human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Although resveratrol has widely been studied for its potential health benefits , little is known about its metabolic effects in humans . Our aims were to determine whether the polyphenol resveratrol improves insulin sensitivity in type 2 diabetic patients and to gain some insight into the mechanism of its action . After an initial general examination ( including blood chemistry ) , nineteen patients enrolled in the 4-week-long double-blind study were r and omly assigned into two groups : a resveratrol group receiving oral 2 × 5 mg resveratrol and a control group receiving placebo . Before and after the second and fourth weeks of the trial , insulin resistance/sensitivity , creatinine-normalised ortho-tyrosine level in urine sample s ( as a measure of oxidative stress ) , incretin levels and phosphorylated protein kinase B (pAkt):protein kinase B ( Akt ) ratio in platelets were assessed and statistically analysed . After the fourth week , resveratrol  significantly decreased insulin resistance ( homeostasis model of assessment for insulin resistance ) and urinary ortho-tyrosine excretion , while it increased the pAkt : Akt ratio in platelets . On the other h and , it had no effect on parameters that relate to β-cell function ( i.e. homeostasis model of assessment of β-cell function ) . The present study shows for the first time that resveratrol  improves insulin sensitivity in humans , which might be due to a resveratrol-induced  decrease in oxidative stress that leads to a more efficient insulin signalling via the Akt pathway The protective role of resveratrol in myocardial ischemia/reperfusion is not well understood . The aim of this study was to investigate whether resveratrol modulates inflammation and oxidative stress and the possible role of nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element ( ARE ) pathway in an ischemia/reperfusion injured rat heart model . Rats were r and omly exposed to sham operation , myocardial ischemia/reperfusion ( MI/R ) alone , and MI/R + resveratrol . The results demonstrated that compared to MI/R , resveratrol improved cardiac function , reduced myocardial infa rct ion area , myocardial myeloperoxidase ( MPO ) levels , serum creatinine kinase ( CK ) and lactate dehydrogenase ( LDH ) levels .  Resveratrol also markedly enhanced the activities of antioxidant enzymes superoxide dismutase ( SOD ) and glutathione peroxidase ( GSH-PX ) , and reduced the level of malondialdehyde ( MDA ) in MI/R rats . Resveratrol also enhanced levels of Nrf2 and heme oxygenase-1 . In summary , these results demonstrated that resveratrol exerted significant antioxidant and cardioprotective effects following myocardial ischemia , possibly through the activation of the Nrf2/ARE signaling pathway Nonalcoholic fatty liver disease ( NAFLD ) is the most common chronic liver disease in the world . Resveratrol is a polyphenolic compound with antioxidant capacity that shows beneficial effects on down-regulation of inflammatory mediators and metabolic disorders . We hypothesized that supplementation with resveratrol can further improve the efficacy of lifestyle modifications in the management of NAFLD . In this r and omized , double-blinded , controlled clinical trial , 50 NAFLD patients were supplemented with either a 500-mg resveratrol capsule or a placebo capsule for 12 weeks . Both groups were advised to follow an energy-balanced diet and received physical activity recommendations  . Serum liver enzymes , inflammatory markers , hepatic steatosis and fibrosis , dietary intake , anthropometric measurements , and physical activity were assessed at both baseline and the end of the study . In both groups , anthropometric measurements ( weight , body mass index , waist circumference ) , liver enzymes , and steatosis grade improved ( P < 005 ) . Resveratrol supplementation was associated with a significant reduction in liver enzyme alanine aminotransferase , inflammatory cytokines , nuclear factor κB activity , serum cytokeratin-18 , and hepatic steatosis grade , as compared with placebo supplementation ( P < .05 ) . For the treatment of NAFLD , our results showed