Min Zhang

Shanghai University of Traditional Chinese Medicine, Shanghai, Shanghai Shi, China

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Publications (282)596.82 Total impact

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    ABSTRACT: Tetrapyrrole biosynthesis is an essential and tightly regulated process, and glutamyl-tRNA reductase (GluTR) is a key target for multiple regulatory factors at the post-translational level. By binding to the thylakoid membrane protein FLUORESCENT (FLU) or the soluble stromal GluTR-binding protein (GBP), the activity of GluTR is down- or up-regulated. Here, we reconstructed a ternary complex composed of the C-terminal tetratricopepetide-repeat domain of FLU, GBP, and GluTR, crystallized and solved the structure of the complex at 3.2 Å. The overall structure resembles the shape of merged two binary complexes as previously reported, and shows a large conformational change within GluTR. We also demonstrated that GluTR binds tightly with GBP but does not bind to GSAM under the same condition. These findings allow us to suggest a biological role of the ternary complex for the regulation of plant GluTR.
    Preview · Article · Jan 2016 · Scientific Reports
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    ABSTRACT: Two new cytochalasans, periconiasin G (1) and periconiasin H (2) were isolated from endophytic fungus Periconia sp. F-31. Compound 1 is the first cytochalasan with a 7/6/5 tricyclic ring system, and compound 2 possesses a rare sulfoxide group. Their structures including absolute configurations were elucidated by extensive spectroscopic analyses and ECD calculations. A possible biogenetic pathway for these two compounds was proposed. Compound 1 showed weak anti-HIV activity with IC50 value of 67.0 μM.
    Full-text · Article · Jan 2016 · Tetrahedron Letters
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    Shihui Yang · Wei Wang · Hui Wei · Himmel ME · Min Zhang
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    ABSTRACT: Advanced biofuels have received increasing consideration due to their compatibility with current fuel infrastructure and high energy densities. Consolidated bioprocessing (CBP) is a promising strategy for economic lignocellulosic biofuel production. Recently, National Renewable Energy Laboratory scientists proposed a novel concept to develop a model fungal cellulase producer Trichoderma reesei as the fungal CBP platform for economic lignocellulosic biofuel production. Although nearly all of the systems biology studies for T. reesei were focused on cellulase induction, and there is no systems biology study reported yet for T. reesei as a CBP candidate for biofuel production, these systems biology datasets still can help us understand the global transcriptional profiles of T. reesei in different environmental conditions. In this study, we used public genomic and transcriptomic datasets to help us reconstruct metabolic pathways of glycolysis/fermentation and terpenoid biosynthesis. Several potential genetic targets were proposed to help improve farnesene production in T. reesei. In addition, the transcriptional profiles of known regulators in T. reesei were investigated, and the possibility to identify promoters with different strength was discussed. Our study thus demonstrated the feasibility of harnessing public genomic and transcriptomic data to guide metabolic engineering practice.
    Full-text · Chapter · Dec 2015
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    ABSTRACT: Hypoxia has been reported to regulate the cancer stem cell (CSC) population yet the underlying mechanism is poorly characterized. Herein, we show that Artemin (ARTN), a member of the glial cell derived neurotrophic factor family of ligands, is a hypoxia-responsive factor and is essential for hypoxia-induced CSC expansion in hepatocellular carcinoma (HCC). Clinically, elevated expression of ARTN in HCC was associated with larger tumor size, faster relapse and shorter survival. In vitro, HCC cells with forced expression of ARTN exhibited reduced apoptosis, increased proliferation, epithelial-mesenchymal transition (EMT) and enhanced motility. Additionally, ARTN dramatically increased xenograft tumor size and metastasis in vivo. Moreover, ARTN also enhanced tumorsphere formation and the tumor initiating capacity of HCC cells, consequent to expansion of the CD133+ CSC population. ARTN transcription was directly activated by hypoxia-induced factor-1α (HIF-1α) and hypoxia induced ARTN promoted EMT and increased the CSC population via AKT signaling. We herein identify a novel HIF-1α/ARTN axis promoting CSC-like behavior in hypoxic environments which implicates ARTN as a valuable therapeutic target for HCC.
