CYP2J2-derived epoxyeicosatrienoic acids protect against doxorubicin-induced cardiotoxicity by reducing oxidative stress and apoptosis via activation of the AMPK pathway.

Objective: Despite the widespread use of doxorubicin (DOX) in chemotherapy, it can cause cardiotoxicity, which severely limits its potential clinical use. CYP2J2-derived epoxyeicosatrienoic acids (EETs) exert cardioprotective effects by maintaining cardiac homeostasis. The roles and latent mechanisms of EETs in DOX cardiotoxicity remain uncertain. We investigated these aspects using mouse tissue and cell culture models. Methods: C57BL/6J mice were injected with rAAV9-CYP2J2 or a control vector via the caudal vein. A five-week intraperitoneal course of DOX (5 mg/kg per week) was administered. After pretreatment with 14,15-EET, H9C2 cells were treated for 24-h with DOX, to use as a cell model to verify the role of EETs in cardiotoxicity in vitro. Results: CYP2J2 overexpression mitigated DOX-induced cardiotoxicity, as shown by the diminished cardiac injury marker levels, improved heart function, reduced oxidative stress, and inhibition of myocardial apoptosis in vivo. These protective roles are associated with the enhancement of antioxidant and anti-apoptotic abilities and the activation of the AMPK pathway. 14,15-EET suppresses DOX-induced oxidative stress, mitochondrial dysfunction, and apoptosis in H9C2 cells. AMPK knockdown partially abolished the cardioprotective effects of 14,15-EET against oxidative damage and apoptosis in DOX-treated cells, suggesting that AMPK is responsible for EET-mediated protection against cardiotoxicity. Conclusion: CYP2J2-derived EETs confer myocardial protection against DOX-induced toxicity by activating the AMPK pathway, which reduces oxidative stress, mitochondrial dysfunction, and apoptosis.

Diagnostic Value of the Combination of Ultrasonographic Optic Nerve Sheath Diameter and Width of Crural Cistern with Respect to the Intracranial Pressure in Patients Treated with Decompressive Craniotomy.

BACKGROUND: The monitoring of intracranial pressure (ICP) and detection of increased ICP are crucial because such increases may cause secondary brain injury and a poor prognosis. Although numerous ultrasound parameters, including optic nerve sheath diameter (ONSD), width of the crural cistern (WCC), and the flow velocities of the central retinal artery and middle cerebral artery, can be measured in patients after hemicraniectomy, researchers have yet to determine which of these is better for evaluating ICP. This study aimed to analyze the correlation between ICP and ultrasound parameters and investigate the best noninvasive estimator of ICP. METHODS: This observational study enrolled 50 patients with brain injury after hemicraniectomy from January 2021 to December 2021. All patients underwent invasive ICP monitoring with microsensor, transcranial, and ocular ultrasound postoperatively. We measured the ONSD including the dura mater (ONSDI), the ONSD excluding the dura mater, the optic nerve diameter (OND), the eyeball transverse diameter (ETD), the WCC, and the flow velocities in the central retinal artery and middle cerebral artery. Then, we calculated the ONSDI-OND (the difference between ONSDI and OND) and ONSDI/ETD (the ratio of ONSDI to ETD). Patients were divided into a normal ICP group (n = 35) and an increased ICP group (≥ 20 mm Hg, n = 15) according to the ICP measurements. Correlations were then assessed between the values of the ultrasound parameters and ICP. RESULTS: The ONSDI, ONSDI-OND, and ONSDI/ETD were positively associated with ICP (r = 0.455, 0.482, 0.423 and p = 0.001, < 0.001, 0.002, respectively), whereas the WCC was negatively associated with ICP (r = - 0.586, p < 0.001). The WCC showed the highest predictive power for increased ICP (area under the receiver operating characteristic curve [AUC] = 0.904), whereas the ONSDI-OND and ONSDI also presented with acceptable predictive power among the ONSD-related parameters (AUC = 0.831, 0.803, respectively). The cutoff values for increased ICP prediction for ONSDI, ONSDI-OND, and WCC were 6.29, 3.03, and 3.68 mm, respectively. The AUC of the combination of ONSDI-OND and WCC was 0.952 (95% confidence interval 0.896-1.0, p < 0.001). CONCLUSIONS: The ONSDI, ONSDI-OND, and WCC were correlated with ICP and had acceptable accuracy levels in estimating ICP in patients after hemicraniectomy. Furthermore, WCC showed a higher diagnostic value than ONSD-related parameters, and the combination of ONSDI-OND and WCC was a satisfactory predictor of increased ICP.

