Cerebral ischemia-reperfusion (I/R) injury is the predominant causes for the poor prognosis of ischemic stroke patients after reperfusion therapy. Currently, potent therapeutic interventions for cerebral I/R injury are still very limited. Melatonin, an endogenous hormone, was found to be valid in preventing I/R injury in a variety of organs. However, a systematic review covering all neuroprotective effects of melatonin in cerebral I/R injury has not been reported yet. Thus, we perform a comprehensive overview of the influence of melatonin on cerebral I/R injury by collecting all available literature exploring the latent effect of melatonin on cerebral I/R injury as well as ischemic stroke. In this systematic review, we outline the extensive scientific studies and summarize the beneficial functions of melatonin, including reducing infarct volume, decreasing brain edema, improving neurological functions and attenuating blood-brain barrier breakdown, as well as its key protective mechanisms on almost every aspect of cerebral I/R injury, including inhibiting oxidative stress, neuroinflammation, apoptosis, excessive autophagy, glutamate excitotoxicity and mitochondrial dysfunction. Subsequently, we also review the predictive and therapeutic implications of melatonin on ischemic stroke reported in clinical studies. We hope that our systematic review can provide the most comprehensive introduction of current advancements on melatonin in cerebral I/R injury and new insights into personalized diagnosis and treatment of ischemic stroke.

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Xu Liu1, Lianghao You2, Ruizhi Zhou2, Jian Zhang2 1Department of Neurology, First Affiliated Hospital of China Medical University, Liaoning, Shenyang 110001, China 2Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, China, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110122, China Correspondence to: Jian Zhang, email: jzhang@cmu.edu.cn Keywords: microRNA, polymorphism, coronary heart disease, meta-analysis Received: October 07, 2016 Accepted: November 30, 2016 Published: December 27, 2016

Introduction: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the rapid loss of motor neurons. Given the significant global economic impact of ALS, effective preventive measures are urgently needed to reduce the incidence of this devastating disease. Recent meta-analyses have explored potential links between environmental factors, biomarkers, and ALS occurrence. However, the findings of these studies have been inconsistent and controversial. Therefore, we present a comprehensive umbrella review of recent meta-analyses to systematically summarize the available epidemiological evidence and evaluate its credibility.Methods: A systematic search was conducted in PubMed and Embase from inception until 01 October 2024, to identify meta-analyses of observational studies examining associations between environmental risk factors, protective factors, biomarkers, and ALS susceptibility. For each meta-analysis, summary effect estimates, 95% confidence intervals (CIs), 95% prediction intervals, study heterogeneity, small study effects, and excess significance biases were calculated independently by two investigators. The methodological quality was evaluated using the AMSTAR 2 criteria. The strength of the epidemiological evidence was categorized into five levels based on predefined criteria.Results: Out of 1,902 articles identified, 43 met the inclusion criteria, resulting in 103 included meta-analyses. These analyses covered 46 environmental risk and protective factors (344,597 cases, 71,415,574 population) and 57 cerebrospinal fluid (CSF) and serum biomarkers (30,941 cases, 2,180,797 population). The evidence was classified as convincing (Class I) for the regular use of antihypertensive drugs (OR: 0.85, 95% CI: 0.81–0.88) and highly suggestive (Class II) for premorbid body mass index (OR: 0.97, 95% CI: 0.95 to 0.98), trauma (OR: 1.51, 95% CI: 1.32 to 1.73), CSF NFL levels (SMD: 2.06, 95% CI: 1.61 to 2.51), serum NFL levels (SMD: 1.57, 95% CI: 1.29 to 1.85), ferritin levels (SMD: 0.66, 95% CI: 0.50 to 0.83), and uric acid levels (SMD: −0.72; 95% CI: −0.98 to −0.46).Discussion: This umbrella review offers new insights into the epidemiological evidence regarding the associations between environmental factors, biomarkers, and ALS susceptibility. We aim for our study to enhance the understanding of the roles of environmental factors and biomarkers in ALS occurrence and assist clinicians in developing evidence-based prevention and control strategies.

Recently, numerous studies have been performed to detect the association between H19 polymorphisms and cancer susceptibility. However, their results were inconsistent and controversial. So, we carried out a meta-analysis aiming to define the association exactly. Eligible studies were collected using PubMed and Embase databases up to March 31, 2019. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of association. Sensitivity analysis and publication bias were established to evaluate the robustness of our results. Totally, 60 studies involving 20763 cases and 27403 patients were analysed in our meta-analysis. Our results indicated that H19 rs217727 C > T polymorphism was significantly associated with increased cancer risk. In subgroup analysis, similarly increased risk could be found in gastrointestinal group for rs2839698 and protective effect was observed in rs2107425 polymorphism for cancer development in Caucasian population. Trial sequential analysis strengthened findings of our meta-analysis that cumulative evidence was adequate. In summary, our meta-analysis supported that H19 polymorphisms may be associated with cancer susceptibility.