Publications by authors named "Yuqiang Chen"

19 Publications

  • Page 1 of 1

Effect of Zr content on microstructure and mechanical properties of lightweight AlNbTiVZr high entropy alloy.

Micron 2021 May 10;144:103031. Epub 2021 Feb 10.

Hunan Provincial Key Laboratory of Advanced Materials for New Energy Storage and Conversion, Hunan Provincial Key Defense Laboratory of High Temperature Wear-resisting Materials and Preparation Technology, School of Materials Science and Engineering, Hunan University of Science and Technology, Xiangtan 411201, China.

Lightweight AlNbTiVZr (x = 1.0, 0.8, 0.6, 0.4, 0.2, 0) high entropy alloys are produced by mechanical milling and vacuum hot pressing. The microstructure, phase evolution and mechanical properties of the alloys are analyzed. The microstructure of the alloys with x = 1.0, 0.8, 0.6 consists of BCC solid solution matrix and two intermetallics (i.e., α and β), and then β phase disappears in AlNbTiVZr alloy. Further decreasing Zr content to below 0.2, α phase vanishes and γ and δ intermetallics emerge in AlNbTiVZr and AlNbTiV alloys. The AlNbTiVZr alloys cannot obtain a single phase structure by decreasing Zr content with current fabrication process, which is likely because that the mixing entropy of the HEA system is not large enough to prohibit the formation of the secondary phases at hot pressing temperature of 1250 °C. All the bulks possess low density ranging from 4.93 to 5.21 g/cm. Hardness of the AlNbTiVZr alloys decreases from 781 HV to 697 HV and then increases to 814 HV with the decrease of Zr from x = 1 to 0. This varying tendency is closely related with the content of secondary intermetallic phases. The compressive test shows the AlNbTiVZr alloy has a yield strength of 1742 MPa, fracture strength of 2420 MPa, compressive strain of 38.2 %, which is probably related to its simplest microstructure. The comprehensive mechanical property of AlNbTiVZr alloy is superior to the majority of other HEAs and Ti64 alloy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.micron.2021.103031DOI Listing
May 2021

Low expression of HIV genes in podocytes accelerates the progression of diabetic kidney disease in mice.

Kidney Int 2021 04 22;99(4):914-925. Epub 2020 Dec 22.

Department of Medicine, Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, USA; Renal Section, James J. Peters VAMC, Bronx, New York, USA. Electronic address:

With the widespread use combination antiretroviral therapy, there has been a dramatic decrease in HIV-associated nephropathy. However, although the patients living with HIV have low or undetectable viral load, the prevalence of chronic kidney disease (CKD) in this population remains high. Additionally, improved survival is associated with aging-related comorbidities such as diabetes and cardiovascular disease. A faster progression of CKD is associated with concurrent HIV infection and diabetes than with HIV infection or diabetes alone. To explore the potential pathogenic mechanisms that synergistically drive CKD progression by diabetes and HIV infection, we generated a new mouse model with a relatively low expression of HIV-1 proviral genes specifically in podocytes (pod-HIV mice) to better mimic the setting of kidney injury in patients living with HIV. While no apparent kidney phenotypes were observed at baseline in pod-HIV mice, the induction of mild diabetic kidney disease with streptozotocin led to significant worsening of albuminuria, glomerular injury, podocyte loss, and kidney dysfunction as compared to the mice with diabetes alone. Mechanistically, diabetes and HIV-1 synergistically increased the glomerular expression of microRNA-34a (miR-34a), thereby reducing the expression of Sirtuin-1 (SIRT1) deacetylase. These changes were also associated with increased acetylation and activation of p53 and p65 NF-κB and with enhanced expression of senescence and inflammatory markers. The treatment of diabetic pod-HIV mice with the specific Sirtuin-1 agonist BF175 significantly attenuated albuminuria and glomerulopathy. Thus, our study highlights the reduction in Sirtuin-1 as a major basis of CKD progression in diabetic patients living with HIV and suggests Sirtuin-1 agonists as a potential therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.kint.2020.12.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006538PMC
April 2021

Mean Platelet Volume: A Novel Predictor for Bone Erosion in Gouty Arthritis?