Soluble Epoxide Hydrolase Inhibition Protected against Diabetic Cardiomyopathy through Inducing Autophagy and Reducing Apoptosis Relying on Nrf2 Upregulation and Transcription Activation.

Background: Many patients with diabetes die from diabetic cardiomyopathy (DCM); however, effective strategies for the prevention or treatment of DCM have not yet been clarified. Methods: Leptin receptor-deficient (db/db) mice were treated with either the soluble epoxide hydrolase (sEH) inhibitor AUDA or vehicle alone. A virus carrying Nrf2 shRNA was used to manipulate Nrf2 expression in db/db mice. Cardiac structures and functions were analyzed using echocardiography and hemodynamic examinations. Primary cardiomyocytes cultured under high glucose and high fat (HGHF) conditions were used to conduct in vitro loss-of-function assays after culture in the presence or absence of AUDA (1 µM). Fluorescence microscopy-based detection of mCherry-GFP-LC3 was performed to assess autophagic flux. Results: The sEH inhibitor AUDA significantly attenuated ventricular remodeling and ameliorated cardiac dysfunction in db/db mice. Interestingly, AUDA upregulated Nrf2 expression and promoted its nuclear translocation in db/db mice and the HGHF-treated cardiomyocytes. Additionally, AUDA increased autophagy and decreased apoptosis in db/db mice heart. Furthermore, the administration of AUDA promoted autophagic flux and elevated LC3-II protein level in the presence of bafilomycin A1. However, AUDA-induced autophagy was abolished, and the antiapoptotic effect was partially inhibited upon Nrf2 knockdown. Conclusion: Our findings suggest that the sEH inhibitor AUDA attenuates cardiac remodeling and dysfunction in DCM via increasing autophagy and reducing apoptosis, which is relevant to activate Nrf2 signaling pathway.

Lentinan Protects against Nonalcoholic Fatty Liver Disease by Reducing Oxidative Stress and Apoptosis via the PPARα Pathway.

Lentinan (LNT), a type of polysaccharide derived from Lentinus edodes, has manifested protective effects during liver injury and hepatocellular carcinoma, but little is known about its effects on nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate whether LNT can affect the progression of NAFLD and the associated mechanisms. C57BL/6J mice were fed a normal chow diet or a high-fat diet (HFD) with or without LNT (6 mg/kg/d). AML12 cells were exposed to 200 µM palmitate acid (PA) with or without LNT (5 µg/mL). After 21 wk of the high-fat diet, LNT significantly decreased plasma triglyceride levels and liver lipid accumulation, reduced excessive reactive oxygen species production, and subsequently attenuated hepatic apoptosis in NAFLD mice. These effects were associated with increased PPARα levels, a decreased Bax/Bcl-2 ratio, and enhancement of the antioxidant defense system in vivo. Similar effects were also observed in cultured cells. More importantly, these protective effects of LNT on palmitate acid-treated AML12 cells were almost abolished by PPARα knockdown. In conclusion, this study demonstrates that LNT may ameliorate hepatic steatosis and decrease oxidative stress and apoptosis by activating the PPARα pathway and is a potential drug target for NAFLD.

