST types, such as ST1768, ST1053 and ST8726 types. The distribution of NG-MAST types was significantly different between the surveillance site in Tianjin (in the Northern part of China) and the other sites (in the Southern part of China), but highly similar among the surveillance sites in Jiangsu, Zhejiang and Shanghai regions. Conclusions There is a high prevalence of PPNG and its blaTEM-135 variants at several gonococcal antimicrobial surveillance sites in China, with significant differences in NG-MAST genotype distribution of PPNG and its blaTEM-135 variants among different regions.

Objective To investigate the relationship between dyslipidemia and nephrolithiasis in a population-based study.Methods All participants were investigated by questionnaires,physical examinations and laboratory tests including liver and renal function,lipid profile,serum fasting glucose,glycosylated hemoglobin.Nephrolithiasis was diagnosed by kidney Bultrasonography.Subjects with estimated glomerular filtration rate (eGFR) ＜ 60 ml · min-1 · (1.73 m2)-1were excluded.Results 10 316 individuals were enrolled with an average age of (54.88 ± 10.27) years (range 17-88 years) and the ratio of male to female 1:1.12.The prevalence of nephrolithiasis was 5.6％,3.7％ and 7.8％ for whole population,women and men,respectively.In women,only eGFR in stone group was significantly lower than that in non-stone group (P ＜ 0.05).However,participants in stone group were significantly older (P ＜ 0.05),of higher blood pressure (P ＜ 0.01),higher serum uric acid (P ＜ 0.01),worse renal function (serum creatinine,P ＜ 0.05;eGFR,P ＜ 0.01),and higher low-density lipoprotein (LDL) (P ＜ 0.05),compared with those in non-stone group in men.Logistic regression analysis showed that only eGFR (P ＜ 0.05) was the independent influential factor for kidney stones in women;In men,LDL was an independent influential factor for nephrolithiasis with a hazard ratio of 1.149 (95％CI 1.003-1.317,P ＜ 0.05),except for mean blood pressure and eGFR.After being divided into normal group,borderline high group and high LDL group according to the LDL level,with the increase of LDL,the prevalence of nephrolithiasis was significantly increased by 7.3％,8.3％ and 10.6％ in men respectively.There was no significant relationship between total cholesterol,triglyceride,high-density lipoprotein and nephrolithiasis.Conclusions Dyslipidemia is associated with nephrolithiasis in men,and high LDL cholesterol is an independent risk factor for nephrolithiasis.Clinical lipid testing not only helps to reduce the risk of atherosclerotic disease,but also reduces the risk of kidney stones.

The effect of the endophytic fungi Botrytis sp. (C1) or Chaetomium globosum (C4) on the drought resistance of Chrysanthemum morifolium was studied. Ch. morifolium plantlets were inoculated with C1, C4 and cultured in the pots for 60 days, then the plantlets were stressed by 0%, 10%, 20%, 30%, 40% PEG6000 respectively in order to simulate different drought conditions. Biomass, the activities of SOD, POD, PAL, the contents of MDA and soluble protein of each group were determined. The results showed that endophytic fungi groups grew better than the control (without inoculation endophytic fungi). With the increasing of the concentration of PEG6000, the biomass of Ch. morifolium of each groups decreased, while the biomass of fungi groups was significantly higher than that of control, moreover C4 group higher than C1 group. With the concentration of PEG increasing, the content of MDA of each group increased too, while POD activity and soluble protein content of all treatments increased at first and then decreased. SOD activity and PAL activity of the control were increased with the increase of PEG concentration, but SOD activity of the two fungi groups were stable. After been stressed by different concentrations of PEG, MDA content of two fungi groups were always lower than the control, while SOD activity, POD activity, PAL activity and soluble protein content were higher. In conclusion, endophytic fungi can increase the drought resistance of Ch. morifolium.
Biomass ; Botrytis ; drug effects ; growth & development ; isolation & purification ; Chaetomium ; drug effects ; growth & development ; isolation & purification ; Chrysanthemum ; drug effects ; metabolism ; microbiology ; Droughts ; Peroxidases ; metabolism ; Polyethylene Glycols ; pharmacology ; Stress, Physiological ; drug effects ; Superoxide Dismutase ; metabolism

The aim of the present study was to investigate the effects of levo-corydalmine(l-CDL)on chronic constrictive injury(CCI)-induced neuropathic pain and central sensitization in spinal cord. The mechanical withdrawal threshold in rats was assessed by Von-Frey fibers and the thermal withdrawal latency was assessed by thermal stimulus apparatus. The level of phosphorylated N-methyl-D-aspartic acid receptor 1(NR1)in L4-L6 spinal cord was analyzed by immunoblotting and the expression of calcitonin gene related peptide(CGRP)and c-fos in spinal cord dorsal horn were analyzed by immunofluorescence. Results showed that l-CDL(7. 5, 15, 30 mg/kg, ig)inhibited CCI-induced mechanical allodynia and thermal hyperalgesia in a dose-dependent manner. l-CDL significantly inhibited the up-regulation of p-NR1, c-fos and CGRP in CCI rats without tolerance. In conclusion, l-CDL has a good relieving effect on central sensitization in spinal cord, thus generating outstanding analgesic activity on CCI-induced neuropathic pain.

Objective:To explore the association between urinary stone disease (USD) and peripheral arterial disease (PAD).Methods:The study was based on the cross-sectional chronic diseases survey performed in Pinggu district, Beijing from March to May, 2014. All subjects completed a questionnaire, physical examination, renal ultrasound examination to detect USD, ankle-brachial index (ABI) examination to detect PAD (defined as ABI<0.9 on either side of the body), and brachial-ankle pulse wave velocity (baPWV) measurement to estimate arterial stiffness. Blood and first morning urine sample were detected for serum creatinine, blood glucose and so on.Results:There were 10 281 participants included in this study. Among these participants, the prevalences of USD and PAD were 5.66% and 3.95%, respectively. Compared with non-stone participants, the persistent USD formers had a higher prevalence of PAD (8.26% vs 3.90%, P<0.001) and baPWV [(16.3±3.5) m/s vs (15.5±3.2) m/s, P<0.001]. Even after adjusting the confounding factors, the persistent USD formers also had a 2.066-fold increased risk of PAD ( OR=2.066, 95% CI 1.276-3.343, P=0.003). In the subgroup analysis, persistent USD patients in older participants who were≥60 years old, women, chronic kidney disease, and central obesity had a significantly increased risk of PAD. Conclusions:In the present population, persistent USD is positively associated with a high risk of PAD and increased arterial stiffness. Patients with persistent USD should be screened for vascular diseases.

Asian Continental Ancestry Group ; Hearing Loss ; genetics ; Humans ; Mutation ; genetics ; Pedigree ; RNA, Ribosomal ; genetics