Ann Clin Lab Sci 2019 Sep;49(5):661-665

Department of Hematology and Oncology, Shenzhen Children's Hospital, Shenzhen, Guangdong, China.

Objective: Gout is a type of inflammatory arthritis that can be complicated with bone erosion through several inflammatory factors. Mean platelet volume (MPV) is regarded as a marker in many inflammatory disorders, but despite this, the metric has not been used for gout.

Material And Methods: This study evaluates the relationship between MPV and bone erosion in patients with gout. In total, 299 patients were evaluated retrospectively, and 120 patients were ultimately included based on inclusion criteria.

Results: Both the duration of this disease and mean platelet volume were related to bone erosion in gout and may be regarded as independent predictors of bone erosion.

Conclusion: These results suggest that mean platelet volume can be a predictor of bone erosion in gout.
View Article and Find Full Text PDF

Download full-text PDF

Source
September 2019

Nicotine induces insulin resistance via downregulation of Nrf2 in cardiomyocyte.

Mol Cell Endocrinol 2019 09 14;495:110507. Epub 2019 Jul 14.

Department of Cardiovascular Medicine, Second Affiliated Hospital of Shantou University Medical College, No. 69, Dongxiabei Road, Shantou, Guangdong, China. Electronic address:

Clinical studies have demonstrated that cigarette smoking is strongly associated with insulin resistance and heart disease. Nicotine is considered the primary toxin constituent associated with smoking. However, the distinct molecular mechanism of nicotine-induced cardiac dysfunction remains unclear. Cardiomyocytes with nicotine-induced insulin resistance are characterized by decreased glucose uptake, as measured by 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose (2-NBDG), a fluorescent derivative of glucose, and reactive oxygen species (ROS) generation. Immunoblotting was used to evaluate the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), extracellular signal-related kinase (ERK) and phosphoinositide 3-kinase (PI3K, p85, Y607). We determined the impact of nicotine on insulin resistance and Nrf2, phospho-ERK and phospho-PI3K expression in the myocardial tissue of a mouse model. Nicotine increased ROS production and depressed insulin-induced glucose uptake in cardiomyocytes. Pretreatment with N-acetyl-L-cysteine (NAC), an antioxidant, reversed nicotine-inhibited glucose uptake induced by insulin. Nicotine exposure directly inhibited Nrf2 and increased ERK phosphorylation in cardiomyocytes, which were obstructed by NAC. Further exploration of signaling cascades revealed nicotine-induced ROS involved in inhibiting PI3K/Nrf2 and activating ERK in cardiomyocytes. Moreover, the mouse model treated with nicotine showed glucose intolerance and impaired insulin tolerance accompanied by inhibited PI3K/Nrf2 and increased ERK in myocardial tissues. Thus, nicotine induces insulin resistance via the downregulation of Nrf2 activity in cardiomyocytes, which is a potential mechanism of the pharmacological effects of nicotine. This study identified potential therapeutic targets against nicotine-related cardiovascular diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mce.2019.110507DOI Listing
September 2019

Contribution of tissue transglutaminase to the severity of hepatic fibrosis resulting from Schistosoma japonicum infection through the regulation of IL-33/ST2 expression.

Parasit Vectors 2019 Jun 14;12(1):302. Epub 2019 Jun 14.

Sino-French Hoffmann Institute, Guangzhou Medical University, Guangzhou, 511436, Guangdong Province, People's Republic of China.

Background: Tissue transglutaminase (tTG)-regulating IL-13 plays an important role in the pathogenesis of liver fibrosis resulting from Schistosoma japonicum (Sj) infection. IL-33 and its receptor ST2 are involved in Th2-biased immune responses through the release of IL-5 and IL-13 and subsequent hepatic granuloma pathology induced by Sj infection. However, the relationship between tTG, IL-33/ST2, and liver fibrosis during Schistosoma infection has not been established.