Effects of green tea consumption on glycemic control: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The results of human clinical trials investigating the effects of green tea on glycemic control are inconsistent. METHODS: We conducted a systematic review and meta-analysis of RCTs that examined the effects of green tea supplementation on glycemic control. A literature search in PubMed, Embase, and Cochrane Library databases for RCTs that investigated the effect of green tea consumption on glycemic control was performed up to February 2020. A random-effects model was used to estimate weighted mean difference (WMD) with 95% confidence intervals (CIs). RESULTS: Twenty-seven trials involving 2194 subjects were included in the meta-analysis. The pooled results showed that green tea significantly lowered fasting blood glucose by - 1.44 mg/dL (95%CI:-2.26, - 0.62 mg/dL; P < 0.001) with no obvious heterogeneity (I 2 = 7.7%). However, green tea consumption did not significantly affect fasting insulin and HbA1c values. The mean differences were - 0.46µIU/mL (95% CI: - 1.10, 0.17µIU/mL; P = 0.21) for fasting insulin and - 0.06%; (95% CI: - 0.12, 0.01%; P = 0.07) for HbA1c concentrations. Heterogeneity was significant in fasting insulin (I 2 = 46.8%) and mild in HbA1c (I 2 = 1.7%). CONCLUSIONS: In short-term trials, green tea supplementation significantly reduced fasting glucose, but had no significant effect on fasting insulin and HbA1c. Long-term trials assessing the effects of green tea supplementation on glycemic control are needed.

Effect of green tea consumption on blood lipids: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Strong epidemiologic evidence indicates that green tea intake is protective against hyperlipidemia; however, randomized controlled studies have presented varying results. In the present study, we aimed to conduct a literature review and meta-analysis to assess the effect of green tea on blood lipids. METHODS: PubMed, Embase, and the Cochrane Library were electronically explored from inception to September 2019 for all relevant studies. Random effect models were used to estimate blood lipid changes between green tea supplementation and control groups by evaluating the weighted mean differences (WMD) with 95% confidence intervals (CIs). The risk of bias for study was assessed using the Cochrane tool. Publication bias was evaluated using funnel plots and Egger's tests. RESULTS: Thirty-one trials with a total of 3321 subjects were included in the meta-analysis. In general, green tea intake significantly lowered the total cholesterol (TC); WMD: - 4.66 mg/dL; 95% CI: - 6.36, - 2.96 mg/dL; P < 0.0001) and low-density lipoprotein (LDL) cholesterol (WMD:- 4.55 mg/dL; 95% CI: - 6.31, - 2.80 mg/dL; P < 0.0001) levels compared with those in the control. Green tea consumption did not affect high-density lipoprotein (HDL) cholesterol; however, it reduced the triglycerides compared with that in the control (WMD: - 3.77 mg/dL; 95% CI: - 8.90, 1.37 mg/dL; P = 0.15). In addition, significant publication bias from funnel plots or Egger's tests was not evident. CONCLUSIONS: Collectively, consumption of green tea lowers LDL cholesterol and TC, but not HDL cholesterol or triglycerides in both normal weight subjects and those who were overweight/obese; however, additional well-designed studies that include more diverse populations and longer duration are warranted.

Essential tremor vs idiopathic Parkinson disease: Utility of transcranial sonography.

Substantia nigra (SN) hyperechogenicity measured by transcranial sonography (TCS) is a promising biomarker for Parkinson disease (PD). The aim of this study was to explore the diagnostic accuracy of SN hyperechogenicity (SN) for differentiating PD from essential tremor (ET). A total of 119 patients with PD, 106 ET patients and 112 healthy controls that underwent TCS from November 2016 to February 2019 were included in this single-center retrospective case-control study. Two reviewers who were blinded to clinical information independently measured the SN by TCS imaging. The diagnostic sensitivity, specificity, and accuracy of TCS imaging were evaluated between the PD and healthy controls and between patients with PD and ET. Interrater agreement was assessed with the Cohen κ statistic. TCS imaging of the SN allowed to differentiate between patients with PD and ET with a sensitivity (91.6% and 90.8%) and specificity (91.5% and 89.6%) for readers 1 and 2, respectively. Interobserver agreement was excellent (к = 0.87). In addition, measurement of the SN allowed to differentiate between patients with PD and healthy subjects with a sensitivity (91.6% and 90.8%) and specificity (88.4% and 89.3%) for readers 1 and 2, respectively. Interobserver agreement was excellent (к = 0.91). Measurement of SN on TCS images could be a useful tool to distinguishing patients with PD from those with ET.

