Neurodegenerative diseases, which occur when neurons begin to deteriorate, affect millions of people worldwide. These age-related disorders are becoming more common partly because the elderly population has increased in recent years. While no treatments are accessible, every year an increasing number of therapeutic and supportive options become available. Various substances that may have neuroprotective effects are currently being researched. One of them is apelin. This review aims to illustrate the results of research on the neuroprotective effect of apelin amino acid oligopeptide which binds to the apelin receptor and exhibits neuroprotective effects in the central nervous system. The collected data indicate that apelin can protect the central nervous system against injury by several mechanisms. More studies are needed to thoroughly investigate the potential neuroprotective effects of this peptide in neurodegenerative diseases and various other types of brain damage.

BACKGROUND: Apelin has been extensively studied, and emerging experimental evidence suggests that Apelin may have effects on stroke by reducing infarct volume and neurological deficits, inhibiting the apoptosis process and reducing brain water content. However, the credibility of the evidence is uncertain. Thus, we aimed to perform a systematic review and meta-analysis to evaluate preclinical studies that used Apelin for the treatment of transient focal cerebral ischemia.
METHODS: Electronic bibliographic databases including PubMed, EMBASE, Scopus, and Google Scholar were searched for finding relevant studies from January 2000 to July 2023. The methodological quality and risk of bias scores for animal studies were calculated based on the CAMARADES and the SYRCLE\'s RoB tools, respectively. The effect sizes were assessed using Comprehensive Meta-Analysis (CMA) software.
RESULTS: A total of twelve eligible studies were used for the systematic review and meta-analysis. The median scores of study quality and risk of bias were 7.5 out of 10, and 5 out of 10, respectively. Apelin treatment effectively decreased infarct volume (primary outcome) [Hedges\' g = 2.72, 95 % CI (1.93, 3.51), p < 0.001], neurological deficit [Hedges\' g = 1.76, 95 % CI (0.96, 2.55), p < 0.001], cleaved caspase 3 [Hedges\' g = 2.16, 95 % CI (0.87, 3.44), p = 0.001], and apoptotic cell number [Hedges\' g = 4.07, 95 % CI (1.25,6.89), p = 0.005] compared with the control group. According to subgroup analysis, more notable neuroprotective effects were observed with intravenous administration than with intracerebroventricular (ICV) administration. Moreover, we determined that effect size of infarct volume was markedly related to the species. The combined measurement of two studies demonstrated that Apelin could reduce BCL2 and TNF-α levels as well as brain water content compared with the control group. However, pooled measurement of two studies showed that no relevancy was discovered between CHOP and altering infarct volume.
CONCLUSIONS: The present meta-analysis was conducted to assess preclinical studies related to Apelin treatment in rodent ischemic stroke. Apelin can exert promising neuroprotective effects by reducing infarct volume, neurological deficit, caspase 3, apoptotic cell number, TNF- α and brain water content and increasing BCL2. The current evidence supports the anti-apoptotic and anti-inflammatory properties of Apelin, but its effectiveness in decreasing CHOP level in animal models of ischemic stroke needs further elucidation. This study was registered within the International Prospective Register of Systematic Reviews (PROSPERO) as number CRD42023460926.

The prevalence of osteoporosis has been on the rise globally. With ageing populations, research has sought therapeutic solutions in novel areas. One such area is that of the adipokines. Current literature points to an important role for these chemical mediators in relation to bone metabolism. Well-established adipokines have been broadly reported upon. These include adiponectin and leptin. However, other novel adipokines such as visfatin, nesfatin-1, meteorin-like protein (Metrnl), apelin and lipocalin-2 are starting to be addressed pre-clinically and clinically. Adipokines hold pro-inflammatory and anti-inflammatory properties that influence the pathophysiology of various bone diseases. Omentin-1 and vaspin, two novel adipokines, share cardioprotective effects and play essential roles in bone metabolism. Studies have reported bone-protective effects of omentin-1, whilst others report negative associations between omentin-1 and bone mineral density. Lipocalin-2 is linked to poor bone microarchitecture in mice and is even suggested to mediate osteoporosis development from prolonged disuse. Nesfatin-1, an anorexigenic adipokine, has been known to preserve bone density. Animal studies have demonstrated that nesfatin-1 treatment limits bone loss and increases bone strength, suggesting exogenous use as a potential treatment for osteopenic disorders. Pre-clinical studies have shown adipokine apelin to have a role in bone metabolism, mediated by the enhancement of osteoblast genesis and the inhibition of programmed cell death. Although many investigations have reported conflicting findings, sufficient literature supports the notion that adipokines have a significant influence on the metabolism of bone. This review aims at highlighting the role of novel adipokines in osteoporosis while also discussing their potential for treating osteoporosis.

