ABSTRACT
The objective of this research is to assess how salvianolate impacts inflammation and oxidative stress in a laboratory setting, as well as to investigate the underlying mechanisms. HK-2 cells were subjected to different treatments, including normal glucose, mannitol, high glucose and high glucose plus salvianolate. Cell proliferation, death, MDA levels, IL-1ß, IL-6, TNF-α, MCP-1 concentrations, ROS levels, MMP, MPTP and ATP levels were assessed using various kits. The protein expressions of NOX4, TGF-ß1, P-Smad2, P-Smad3, Smad4 and Smad7 were ascertained through western blot analysis. Our results indicated salvianolate could reduce the release of IL-1ß, IL-6, TNF-α, as well as MCP-1, alleviate the levels of oxidative stress markers NOX4 and MDA, and improve mitochondrial function by increasing MMP and ATP levels while reducing ROS and MPTP opening. Furthermore, salvianolate inhibited the TGF-ß1/Smad2, Smad3 signaling pathway, suppressed Smad4 expression and increased Smad7 expression. Salvianolate seems to mitigate inflammation and oxidative stress through a variety of mechanisms. These discoveries offer valuable understanding into the possible mechanisms by which salvianolate may be employed in the treatment of diabetic nephropathy.
Subject(s)
Glucose , Inflammation , Oxidative Stress , Signal Transduction , Humans , Anti-Inflammatory Agents/pharmacology , Cell Line , Cell Proliferation/drug effects , Glucose/metabolism , Inflammation/drug therapy , Inflammation/metabolism , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Smad Proteins/drug effects , Smad Proteins/metabolism , Transforming Growth Factor beta/drug effects , Transforming Growth Factor beta/metabolism , Transforming Growth Factor beta1/drug effects , Transforming Growth Factor beta1/metabolismABSTRACT
The current study evaluated the effect of SGLT-2 inhibitor, dapagliflozin, on left ventricular remodeling in patients with type 2 diabetes and HFrEF. 60 patients were randomized (1:1) to receive dapagliflozin 10 mg once daily, or placebo double blind for 1 year. Patients underwent transthoracic echocardiography and doppler evaluation prior to dapagliflozin initiation and at 1 year. At 1year, adjusted mean difference versus placebo in change from baseline in LVEF was 2.5% (95% CI: 1.00-4.06, P = 0.002). Adjusted mean difference versus placebo in change from baseline in LVED volume was - 6.0ml (95% CI: -8.07 --3.87, P<0.001). Adjusted mean difference versus placebo in change from baseline in LVES volume was - 8.1ml (95% CI: -11.07 --5.14, P<0.001). Similarly, adjusted mean difference versus placebo in change from baseline in LVED diameter was - 1.6 mm (95% CI: -2.67 --0.62, P = 0.002). Adjusted mean difference versus placebo in change from baseline in VTI was 0.20 cm (95% CI: 0.01-0.38, P = 0.036). Dapagliflozin was well tolerated. Dapagliflozin was associated with significant and clinically meaningful improvement in echocardiographic parameters versus placebo in patients with type 2 diabetes and HFrEF.Registration number and date: ChiCTR2300072707, 21/06/2023.
Subject(s)
Diabetes Mellitus, Type 2 , Heart Failure , Sodium-Glucose Transporter 2 Inhibitors , Humans , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/adverse effects , Stroke Volume , Ventricular Function, Left , Ventricular Remodeling , Double-Blind MethodABSTRACT
The current study evaluated the effect of SGLT-2 inhibitor, empagliflozin, on blood pressure reduction in Chinese elderly hypertension patients with type 2 diabetes and investigated its possible mechanisms. 124 patients were randomized to receive 25 mg empagliflozin QD, or placebo double blind for 12 weeks. Patients underwent 24-h ABPM. Endothelial function and arterial stiffness were also measured prior to randomization and at week 12. At week 12, adjusted mean difference versus placebo in change from baseline in mean 24-h SBP was - 8.14 mmHg (95% CI - 10.32, - 3.96, P = 0.005). At week 12, adjusted mean difference versus placebo in change from baseline in mean 24-h DBP was - 5.27 mmHg (95% CI - 8.19, - 1.35, P < 0.001). Changes in office BP were consistent with ABPM. Empagliflozin was well tolerated. Empagliflozin was associated with significant and clinically meaningful reductions in BP versus placebo in Chinese elderly patients with type 2 diabetes and hypertension. The underlying mechanisms possiblely at least in part were the improvements of endothelial function and arterial stiffness associated with empagliflozin.Registration number: ChiCTR2100054678, Registration date: December 23, 2021.