Diagnostic Performance of Transcranial Sonography for Evaluating Substantia Nigra Hyper-echogenicity in Patients with Parkinson's Disease.

To determine the diagnostic performance of transcranial sonography (TCS) in assessing increased echogenic area of the substantia nigra (SN) in patients with Parkinson's disease (PD). Institutional review board approval was obtained for this retrospective study. A total of 278 PD patients (mean age: 64.7 ± 9.8 y, 100 women) and 300 healthy control patients (mean age: 63.6 ± 9.3 y, 97 women) were referred for TCS assessment of SN hyper-echogenicity (SN+) from June 2016 to December 2018. Two sonographers independently measured the sizes of the echogenic areas of the SN by TCS imaging in both PD patients and healthy controls. The diagnostic sensitivity, specificity and accuracy of TCS imaging were compared between PD patients and healthy controls. Inter-rater agreement was assessed with the Cohen's κ statistic. The sensitivity, specificity and accuracy of readers 1 and 2, respectively, for the identification of SN+ in TCS were 90.3% and 89.6% (251 and 249 of 278), 89.3% and 88.3% (268 and 265 of 300) and 89.8% and 88.9% (519 and 514 of 578). Inter-observer agreement was excellent (к = 0.84). The area under the receiver operating characteristic curve (AUC) for differentiation of PD patients from healthy controls was 0.92 for reader 1 and 0.91 for reader 2. Cutoff values of 0.20 and 0.21 cm2 were derived from the assessments performed by readers 1 and 2, respectively. We defined 0.20 cm2 as the optimal cutoff value because it had a higher AUC. TCS is a promising diagnostic technique and can be very helpful in differentiating PD patients from healthy individuals.

Effect of green tea supplementation on blood pressure: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Although evidence from animal and observational studies has supported the beneficial effects of green tea intake for lowering blood pressure (BP), randomized placebo-controlled trials (RCTs) have yielded conflicting results. In this meta-analysis of RCTs, we aimed to assess the effects of green tea supplementation on measures of BP control. METHODS: The PubMed, Embase, and Cochrane Library databases were electronically searched from inception to August 2019 for all relevant studies. The results were pooled using the generic inverse-variance method with random-effects weighting and expressed as mean differences (MDs) with 95% confidence intervals (CIs). The quality of studies was assessed using the Jadad score. Publication bias was evaluated using funnel plots, Egger test, and Begg test. RESULTS: Twenty-four trials with 1697 subjects were included in the meta-analysis. The pooled results showed that green tea significantly lowered systolic BP (SBP; MD: -1.17 mm Hg; 95%CI: -2.18 to -0.16mm Hg; P = .02) and diastolic BP (DBP; MD: -1.24 mm Hg; 95%CI:-2.07 to -0.40mm Hg; P = .004). Significant heterogeneity was found for both SBP (I = 43%) and DBP (I = 57%). In addition, no evidence of significant publication bias was found from funnel plots or Egger test (P = .674 and P = .270 for SBP and DBP, respectively). CONCLUSION: Overall, green tea significantly reduced SBP and DBP over the duration of the short-term trials. Larger and longer-term trials are needed to further investigate the effects of green tea supplementation on BP control and clinical events.

Accuracy of Transcranial Sonography of the Substantia Nigra for Detection of Parkinson's Disease: A Systematic Review and Meta-analysis.

A systematic review and meta-analysis were conducted to evaluate the diagnostic accuracy of substantia nigra hyper-echogenicity by transcranial sonography (TCS) for the diagnosis of Parkinson's disease (PD). PubMed, Embase and the Cochrane Library were electronically searched from inception to June 2018 for all relevant studies. The methodological quality of each study was evaluated by two independent reviewers, who used the Quality Assessment of Diagnostic Accuracy Studies 2 tool. Articles reporting information sufficient to calculate the sensitivity and specificity of TCS to diagnose PD were included. Statistical analysis included data pooling, heterogeneity testing, sensitivity analyses and forest meta-regression. Thirty-nine studies (3123 participants with PD) were analyzed. The pooled sensitivity and specificity of TCS were 0.84 (95% confidence interval: 0.81-0.87) and 0.85 (0.80-0.88), respectively, for differentiating PD from normal controls or participants with other parkinsonian syndromes. In the secondary outcome, PD participants exhibited a significant increase in substantia nigra areas than either normal controls (0.14 [0.12-0.16], p < 0.0001) or participants with other parkinsonian syndromes (0.11 [0.08-0.13], p < 0.0001). This meta-analysis revealed the high diagnostic performance of TCS in differentiating patients with PD from both normal controls and participants with other parkinsonian syndromes.

