The effect of green coffee extract supplementation on obesity indices: critical umbrella review of interventional meta-analyses.

Despite a multitude of investigations assessing the impact of green coffee extract supplementation on obesity indices, there is still a great deal of heated debate regarding the benefits of this intervention in obesity management. Therefore, in order to clarify the effect of green coffee extract on waist circumference (WC), body mass index (BMI) and body weight (BW), we conducted an umbrella review of interventional meta-analyses. The Web of Science, Scopus, PubMed/Medline, and Embase databases were searched using specific keywords and word combinations. The umbrella meta-analysis was performed using the Stata software version 17 (Stata Corp. College Station, Texas, USA). We pooled effect sizes (ES) and confidence intervals (CI) for the outcomes using the random effects model (the DerSimonian and Laird method). In total, 5 eligible meta-analyses were included in the final quantitative assessment. Data pooled from 5 eligible papers revealed that green coffee extract can reduce BW (WMD: -1.22 kg, 95% CI: -1.53 to -0.92, p < 0.001), BMI (WMD: -0.48 kg/m2, 95% CI: -0.67 to -0.29, p < 0.001) and WC (WMD: -0.55 cm, 95% CI: -0.80 to -0.31, p < 0.001). Subgroup analyses highlighted that green coffee extract supplementation in dosages ≤600 mg/day and interventions lasting >7 wk are more likely to decrease BW. The present umbrella meta-analysis confirms the beneficial effects of green coffee extract in reducing WC, BMI, and BW. Thus, we may infer that green coffee extract can be used as a complementary therapy in the management of obesity.

Development of screening tools to predict the risk of recurrence and related complications following anal fistula surgery: protocol for a prospective cohort study.

INTRODUCTION: Postoperative recurrence and related complications are common and related to poor outcomes in patients with anal fistula (AF). Due to being associated with short-term and long-term cure rates, perioperative complications have received widespread attention following AF surgery. This study aims to identify a set of predictive factors to develop risk prediction models for recurrence and related complications following AF surgery. We plan to develop and validate risk prediction models, using information collected through a WeChat patient-reported questionnaire system combined with clinical, laboratory and imaging findings from the perioperative period until 3-6 months following AF surgery. METHODS AND ANALYSIS: This is a prospective hospital-based cohort study using a linked database of collected health data as well as the follow-up outcomes for all adult patients who suffered from AF at a tertiary referral hospital in Shanghai, China. We will perform logistic regression models to predict anal fistula recurrence (AFR) as well as related complications (eg, wound haemorrhage, faecal impaction, urinary retention, delayed wound healing and unplanned hospitalisation) during and after AF surgery, and machine learning approaches will also be applied to develop risk prediction models. This prospective study aims to develop the first risk prediction models for AFR and related complications using multidimensional variables. These tools can be used to warn, motivate and empower patients to avoid some modifiable risk factors to prevent postoperative complications early. This study will also provide alternative tools for the early screening of high-risk patients with AFR and related complications, helping surgeons better understand the aetiology and outcomes of AF in an earlier stage. ETHICS AND DISSEMINATION: The study was approved by the Institutional Review Board of Shuguang Hospital affiliated with Shanghai University of Traditional Chinese Medicine (approval number: 2019-699-54-01). The results of this study will be submitted to international scientific peer-reviewed journals or conferences in surgery, anorectal surgery or anorectal diseases. TRIAL REGISTRATION NUMBER: ChiCTR1900025069; Pre-results.

Fenofibrate Inhibits Cytochrome P450 Epoxygenase 2C Activity to Suppress Pathological Ocular Angiogenesis.

