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Ouyang X.,Jiangsu Province Institute of Geriatrics | Lou Q.,Jiangsu Province Institute of Geriatrics | Gu L.,Jiangsu Province Institute of Geriatrics | Mo Y.,Jiangsu Province Institute of Geriatrics | And 8 more authors.
International Journal of Cardiology | Year: 2012

Objective: To establish a profile of the modifiable cardiovascular disease (CVD) risk factors in the office-working population of Nanjing, China. Background: With increasing modernization in China, CVD is now common among Chinese. Relevant information on the prevalence of CVD risk factors in China is, however, limited. Methods: We recruited 2648 office working people aged 23-79 years without history of CVD or diabetes from 7 work units of Nanjing during the years 2003 to 2005. Information from a self-reported questionnaire on lifestyle, physical examination, fasting blood for lipid profiles, and a 75-gram oral glucose tolerance test (OGTT) were obtained from each participant. We analyzed the following 7 CVD risk factors: smoking, inadequate physical activity, unhealthy dietary habit, obesity, hypertension, dyslipidemia, and hyperglycemia. Results: The whole study population had an average of 2.8 risk factors, while 95.6%, 79.4% and 55.6% of them had respectively ≥ 1, ≥ 2 and ≥ 3 of the 7 CVD risk factors. Men had a higher proportion of smoking, hypertension, dyslipidemia, hyperglycemia, but lower in light physical activity compared with women. Number of CVD risk factors increased with age. Although risk factors in men were more common than women, they increased alarmingly in postmenopausal women. Conclusions: CVD risk factors are common in office-working people in Nanjing, China. Effective interventions and treatment against risk factors should be adopted in the high risk population, which may greatly reduce the future burden of CVD in the Chinese population. © 2010 Elsevier Ireland Ltd. All rights reserved.


Chen L.,Nanjing Medical University | Li C.,Nanjing Medical University | Zhang R.,Nanjing Medical University | Gao X.,Nanjing Medical University | And 5 more authors.
Cancer Letters | Year: 2011

miRNAs play important roles in the regulation of cell proliferation, differentiation and apoptosis. The deregulation of miRNAs expression contributes to tumorigenesis by modulating oncogenic and tumor suppressor signaling pathways. Oncogenic transcription factor Myc can control expression of a large set of microRNAs (miRNAs). Previous studies have shown that the expression of miR-17-92 cluster, a polycistron encoding six microRNAs (miRNA), has close relationship with the expression of Myc. In current study, silencing Myc in multiple myeloma (MM)cells induced cell death and growth inhibition, and downregulated expression of miR-17-92 cluster. Overexpression of miR-17 or miR-18 could partly abrogated Myc-knockdown-induced MM cell apoptosis. One of the mechanism of Myc inhibiting MM cell apoptosis is through Myc activates miR-17-92 cluster and subsequently down-modulates proapoptotic protein Bim. Although miR-17-92 cluster are located at 13q31.3, the expression of miR-18, miR-19 and miR-20 (especially miR-19) in patients with del(13q14) was higher than those without del(13q14). Patients with miR-17, miR-20 and miR-92 high-expression had shorter PFS compared to those with miR-17, miR-20 and miR-92 low-expression. These results suggest the Myc-inducible miR-17-92 cluster miRNAs contribute to tumorigenesis and poor prognosis in multiple myeloma. © 2011 Elsevier Ireland Ltd.


Gu L.,Yamanashi University | Gu L.,Jiangsu Province Institute of Geriatrics | Kitamura M.,Yamanashi University
PLoS ONE | Year: 2012

Senescence-associated secretory phenotype (SASP) is characterized by abundant secretion of various proteins in senescent cells and implicated in tumor progression and inflammatory responses. However, the profile of secreted proteins in SASP is different from cell type to cell type, and currently, universal markers for SASP have not been reported. In the present investigation, we show that SASP-responsive alkaline phosphatase (SASP-RAP) serves as a sensitive, general and convenient marker for SASP. Etoposide-treated cells exhibited a senescent phenotype characterized by senile morphology, positive staining for senescence-associated β-galactosidase, growth arrest and induction of p53 and p21WAF1/CIP1. In SASP-RAP-transfected cells, exposure to etoposide increased secretion of SASP-RAP time-dependently. The kinetics of secretion was closely correlated with that of activation of the p21WAF1/CIP1 promoter and the p16INK4a promoter. The enhanced secretion of SASP-RAP by senescence was also observed in cells treated with other senescence inducers such as trichostatin A, doxorubicin and 4-phenylbutylic acid. The induction of SASP-RAP by senescence was similarly observed in natural replicative senescence. To confirm selectivity of the SASP-RAP response, cells were treated with senescence-related and -unrelated stimuli (IL-1β, LPS, TNF-α and TGF-β), and induction of senescence markers and activity of SASP-RAP were evaluated in parallel. Unlike etoposide, senescence-unrelated stimuli did not induce p53 and p21WAF1/CIP1, and it was correlated with lack of induction of SASP-RAP. In contrast, senescence-unrelated stimuli up-regulated conventional indicators for SASP, e.g., MMP-3, IL-6 and TIMP, without induction of senescence. SASP-RAP thus serves as a selective, convenient and general marker for detection and monitoring of SASP during cellular senescence. © 2012 Gu, Kitamura.