Effectiveness of N-Acetylcysteine for the Prevention of Contrast-Induced Nephropathy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Conflicting results have been obtained in trials that have evaluated the prophylactic efficacy of N-acetylcysteine (NAC) pretreatment in the prevention of contrast-induced nephropathy (CIN). In this meta-analysis of randomized controlled trials, we aimed to assess the effectiveness of NAC treatment for the prevention of CIN. METHODS AND RESULTS: PubMed, EMBASE, and the Cochrane Library were electronically searched from inception to January 2016 for all relevant studies. The weighted relative risk (RR) and corresponding 95% CI for incident CIN were estimated using random effects models. Standard methods for assessing statistical heterogeneity and publication bias were used. The study included 11 480 participants and 1653 cases of CIN. The incidence of CIN was 12.8% in the NAC group versus 16.0% in the control group (RR: 0.76, 95% CI: 0.66-0.88, P=0.0002). In the patients undergoing coronary angiography, the incidence of CIN in the NAC group versus the control group was 13.7% versus 17.2% (RR: 0.74, 95% CI: 0.63-0.87, P=0.0002); in those undergoing peripheral angiography, the incidence was 6.4% versus 5.8% (RR: 1.00, 95% CI: 0.42-2.40, P=1.00); in those undergoing computed tomography, the incidence was 7.7% versus 14.8% (RR: 0.51, 95% CI: 0.29-0.89, P=0.02). CONCLUSIONS: Our meta-analysis showed an inverse and significant association between NAC supplementation and risk of CIN in patients undergoing coronary angiography and computed tomography, while a protective role for NAC in patients undergoing peripheral angiography was not obvious.

Zero-fluoroscopy catheter ablation of severe drug-resistant arrhythmia guided by Ensite NavX system during pregnancy: Two case reports and literature review.

BACKGROUND: Cardiac arrhythmias can occur during pregnancy. Owing to radiation exposure and other uncertain risks for the mother and fetus, catheter ablation has rarely been performed and is often delayed until the postpartum period. We reported 2 pregnant women who were experiencing severe arrhythmias and were successfully ablated without fluoroscopic guidance. We also carried out a literature review of cases of pregnant women who underwent zero-fluoroscopy ablation. METHODS AND RESULTS: One woman had drug-resistant and poorly tolerated frequent premature ventricular contraction (PVC) and ventricular tachycardia (VT). The other one had persistent and hardly terminated supraventricular tachycardia (SVT) via a right accessory pathway. The 2 patients were successfully underwent zero-fluoroscopy ablation guided by Ensite NavX system. The procedure time was 42 and 71 minutes, respectively. CONCLUSION: Catheter ablation of SVT or PVC/VT in pregnant patients can be safely and effectively performed with a completely zero-fluoroscopy approach guided by the Ensite NavX system. In the case of a drug refractory, life-threatening arrhythmia during pregnancy, catheter ablation may be considered.

Association between vitamin E and non-alcoholic steatohepatitis: a meta-analysis.