Diabetic retinopathy (DR) is a common complication of diabetes. The adipocytokines are closely associated with the occurrence and development of diabetes and its related complications. Literature confirms that the level of adiponectin in patients with DR is significantly higher; however, the relationship between other adipocytokines (leptin, chemerin, apelin, and omentin-1) and DR remains unclear.
This study aimed to systematically evaluate the association between adipocytokines (leptin, chemerin, apelin, and omentin-1) and DR.
The PubMed, Web of Science, Embase, EBSCO and Willy databases were used to search for potential studies with keywords such as \"diabetic retinopathy\" or \"DR\" in combination with the terms \"leptin,\" \"chemerin\", \"apelin\" or \"omentin-1\" in the search titles or abstracts. Standardized mean differences (SMD) with corresponding 95% confidence intervals (CIs) were determined as the results of the meta-analysis.
After screening, 18 articles were included in the meta-analysis including 750 DR cases and 993 controls. Leptin and chemerin levels in patients with DR were significantly higher than those in the control group (SMD: 0.68, 95% CI [0.1, 1.26]; SMD: 0.79, 95% CI [0.35, 1.23]). The omentin-1 levels in patients with DR were significantly lower than those in the controls (SMD: -0.85, 95% CI [-1.08, -0.62]).
To the best of our knowledge, this is the first meta-analysis to evaluate the leptin, chemerin, apelin, and omentin-1 levels in patients with DR. Further high-quality studies are warranted to support the association between these adipocytokines and DR.
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=443770, identifier CRD42023443770.

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Apelin and ELABELA (ELA), which are peptides belonging to the adipokines group, are endogenous peptide ligands of their receptor, APJ, which together constitute the apelinergic system. The apelinergic system is expressed in numerous human tissues and organs, including the heart, blood vessels, adipose tissue, central nervous system, lungs, kidneys, and liver. Apelin, being the most widely studied member of the apelinergic system, plays a key role in the cardiovascular system and exerts a pleiotropic effect in tissues. Under physiological conditions, the peripheral actions of apelin include augmented cardiac contractility, increased left ventricular stroke volume, vasodilation, increased diuresis, and lowered systemic blood pressure. Multiple studies suggest that activation of the apelinergic system exerts beneficial effects on the treatment of cardiovascular diseases (CVD), including hypertension and heart failure, whereas the silencing of the apelin/APJ axis results in attenuation of inflammatory processes and prevents formation of atherosclerotic plaques. As numerous effects of apelin are not entirely explained, further studies of the cardiovascular actions of apelin and ELA are necessary to help establish effective pharmacological treatments of CVDs. This article aims to review the roles of apelin and elabela peptide ligands in cardiovascular diseases, including heart failure and hypertension.

This study investigates the effects of exercise training on exerkines in patients with type 2 diabetes mellitus to determine the optimal exercise prescription.
A systematic search for relevant studies was performed in 3 databases. Randomized controlled trials investigating the effects of exercise training on at least one of the following exerkines were included: adiponectin, apelin, brain-derived neurotrophic factor, fetuin-A, fibroblast growth factor-21, follistatin, ghrelin, interleukin (IL)-6, IL-8, IL-10, IL-15, IL-18, leptin, myostatin, omentin, resistin, retinol-binding protein 4, tumor necrosis factor-α, and visfatin.
Forty randomized controlled trials were selected for data extraction (n = 2160). Exercise training induces changes in adiponectin, fetuin-A, fibroblast growth factor-21, IL-6, IL-10, leptin, resistin, and tumor necrosis factor-α levels but has no significant effects on apelin, IL-18, and ghrelin compared to controls. Physical exercise training favored large and positive changes in pooled exerkines (i.e., an overall effect size calculated from several exerkines) (Hedge\'s g = 1.02, 95% confidence interval (95%CI): 0.76-1.28), which in turn were related to changes in glycated hemoglobin (mean difference (MD) = -0.81%, 95%CI: -0.95% to -0.67%), fasting glucose (MD = -23.43 mg/dL, 95%CI: -30.07 mg/dL to -16.80 mg/dL), waist circumference (MD = -3.04 cm, 95%CI: -4.02 cm to -2.07 cm), and body mass (MD = -1.93 kg, 95%CI: -2.00 kg to -1.86 kg). Slightly stronger effects were observed with aerobic, resistance, or high-intensity interval protocols at moderate- to vigorous-intensity and with programs longer than 24 weeks that comprise at least 3 sessions per week and more than 60 min per session.
Exercise training represents an anti-inflammatory therapy and metabolism-improving strategy with minimal side effects for patients with type 2 diabetes mellitus.