Neovascular eye diseases including retinopathy of prematurity, diabetic retinopathy and age-related-macular-degeneration are major causes of blindness. Fenofibrate treatment in type 2 diabetes patients reduces progression of diabetic retinopathy independent of its peroxisome proliferator-activated receptor (PPAR)α agonist lipid lowering effect. The mechanism is unknown. Fenofibrate binds to and inhibits cytochrome P450 epoxygenase (CYP)2C with higher affinity than to PPARα. CYP2C metabolizes ω-3 long-chain polyunsaturated fatty acids (LCPUFAs). While ω-3 LCPUFA products from other metabolizing pathways decrease retinal and choroidal neovascularization, CYP2C products of both ω-3 and ω-6 LCPUFAs promote angiogenesis. We hypothesized that fenofibrate inhibits retinopathy by reducing CYP2C ω-3 LCPUFA (and ω-6 LCPUFA) pro-angiogenic metabolites. Fenofibrate reduced retinal and choroidal neovascularization in PPARα-/-mice and augmented ω-3 LCPUFA protection via CYP2C inhibition. Fenofibrate suppressed retinal and choroidal neovascularization in mice overexpressing human CYP2C8 in endothelial cells and reduced plasma levels of the pro-angiogenic ω-3 LCPUFA CYP2C8 product, 19,20-epoxydocosapentaenoic acid. 19,20-epoxydocosapentaenoic acid reversed fenofibrate-induced suppression of angiogenesis ex vivo and suppression of endothelial cell functions in vitro. In summary fenofibrate suppressed retinal and choroidal neovascularization via CYP2C inhibition as well as by acting as an agonist of PPARα. Fenofibrate augmented the overall protective effects of ω-3 LCPUFAs on neovascular eye diseases.

Cytochrome P450 Oxidase 2C Inhibition Adds to ω-3 Long-Chain Polyunsaturated Fatty Acids Protection Against Retinal and Choroidal Neovascularization.

OBJECTIVE: Pathological ocular neovascularization is a major cause of blindness. Increased dietary intake of ω-3 long-chain polyunsaturated fatty acids (LCPUFA) reduces retinal neovascularization and choroidal neovascularization (CNV), but ω-3 LCPUFA metabolites of a major metabolizing pathway, cytochrome P450 oxidase (CYP) 2C, promote ocular pathological angiogenesis. We hypothesized that inhibition of CYP2C activity will add to the protective effects of ω-3 LCPUFA on neovascular eye diseases. APPROACH AND RESULTS: The mouse models of oxygen-induced retinopathy and laser-induced CNV were used to investigate pathological angiogenesis in the retina and choroid, respectively. The plasma levels of ω-3 LCPUFA metabolites of CYP2C were determined by mass spectroscopy. Aortic ring and choroidal explant sprouting assays were used to investigate the effects of CYP2C inhibition and ω-3 LCPUFA-derived CYP2C metabolic products on angiogenesis ex vivo. We found that inhibition of CYP2C activity by montelukast added to the protective effects of ω-3 LCPUFA on retinal neovascularization and CNV by 30% and 20%, respectively. In CYP2C8-overexpressing mice fed a ω-3 LCPUFA diet, montelukast suppressed retinal neovascularization and CNV by 36% and 39% and reduced the plasma levels of CYP2C8 products. Soluble epoxide hydrolase inhibition, which blocks breakdown and inactivation of CYP2C ω-3 LCPUFA-derived active metabolites, increased oxygen-induced retinopathy and CNV in vivo. Exposure to selected ω-3 LCPUFA metabolites of CYP2C significantly reversed the suppression of both angiogenesis ex vivo and endothelial cell functions in vitro by the CYP2C inhibitor montelukast. CONCLUSIONS: Inhibition of CYP2C activity adds to the protective effects of ω-3 LCPUFA on pathological retinal neovascularization and CNV.

Dietary ω-3 polyunsaturated fatty acids decrease retinal neovascularization by adipose-endoplasmic reticulum stress reduction to increase adiponectin.

BACKGROUND: Retinopathy of prematurity (ROP) is a vision-threatening disease in premature infants. Serum adiponectin (APN) concentrations positively correlate with postnatal growth and gestational age, important risk factors for ROP development. Dietary ω-3 (n-3) long-chain polyunsaturated fatty acids (ω-3 LCPUFAs) suppress ROP and oxygen-induced retinopathy (OIR) in a mouse model of human ROP, but the mechanism is not fully understood. OBJECTIVE: We examined the role of APN in ROP development and whether circulating APN concentrations are increased by dietary ω-3 LCPUFAs to mediate the protective effect in ROP. DESIGN: Serum APN concentrations were correlated with ROP development and serum ω-3 LCPUFA concentrations in preterm infants. Mouse OIR was then used to determine whether ω-3 LCPUFA supplementation increases serum APN concentrations, which then suppress retinopathy. RESULTS: We found that in preterm infants, low serum APN concentrations positively correlate with ROP, and serum APN concentrations positively correlate with serum ω-3 LCPUFA concentrations. In mouse OIR, serum total APN and bioactive high-molecular-weight APN concentrations are increased by ω-3 LCPUFA feed. White adipose tissue, where APN is produced and assembled in the endoplasmic reticulum, is the major source of serum APN. In mouse OIR, adipose endoplasmic reticulum stress is increased, and APN production is suppressed. ω-3 LCPUFA feed in mice increases APN production by reducing adipose endoplasmic reticulum stress markers. Dietary ω-3 LCPUFA suppression of neovascularization is reduced from 70% to 10% with APN deficiency. APN receptors localize in the retina, particularly to pathologic neovessels. CONCLUSION: Our findings suggest that increasing APN by ω-3 LCPUFA supplementation in total parental nutrition for preterm infants may suppress ROP.