that 12 weeks of supplementation of 500 mg resveratrol , along with lifestyle modification , is superior to lifestyle modification alone . This is at least partially due to the attenuation of inflammatory markers and hepatocellular apoptosis . More studies are needed to confirm and increase the clinical application of the present results Purpose The grape and wine polyphenol resveratrol exerts cardiovascular benefits but evidence from r and omized human clinical trials is very limited . We investigated dose-depending effects of a resveratrol-containing grape supplement on stable patients with coronary artery disease ( CAD ) treated according to currently accepted guidelines for secondary prevention of cardiovascular disease . Methods In a triple-blind , r and omized , placebo-controlled , one-year follow-up , 3-arm pilot clinical trial , 75 stable-CAD patients received 350 mg/day of placebo , resveratrol-containing grape extract ( grape phenolics plus 8 mg resveratrol ) or conventional grape extract lacking resveratrol during 6 months , and a double dose for the following 6 months . Changes in circulating inflammatory and fibrinolytic biomarkers were analyzed . Moreover , the transcriptional profiling of inflammatory genes in peripheral blood mononuclear cells ( P BMC s ) was explored using microarrays and functional gene expression analysis . Results After 1 year , in contrast to the placebo and conventional grape extract groups , the resveratrol-containing grape extract group showed an increase of the anti-inflammatory serum adiponectin ( 9.6 % , p = 0.01 ) and a decrease of the thrombogenic plasminogen activator inhibitor type 1 ( PAI-1 ) ( −18.6 % , p = 0.05 ) . In addition , 6 key inflammation-related transcription factors were predicted to be significantly activated or inhibited , with 27 extracellular-space acting genes involved in inflammation , cell migration and T-cell interaction signals presenting downregulation ( p < 0.05 ) in P BMC s. No adverse effects were detected in relation to the study products . Conclusions Chronic daily consumption of a resveratrol-containing grape nutraceutical could exert cardiovascular benefits in stable-CAD patients treated according to current evidence -based st and ards , by increasing serum adiponectin , preventing PAI-1 increase and inhibiting atherothrombotic signals in P BMC Background : Exercise can lead to acute oxidative stress , which can result in oxidative damage and induce inflammation . Resveratrol may reduce the levels of inflammatory cytokines . Thus , we investigated the effects of this compound on the plasma levels of tumor necrosis factor-α ( TNF-α ) and interleukin 6 ( IL-6 ) in male professional basketball players . Methods : Twenty healthy male professional basketball players were r and omized into two groups ( 10 each ) . For 6 weeks , they received daily either 200 mg of polygonum cuspidatum extract ( PCE ) st and ardized to contain 20 % trans-resveratrol equivalent to 40 mg trans-resveratrol or placebo . Indices of inflammation were measured before and after 6 weeks of supplementation . Results : There was a significant reduction in plasma levels of TNF-a and IL-6 after 6 weeks of supplementation ; while no change was observed in these markers in the control group . Conclusions : Present study shows that 6 weeks of PCE containing resveratrol supplementation reduces the inflammation in male professional basketball players It has been previously reported that Toll‑like receptor 4 (TLR4)/NF‑κB signaling mediates early inflammation during myocardial ischemia and reperfusion . It has additionally been suggested that resveratrol produces cardioprotective and anti‑inflammatory effects . The aim of the present study was to investigate whether resveratrol could modulate TLR4/NF‑κB signaling , reduce neutrophil accumulation and TNF‑α induction in an ischemia/reperfusion injured rat heart model . Rats were r and omly exposed to a sham operation , myocardial ischemia and reperfusion ( MI/R ) , MI/R + resveratrol or MI/R + resveratrol + L‑NAME . The data showed that following MI/R , the expression of myocardial TLR4 and NF‑κB increased significantly in the area of induced