Results: This study investigated the link between tTG and IL-33/ST2 in the induction of liver fibrogenesis during Sj infection in mice. The extent of liver fibrosis coincided with an increase in tTG and IL-33/ST2 expression in the liver of infected mice between five to eight weeks, with a peak of correlation at six weeks after Sj infection. The inhibition of tTG activity through cystamine administration or gene knockout alleviated the level of TLR4, NF-κB pathway molecules, IL-33/ST2, and the severity of liver fibrosis resulting from Sj infection.

Conclusions: These results indicate that during Sj infection tTG may control liver fibrosis at least partially through TLR4, NF-κB pathway activation and then IL-33/ST2. tTG, IL-33 or ST2 might be promising drug targets against liver fibrosis induced by Sj infection.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13071-019-3542-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6570881PMC
June 2019

Establishment of rapid detection method and surveillance of budgerigar fledgling disease virus using a TaqMan Real-Time PCR.

Mol Cell Probes 2019 02 8;43:80-83. Epub 2018 Nov 8.

Shanghai Key Laboratory of Veterinary Biotechnology, Key Laboratory of Urban Agriculture (South), Ministry of Agriculture, School of Agriculture and Biology, Shanghai Jiao Tong University, Shanghai, 200240, China. Electronic address:

Budgerigar fledgling disease virus (BFDV) infection causes sudden death, abdominal distention, and feather abnormality in psittacine birds. In this study, we developed a TaqMan Real-time PCR assay to detect BFDV by targeting a conserved region in VP1 gene. The detection limit of the assay was 30 DNA gene copies, 1000 times more sensitive than conventional PCR. The coefficients of variation were less than 1.09% in either intra- or inter-assays, indicating high reproducibility. By using this method, the prevalence of BFDV in China was evaluated. 56 feces samples were collected from four psittacine birds breeding facilities in China. The results showed 28 out of 56 samples were positive for BFDV in Real-Time PCR assay, while only 19 samples were positive in PCR assay. Three facilities were positive for BFDV with positive rates from 60% to 87.5%. Further sequence analysis of VP1 genes from the positive samples indicated that VP1 genes fell into two different lineages in phylogenetic tree, suggesting that different genotypes BFDV are co-circulating in China.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mcp.2018.11.002DOI Listing
February 2019

Effect of high-volume hemofiltration on mortality in critically ill patients: A PRISMA-compliant systematic review and meta-analysis.

Medicine (Baltimore) 2018 Sep;97(38):e12406

Department of Intensive Care Medicine Emergency Department Ultrasound Services Nursing Department, Tangshan Caofeidian-District Hospital, Tang Shan, Hebei, PR China.

Background: High-volume hemofiltration (HVHF) is widely used for blood purification in critically ill patients with systemic inflammatory syndromes. The purpose of this study was to evaluate the effect of HVHF on mortality at different follow-up periods in critically ill patients.

Methods: We systematically searched PubMed, Embase, and the Cochrane Library through April 2017 to identify trials that evaluated the effect of HVHF on mortality in critically ill patients. Summary relative risks (RRs) and 95% confidence intervals (CIs) were employed to calculate the treatment effect using a random effects model. Eleven trials involving 1048 critically ill patients were included in this study.

Results: The summary results indicated no significant differences between HVHF and usual care for the incidence of 28-day mortality (RR: 0.93; 95%CI: 0.80-1.08; P = .321), 7-day mortality (RR: 0.72; 95%CI: 0.50-1.03; P = .072), 60-day mortality (RR: 1.00; 95%CI: 0.86-1.16; P = .997), and 90-day mortality (RR: 1.01; 95%CI: 0.88-1.16; P = .927). Subgroup analysis suggested HVHF significantly reduced the risk of 28-day mortality (RR: 0.64; 95%CI: 0.42-0.97; P = .035) if pooled the study sample size < 100.

Conclusion: Our findings suggest HVHF significantly reduced the incidence of 28-day mortality when pooled the study sample size < 100. Further, HVHF had a marginal effect on the incidence of 7-day mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000012406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6160258PMC
September 2018

Anti-neuropilin-1 monoclonal antibody suppresses the migration and invasion of human gastric cancer cells via Akt dephosphorylation.

