The role of mitochondrial genes in ischemia-reperfusion injury: A systematic review of experimental studies.

Mitochondrial dysfunction contributes to pathological conditions like ischemia-reperfusion (IR) injury. To address the lack of effective therapeutic interventions for IR injury and potential knowledge gaps in the current literature, we systematically reviewed 3800 experimental studies across 5 databases and identified 20 mitochondrial genes impacting IR injury in various organs. Notably, CyPD, Nrf2, and GPX4 are well-studied genes consistently influencing IR injury outcomes. Emerging genes like ALDH2, BNIP3, and OPA1 are supported by human genetic evidence, thereby warranting further investigation. Findings of this review can inform future research directions and inspire therapeutic advancements.

The effects of inulin-type fructans on cardiovascular disease risk factors: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Inulin-type fructans (ITF) are the leading prebiotics in the market. Available evidence provides conflicting results regarding the beneficial effects of ITF on cardiovascular disease risk factors. OBJECTIVES: This study aimed to evaluate the effects of ITF supplementation on cardiovascular disease risk factors in adults. METHODS: We searched MEDLINE, EMBASE, Emcare, AMED, CINAHL, and the Cochrane Library databases from inception through May 15, 2022. Eligible randomized controlled trials (RCTs) administered ITF or placebo (for example, control, foods, diets) to adults for ≥2 weeks and reported one or more of the following: low, very-low, or high-density lipoprotein cholesterol (LDL-C, VLDL-C, HDL-C); total cholesterol; apolipoprotein A1 or B; triglycerides; fasting blood glucose; body mass index; body weight; waist circumference; waist-to-hip ratio; systolic or diastolic blood pressure; or hemoglobin A1c. Two reviewers independently and in duplicate screened studies, extracted data, and assessed risk of bias. We pooled data using random-effects model, and assessed the certainty of evidence (CoE) using the Grading of Recommendations, Assessment, Development and Evaluation approach. RESULTS: We identified 1767 studies and included 55 RCTs with 2518 participants in meta-analyses. The pooled estimate showed that ITF supplementation reduced LDL-C [mean difference (MD) -0.14 mmol/L, 95% confidence interval (95% CI: -0.24, -0.05), 38 RCTs, 1879 participants, very low CoE], triglycerides (MD -0.06 mmol/L, 95% CI: -0.12, -0.01, 40 RCTs, 1732 participants, low CoE), and body weight (MD -0.97 kg, 95% CI: -1.28, -0.66, 36 RCTs, 1672 participants, low CoE) but little to no significant effect on other cardiovascular disease risk factors. The effects were larger when study duration was ≥6 weeks and in pre-obese and obese participants. CONCLUSION: ITF may reduce low-density lipoprotein, triglycerides, and body weight. However, due to low to very low CoE, further well-designed and executed trials are needed to confirm these effects. PROSPERO REGISTRATION NUMBER: CRD42019136745.

Effects of ambient air pollution on obesity and ectopic fat deposition: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Globally, the prevalence of obesity tripled from 1975 to 2016. There is evidence that air pollution may contribute to the obesity epidemic through an increase in oxidative stress and inflammation of adipose tissue. However, the impact of air pollution on body weight at a population level remains inconclusive. This systematic review and meta-analysis will estimate the association of ambient air pollution with obesity, distribution of ectopic adipose tissue, and the incidence and prevalence of non-alcoholic fatty liver disease among adults. METHODS AND ANALYSIS: The study will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for conduct and reporting. The search will include the following databases: Ovid Medline, Embase, PubMed, Web of Science and Latin America and the Caribbean Literature on Health Sciences, and will be supplemented by a grey literature search. Each article will be independently screened by two reviewers, and relevant data will be extracted independently and in duplicate. Study-specific estimates of associations and their 95% Confidence Intervals will be pooled using a DerSimonian and Laird random-effects model, implemented using the RevMan software. The I2 statistic will be used to assess interstudy heterogeneity. The confidence in the body of evidence will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. ETHICS AND DISSEMINATION: As per institutional policy, ethical approval is not required for secondary data analysis. In addition to being published in a peer-reviewed journal and presented at conferences, the results of the meta-analysis will be shared with key stakeholders, health policymakers and healthcare professionals. PROSPERO REGISTRATION NUMBER: CRD42023423955.

Twenty years of participation of racialised groups in type 2 diabetes randomised clinical trials: a meta-epidemiological review.

AIMS/HYPOTHESIS: Type 2 diabetes mellitus prevalence is increasing globally and the greatest burden is borne by racialised people. However, there are concerns that the enrolment of racialised people into RCTs is limited, resulting in a lack of ethnic and racial diversity. This may differ depending whether an RCT is government funded or industry funded. The aim of this study was to review the proportions of racialised and white participants included in large RCTs of type 2 diabetes pharmacotherapies relative to the disease burden of type 2 diabetes in these groups. METHODS: The Ovid MEDLINE database was searched from 1 January 2000 to 31 December 2020. English language reports of RCTs of type 2 diabetes pharmacotherapies published in select medical journals were included. Studies were included in this review if they had a sample size of at least 100 participants and all participants were adults with type 2 diabetes. Industry-funded trials must have recruited participants from at least two countries. Government-funded trials were not held to the same standard because they are typically conducted in a single country. Data including the numbers and proportions of participants by ethnicity and race were extracted from trial reports. The participation-to-prevalence ratio (PPR) was calculated for each trial by dividing the percentage of white and racialised participants in each trial by the percentage of white and racialised participants with type 2 diabetes, respectively, for the regions of recruitment. A random-effects meta-analysis was used to generate the pooled PPRs and 95% CIs across study types. A PPR <0.80 indicates under-representation and a PPR >1.20 indicates over-representation. Risk of bias assessments were not conducted for this study as the objective was to examine recruitment of racialised and white participants rather than evaluate the trustworthiness of clinical trial outcomes. RESULTS: A total of 83 trials were included, involving 283,122 participants, of which 15 were government-funded and 68 were industry-funded trials. In government-funded trials, the PPR for white participants was 1.11 (95% CI 0.99, 1.24) and the PPR for racialised participants was 0.72 (95% CI 0.60, 0.86). In industry-funded trials, the PPR for white participants was 1.95 (95% CI 1.74, 2.18) and the PPR for racialised participants was 0.36 (95% CI 0.32, 0.42). The limitations of this study include the reliance on investigator-reported ethnicity and race to classify participants as 'white' or 'racialised', the use of estimates for type 2 diabetes prevalence and demographic data, and the high levels of heterogeneity of pooled estimates. However, despite these limitations, the results were consistent with respect to direction. CONCLUSIONS/INTERPRETATION: Racialised participants are under-represented in government- and industry-funded type 2 diabetes trials. Strategies to improve recruitment and enrolment of racialised participants into RCTs should be developed. REGISTRATION: Open Science Framework registration no. f59mk ( https://osf.io/f59mk ) FUNDING: The authors received no financial support for this research or authorship of the article.