Cytochrome P450 2C8 ω3-long-chain polyunsaturated fatty acid metabolites increase mouse retinal pathologic neovascularization--brief report.

OBJECTIVE: Regulation of angiogenesis is critical for many diseases. Specifically, pathological retinal neovascularization, a major cause of blindness, is suppressed with dietary ω3-long-chain polyunsaturated fatty acids (ω3LCPUFAs) through antiangiogenic metabolites of cyclooxygenase and lipoxygenase. Cytochrome P450 epoxygenases (CYP2C8) also metabolize LCPUFAs, producing bioactive epoxides, which are inactivated by soluble epoxide hydrolase (sEH) to transdihydrodiols. The effect of these enzymes and their metabolites on neovascularization is unknown. APPROACH AND RESULTS: The mouse model of oxygen-induced retinopathy was used to investigate retinal neovascularization. We found that CYP2C (localized in wild-type monocytes/macrophages) is upregulated in oxygen-induced retinopathy, whereas sEH is suppressed, resulting in an increased retinal epoxide:diol ratio. With a ω3LCPUFA-enriched diet, retinal neovascularization increases in Tie2-driven human-CYP2C8-overexpressing mice (Tie2-CYP2C8-Tg), associated with increased plasma 19,20-epoxydocosapentaenoic acid and retinal epoxide:diol ratio. 19,20-Epoxydocosapentaenoic acids and the epoxide:diol ratio are decreased with overexpression of sEH (Tie2-sEH-Tg). Overexpression of CYP2C8 or sEH in mice does not change normal retinal vascular development compared with their wild-type littermate controls. The proangiogenic role in retina of CYP2C8 with both ω3LCPUFA and ω6LCPUFA and antiangiogenic role of sEH in ω3LCPUFA metabolism were corroborated in aortic ring assays. CONCLUSIONS: Our results suggest that CYP2C ω3LCPUFA metabolites promote retinal pathological angiogenesis. CYP2C8 is part of a novel lipid metabolic pathway influencing retinal neovascularization.

Understanding retinopathy of prematurity: update on pathogenesis.

Retinopathy of prematurity (ROP), an ocular disease characterized by the onset of vascular abnormalities in the developing retina, is the major cause of visual impairment and blindness in premature neonates. ROP is a complex condition in which various factors participate at different stages of the disease leading to microvascular degeneration followed by neovascularization, which in turn predisposes to retinal detachment. Current ablative therapies (cryotherapy and laser photocoagulation) used in the clinic for the treatment of ROP have limitations and patients can still have long-term effects even after successful treatment. New treatment modalities are still emerging. The most promising are the therapies directed against VEGF; more recently the use of preventive dietary supplementation with ω-3 polyunsaturated fatty acid may also be promising. Other than pharmacologic and nutritional approaches, cell-based strategies for vascular repair are likely to arise from advances in regenerative medicine using stem cells. In addition to all of these, a greater understanding of other factors involved in regulating pathologic retinal angiogenesis continues to emerge, suggesting potential targets for therapeutic approaches. This review summarizes an update on the current state of knowledge on ROP from our and other laboratories, with particular focus on the role of nitro-oxidative stress and notably trans-arachidonic acids in microvascular degeneration, semaphorin 3 operating as vasorepulsive molecules in the avascular hypoxic retina and in turn impairing revascularization, succinate and its receptor GPR91 in neuron-mediated retinal neovascularization, and ω-3 lipids as modulators of preretinal neovascularization.