Exp Ther Med 2018 Aug 30;16(2):537-546. Epub 2018 May 30.

Cancer Research Center, Medical College of Xiamen University, Xiamen, Fujian 361102, P.R. China.

Neuropilin-1 (NRP-1) is involved in a range of physiological and pathological processes, including neuronal cell guidance, cardiovascular development, immunity, angiogenesis and the pathogenesis of cancer. Targeting of NRP-1 is considered to be a potential cancer therapy and a number of approaches have been investigated, including the use of small interfering RNA, peptides, soluble NRP antagonists and monoclonal antibodies. The present study used a novel anti-neuropilin-1 monoclonal antibody (anti-NRP-1 mAb) to investigate its potential anti-tumor effects on human gastric cancer cells and , as well as its underlying mechanisms of action. Using an MTT assay, it was observed that anti-NRP-1 mAb (<150 µg/ml) had no effects on the viability of gastric cancer cell line BGC-823, while a Boyden chamber assay indicated that treatment with anti-NRP-1 mAb suppressed the migration and invasion of BGC-823 cells. Western blot analysis also demonstrated that phosphorylation of Akt was reduced in BGC-823 cells treated with anti-NRP-1 mAb. Furthermore, anti-NRP-1 mAb suppressed the growth of gastric cancer xenograft tumors and downregulated the expression of vascular endothelial growth factor proteins within tumors in nude mice. These data indicate the potential effects of anti-NRP-1 mAb on malignant tumors and suggest that inhibition of NRP-1 function with anti-NRP-1 mAb may be a novel therapeutic approach in the treatment of cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/etm.2018.6234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6090285PMC
August 2018

Increased Serum Uric Acid Level Is a Risk Factor for Left Ventricular Hypertrophy but Not Independent of eGFR in Patients with Type 2 Diabetic Kidney Disease.

J Diabetes Res 2017 20;2017:5016093. Epub 2017 Jun 20.

Department of Nephrology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 200233 Shanghai, China.

Background: Although the relation between serum uric acid (SUA) and left ventricular hypertrophy (LVH) has been studied for decades, however, their association remains debatable.

Methods: This is a retrospective study in which a total of 435 hospitalized Chinese patients with type 2 DKD were enrolled. The subjects were stratified into quartiles according to SUA level. LVH was assessed by two-dimensional guided M-mode echocardiography.

Results: There was a significant increase in the prevalence of LVH in patients with type 2 DKD across SUA quartiles (28.9, 26.5, 36.1, and 49.5%; < 0.001). The Spearman analysis indicated that SUA was positively correlated to LVMI and negatively correlated to eGFR. The logistic regression analysis revealed that the odd ratio for LVH in the highest SUA quartile was 2.439 (95% CI 1.265-4.699; = 0.008; model 1) or 2.576 (95% CI 1.150-5.768; = 0.021; model 2) compared with that in the lowest SUA quartile. However, there was no significant increased risk of LVH in the subjects with the highest SUA quartile after adjusting the eGFR (OR = 1.750; 95% CI 0.685-4.470; = 0.242; model 3).

Conclusions: In selected population, such as type 2 DKD, the elevated SUA level is positively linked with the increased risk of LVH, but this relationship is not independent of eGFR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2017/5016093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5496120PMC
April 2018

Cross talk between miR-214 and PTEN attenuates glomerular hypertrophy under diabetic conditions.

Sci Rep 2016 08 23;6:31506. Epub 2016 Aug 23.

Department of Nephrology and Rheumatology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P. R. China.

