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      Resveratrol alleviates obesity-associated podocyte injury in ovariectomized obese rats

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          Abstract

          Obesity-associated podocyte injury increases in parallel with inflammatory responses. Resveratrol, as an anti-inflammatory and antioxidative agent, has been proven to be effective in obesity. The purpose of the present study was to investigate the function of resveratrol in the early stages of podocyte injury in ovariectomized rats fed a high-fat diet (HFD). The 3-month-old female Wistar rats were randomly divided into four groups: Sham operation with a standard diet; sham operation with a HFD; ovariectomy with a HFD (O+H); and ovariectomy plus HFD treatment with resveratrol (40 mg/kg/day) (O+H+R). Following 12 weeks, the weights of the rats were measured and serum was obtained to measure the levels of 17β-estradiol (E2), serum lipids, serum creatinine, fasting blood glucose (FBG) and insulin. Periodic acid-schiff staining was used to detect renal pathological changes. Meanwhile, the expression of the podocyte-associated proteins nephrin and Wilms' tumor-1 was investigated using immunohistochemical staining, and the levels of tumor necrosis factor-α, interleukin-6 and monocyte chemotactic protein-1 in renal tissues were determined using western blotting. Compared with the O+H group, resveratrol significantly reduced the body weight, serum levels of total cholesterol, low-density lipoprotein cholesterol, FBG and insulin resistance, and increased the levels of E2 in obese rats with an ovariectomy combined with an HFD (P<0.05). Compared with the O+H group, although the O+H+R group had no significant changes in renal pathology, the changes in the levels of podocyte-associated proteins and inflammatory markers were significantly reversed (P<0.05). These results suggest that resveratrol may attenuate early podocyte injury by improving lipid metabolism and insulin sensitivity, and subsequently inhibiting inflammatory responses in obese rats induced by an ovariectomy with a HFD.

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          National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9·1 million participants.

          Excess bodyweight is a major public health concern. However, few worldwide comparative analyses of long-term trends of body-mass index (BMI) have been done, and none have used recent national health examination surveys. We estimated worldwide trends in population mean BMI. We estimated trends and their uncertainties of mean BMI for adults 20 years and older in 199 countries and territories. We obtained data from published and unpublished health examination surveys and epidemiological studies (960 country-years and 9·1 million participants). For each sex, we used a Bayesian hierarchical model to estimate mean BMI by age, country, and year, accounting for whether a study was nationally representative. Between 1980 and 2008, mean BMI worldwide increased by 0·4 kg/m(2) per decade (95% uncertainty interval 0·2-0·6, posterior probability of being a true increase >0·999) for men and 0·5 kg/m(2) per decade (0·3-0·7, posterior probability >0·999) for women. National BMI change for women ranged from non-significant decreases in 19 countries to increases of more than 2·0 kg/m(2) per decade (posterior probabilities >0·99) in nine countries in Oceania. Male BMI increased in all but eight countries, by more than 2 kg/m(2) per decade in Nauru and Cook Islands (posterior probabilities >0·999). Male and female BMIs in 2008 were highest in some Oceania countries, reaching 33·9 kg/m(2) (32·8-35·0) for men and 35·0 kg/m(2) (33·6-36·3) for women in Nauru. Female BMI was lowest in Bangladesh (20·5 kg/m(2), 19·8-21·3) and male BMI in Democratic Republic of the Congo 19·9 kg/m(2) (18·2-21·5), with BMI less than 21·5 kg/m(2) for both sexes in a few countries in sub-Saharan Africa, and east, south, and southeast Asia. The USA had the highest BMI of high-income countries. In 2008, an estimated 1·46 billion adults (1·41-1·51 billion) worldwide had BMI of 25 kg/m(2) or greater, of these 205 million men (193-217 million) and 297 million women (280-315 million) were obese. Globally, mean BMI has increased since 1980. The trends since 1980, and mean population BMI in 2008, varied substantially between nations. Interventions and policies that can curb or reverse the increase, and mitigate the health effects of high BMI by targeting its metabolic mediators, are needed in most countries. Bill & Melinda Gates Foundation and WHO. Copyright © 2011 Elsevier Ltd. All rights reserved.
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            New insights into TGF-β/Smad signaling in tissue fibrosis