ischemia . As compared with MI/R , resveratrol significantly attenuated the expression of TLR4 and NF‑κB and reduced the levels of myeloperoxidase , serum and myocardial TNF‑α production , myocardial infa rct size and myocardial apoptosis induced by MI/R. All the effects of resveratrol were abolished upon application of L‑NAME , a nitric oxide ( NO ) synthase inhibitor . These data provide evidence that resveratrol inhibits TLR4/NF‑κB signaling in the rat heart subjected to MI/R , and the anti‑inflammatory effect of resveratrol is associated with NO production The polyphenol resveratrol is considered to exert many beneficial actions , such as antioxidant , anti-inflammatory , insulin-sensitizer and anticancer effects . Its benefits in patients with type 2 diabetes mellitus ( T2DM ) are controversial . Our aims were to determine whether resveratrol supplementation at two different dosages ( 500 and 40mg/day ) for 6 months i ) reduced the concentrations of C-reactive-protein ( CRP ) and ii ) ameliorated the metabolic pattern of T2DM patients .  In the present double-blind , r and omized , placebo-controlled trial , 192 T2DM patients were r and omized to receive resveratrol 500mg/day ( Resv500arm ) , resveratrol 40mg/day ( Resv40arm ) or placebo for 6-months . At baseline and at the trial end , CRP values , anthropometric , metabolic and liver parameters were determined . No serious adverse event occurred . A dose-dependent , though not significant , CRP decrease of 5.6 % ( Resv40arm ) and 15.9 % ( Resv500arm ) was observed vs placebo . We failed to detect significant differences in weight , BMI , waist circumference , and values of arterial blood pressure , fasting glucose , glycated hemoglobin , insulin , C-peptide , free fatty acids , liver transaminases , uric acid , adiponectin , interleukin-6 , in both the Resv500 and Resv40 arms vs placebo . Total cholesterol and triglycerides slightly increased in the Resv500arm . Subgroup analyses revealed that lower diabetes duration ( in both Resv500 and Resv40arms ) , and , in the Resv500arm , younger age , aspirin use and being a smoker were associated with a significantly higher CRP reduction vs placebo . The supplementations with 40mg/day or 500mg/day resveratrol did neither reduce CRP concentrations , nor improve the metabolic pattern of T2DM patients OBJECTIVE Smokers are characterized by a low- grade systemic inflammatory state and an oxidant-antioxidant imbalance . Few human studies were conducted on the effects of resveratrol , a natural compound with anti-inflammatory and antioxidant properties , and no trial on smokers has been performed to date . We evaluated whether resveratrol has beneficial effects on markers of inflammation and oxidative stress in smokers . METHODS AND RESULTS A r and omized , double- blind , cross-over trial was performed in 50 healthy adult smokers : 25 were r and omly allocated to " resveratrol-first " ( 30-days : 500 mg resveratrol/day , 30-days wash-out , 30-days placebo ) and 25 to " placebo-first " ( 30-days placebo , 30-days wash-out , 30-days 500 mg resveratrol/day ) . Resveratrol significantly reduced C-reactive protein ( CRP ) and triglyceride concentrations , and increased Total Antioxidant Status ( TAS ) values . After analyzing data with general linear models to assess period and carry-over effects , the ratios of the values after resveratrol to those after placebo were respectively : 0.47 ( 95%CI 0.38 - 0.59 ) -CRP- and 0.71 ( 95%CI 0.65 - 0.78 ) -triglycerides- , while TAS increased by 74.2 μmol/L ( 95%CI 60.8 - 87.6 ) . Uric acid , glucose , insulin , cholesterol , liver enzyme concentrations , and weight , waist circumference , and blood pressure values did not significantly change after resveratrol supplementation . CONCLUSIONS Because resveratrol has anti-inflammatory , anti-oxidant , and hypotriglyceridemic effects , its supplementation may beneficially affect the increased cardiovascular risk of healthy smokers OBJECTIVE This study aim ed to evaluate the effects of short-term ( 60-d ) 
    Output:
    
agent
IMPLICATION S Available evidence from RCTs suggests that resveratrol supplementation significantly reduced TNF-α and hs-CRP levels .