    Preview · Article · Dec 2015 · Oncotarget
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    ABSTRACT: Platelet to lymphocyte ratio (PLR) is a prognostic factor for various tumors, but the current opinion on the prognostic value of PLR in liver transplantation (LT) for hepatocellular carcinoma (HCC) is still controversial. The aim of this study was to investigate the value of pre-transplant PLR for predicting post-LT HCC recurrence and further evaluate the correlation of PLR with tumor-related characteristics. The clinical data of 343 LT for HCC was retrospectively analyzed. The receiver operating characteristic (ROC) curve was used to determine the optimal PLR cut-off value to predict HCC recurrence after LT. The tumor-free survival rates were compared between high and low PLR groups divided by different pre-transplant PLR cut-off values. The relationship of elevated PLR and tumor-related characteristics were also analyzed. Additionally, the tumor-free survival was compared according to different platelet and lymphocyte counts. PLR 125 was the most significant cut-off value in predicting tumor-free survival after LT, with the sensitivity and specificity of 61.6% and 62.7%, respectively. PLR ≥125 was associated with significantly higher proportion of multiple tumors, large tumor size, and micro- and macro-vascular invasion than PLR <125. Of patient with PLR <125, 46.9%, 54.2%, and 61.5% were within Milan, UCSF, and Hangzhou criteria, respectively, significantly higher than 16.4%, 18.2%, and 29.1% in the PLR ≥125 group, respectively. There was no relationship between tumor-free survival and platelet or lymphocyte count independently. Pre-transplant PLR ≥125 was associated with advanced tumor stage and aggressive tumor behavior, and it can be used as a prognostic factor for post-transplant HCC recurrence.
    Preview · Article · Dec 2015 · World Journal of Surgical Oncology
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    ABSTRACT: There is a great demand for developing efficient extraction methods to reduce the extraction time and increase the yields and activities of functional antioxidants. The yields, physicochemical, functional properties and antioxidant activities of ultrasound-pretreated porcine cerebral hydrolysate peptides (UPCHPs) were studied and compared with traditional enzymolysis (PCHPs). The results showed that UPCHPs had higher peptides concentration, smaller molecular weight, and higher concentration of hydrophilic and late-eluting hydrophobic peptides than PCHPs at hydrolysis time of 20 min. However, the contents of antioxidant amino acids (Gly, Ala, Arg, Pro, His, Val, Leu, Lys and Phe) in both hydrolysate peptides were above 60%. UPCHPs with an excellent solubility had high reducing power activity and scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals (72%), 2,2′-azino-bis-(3-ethylbenzothiazoline)-6-sulfonic acid (ABTS) radicals (73%) and hydroxyl radicals (56%) at 2 mg/mL. Moreover, UPCHPs showed the moderate iron chelating activity (60%). In general, UPCHPs with good functional properties could serve as a potential antioxidant food ingredients.
    No preview · Article · Dec 2015
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    ABSTRACT: Objective. Chinese herbal bath therapy (CHBT) has traditionally been considered to have analgesic and anti-inflammatory effects. We conducted the first meta-analysis evaluating its benefits for patients with knee osteoarthritis (OA). Methods. We searched three English and four Chinese databases through October, 2014. Randomized trials evaluating at least 2 weeks of CHBT for knee OA were selected. The effects of CHBT on clinical symptoms included both pain level (via the visual analog scale) and total effectiveness rate, which assessed pain, physical performance, and wellness. We performed random-effects meta-analyses using mean difference. Results. Fifteen studies totaling 1618 subjects met eligibility criteria. Bath prescription included, on average, 13 Chinese herbs with directions to steam and wash around the knee for 20-40 minutes once or twice daily. Mean treatment duration was 3 weeks. Results from meta-analysis showed superior pain improvement (mean difference = -0.59 points; 95% confidence intervals [CI], -0.83 to -0.36; p < 0.00001) and higher total effectiveness rate (risk ratio = 1.21; 95% CI, 1.15 to 1.28; p < 0.00001) when compared with standard western treatment. No serious adverse events were reported. Conclusion. Chinese herbal bath therapy may be a safe, effective, and simple alternative treatment modality for knee OA. Further rigorously designed, randomized trials are warranted.