Non-alcoholic fatty liver disease (NAFLD) generally has a relatively favorable clinical course; however, non-alcoholic steatohepatitis (NASH) was much more frequently progresses to cirrhosis and hepatocellular carcinoma. We performed a systematic review and meta-analysis of clinical trials to examine the effects of vitamin E supplementation in improving liver histology in NASH. We performed a comprehensive search of the PubMed, Embase and Cochrane databases through October 2014. Weighted mean differences (WMDs) and their respective 95% confidence intervals (CIs) were calculated to assess the efficacy of vitamin E in improving liver histological scores by using fixed effects or random effects. Standard methods were performed to explore statistical heterogeneity and publication bias. Compared with controls, vitamin E supplementation significantly improved all histological parameters, including steatosis (WMD = -0.62, 95% CI: -0.95, -0.77, P = 0.0002), hepatocyte ballooning (WMD = -0.30, 95% CI: -0.56, -0.04, P = 0.03), lobular inflammation (WMD = -0.39, 95% CI: -0.67, -0.11, P = 0.007) and fibrosis (WMD = -0.39, 95% CI: -0.72, -0.06, P = 0.02). Our analysis also indicated the absence of publication bias between NASH and Vitamin E intake. This meta-analysis indicates that vitamin E supplementation had a significant and positive effect in the improvement of steatosis, ballooning degeneration, lobular inflammation and fibrosis in patients with NASH.

Association between patatin-like phospholipase domain containing 3 gene (PNPLA3) polymorphisms and nonalcoholic fatty liver disease: a HuGE review and meta-analysis.

We conducted a meta-analysis to assess the association between patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 polymorphism and nonalcoholic fatty liver disease (NAFLD) and its subtypes simple steatosis(SS) and nonalcoholic steatohepatitis (NASH). The study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using fixed-effects or random-effects models, with assessment for heterogeneity and publication bias. Twenty-three case-control studies involving 6071 NAFLD patients and 10366 controls were identified. The combined results showed a significant association between NAFLD risk and the rs738409 polymorphism in all genetic models (additive model: OR = 3.41, 95% CI = 2.57-4.52; P < 0.00001). In addition, evidence indicated that the rs738409 polymorphism was significantly associated with NASH in all genetic models (additive model: OR = 4.44, 95% CI = 3.39-5.82; P < 0.00001). The subgroup and sensitivity analyses showed that these changes were not influenced by the ethnicities and ages of subjects or by the source of controls. The rs738409 polymorphism was only significantly associated with risk of simple steatosis in the allele contrast and had no effect in the other genetic models. These findings suggest that the rs738409 polymorphism in PNPLA3 gene confers high cross-ethnicity risk for NAFLD and NASH development.

CYP2J2 overexpression attenuates nonalcoholic fatty liver disease induced by high-fat diet in mice.

Cytochrome P-450 epoxygenase-derived epoxyeicosatrienoic acids (EETs) exert diverse biological activities, which include potent vasodilatory, anti-inflammatory, antiapoptotic, and antioxidatant effects, and cardiovascular protection. Liver has abundant epoxygenase expression and high levels of EET production; however, the roles of epoxygenases in liver diseases remain to be elucidated. In this study, we investigated the protection against high-fat diet-induced nonalcoholic fatty liver disease (NAFLD) in mice with endothelial-specific CYP2J2 overexpression (Tie2-CYP2J2-Tr). After 24 wk of high-fat diet, Tie2-CYP2J2-Tr mice displayed attenuated NAFLD compared with controls. Tie2-CYP2J2-Tr mice showed significantly decreased plasma triglyceride levels and liver lipid accumulation, improved liver function, reduced inflammatory responses, and less increase in hepatic oxidative stress than wild-type control mice. These effects were associated with inhibition of NF-κB/JNK signaling pathway activation and enhancement of the antioxidant defense system in Tie2-CYP2J2-Tr mice in vivo. We also demonstrated that 14,15-EET treatment protected HepG2 cells against palmitic acid-induced inflammation and oxidative stress. 14,15-EET attenuated palmitic acid-induced changes in NF-κB/JNK signaling pathways, malondialdehyde generation, glutathione levels, reactive oxygen species production, and NADPH oxidase and antioxidant enzyme expression in HepG2 cells in vitro. Together, these results highlight a new role for CYP epoxygenase-derived EETs in lipotoxicity-related inflammation and oxidative stress and reveal a new molecular mechanism underlying EETs-mediated anti-inflammatory and antioxidant effects that could aid in the design of new therapies for the prevention and treatment of NAFLD.

Influence of vitamin E supplementation on glycaemic control: a meta-analysis of randomised controlled trials.