Liu H.,Nanjing University | Gu L.-B.,Jiangsu Province Institute of Geriatrics | Tu Y.,Nanjing University | Hu H.,Nanjing University | And 2 more authors.
Acta Pharmacologica Sinica | Year: 2016

Aim:A previous report shows that emodin extracted from the Chinese herbs rhubarb and giant knotweed rhizome can ameliorate the anticancer drug cisplatin-induced injury of HEK293 cells. In this study, we investigated whether and how emodin could protect renal tubular epithelial cells against cisplatin-induced nephrotoxicity in vitro.Methods:The viability and apoptosis of normal rat renal tubular epithelial cells (NRK-52E) were detected using formazan assay and flow cytometry analysis, respectively. The expression levels of cleaved caspase-3, autophagy maker LC3 I/II, and AMPK/mTOR signaling pathway-related proteins were measured with Western blot analysis. The changes of morphology and RFP-LC3 fluorescence were observed under microscopy.Results:Cisplatin (10-50 μmol/L) dose-dependently induced cell damage and apoptosis in NRK-52E cells, whereas emodin (10 and 100 μmol/L) significantly ameliorated cisplatin-induced cell damage, apoptosis and caspase-3 cleavage. Emodin dose-dependently increased LC3-II levels and induced RFP-LC3-containing punctate structures in NRK-52E cells. Furthermore, the protective effects of emodin were abolished by bafilomycin A1 (10 nmol/L), and mimicked by rapamycin (100 nmol/L). Moreover, emodin increased the phosphorylation of AMPK and suppressed the phosphorylation of mTOR. The AMPK inhibitor compound C (10 μmol/L) not only abolished emodin-induced autophagy activation, but also emodin-induced anti-apoptotic effects.Conclusion:Emodin ameliorates cisplatin-induced apoptosis of rat renal tubular cells in vitro through modulating the AMPK/mTOR signaling pathways and activating autophagy. Emodin may have therapeutic potential for the prevention of cisplatin-induced nephrotoxicity. © 2016 CPS and SIMM All rights reserved.


Gu L.,Yamanashi University | Gu L.,Jiangsu Province Institute of Geriatrics | Johno H.,Yamanashi University | Nakajima S.,Yamanashi University | And 4 more authors.
Laboratory Investigation | Year: 2013

Cordyceps militaris has been used in Eastern countries for the treatment of various diseases including chronic kidney diseases. However, there are no reports that identified its active entities and molecular mechanisms underlying its therapeutic effectiveness. 3′-Deoxyadenosine is a major nucleoside derivative isolated from C. militaris. Some reports suggested that both C. militaris and 3′-deoxyadenosine have anti-inflammatory and anti-fibrotic effects. In the present report, we investigated whether and how 3′-deoxyadenosine interferes with fibrogenic processes in the kidney. For this purpose, we examined effects of 3′-deoxyadenosine on the expression of collagens triggered by transforming growth factor-β (TGF-β1) and bone morphogenetic protein-4 (BMP-4), especially focusing on the regulation of Smad signaling in vitro and in vivo. We found that 3′-deoxyadenosine suppressed expression of collagens induced by TGF-β1 and BMP-4 dose dependently. This suppression occurred at the transcriptional level and was correlated with blunted activation of the CAGA box and the BMP-responsive element. The suppressive effect on the TGF-β/BMP signaling was mediated mainly by adenosine transporter and partially by the A3 adenosine receptor, but not A1/A2 adenosine receptors. 3′-Deoxyadenosine reduced levels of both phosphorylated and total Smad proteins (Smad1, 2 and 3) dose dependently. It was mainly ascribed to transcriptional suppression, but not to enhanced protein degradation and eIF2α-mediated translational suppression. Consistent with the in vitro results, in vivo administration with 3′-deoxyadenosine reduced the levels of phosphorylated and total Smad proteins, as well as the levels of Smad mRNAs, in the kidney subjected to unilateral ureteral obstruction. It was associated with blunted induction of type I collagen and α-smooth muscle actin, a decrease in the number of interstitial myofibroblasts and reduced fibrotic area. These results suggest that 3′-deoxyadenosine interferes with the TGF-β and BMP signaling via downregulation of Smads, which may underlie the anti-fibrotic effect of this agent. 3′-Deoxyadenosine may be useful for therapeutic intervention in various TGF-β-related fibrotic disorders.