Significant improvement in inflammatory markers  support resveratrol as an adjunct to pharmacologic management of metabolic diseases
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Although resveratrol has widely been studied for its potential health benefits , little is known about its metabolic effects in humans . Our aims were to determine whether the polyphenol resveratrol improves insulin sensitivity in type 2 diabetic patients and to gain some insight into the mechanism of its action . After an initial general examination ( including blood chemistry ) , nineteen patients enrolled in the 4-week-long double-blind study were r and omly assigned into two groups : a resveratrol group receiving oral 2 × 5 mg resveratrol and a control group receiving placebo . Before and after the second and fourth weeks of the trial , insulin resistance/sensitivity , creatinine-normalised ortho-tyrosine level in urine sample s ( as a measure of oxidative stress ) , incretin levels and phosphorylated protein kinase B (pAkt):protein kinase B ( Akt ) ratio in platelets were assessed and statistically analysed . After the fourth week , resveratrol  significantly decreased insulin resistance ( homeostasis model of assessment for insulin resistance ) and urinary ortho-tyrosine excretion , while it increased the pAkt : Akt ratio in platelets . On the other h and , it had no effect on parameters that relate to β-cell function ( i.e. homeostasis model of assessment of β-cell function ) . The present study shows for the first time that resveratrol  improves insulin sensitivity in humans , which might be due to a resveratrol-induced  decrease in oxidative stress that leads to a more efficient insulin signalling via the Akt pathway The protective role of resveratrol in myocardial ischemia/reperfusion is not well understood . The aim of this study was to investigate whether resveratrol modulates inflammation and oxidative stress and the possible role of nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element ( ARE ) pathway in an ischemia/reperfusion injured rat heart model . Rats were r and omly exposed to sham operation , myocardial ischemia/reperfusion ( MI/R ) alone , and MI/R + resveratrol . The results demonstrated that compared to MI/R , resveratrol improved cardiac function , reduced myocardial infa rct ion area , myocardial myeloperoxidase ( MPO ) levels , serum creatinine kinase ( CK ) and lactate dehydrogenase ( LDH ) levels .  Resveratrol also markedly enhanced the activities of antioxidant enzymes superoxide dismutase ( SOD ) and glutathione peroxidase ( GSH-PX ) , and reduced the level of malondialdehyde ( MDA ) in MI/R rats . Resveratrol also enhanced levels of Nrf2 and heme oxygenase-1 . In summary , these results demonstrated that resveratrol exerted significant antioxidant and cardioprotective effects following myocardial ischemia , possibly through the activation of the Nrf2/ARE signaling pathway Nonalcoholic fatty liver disease ( NAFLD ) is the most common chronic liver disease in the world . Resveratrol is a polyphenolic compound with antioxidant capacity that shows beneficial effects on down-regulation of inflammatory mediators and metabolic disorders . We hypothesized that supplementation with resveratrol can further improve the efficacy of lifestyle modifications in the management of NAFLD . In this r and omized , double-blinded , controlled clinical trial , 50 NAFLD patients were supplemented with either a 500-mg resveratrol capsule or a placebo capsule for 12 weeks . Both groups were advised to follow an energy-balanced diet and received physical activity recommendations  . Serum liver enzymes , inflammatory markers , hepatic steatosis and fibrosis , dietary intake , anthropometric measurements , and physical activity were assessed at both baseline and the end of the study . In both groups , anthropometric measurements ( weight , body mass index , waist circumference ) , liver enzymes , and steatosis grade improved ( P < 005 ) . Resveratrol supplementation was associated with a significant reduction in liver enzyme alanine aminotransferase , inflammatory cytokines , nuclear factor κB activity , serum cytokeratin-18 , and