Glomerular mesangial cells (MCs) hypertrophy is one of the earliest pathological abnormalities in diabetic nephropathy (DN), which correlates with eventual glomerulosclerosis. This study aimed to investigate the therapeutic role of miRNA in diabetic glomerular MCs hypertrophy and synthesis of extracellular matrix (ECM). Microarray analysis revealed a significant up-regulation of miR-214 in the renal cortex of diabetic db/db mice, which was confirmed by real-time PCR of isolated glomeruli and primary cultured human MCs. In vitro studies showed that inhibition of miR-214 significantly reduced expression of α-SMA, SM22 and collagen IV, and partially restored phosphatase and tensin homolog (PTEN) protein level in high glucose-stimulated human MCs. Furthermore, we identified PTEN as the target of miR-214 by a luciferase assay in HEK293 cells. Moreover, overexpression of PTEN ameliorated miR-214-mediated diabetic MC hypertrophy while knockdown of PTEN mimicked the MC hypertrophy. In vivo study further confirmed that inhibition of miR-214 significantly decreased the expression of SM22, α-SMA and collagen IV, partially restored PTEN level, and attenuated albuminuria and mesangial expansion in db/db mice. In conclusion, cross talk between miR-214 and PTEN attenuated glomerular hypertrophy under diabetic conditions in vivo and in vitro. Therefore, miR-214 may represent a novel therapeutic target for DN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/srep31506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4994004PMC
August 2016

Congenital Heart Disease in Local and Migrant Elementary Schoolchildren in Dongguan, China.

Am J Cardiol 2016 Feb 18;117(3):461-4. Epub 2015 Nov 18.

Department of Cardiology, the Dongguan Affiliated Hospital of Medical College of Jinan University, the Fifth People's Hospital of Dongguan (also called Taiping People's Hospital of Dongguan), Guangdong, China.

The aim of this study was to determine the prevalence and treated status of congenital heart disease (CHD) in elementary schoolchildren and facilitate the long-term planning of health care, resource allocation, and development of targeted primary prevention strategies. From November 2011 to November 2012, 540,574 schoolchildren from 449 elementary schools were screened for CHD by trained doctors in Dongguan City. The schoolchildren who were suspected to have CHD were referred to a pediatric cardiologist and/or an echocardiographist for complete evaluation. Of them, 214,634 (39.7%) were local children and 325,940 (60.3%) were migrant children. The total prevalence of CHD was 2.14‰, and there was a significant difference (p <0.05) of the CHD prevalence between local (1.97‰) and migrant children (2.26‰). The treatment rates of CHD in local children and in migrant children were 63.51% and 47.21%, respectively (p <0.01). The commonest CHD was ventricular septal defect (43.13%), followed by atrial septal defect (25.84%) and patent ductus arteriosus (12.79%). With respect to gender, CHD was equally distributed between men and women. In conclusion, social, economic, and environmental risk factors that affect health of migrant children with CHD call for more attention from health policy makers and researchers in contemporary China. Efforts should be made to increase public health investment, establish health care manage system for children from migrant families, and increase the parents' awareness of preventing the CHD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.amjcard.2015.10.061DOI Listing
February 2016

Impact of subtropical climate on frequency of ambulance use for trauma patients in a coastal area of China.

Chin J Traumatol 2015 ;18(3):141-6

Emergency Department, the Second Affiliated Hospital of Shantou University Medical College, Guangdong 515041, China.

Purpose: To explore the impact of subtropical maritime monsoon climate on the frequency of ambulance use for trauma patients in a coastal region in China.

Method: Statistical analysis of data on ambulance use from the 120 Emergency Command Center in Shantou City, Guangdong Province, from January to December 2012 as well as daily meteorological data from a Shantou observatory was performed to determine how climatic factors (seasons, time, and weather) affect the frequency of ambulance use for trauma patients.

Results: The daily ambulance use for trauma patients differed between spring and summer or autumn (p<0.05), between sunny and rainy days (p<0.05), and between cloudy and lightly or moderately rainy days (p<0.05).We found a linear correlation between daily maximum temperature and daily ambulance use for trauma patients (R² =0.103, p<0.05). In addition, there was significant difference in ambulance use between good and bad weather (p<0.05).

Conclusion: Frequency of ambulance use for trauma patients is affected by the subtropical maritime monsoon climate in the coastal region. Better weather contributes to increased daily frequency of ambulance use, which is the highest in autumn and lowest in spring.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cjtee.2015.08.002DOI Listing
January 2017

Prevalence and clinical significance of cardiac murmurs in schoolchildren.

Arch Dis Child 2015 Nov 12;100(11):1028-31. Epub 2015 Jun 12.