    Preview · Article · Oct 2015 · Evidence-based Complementary and Alternative Medicine
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    ABSTRACT: 目的 :通过三维运动捕捉与分析系统,采集与分析手法运动数据,归纳肩、肘、膝和踝关节运动特点。方法:由1位施术者在头部、躯干、左右肩峰、肘关节内外侧、腕关节内外侧、前臂外侧、上臂外侧、髂前上棘、髂后上棘、股骨大转子、胫骨结节、内外侧膝、腓骨小头、内外侧踝、足跟、双侧大腿、小腿胫骨外侧以及第1、2、5跖骨头、粘贴光标,对1位受试者完成1次颈椎"骨错缝、筋出槽"治疗的右手手法操作周期,重复5次,对施术者右侧肩、肘、膝和踝关节运动轨迹进行捕捉、记录、计算和分析。结果:手法操作过程中4个关节运动轨迹的趋势一致,其中肘关节的离散度最为明显。肩关节和肘关节的三维活动度明显,而膝关节和踝关节相对较小,然而膝关节的屈伸活动明显大于旋转和侧弯活动。结论:石氏伤科颈椎整复手法的上肢关节灵活性较高,而下肢关节的稳定性是重要保证,其中同侧膝关节通过屈伸活动来辅助上肢发力;红外线三维运动捕捉与分析系统建立的手法模型可以为教学和基础研究提供新的研究思路。
    Full-text · Article · Oct 2015
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    ABSTRACT: Two new flavonoids (1 and 2), along with 14 known ones (3-16), were isolated from the cultured cells of Glycyrrhiza uralensis. Most of them were prenylated flavonoids. Their structures were elucidated on the basis of spectroscopic data analysis. All compounds showed non-cytotoxicity against five human tumor cell lines. The results suggest that plant cultured cells can yield the secondary metabolites that have not been found in parent plant.
    No preview · Article · Oct 2015 · Journal of Asian natural products research
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    ABSTRACT: The rare earth complexes [Ln(L)2K(thf)] bearing a bis(phenolate) N-heterocyclic carbene (NHC) ligand (L = 1,3-bis[O-4,6-di-tBu-C6H2-2-CH2][C(NCH2CH2CH2N)], Ln = Nd (1), Y (2)) were synthesized in situ by the reaction of L1 with KN(SiMe3)2 and Ln[N(SiMe3)2]. The bis(phenolate) NHC precursor L1 also coordinated with rare earth metal forming bis(phenolate) pyrimidinium-bridged rare earth metal complexes [ Ln2(L1)3] (L1 = 1,3-bis[O-4,6-di-tBu-C6H2-2-CH2][CH(NCH2CH2CH2N)]+Cl−, Ln = Sm (3), Y (4)). Very high molecular weight (up to 106) and narrow molecular weight distribution (Mw/Mn = 1.7–2.3) polyhexyl isocyanate could be obtained by using the pyrimidinium based NHC rare earth metal complexes 1, 2 as well as imidazolinium based NHC rare earth complexes 5–7. The NHC complexes were found to be highly active towards the polymerization of n-hexyl isocyanate whereas non-NHC rare earth metal complexes 3, 4, 8 were inactive. The radius of rare earth metal, solvent, polymerization temperature and the structure of the ligand greatly affected the catalytic activity of polymerization. The mechanism of the initiation of the polymerization was studied and the NHC moiety played an important role in the initiation step which was evidenced via NMR analysis.
    No preview · Article · Sep 2015 · RSC Advances
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    ABSTRACT: Flowering time of plants must be tightly regulated to maximize reproductive success. Plants have evolved sophisticated signaling network to coordinate the timing of flowering in response to their ever-changing environmental conditions. Besides being a key immune signal, the lipid-derived plant hormone jasmonate (JA) also regulates a wide range of developmental processes including flowering time. Here, we report that the CORONATINE INSENSITIVE1 (COI1)-dependent signaling pathway delays the flowering time of Arabidopsis thaliana by inhibiting the expression of the florigen gene FLOWERING LOCUS T (FT). We provide genetic and biochemical evidence that the APETALA2 transcription factors (TFs) TARGET OF EAT1 (TOE1) and TOE2 interact with a subset of JAZ (jasmonate-ZIM domain) proteins and repress the transcription of FT. Our results support a scenario that, when plants encounter stress conditions, bioactive JA promotes COI1-dependent degradation of JAZs. Degradation of the JAZ repressors liberates the transcriptional function of the TOEs to repress the expression of FT and thereby triggers the signaling cascades to delay flowering. Our study identified interacting pairs of TF and JAZ transcriptional regulators that underlie JA-mediated regulation of flowering, suggesting that JA signals are converted into specific context-dependent responses by matching pairs of TF and JAZ proteins.