            Transforming growth factor-β1 (TGF-β1) is considered as a crucial mediator in tissue fibrosis and causes tissue scarring largely by activating its downstream small mother against decapentaplegic (Smad) signaling. Different TGF-β signalings play different roles in fibrogenesis. TGF-β1 directly activates Smad signaling which triggers pro-fibrotic gene overexpression. Excessive studies have demonstrated that dysregulation of TGF-β1/Smad pathway was an important pathogenic mechanism in tissue fibrosis. Smad2 and Smad3 are the two major downstream regulator that promote TGF-β1-mediated tissue fibrosis, while Smad7 serves as a negative feedback regulator of TGF-β1/Smad pathway thereby protects against TGF-β1-mediated fibrosis. This review presents an overview of the molecular mechanisms of TGF-β/Smad signaling pathway in renal, hepatic, pulmonary and cardiac fibrosis, followed by an in-depth discussion of their molecular mechanisms of intervention effects both in vitro and in vivo. The role of TGF-β/Smad signaling pathway in tumor or cancer is also discussed. Additionally, the current advances also highlight targeting TGF-β/Smad signaling pathway for the prevention of tissue fibrosis. The review reveals comprehensive pathophysiological mechanisms of tissue fibrosis. Particular challenges are presented and placed within the context of future applications against tissue fibrosis.
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              Risk factors for end-stage renal disease: 25-year follow-up.

              Few cohort studies have focused on risk factors for end-stage renal disease (ESRD). This investigation evaluated the prognostic value of several potential novel risk factors for ESRD after considering established risk factors. We studied 177 570 individuals from a large integrated health care delivery system in northern California who volunteered for health checkups between June 1, 1964, and August 31, 1973. Initiation of ESRD treatment was ascertained using US Renal Data System registry data through December 31, 2000. A total of 842 cases of ESRD were observed during 5 275 957 person-years of follow-up. This comprehensive evaluation confirmed the importance of established risk factors, including the following: male sex, older age, proteinuria, diabetes mellitus, lower educational attainment, and African American race, as well as higher blood pressure, body mass index, and serum creatinine level. The 2 most potent risk factors were proteinuria and excess weight. For proteinuria, the adjusted hazard ratios (HRs) were 7.90 (95% confidence interval [CI], 5.35-11.67) for 3 to 4+ on urine dipstick, 3.59 (2.82-4.57) for 1 to 2+ on urine dipstick, and 2.37 (1.79-3.14) for trace vs negative on urine dipstick. For excess weight, the HRs were 4.39 (95% CI, 3.38-5.70) for class 2 to class 3 obesity, 3.11 (2.51-3.84) for class 1 obesity, and 1.65 (1.39-1.97) for overweight vs normal weight. Furthermore, several independent novel risk factors for ESRD were identified, including lower hemoglobin level (1.33 [1.08-1.63] for lowest vs highest quartile), higher serum uric acid level (2.14 [1.65-2.77] for highest vs lowest quartile), self-reported history of nocturia (1.36 [1.17-1.58]), and family history of kidney disease (HR, 1.40 [95% CI, 1.02-1.90]). We confirmed the importance of established ESRD risk factors in this large cohort with broad sex and racial/ethnic representation. Lower hemoglobin level, higher serum uric acid level, self-reported history of nocturia, and family history of kidney disease are independent risk factors for ESRD.
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                Author and article information

                Journal
                Exp Ther Med
                Exp Ther Med
                ETM
                Experimental and Therapeutic Medicine
                D.A. Spandidos
                1792-0981
                1792-1015
                January 2020
                08 November 2019
                08 November 2019
                : 19
                : 1
                : 123-130
                Affiliations
                [1 ]Department of Nephrology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
                [2 ]Department of Nephrology, Qilu Hospital of Shandong University Qing-Dao, Qingdao, Shandong 266000, P.R. China
                [3 ]Department of Medical Administration, Weifang Traditional Chinese Medicine Hospital, Weifang, Shandong 261041, P.R. China
                [4 ]Department of Pathology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China
                Author notes
                Correspondence to: Professor Bei Jiang, Department of Nephrology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong 250012, P.R. China, E-mail: qilujiangbei@ 123456sdu.edu.cn
                [*]

                Contributed equally

                Article
                ETM-0-0-8178
                10.3892/etm.2019.8178
                6909629
                31853281
                7b0702b4-0052-46b1-a224-8adaf573570d
                Copyright: © Li et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 29 April 2018
                : 22 October 2019
                Categories
                Articles

                Medicine
                resveratrol,obesity,podocyte,inflammation,nephrin,wilms' tumor-1
                Medicine
                resveratrol, obesity, podocyte, inflammation, nephrin, wilms' tumor-1

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