hepatic steatosis grade , as compared with placebo supplementation ( P < .05 ) . For the treatment of NAFLD , our results showed that 12 weeks of supplementation of 500 mg resveratrol , along with lifestyle modification , is superior to lifestyle modification alone . This is at least partially due to the attenuation of inflammatory markers and hepatocellular apoptosis . More studies are needed to confirm and increase the clinical application of the present results Purpose The grape and wine polyphenol resveratrol exerts cardiovascular benefits but evidence from r and omized human clinical trials is very limited . We investigated dose-depending effects of a resveratrol-containing grape supplement on stable patients with coronary artery disease ( CAD ) treated according to currently accepted guidelines for secondary prevention of cardiovascular disease . Methods In a triple-blind , r and omized , placebo-controlled , one-year follow-up , 3-arm pilot clinical trial , 75 stable-CAD patients received 350 mg/day of placebo , resveratrol-containing grape extract ( grape phenolics plus 8 mg resveratrol ) or conventional grape extract lacking resveratrol during 6 months , and a double dose for the following 6 months . Changes in circulating inflammatory and fibrinolytic biomarkers were analyzed . Moreover , the transcriptional profiling of inflammatory genes in peripheral blood mononuclear cells ( P BMC s ) was explored using microarrays and functional gene expression analysis . Results After 1 year , in contrast to the placebo and conventional grape extract groups , the resveratrol-containing grape extract group showed an increase of the anti-inflammatory serum adiponectin ( 9.6 % , p = 0.01 ) and a decrease of the thrombogenic plasminogen activator inhibitor type 1 ( PAI-1 ) ( −18.6 % , p = 0.05 ) . In addition , 6 key inflammation-related transcription factors were predicted to be significantly activated or inhibited , with 27 extracellular-space acting genes involved in inflammation , cell migration and T-cell interaction signals presenting downregulation ( p < 0.05 ) in P BMC s. No adverse effects were detected in relation to the study products . Conclusions Chronic daily consumption of a resveratrol-containing grape nutraceutical could exert cardiovascular benefits in stable-CAD patients treated according to current evidence -based st and ards , by increasing serum adiponectin , preventing PAI-1 increase and inhibiting atherothrombotic signals in P BMC Background : Exercise can lead to acute oxidative stress , which can result in oxidative damage and induce inflammation . Resveratrol may reduce the levels of inflammatory cytokines . Thus , we investigated the effects of this compound on the plasma levels of tumor necrosis factor-α ( TNF-α ) and interleukin 6 ( IL-6 ) in male professional basketball players . Methods : Twenty healthy male professional basketball players were r and omized into two groups ( 10 each ) . For 6 weeks , they received daily either 200 mg of polygonum cuspidatum extract ( PCE ) st and ardized to contain 20 % trans-resveratrol equivalent to 40 mg trans-resveratrol or placebo . Indices of inflammation were measured before and after 6 weeks of supplementation . Results : There was a significant reduction in plasma levels of TNF-a and IL-6 after 6 weeks of supplementation ; while no change was observed in these markers in the control group . Conclusions : Present study shows that 6 weeks of PCE containing resveratrol supplementation reduces the inflammation in male professional basketball players It has been previously reported that Toll‑like receptor 4 (TLR4)/NF‑κB signaling mediates early inflammation during myocardial ischemia and reperfusion . It has additionally been suggested that resveratrol produces cardioprotective and anti‑inflammatory effects . The aim of the present study was to investigate whether resveratrol could modulate TLR4/NF‑κB signaling , reduce neutrophil accumulation and TNF‑α induction in an ischemia/reperfusion injured rat heart model . Rats were r and omly exposed to a sham operation , myocardial ischemia and reperfusion ( MI/R ) , MI/R + resveratrol or MI/R + resveratrol + L‑NAME . The data showed that following MI/R , the expression of myocardial TLR4 and NF‑κB increased significantly in the area of induced ischemia . As compared with MI/R , resveratrol significantly attenuated the expression of TLR4 and NF‑κB and reduced the levels of myeloperoxidase , serum and myocardial TNF‑α production , myocardial infa rct size and myocardial apoptosis induced by MI/R. All the effects of resveratrol were abolished upon application of L‑NAME , a nitric oxide ( NO ) synthase inhibitor . These data provide evidence that resveratrol inhibits TLR4/NF‑κB signaling in the rat heart subjected to MI/R , and the anti‑inflammatory effect of resveratrol is associated with NO production The polyphenol resveratrol is considered to exert many beneficial actions , such as antioxidant , anti-inflammatory , insulin-sensitizer and anticancer effects . Its benefits in patients with type 2 diabetes mellitus ( T2DM ) are controversial . Our aims were to determine whether resveratrol supplementation at two different dosages ( 500 and 40mg/day ) for 6 months i ) reduced the concentrations of C-reactive-protein ( CRP ) and ii ) ameliorated the metabolic pattern of T2DM patients .  In the present double-blind , r and omized , placebo-controlled trial , 192 T2DM patients were r and omized to receive resveratrol 500mg/day ( Resv500arm ) , resveratrol 40mg/day ( Resv40arm ) or placebo for 6-months . At baseline and at the trial end , CRP values , anthropometric , metabolic and liver parameters were determined . No serious adverse event occurred . A dose-dependent , though not significant , CRP decrease of 5.6 % ( Resv40arm ) and 15.9 % ( Resv500arm ) was observed vs placebo . We failed to detect significant differences in weight , BMI , waist circumference , and values of arterial blood pressure , fasting glucose , glycated hemoglobin , insulin , C-peptide , free fatty acids , liver transaminases , uric acid , adiponectin , interleukin-6 , in both the Resv500 and Resv40 arms vs placebo . Total cholesterol and triglycerides slightly increased in the Resv500arm . Subgroup analyses revealed that lower diabetes duration ( in both Resv500 and Resv40arms ) , and , in the Resv500arm , younger age , aspirin use and being a smoker were associated with a significantly higher CRP reduction vs placebo . The supplementations with 40mg/day or 500mg/day resveratrol did neither reduce CRP concentrations , nor improve the metabolic pattern of T2DM patients OBJECTIVE Smokers are characterized by a low- grade systemic inflammatory state and an oxidant-antioxidant imbalance . Few human studies were conducted on the effects of resveratrol , a natural compound with anti-inflammatory and antioxidant properties , and no trial on smokers has been performed to date . We evaluated whether resveratrol has beneficial effects on markers of inflammation and oxidative stress in smokers . METHODS AND RESULTS A r and omized , double- blind , cross-over trial was performed in 50 healthy adult smokers : 25 were r and omly allocated to " resveratrol-first " ( 30-days : 500 mg resveratrol/day , 30-days wash-out , 30-days placebo ) and 25 to " placebo-first " ( 30-days placebo , 30-days wash-out , 30-days 500 mg resveratrol/day ) . Resveratrol significantly reduced C-reactive protein ( CRP ) and triglyceride concentrations , and increased Total Antioxidant Status ( TAS ) values . After analyzing data with general linear models to assess period and carry-over effects , the ratios of the values after resveratrol to those after placebo were respectively : 0.47 ( 95%CI 0.38 - 0.59 ) -CRP- and 0.71 ( 95%CI 0.65 - 0.78 ) -triglycerides- , while TAS increased by 74.2 μmol/L ( 95%CI 60.8 - 87.6 ) . Uric acid , glucose , insulin , cholesterol , liver enzyme concentrations , and weight , waist circumference , and blood pressure values did not significantly change after resveratrol supplementation . CONCLUSIONS Because resveratrol has anti-inflammatory , anti-oxidant , and hypotriglyceridemic effects , its supplementation may beneficially affect the increased cardiovascular risk of healthy smokers OBJECTIVE This study aim ed to evaluate the effects of short-term ( 60-d ) 
    Output:
    