    Full-text · Article · Sep 2015 · The Plant Cell
  • Zhenhua Hu · Ze Qian · Jian Wu · Jie Zhou · Min Zhang · Lin Zhou · Shusen Zheng
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    ABSTRACT: Background: The different outcomes of deceased donor liver transplantation (DDLT) and living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC) are currently being debated. We aimed to retrospectively compare the outcomes following LDLT and DDLT and to analyse the factors influencing this. Methods: We compared the overall survival (OS) and disease-free survival (DFS) rates of HCC patients after LDLT (n=389) and DDLT (n=6471) from 81 centres over a 10-year period. OS and DFS rates were calculated with the Kaplan-Meier method. And univariate and multivariate Cox proportional hazards regressions were performed on the entire cohort to identify predictors. Results: Of 6860 patients, the 1-, 3-, and 5-year OS rates were 86.79%, 70.16%, and 66.31% after LDLT, respectively, and 74.2%, 54.21%, and 46.97% after DDLT, respectively (P<0.001). The 1-, 3-, and 5-year DFS rates were 78.46%, 63.68%, and 61.63% after LDLT, respectively, and 65.65%, 48.61%, and 41.87% after DDLT, respectively (P<0.001). The multivariate Cox regression model determined that the DFS and OS of HCC patients post-liver transplantation (LT) were strongly associated with tumour morphology and biology, but not graft type. Conclusions: With regards to OS and DFS, there were no disadvantages to LDLT as compared with DDLT; tumour morphology and biology may affect the prognosis of LT.
    No preview · Article · Sep 2015 · Gastroentérologie Clinique et Biologique
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    ABSTRACT: Objectives Salvage liver transplantation (SLT) is a controversial technique that has been reported to be acceptable for the management of patients with recurrent hepatocellular carcinoma (HCC) after primary hepatic resection (HR). However, whether the number of times liver resection is performed has an impact on survival after SLT has not yet been reported. Design Retrospective study. Setting The level of care is primary and the study was carried out at only 1 centre. Participants The study included 59 patients who underwent SLT for HCC from September 2001 to December 2012. 51 patients underwent HR only once before SLT, while the remaining 8 patients underwent HR more than once before SLT (HR=2 [7], HR=3, [1]). Primary and secondary outcome measures In this study, the 1-year, 3-year and 5-year overall and tumour-free survival outcomes between the 2 groups were compared. Results There were no significant differences between patients who underwent HR once and those who underwent HR more than once with respect to overall or tumour-free survival after receiving SLT. The 1-year, 3-year and 5-year overall survival rates for patients who underwent HR once were 72.9%, 35.3% and 35.5% vs 50%, 50% and 50%, respectively (p=0.986), while the 1-year, 3-year and 5-year tumour-free survival rates for those who underwent HR more than once were 66.3%, 55.3% and 44.4% vs 40%, 40% and 40%, respectively (p=0.790). Conclusions There was no significant difference in the survival rate of patients who underwent HR once before SLT and those who underwent HR more than once. This suggests that SLT is a reasonable choice for patients who suffer from recurrent HCC after HR. Trial registration number This is a retrospective study and no registry or number is required.
    Full-text · Article · Sep 2015 · BMJ Open
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    ABSTRACT: Tetrapyrroles, including haem and chlorophyll, play vital roles for various biological processes, such as respiration and photosynthesis, and their biosynthesis is critical for virtually all organisms. In photosynthetic organisms, magnesium chelatase (MgCh) catalyses insertion of magnesium into the centre of protoporphyrin IX, the branch-point precursor for both haem and chlorophyll, leading tetrapyrrole biosynthesis into the magnesium branch1,2. This reaction needs a cooperated action of the three subunits of MgCh: the catalytic subunit ChlH and two AAA+ subunits, ChlI and ChlD (refs 3, 4, 5). To date, the mechanism of MgCh awaits further elucidation due to a lack of high-resolution structures, especially for the ∼150 kDa catalytic subunit. Here we report the crystal structure of ChlH from the photosynthetic cyanobacterium Synechocystis PCC 6803, solved at 2.5 Å resolution. The active site is buried deeply inside the protein interior, and the surrounding residues are conserved throughout evolution. This structure helps to explain the loss of function reported for the cch and gun5 mutations of the ChlH subunit, and to provide the molecular basis of substrate channelling during the magnesium-chelating process. The structure advances our understanding of the holoenzyme of MgCh, a metal chelating enzyme other than ferrochelatase.