Apelin is a promising biomarker for the detection and prognosis of cancer. This review aims to synthesize current knowledge on associations of circulating apelin with cancer, illustrate knowledge gaps, and discuss future research. Following PRISMA guidelines, CINAHL, EMBASE, and PubMed were searched using terms \"cancer AND apelin\" between 2011 and 2021, full text, and English language. Inclusion criteria: measured circulating apelin in adults 18 years or older with cancer, and observational, cross-sectional, longitudinal, case-control, cohort, quasi-experimental, or randomized control trials. Excluded were studies with animal models, tissue samples only, secondary data analyses, systematic reviews, literature reviews, grey literature, and conference abstracts. 16 articles were included. There were significant variations in measurement methods between studies. Comparison of circulating apelin between cases and controls and associations of circulating apelin with clinicopathological characteristics were inconsistent. Variations in results suggest that the relationship between circulating apelin and cancer differs among cancer types. Differences in measurement methods between studies highlight the need for consistency in future research to draw meaningful conclusions. Future research should seek to standardize methods of detecting circulating apelin and examine its associations with specific cancer types to determine what role that circulating apelin may play in cancer development and progression.

Aims: To investigate maternal circulating apelin levels in pregnancies with and without preeclampsia.Design and Method: Systematic review and meta-analysis of observational studies reporting circulating apelin in women who develop preeclampsia. We searched databases for appropriate studies published through December 2021, without language restriction. The quality of studies was evaluated using the Newcastle-Ottawa-Scale. Data were pooled as mean difference (MDs) or standardized MDs (SMDs) and 95% confidence interval (95% CI). A random-effects model enabled reporting of differences between groups, minimizing the effects of uncertainty associated with inter-study variability on the effects of different endpoints.Results: We identified a total of 122 studies, and ten of them reported circulating apelin in women with and without preeclampsia. Maternal apelin did not show a difference in preeclamptic compared to normotensive women (SMD: -0.38, 95%CI -0.91 to 0.15), although there was high heterogeneity between the included studies (I2 = 95%). Participants with preeclampsia had higher body mass index, lower gestational age at delivery, and birth weight. Preeclamptic pregnant women with higher BMI showed significantly lower apelin levels in the subgroup analysis. There was no significant apelin difference in the preeclampsia severity sub-analysis.Conclusion: There was no significant difference in apelin levels in pregnant women with and without preeclampsia.

Aims: This systematic review and meta-analysis investigated maternal apelin levels in pregnant women with and without GDM. Secondary outcomes were glucose- and lipid-related results.Methods: Databases including PubMed, Embase, Cochrane Library, LILACS, CNKI, and Wang Fang were searched. The methodological quality of included studies was evaluated with the Newcastle-Ottawa Scale. Mean differences (MDs) or standardized MDs (SMDs) with their 95% confidence intervals (CIs) were evaluated. Random effect model analyses were carried out and heterogeneity with the I2 and Tau2 statistics.Results: Fourteen observational studies (sample size: 1033 women with GDM and 1053 for control women) with a low or moderate risk of bias were included in the analysis. During the second half of pregnancy, maternal apelin estimate was significantly higher in women with GDM (SMD = 0.64; 95% CI: 0.03 to 1.25), as well as insulin (SMD = 1.41% CI: 0.84 to 1.99), glucose (SMD = 1.56; 95% CI 1.20 to 1.91), glycated hemoglobin (SMD = 1.11, 95% CI: 0.69 to 1.54), HOMA-IR (MD = 2.25; 95%CI: 1.51 to 2.98), BMI (MD = 0.80 kg/m2, 95%CI: 0.52 to 1.08), total cholesterol (SMD = 0.42, 0.12 to 0.73), LDL-cholesterol (SMD = 0.63, 95%CI: 0.23 to 1.02), and triglycerides (SMD = 0.40, 95%CI: 0.19 to 0.61) as compared to control women. There was heterogeneity between studies as evidence by high I2 values. Meta-regression analysis indicated statistically significant regression coefficients for age of women, glucose and total cholesterol.Conclusions: GDM was associated with increased circulating apelin, insulin, glucose, glycated hemoglobin, total cholesterol, LDL-cholesterol levels, and HOMA-IR index.