Department of Cardiology, The Dongguan Affiliated Hospital of Medical College of Jinan University, the Fifth People's Hospital of Dongguan (also called Taiping People's Hospital of Dongguan), Dongguan, Guangdong, China.

Objective: To determine the prevalence and clinical significance of heart murmurs detected during heart disease screening among apparently healthy schoolchildren.

Design: Cross-sectional study.

Setting: 32 elementary schools in Dongguan City of China.

Patients: 81,213 schoolchildren aged 5-13 years from different elementary schools.

Main Outcome Measures: The prevalence and clinical significance of heart murmurs among schoolchildren.

Results: Murmurs were detected in 2193 schoolchildren (2.7%), of whom 215 had a structural heart disease (SHD). Of patients who had SHD, 198 children had congenital heart disease (CHD), 12 had mitral valve prolapse and 5 had rheumatic heart disease. In patients who had CHD, the most common diagnosis was a ventricular septal defect. With respect to sex, SHDs were equally distributed between males and females. Of the schoolchildren who had a murmur, 1797 (81.9%) had a murmur with the loudness of grade 1 or 2 and 396 (18.1%) had a murmur with the loudness of grades 3-6. The prevalence of SHD fell significantly with increasing age.

Conclusions: The study suggested that apparently healthy schoolchildren with grade ≤2 cardiac murmurs are least likely to have underlying SHD, especially in those aged ≥10 years. However, echocardiography should be performed in younger schoolchildren with cardiac murmur grade ≥3.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/archdischild-2014-307819DOI Listing
November 2015

Efficacy and safety of dipeptidyl peptidase-4 inhibitors in type 2 diabetes mellitus patients with moderate to severe renal impairment: a systematic review and meta-analysis.

PLoS One 2014 31;9(10):e111543. Epub 2014 Oct 31.

Department of Nephrology and Rheumatology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, P.R. China.

Objective: To perform a systematic review and meta-analysis regarding the efficacy and safety of dipeptidyl peptidase-4 (DDP-4) inhibitors ("gliptins") for the treatment of type 2 diabetes mellitus (T2DM) patients with moderate to severe renal impairment.

Methods: All available randomized-controlled trials (RCTs) that assessed the efficacy and safety of DDP-4 inhibitors compared with placebo, no treatment, or active drugs were identified using PubMed, EMBASE, Cochrane CENTRAL, conference abstracts, clinical trials.gov, pharmaceutical company websites, the FDA, and the EMA (up to June 2014). Two independent reviewers extracted the data, and a random-effects model was applied to estimate summary effects.

Results: Thirteen reports of ten studies with a total of 1,915 participants were included in the final analysis. Compared with placebo or no treatment, DPP-4 inhibitors reduced HbA1c significantly (-0.52%, 95%CI -0.64 to -0.39) and had no increased risk of hypoglycemia (RR 1.10, 95%CI 0.92 to 1.32) or weight gain. In contrast to glipizide monotherapy, DPP-4 inhibitors showed no difference in HbA1c lowering effect (-0.08%, 95% CI -0.40 to 0.25) but had a lower incidence of hypoglycemia (RR 0.40, 95%CI 0.23 to 0.69). Furthermore, DPP-4 inhibitors were well-tolerated, without any additional mortality and adverse events. However, the quality of evidence was mostly as low, as assessed using the GRADE system for each outcome.

Conclusions: DPP-4 inhibitors are effective at lowering HbA1c in T2DM patients with moderate to severe renal impairment. DPP-4 inhibitors also have a potential advantage in lowering the risk of adverse events. Regarding the low quality of the evidence according to GRADE, additional well-designed randomized trials that focus on the safety and efficacy of DPP-4 inhibitors in various CKD stages are needed urgently.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0111543PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4216116PMC
January 2016

A monoclonal antibody targeting neuropilin-1 inhibits adhesion of MCF7 breast cancer cells to fibronectin by suppressing the FAK/p130cas signaling pathway.