    No preview · Article · Aug 2015 · Nature Plants
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    ABSTRACT: In this study, the adsorption/desorption characteristics of mulberry anthocyanins (MA) on five types of macroporous resins (XAD-7HP, AB-8, HP-20, D-101 and X-5) were evaluated, XAD-7HP and AB-8 showed higher adsorption/desorption capacities. On the basis of static adsorption test, XAD-7HP and AB-8 resins were selected for kinetics, isotherms and thermodynamics. The adsorption mechanism indicated that the process was better explained by pseudo-first-order kinetics and the Langmuir isotherm model, and the thermodynamics tests showed that the processes were exothermic, spontaneous and thermodynamically feasible. Dynamic tests were performed on a column packed with XAD-7HP and AB-8, and breakthrough volume was reached at 15 and 14 bed volumes of MA solution, respectively. The purity of the fraction by 40% ethanol elution on XAD-7HP reached 93.6%, from which cyanidin-3-glucoside and cyanidin-3-rutinoside were identified by HPLC-ESI-MS/MS. The method could be used to prepare high purity anthocyanins from mulberry fruits as well as other plants. Chemical compounds studies in this article: Cyanidin-3-glucoside (PubChem CID:12303203); Cyanidin-3-rutinoside (PubChem CID:29231); Cyanidin (PubChem CID:128861); Hexose (PubChem CID:169005); Rutinose (PubChem CID:441429); Methanol (PubChem CID:887); Ethanol (PubChem CID:702); Ammonium sulfate (PubChem CID:6097028); Acetic acid (PubChem CID:176); Muriatic acid (PubChem CID:313)
    Full-text · Article · Aug 2015 · Food Chemistry
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    ABSTRACT: Huqi San (HQS) is a Chinese herbal preparation of eight medicinal herbs that promote diuresis, detoxification, blood circulation, and cholestasis. Defects in transporter expression and function can cause cholestasis and jaundice. However, the mechanism of the cholestasis underlying HQS effects, especially on the gastrointestinal tract ion secretion, has not been elucidated. Real-time RT-PCR and Western blotting were used to study the expression and localization of cystic fibrosis transmembrane conductance regulator (CFTR) and α-ENaC in rat alimentary tract, and then the effect of HQS on the ion transport in rat distal colon mucosa was investigated using the short-circuit current (I SC) technique. The results showed that pretreatment with HQS significantly enhanced mRNA transcripts and protein content of CFTR in liver and distal colon but not α-ENaC in alimentary organs. HQS increases I SC and decreases the transepithelial resistance. Pretreatment with epithelial Na(+) channel blocker did not affect the I SC responses elicited by HQS, but removal of extracellular Cl(-) or pretreatment with Cl(-) channel or Na(+)-K(+)-2Cl(-) cotransporter blocker inhibited HQS-elicited I SC responses. These findings demonstrated that HQS, RA, and RP can stimulate Cl(-) secretion in the distal colon by increasing the mRNA transcripts and protein content of CFTR in liver and distal colon.
    Preview · Article · Aug 2015 · Evidence-based Complementary and Alternative Medicine
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    ABSTRACT: The gap between the growing demand for available organs and the cadaveric organs facilitates the adoption of living donor liver transplantation. We retrospectively identified and evaluated the post-operative complications as per the modified Clavien classification system in 152 living liver donors at at the First Affiliated Hospital, College of Medicine, Zhejiang University between December, 2006 and June, 2014. Post-operative complications were observed in 61 patients (40.1%) in the present study, but no mortality was reported. Complications developed in 58 (40.0%) right, 1 (33.3%) left, and 2 (66.7%) lateral left hepatectomy donors. The prevalence of re-operation was 1.3%. Grade I and II complications were observed in 38 (25.0%) and 11 (7.2%) donors, respectively. Grade IIIa complications developed in 9 (5.9%) donors and only 3 (2.0%) patients reported grade IIIb complications. The most common complication was pleural effusion that occurred in 31 (20.4%) donors. No significant prognostic baseline factor was identified in this study. In conclusion, living donors experienced various complications, which were usually mild and had a good prognosis.