Subject(s)
Diabetes Mellitus, Type 2 , Hypertension , Hypotension , Sodium-Glucose Transporter 2 Inhibitors , Aged , Benzhydryl Compounds , Blood Pressure , China , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Double-Blind Method , Glucosides , Humans , Hypertension/complications , Hypertension/drug therapy , Hypotension/chemically induced , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Treatment OutcomeABSTRACT
OBJECTIVE: This study aimed to investigate the association between D-dimer and cardiovascular diseases outcomes in patients with type 2 diabetes. METHODS: This is a single-center retrospective cohort study which was performed in a population who had health examinations between 2010 and 2015 in Jiangxi Provincial People's Hospital. All adult patients who were diagnosed with type 2 diabetes were screened. The cardiovascular diseases events were defined as all-cause mortality, new cardiovascular diseases incidence (acute myocardial infarction, unstable angina, stroke), or cardiovascular mortality. RESULTS: The median age was 59.6 years; 50.1% of participants were women; D-dimer was significantly associated with endpoint events. After multivariable adjustment for form of treatments and traditional risk factors, the odds ratio was 3.62 (95% CI 2.07-6.03) for the highest quartile of D-dimer with the lowest quartile as reference. Meanwhile, higher D-dimer levels were associated with a significant and independent higher risk of cause-specific cardiovascular disease events. CONCLUSION: High plasma concentrations of D-dimer were associated with increased risk of cardiovascular diseases events in patients with type 2 diabetes, even after adjusting for cardiovascular risk factors and form of treatments. Measurement of D-dimer may lead to a practical improvement in the current risk stratification criteria for patients with type 2 diabetes.
Subject(s)
Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Myocardial Infarction , Adult , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Female , Fibrin Fibrinogen Degradation Products , Humans , Male , Middle Aged , Retrospective Studies , Risk FactorsABSTRACT
The present study evaluated the effects of dapagliflozin, a SGLT2 inhibitor, or dapagliflozin plus metformin versus metformin monotherapy in patients with metabolic syndrome. This study included patients who admitted in Jiangxi Provincial People's Hospital from January 1, 2017 to December 31, 2019 and were diagnosed with metabolic syndrome. A total of 248 participants were randomly assigned to divide into three groups: dapagliflozin group; metformin group; dapagliflozin in combined with metformin group. Dapagliflozin group and metformin group were associated with similar improvements in components of metabolic syndrome. Relative to dapagliflozin or metformin monotherapy, dapagliflozin combined with metformin provided greater improvements in components of metabolic syndrome. So did HOMA-IR scores, fasting plasma insulin and inflammatory indicators (hsCRP, PMN/HDL-C and Monocytes/HDL-C). Dapagliflozin improved all components of metabolic syndrome in patients with metabolic syndrome. Furthermore, dapagliflozin combined with metformin showed more meaningful improvements in any of components of metabolic syndrome than dapagliflozin or metformin monotherapy.
Subject(s)
Benzhydryl Compounds/administration & dosage , Glucosides/administration & dosage , Hypoglycemic Agents/administration & dosage , Metabolic Syndrome/drug therapy , Metformin/administration & dosage , Adult , Body Weight , C-Reactive Protein/biosynthesis , Cholesterol, HDL/blood , Diabetes Mellitus, Type 2/blood , Female , Glycated Hemoglobin/metabolism , Humans , Hypoglycemic Agents/therapeutic use , Inflammation , Insulin/blood , Male , Middle Aged , Monocytes/cytologyABSTRACT
Fermented soybean lipids (FSE-C) is an extract enriched in active lipid classes. To explore whether FSE-C can alleviate cognitive damage triggered by the exposure to microwave radiation through regulating lipid metabolism, we employed lipidomic profiling based on a UPLC-MS to investigate differential lipid metabolites in the serum and hippocampus of rats. The results showed that orally administered FSE-C could protect from cognitive damage in microwave-induced rats. Serum lipidomics indicated that FSE-C effectively facilitated the recovery of 43 differential lipid metabolites including 6 phosphatidylcholines (PCs), 5 phosphatidylethanolamines (PEs), 1 phosphatidylinositol, 3 lysophosphatidylcholines (LPCs), 6 lysophosphatidylethanolamines (LPEs), and 22 triglycerides (TGs), which was consistent with the analysis of serum TG levels. Moreover, FSE-C positively coordinated hexacosanoic acid, 2 PCs, 4 sphingomyelins (SMs), and 11 TGs, through the hippocampal lipidomics. Collectively, these findings suggested that phospholipid and TG metabolisms were significantly modified in microwave-exposed rats. TGs may be regarded as potential biomarkers to further investigate and evaluate the roles and functions of FSE-C on the attenuation of cognitive damage induced by microwave radiation.