Ouyang X.,Jiangsu Province Institute of Geriatrics | Lou Q.,Jiangsu Province Institute of Geriatrics | Gu L.,Jiangsu Province Institute of Geriatrics | Ko G.T.,Chinese University of Hong Kong | And 3 more authors.
Diabetology and Metabolic Syndrome | Year: 2015

Background: There remains controversy regarding which of the anthropometric indicators best defines obesity. In this study, we compared the efficacy of using body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) in the diagnosis of obesity and assessed their associations with diabetes, hypertension, and dyslipidemia in an urban working population in China. Methods: Anthropometric measurements, blood pressure, plasma lipids, fasting and 2-hour plasma glucose (PG) levels by a 75 gram oral glucose tolerance test (OGTT) were obtained from 2603 working Chinese who had no history of cardiovascular diseases or diabetes. Cardio-metabolic risk factors including high blood pressure, dyslipidemia, and glucose intolerance were evaluated. The diagnoses of overweight and obesity were based on the WHO definitions with BMI for general obesity and WC and WHR for central obesity. Results: Based on BMI, WC and WHR, there were 31.3%, 16.6%, 35.2% of the studied subjects, respectively, being overweight and 2.0%, 5.6%, 9.2% being obese. Among women but not men, more overweight and obese subjects were diagnosed using WHR and WC. The number of cardio-metabolic risks was higher by WC criterion than BMI and WHR in the whole group (p <0.05) and female subjects (p <0.01). Comparing the three anthropometric indexes predicting hypertension, hyperglycemia, dyslipidemia and multiple cardio-metabolic risks, for women, it was WC having the largest areas under ROC curves (0.759, 0.746, 0.701 and 0.773 respectively); while in men, it was WC for hypertension, WHR for hyperglycemia, BMI for dyslipidemia and WC for multiple cardio-metabolic risks (areas under ROC curves were 0.658, 0.686, 0.618 and 0.695 respectively). Conclusions: Among Chinese working population, the need of lower cutoff values to define overweight and obesity were observed. Central obesity indicator (WC) is the preferred measure to predict the presence of cardio-metabolic risk in Chinese female subjects. © 2015 Ouyang et al.; licensee BioMed Central.


PubMed | Jiangsu Province Institute of Geriatrics and Nanjing University
Type: | Journal: Chinese journal of integrative medicine | Year: 2015

To investigate the effects of Huaiqihuang Granules (, HQH), a mixture of Chinese herbs including Trametes robiniophila Murr, Fructus Lycii and Polygonatum sibiricum, on adriamycininduced nephropathy (ADRN) in rats and its underlying mechanisms.Rats with ADRN were divided into four groups: the sham group, the model group (distilled water), the low-dose HQH-treated (2 g/kg) group, and the high-dose HQH-treated (4 g/kg) group. Body weight and 24-h urinary protein (Upro) were checked every week. After 5-week intervention, at the end of the study, the rats were sacrifificed and blood samples were collected for examination of biochemical parameters, including glomerular morphological makers, podocyte shape, cellular apoptosis, expressions of nephrin, inflammatory and apoptosis markers.HQH ameliorated the rats general status, proteinuria, renal morphological appearance and glomerulosclerosis. The decreased expression of nephrin in ADRN rats was increased by HQH, as well as the impaired podocyte foot process fusion. Cytosolic levels of p65 and inhibitor of nuclear factor B (IB) were decreased in ADRN rats, and recovered by the treatment of HQH. Consistently, the induced expression of tumor necrosis factor (TNF-), phosphorylated nuclear factor B p65 (p-NFB p65) and IB in ADRN were markedly suppressed by HQH. In addition, induction of Bax, cleaved caspase-3 and cytochrome C in ADRN rats were suppressed by HQH, indicating the amelioration of apoptosis.HQH could ameliorate renal impairments in ADRN rats by increasing nephrin expression, inhibiting NF-B signaling pathway via the down-regulation of p-NF-B p65 and p-IB, and suppression of glomerular and tubular apoptosis.