    Preview · Article · Aug 2015 · PLoS ONE
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    ABSTRACT: With the development of new surgical techniques, pancreaticoduodenectomy (PD) with portal vein or superior mesenteric vein (PV/SMV) resection has been used in the treatment of patients with borderline resectable pancreatic cancer. However, opinions of surgeons differ in the effectiveness of this surgical technique. This study aimed to investigate the effectiveness of this approach in patients with pancreatic cancer. Follow-up visits and retrospective analysis were carried out of 208 patients with pancreatic cancer who had undergone PD (PD group) and PD combined with PV/SMV resection and reconstruction (PDVR group) from June 2009 to May 2013 at our center. Statistical analysis was performed to compare the clinical features, the difference of survival time and risk factors of venous invasion in pancreatic cancer. Factors relating to postoperative survival time of pancreatic cancer were also investigated. In the PDVR group, which consisted of 42 cases, the 1-, 2- and 3-year survival rates were 70%, 41% and 16%, respectively and the median survival time was 20.0 months. Among the 166 patients in the PD group, the 1-, 2- and 3-year survival rates were 80%, 52%, and 12%, respectively with the median survival time of 26.0 months. No significant difference in survival time and R0 resection ratio was found between the two groups. Lumbodorsal pain, tumor with pancreatic capsular invasion and bile duct infiltration were found to be independent risk factors for PV invasion in pancreatic cancer. In addition, non R0 resection, large tumor size (>2 cm) and poorly differentiated tumor were independent risk factors for survival time in post-PD. The tumor has a higher chance of venous invasion if preoperative imagings indicate that it juxtaposes with the vessel. Lumbodorsal pain is the chief complaint. Patients with pancreatic cancer associated with PV involvement should receive PDVR for R0 resection when preoperational assessment shows the chance for eradication.
    No preview · Article · Aug 2015 · Hepatobiliary & pancreatic diseases international: HBPD INT
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    ABSTRACT: Matrix metalloproteinase-9 (MMP-9), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and their ratio (MMP-9/TIMP-1) are involved in multiple processes that are associated with coronary heart disease and are especially associated with cardiovascular events. However, few long-term population-based clinical studies have evaluated the role of these factors in cardiovascular events in a Chinese population. A prospective study was performed on 560 patients with mild to moderate coronary artery lesions. MMP-9, TIMP-1 and their ratio were determined. A total of 522 of patients completed the follow-up. The median follow-up time was 64 months. Kaplan-Meier analysis demonstrated a clear increase of the incidence of major adverse cardiac events (MACEs) during the follow-up period in subjects with above-median levels of TIMP-1 (p = 0.033), whereas there was no association with either MMP-9 (p = 0.199) or MMP-9/TIMP-1 (p = 0.631). Multivariate Cox proportional hazards analysis showed the same results after further adjustment for covariates. Patients with above-median levels of TIMP-1 were more likely to suffer from adverse outcomes than patients with below-median levels of TIMP-1. However, the lack of relationship of MACEs with MMP-9 and MMP-9/TIMP-1 remained. Higher circulating TIMP-1 concentrations were associated with cardiovascular events during long-term follow-up of Chinese patients with mild to moderate coronary artery lesions. © 2015 S. Karger AG, Basel.
    No preview · Article · Aug 2015 · Cardiology
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    ABSTRACT: Difenoconazole is one of the triazole compounds, and is widely used as environmental fungicides. Recently, it is suspected that long-term exposure to difenoconazole through drinking water and food may induce health effects including hepatotoxicity and tumorigenesis. However, there is a little information regarding the molecular mechanism of difenoconazole-induced cytotoxicity and/or human health risk. The present study was aimed to investigate the toxic effects of difenoconazole on human hepatocellular carcinoma HepG2 cells in terms of cell viability, generation of reactive oxygen species (ROS) and cellular apoptosis. Difenoconazole significantly activated the apoptosis related proteins namely caspase-8 and -9 as well as cleavage of poly-ADP ribose polymerase (PARP) in a dose-dependent manner whereas the IC50 value for difenoconazole was calculated to be 70µM. Correspondingly, intracellular generation of ROS was also markedly increased after exposure to difenoconazole and was observed to occur specifically in mitochondria and endoplasmic reticulum (ER), suggesting mitochondria and ER being the target organelles for difenoconazole-induced cytotoxicity. Moreover, phosphorylation of protein kinase-like endoplasmic reticulum kinase (PERK), followed by initiation of ATF4, phosphorylation of eif2α and activation of Chop were observed to be up-regulated by difenoconazole, indicating that difenoconazole is capable of inducing ER-stress in HepG2 cells. More interestingly, either activation of caspase-8, -9 and cleavage of PARP or induction of ER-stress can be attenuated by pretreatment with antioxidants either N-acetylcysteine (NAC) or lipoic acid (LA), indicating that generation of ROS may result in induction of apoptosis and cell death probably through ROS-mediated mitochondria and ER-stress dependent signaling pathway.