Anticancer Drugs 2014 Jul;25(6):663-72

aCancer Research Center, Medical College bDepartment of Materials Science and Engineering, College of Chemistry and Chemical Engineering, Xiamen University cDepartment of Oncology, The Affiliated Chenggong Hospital of Xiamen University, Xiamen, Fujian Province, China.

Neuropilin-1 (NRP-1) is a nontyrosine kinase coreceptor for semaphorin 3A and the vascular endothelial growth factor involved in tumor angiogenesis, growth, and metastasis and is regarded as a promising target for cancer therapy. In the present study, we investigated the effects of an anti-NRP-1 monoclonal antibody (mAb) that we generated for MCF7 breast cancer cellular adhesion studies. MTT, colony formation, and adhesion assays showed that our anti-NRP-1 mAb dose-dependently inhibited MCF7 proliferation and fibronectin adhesion, leading to a rounded cellular morphology. Further, rhodamine phalloidin stain revealed that fibronectin-dependent formation of actin stress fibers was inhibited by anti-NRP-1 mAb. Immunoprecipitation and western blot showed that anti-NRP-1 mAb treatment inhibited the formation of NRP-1-α5β1 integrin complexes and suppressed the phosphorylation of focal adhesion kinase and p130cas in MCF7 cells. These findings contribute to further understanding the NRP-1 function in cell adhesion and tumor metastasis. Moreover, our anti-NRP-1 mAb is a prospective drug candidate for tumor treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/CAD.0000000000000091DOI Listing
July 2014

A suppressor of cytokine signaling 1 antagonist enhances antigen-presenting capacity and tumor cell antigen-specific cytotoxic T lymphocyte responses by human monocyte-derived dendritic cells.

Clin Vaccine Immunol 2013 Sep 24;20(9):1449-56. Epub 2013 Jul 24.

Department of Oncology, 174th Hospital of the Chinese People's Liberation Army, Affiliated Chenggong Hospital of Xiamen University, Xiamen, Fujian Province, People's Republic of China.

The suppressor of cytokine signaling 1 (SOCS1) has emerged as a critical inhibitory molecule for controlling the cytokine response and antigen presentation by dendritic cells (DCs), thereby regulating the magnitude of both innate and adaptive immunity. The aim of this study was to investigate whether the SOCS1 antagonist pJAK2(1001-1013) peptide can weaken or block the inhibition function of SOCS1 in DCs by evaluating the phenotype and cytokine production, antigen-presenting, and specific T-cell-activating capacities of DCs electroporated with human gastric cancer cell total RNA. Furthermore, STAT1 activation of the JAK/STAT signal pathway mediated by SOCS1 was analyzed by Western blotting. The results demonstrate that the SOCS1 antagonist pJAK2(1001-1013) peptide upregulated the expression of the maturation marker (CD83) and costimulatory molecule (CD86) of RNA-electroporated human monocyte-derived mature DCs (mDCs), potentiated the capacity of mDCs to induce T-cell proliferation, stimulated the secretion of proinflammatory cytokines, and enhanced the cytotoxicity of tumor cell antigen-specific CTLs activated by human gastric cancer cell total RNA-electroporated mDCs. Data from Western blot analysis indicate that STAT1 was further activated in pJAK2(1001-1013) peptide-loaded mDCs. These results imply that the SOCS1 antagonist pJAK2(1001-1013) peptide is an effective reagent for the enhancement of antigen-specific antitumor immunity by DCs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1128/CVI.00130-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3889590PMC
September 2013

Recombinant human leptin induces growth inhibition and apoptosis in human gastric cancer MGC-803 cells.

Clin Exp Med 2013 Nov 23;13(4):305-14. Epub 2012 Sep 23.

Cancer Research Center, Medical College of Xiamen University, No. 422 SiMing South Road, Xiamen, 361005, Fujian Province, People's Republic of China.