PubMed | Yamanashi University, Jiangsu Province Institute of Geriatrics and Nanjing University
Type: Journal Article | Journal: Acta pharmacologica Sinica | Year: 2016

A previous report shows that emodin extracted from the Chinese herbs rhubarb and giant knotweed rhizome can ameliorate the anticancer drug cisplatin-induced injury of HEK293 cells. In this study, we investigated whether and how emodin could protect renal tubular epithelial cells against cisplatin-induced nephrotoxicity in vitro.The viability and apoptosis of normal rat renal tubular epithelial cells (NRK-52E) were detected using formazan assay and flow cytometry analysis, respectively. The expression levels of cleaved caspase-3, autophagy maker LC3 I/II, and AMPK/mTOR signaling pathway-related proteins were measured with Western blot analysis. The changes of morphology and RFP-LC3 fluorescence were observed under microscopy.Cisplatin (10-50 mol/L) dose-dependently induced cell damage and apoptosis in NRK-52E cells, whereas emodin (10 and 100 mol/L) significantly ameliorated cisplatin-induced cell damage, apoptosis and caspase-3 cleavage. Emodin dose-dependently increased LC3-II levels and induced RFP-LC3-containing punctate structures in NRK-52E cells. Furthermore, the protective effects of emodin were abolished by bafilomycin A1 (10 nmol/L), and mimicked by rapamycin (100 nmol/L). Moreover, emodin increased the phosphorylation of AMPK and suppressed the phosphorylation of mTOR. The AMPK inhibitor compound C (10 mol/L) not only abolished emodin-induced autophagy activation, but also emodin-induced anti-apoptotic effects.Emodin ameliorates cisplatin-induced apoptosis of rat renal tubular cells in vitro through modulating the AMPK/mTOR signaling pathways and activating autophagy. Emodin may have therapeutic potential for the prevention of cisplatin-induced nephrotoxicity.


PubMed | Jiangsu Province Institute of Geriatrics
Type: | Journal: Clinical and experimental medicine | Year: 2015

This study aimed to evaluate the glycemic levels in Chinese patients with type 2 diabetes mellitus (T2DM) and to explore the factors related to the results of glycemic control. A total of 2454 T2DM patients from 11 communities were examined for glycosylated hemoglobin levels and glycemic control options. Potential factors related to the results of glycemic control were analyzed using logistic regression. Of all the patients, 55.3% achieved the glycemic control target of HbA1c<7%. Multivariate analysis showed that male sex (OR 1.345, 95% CI 1.022-1.769; P=0.034), higher levels of fasting blood glucose (OR 1.954, 95% CI 1.778-2.147; P<0.001), and low-density lipoprotein cholesterol (OR 1.181, 95% CI 1.020-1.367; P=0.026) were significantly associated with poor glycemic control. The complexity of antidiabetics was also associated with poor glycemic control (P<0.05). Compared to diet and exercise, insulin injection was most strongly associated with poor glycemic control (OR 6.210, 95% CI 4.054-9.514; P<0.001). Male patients with higher levels of total cholesterol, lower levels of high-density lipoprotein cholesterol, or longer diabetic durations showed poor glycemic control, which was not found in female patients. Glycemic control was not satisfactory in T2DM patients of Nanjing communities. Various factors are associated with poor results of glycemic control.


Yusuf S.,Hamilton Health Sciences | Rangarajan S.,Hamilton Health Sciences | Teo K.,Hamilton Health Sciences | Islam S.,Hamilton Health Sciences | And 37 more authors.
New England Journal of Medicine | Year: 2014

BACKGROUND: More than 80% of deaths from cardiovascular disease are estimated to occur in low-income and middle-income countries, but the reasons are unknown. METHODS: We enrolled 156,424 persons from 628 urban and rural communities in 17 countries (3 high-income, 10 middle-income, and 4 low-income countries) and assessed their cardiovascular risk using the INTERHEART Risk Score, a validated score for quantifying risk-factor burden without the use of laboratory testing (with higher scores indicating greater risk-factor burden). Participants were followed for incident cardiovascular disease and death for a mean of 4.1 years. RESULTS: The mean INTERHEART Risk Score was highest in high-income countries, intermediate in middle-income countries, and lowest in low-income countries (P<0.001). However, the rates of major cardiovascular events (death from cardiovascular causes, myocardial infarction, stroke, or heart failure) were lower in high-income countries than in middle- and low-income countries (3.99 events per 1000 person-years vs. 5.38 and 6.43 events per 1000 person-years, respectively; P<0.001). Case fatality rates were also lowest in high-income countries (6.5%, 15.9%, and 17.3% in high-, middle-, and low-income countries, respectively; P = 0.01). Urban communities had a higher risk-factor burden than rural communities but lower rates of cardiovascular events (4.83 vs. 6.25 events per 1000 person-years, P<0.001) and case fatality rates (13.52% vs. 17.25%, P<0.001). The use of preventive medications and revascularization procedures was significantly more common in high-income countries than in middle- or low-income countries (P<0.001). CONCLUSIONS: Although the risk-factor burden was lowest in low-income countries, the rates of major cardiovascular disease and death were substantially higher in low-income countries than in high-income countries. The high burden of risk factors in high-income countries may have been mitigated by better control of risk factors and more frequent use of proven pharmacologic therapies and revascularization. Copyright © 2014 Massachusetts Medical Society.

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