Observational studies have revealed that higher serum vitamin E concentrations and increased vitamin E intake and vitamin E supplementation are associated with beneficial effects on glycaemic control in type 2 diabetes mellitus (T2DM). However, whether vitamin E supplementation exerts a definitive effect on glycaemic control remains unclear. This article involves a meta-analysis of randomised controlled trials of vitamin E to better characterise its impact on HbA1c, fasting glucose and fasting insulin. PubMed, EMBASE and the Cochrane Library were electronically searched from the earliest possible date through April 2013 for all relevant studies. Weighted mean difference (WMD) was calculated for net changes using fixed-effects or random-effects models. Standard methods for assessing statistical heterogeneity and publication bias were used. Fourteen randomised controlled trials involving individual data on 714 subjects were collected in this meta-analysis. Increased vitamin E supplementation did not result in significant benefits in glycaemic control as measured by reductions in HbA1c, fasting glucose and fasting insulin. Subgroup analyses revealed a significant reduction in HbA1c (-0.58%, 95% CI -0.83 to -0.34) and fasting insulin (-9.0 pmol/l, 95% CI -15.90 to -2.10) compared with controls in patients with low baseline vitamin E status. Subgroup analyses also demonstrated that the outcomes may have been influenced by the vitamin E dosage, study duration, ethnic group, serum HbA1c concentration, and fasting glucose control status. In conclusion, there is currently insufficient evidence to support a potential beneficial effect of vitamin E supplementation on improvements of HbA1c and fasting glucose and insulin concentrations in subjects with T2DM.

Neutralization of interleukin-17 attenuates high fat diet-induced non-alcoholic fatty liver disease in mice.

Non-alcoholic fatty liver disease (NAFLD) is hepatic manifestation of a metabolic syndrome and includes a spectrum of hepatic steatosis, steatohepatitis, and fibrosis. Interleukin-17 (IL-17) has been reported to play a critical role in inflammatory progression of some liver diseases. The present study was designed to investigate the role of IL-17 on high fat diet-induced NAFLD in C57BL/6 mice. IL-17 blockade with anti-IL-17mAb significantly improved liver function, attenuated hepatic lipid accumulation, suppressed Kuffer cells activation, and decreased pro-inflammatory cytokines levels, which were associated with inhibition of NF-κB signaling cascades activation. Our data suggested that IL-17 was related to disease progression in NAFLD mouse model and blocking IL-17 may be a promising novel therapeutic approach for patients with NAFLD.

Genetic disruption of soluble epoxide hydrolase is protective against streptozotocin-induced diabetic nephropathy.

Cytochrome P-450 (CYP) epoxygenases metabolize arachidonic acid into epoxyeicosatrienoic acids (EETs), which play important roles in regulating cardiovascular functions. The anti-inflammatory, antiapoptotic, proangiogenic, and antihypertensive properties of EETs suggest a beneficial role for EETs in diabetic nephropathy. Endogenous EET levels are maintained by a balance between synthesis by CYP epoxygenases and hydrolysis by epoxide hydrolases into physiologically less active dihydroxyeicosatrienoic acids. Genetic disruption of soluble epoxide hydrolase (sEH/EPHX2) results in increased EET levels through decreased hydrolysis. This study investigated the effects of sEH gene disruption on diabetic nephropathy in streptozotocin-induced diabetic mice. Streptozotocin-induced diabetic manifestations were attenuated in sEH-deficient mice relative to wild-type controls, with significantly decreased levels of Hb A(1c), creatinine, and blood urea nitrogen and urinary microalbumin excretion. The sEH-deficient diabetic mice also had decreased renal tubular apoptosis that coincided with increased levels of antiapoptotic Bcl-2 and Bcl-xl, and decreased levels of the proapoptotic Bax. These effects were associated with activation of the PI3K-Akt-NOS3 and AMPK signaling cascades. sEH gene inhibition and exogenous EETs significantly protected HK-2 cells from TNFα-induced apoptosis in vitro. These findings highlight the beneficial role of the CYP epoxygenase-EETs-sEH system in the pathogenesis of diabetic nephropathy and suggest that the sEH inhibitors available may be potential therapeutic agents for this condition.