    Full-text · Article · Jul 2015

Publication Stats

3k Citations
596.82 Total Impact Points


  • 2015
    • Shanghai University of Traditional Chinese Medicine
      Shanghai, Shanghai Shi, China
    • Fudan University
      • Department of Biochemistry and Molecular Biology
      Shanghai, Shanghai Shi, China
  • 2013-2015
    • Nanjing University
      Nan-ching, Jiangsu, China
  • 2012-2015
    • Capital Medical University
      • Department of Cardiology
      Peping, Beijing, China
    • Chinese Center For Disease Control And Prevention
      • National Center for AIDS/STD Control and Prevention
      Peping, Beijing, China
  • 2009-2015
    • Jiangsu University
      • School of Chemistry and Chemical Engineering
      Chenkiang, Jiangsu, China
    • Chongqing Center for Disease Control and Prevention
      Ch’ung-ch’ing-shih, Chongqing Shi, China
  • 2008-2015
    • Shenzhen Children's Hospital
      Shechenzhuang, Jiangsu, China
  • 2006-2015
    • Anhui University
      • School of Life Sciences
      Luchow, Anhui Sheng, China
    • University of Science and Technology of China
      • • Hefei National Laboratory for Physical Sciences at the Microscale
      • • School of Life Sciences
      Luchow, Anhui Sheng, China
  • 2002-2015
    • Zhejiang Medical University
      • • Department of Surgery
      • • Department of Respiratory Medicine
      • • First Affiliated Hospital
      Hang-hsien, Zhejiang Sheng, China
    • Zhejiang University
      • • School of Medicine
      • • Department of Surgery
      • • First Affiliated Hospital of Medical College
      Hang-hsien, Zhejiang Sheng, China
  • 2014
    • Nanjing Medical University
      Nan-ching, Jiangsu Sheng, China
    • Shanghai Municipal Center for Disease Control and Prevention
      Shanghai, Shanghai Shi, China
  • 2013-2014
    • Guangzhou Medical University
      Feng-t’ien, Liaoning, China
  • 2008-2014
    • China Medical University (PRC)
      • • Key Laboratory of AIDS Immunology, Ministry of Health
      • • Key Laboratory of AIDS
      Feng-t’ien, Liaoning, China
  • 2005-2014
    • Nankai University
      • • Institute of Elemento-Organic Chemistry
      • • State Key Laboratory of Elemento-Organic Chemistry
      T’ien-ching-shih, Tianjin Shi, China
    • Northeastern University (Shenyang, China)
      Feng-t’ien, Liaoning, China
  • 2002-2014
    • National Renewable Energy Laboratory
      • Biosciences Center
      گلدن، کلرادو, Colorado, United States
  • 2010-2013
    • Jiangsu Provincial Center for Disease Control and Prevention
      Chiang-tu, Jiangsu Sheng, China
    • ShenJing Hospital of China Medical University
      Feng-t’ien, Liaoning, China
    • Hangzhou First People's Hospital
      Hang-hsien, Zhejiang Sheng, China
  • 2007-2012
    • Southern Medical University
      • Department of Neurology
      Shengcheng, Guangdong, China
  • 2011
    • Chinese Academy of Sciences
      • State Key Laboratory of Microbial Resources
      Peping, Beijing, China
    • HangZhou Institute of Electronic Engineering
      Luchow, Anhui Sheng, China
  • 2010-2011
    • Xidian University
      • School of Telecommunications Engineering
      Ch’ang-an, Shaanxi, China
    • Changchun Normal University
      Hsin-ching, Jilin Sheng, China