The aim of this study is to investigate the effect of recombinant human leptin (rhLep) on the proliferation of human gastric cancer MGC-803 cells and its underlying mechanisms. RT-PCR was performed to identify the expression of leptin receptor (Ob-R). Cell proliferation was measured with MTT assay. DNA content and cell cycle were analyzed by flow cytometry. Apoptosis was assessed by DNA ladder assay and flow cytometry analysis using Annexin V-FITC/PI double staining. Underlying mechanisms of rhLep-induced apoptosis were evaluated by the activities of caspase-3, -8, -9, and cytochrome c release from mitochondria. Moreover, the phosphorylation of STAT3 in MGC-803 cells upon rhLep administration was detected by Western blot analysis. Our results demonstrated that two leptin receptors (Ob-Ra and Ob-Rb) were expressed in MGC-803 cells. rhLep diminished the proliferation rate of MGC-803 cells in a time- and concentration-dependent manner and induced MGC-803 cell apoptosis involving in the activation of caspase-8 and caspase-3 but not caspase-9. In addition, rhLep failed to induce cytochrome c release from mitochondria and had no effect on the activation of STAT3 in MGC-803 cells. Therefore, from these results, we concluded that rhLep significantly inhibited cell proliferation via G0/G1 phase cell cycle arrest and induced apoptosis through the extrinsic apoptotic pathway in human gastric cancer MGC-803 cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10238-012-0211-8DOI Listing
November 2013

Metformin interacts with AMPK through binding to γ subunit.

Mol Cell Biochem 2012 Sep 30;368(1-2):69-76. Epub 2012 May 30.

Department of Oncology, The 174th Hospital of the Chinese People's Liberation Army, The Affiliated Chenggong Hospital of Xiamen University, Xiamen 361003, Fujian, People's Republic of China.

Metformin acts as an energy regulator by activating 5'-adenosine monophosphate-activated protein kinase (AMPK), which is a key player in the regulation of energy homeostasis, but it is uncertain whether AMPK is its direct target. This study aims to investigate the possible interaction between metformin and AMPK. First, we verified that metformin can promote AMPK activation and induce ACC inactivation in human HepG2 cells using western blot. Then we predicted that metformin may interact with the γ subunit of AMPK by molecular docking analysis. The fluorescence spectrum and ForteBio assays indicated that metformin has a stronger binding ability to the γ subunit of AMPK than to α subunit. In addition, interaction of metformin with γ-AMPK resulted in a decrease in the α-helicity determined by CD spectra, but relatively little change was seen with α-AMPK. These results demonstrate that metformin may interact with AMPK through binding to the γ subunit.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11010-012-1344-5DOI Listing
September 2012

Retinoic acid receptor beta is required for anti-activator protein-1 activity by retinoic acid in gastric cancer cells.

Chin Med J (Engl) 2002 Jun;115(6):810-4

Key Laboratory of the Ministry of Education for Cell Biology and Tumor Cell Engineering, the School of Life Sciences, Xiamen University, China.

Objective: To investigate the role of retinoic acid receptor beta (RARbeta) in mediating inhibitory effect of all-trans retinoic acid (ATRA) on activator protein-1 (AP-1) activity in gastric cancer cells.

Methods: Transient transfection and chloramphenicol acetyltransferase (CAT) assay, Nort hern blot, gene transfection, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay, and anchorage independent growth assay were used.

Results: Transient transfection of RARbeta expression vector into MKN-45 cells resulted in the RARbeta concentration dependent repression of AP-1 activity induced by 12-o-tetradecanoylphorbol-13-acetate (TPA), regardless of the presence of ATRA. When the c-jun and c-fos expression vectors were cotransfected with the RARbeta expression vector into MKN-45 cells, AP-1 activity was also obviously repressed. The inhibitory effect, again, was RARbeta-concentration-dependent. The stable transfection of the RARbeta gene into MKN-45 cells led to cell growth inhibition and colony formation inhibition by ATRA. Furthermore, Cotransfection of both RARbeta/DNA binding domain (DBD) and reporter gene could not alter AP-1 activity, even in the presence of ATRA.However, when the cotransfection was substituted with the RARbeta/ligand binding domain (LBD), the inhibition was significantly enhanced by ATRA.

Conclusion: RARbeta might be required for anti-AP-1 activity, and contribute to growth inhibition of gastric cancer cells by ATRA.
View Article and Find Full Text PDF

Download full-text PDF

Source
June 2002