UNASSIGNED: Apelin is one of the endogenous peptides that play a key role in the homeostasis of cardiovascular diseases. The purpose of the current study was to evaluate the correlation between apelin levels and epicardial fat thickness (EFT) in patients with stable angina and acute myocardial infarction (AMI).
UNASSIGNED: In a case-control study, 90 patients nominated for angiography were enrolled in the study and divided into three groups: healthy subjects without angiographic findings (Con), stable angina pectoris group (SAP), and acute AMI group. Data collected from all subjects included biochemical, echocardiographic, and angiographical parameters. The Gensini score analyzed the severity of coronary artery disease (CAD).
UNASSIGNED: A decrease in adjusted apelin levels was evident in the AMI and SAP groups compared with healthy individuals (for both P < 0.001), especially in the AMI group. In addition, a detectable negative association was identified between apelin and Gensini score (r = -0.288, P = 0.006), Ck-MB (r = -0.300, P = 0.004), EFT (r = -0.300, P = 0.004), and troponin-T (r = -0.288, P = 0.006).
UNASSIGNED: Myocardial injury in patients with CAD appears to play a significant role in apelin concentration independent of the role of adipose tissue, which requires further studies.

Liver cancer, classified as a malignant hepatic tumor, can be divided into two categories: primary, originating within the liver, and secondary, resulting from metastasis to the liver from other organs. Hepatocellular carcinoma (HCC) is the main form of primary liver cancer and the third leading cause of cancer-related deaths. The diagnosis and prognosis of HCC using current methods still face numerous challenges. This study aims to develop novel diagnostic and prognostic models while identifying new biomarkers for improved HCC treatment. Diagnostic and prognostic models for HCC were constructed using traditional binary classification methods and machine learning algorithms based on the TCGA database (Downloaded in August 2023). The mechanisms by which APLN (Apelin) affects HCC were investigated using single-cell sequencing data sourced from the GEO database (GSE149614). The diagnostic models yielded by various algorithms could effectively distinguished HCC samples from normal ones. The prognostic model, composed of four genes, was constructed using LASSO and Cox regression algorithms, demonstrating good performance in predicting the three-year survival rate of HCC patients. The HCC biomarker Apelin (APLN) was identified in this study. APLN in liver cancer tissues mainly comes from endothelial cells and is associated with the carcinogenesis of these cells. APLN expression is significantly upregulated in liver cancer tissues, marking it as a viable indicator of endothelial cell malignancy in HCC. Furthermore, APLN expression was determined to be an independent predictor of tumor endothelial cell carcinogenesis, unaffected by its modifications such as single nucleotide variation, copy number variation, and methylation. Additionally, liver cancers characterized by high APLN expression are likely to progress rapidly after T2 stage. Our study presents diagnostic and prognostic models for HCC with appreciably improved accuracy and reliability compared to previous reports. APLN is a reliable HCC biomarker and contributes to the establishment of our models.

We investigated the effects of tobacco smoke exposure and abnormal body weight on selected peptide hormones and their association with metabolic and hormonal disorders in women with polycystic ovary syndrome (PCOS). The study group included 88 women with PCOS and 28 women without the disease. In women with PCOS, chemerin, lipocalin, and apelin concentrations were influenced by overweight and obesity status, with the highest concentrations observed in those with a body mass index (BMI) ≥ 30.0. Exposure to tobacco smoke significantly increased only lipocalin-2 concentration. The disease itself did not affect the concentrations of chemerin, lipocalin, and apelin. Additionally, we found a positive correlation between chemerin concentration and fasting glucose, fasting insulin, and triglycerides levels, while a negative correlation was observed with high-density lipoprotein (HDL-C) concentration. In the smoking subgroup, chemerin concentration was positively correlated with free testosterone concentration and the free androgen index and negatively associated with sex hormone-binding globulin concentration. Our findings indicate that abnormal body weight has a stronger impact than tobacco smoke exposure on metabolic and hormonal disorders in women with PCOS, highlighting the important role of weight control in such individuals. However, smoking appears to be an additional factor that intensifies hormonal disorders associated with adipose tissue.

The aim of this study was to investigate the possible protective effects of apelin, which is known to have antioxidant and anti-inflammatory effects, on changes in neurogenesis in newborns of pregnant rats with L-NAME-induced preeclampsia. Wistar albino female rats were divided into four experimental groups: Control, Apelin, Preeclampsia and Preeclampsia + Apelin. Blood pressure was measured on the 5th, 11th and 17th days of gestation, urine protein was analyzed from urine samples collected for 24 h on the 6th, 12th and 18th days and serum creatinine was analyzed from serum samples. Maternal kidney and placenta tissues were obtained to establish the preeclampsia model, and neonatal brain tissues including the cortex, hippocampus and cerebellum regions were obtained to investigate neurogenesis and examined by histological and immunohistochemical methods. The number of newborns, body weight and brain weight of the newborns were measured. eNOS, IL-10, nNOS and NO levels in the brain analyzed via ELISA. Mean arterial pressure, urine protein and serum creatinine increased in the preeclampsia. Newborn weight decreased in the Preeclampsia group, the values in the Preeclampsia + Apelin group were closer to the Control and Apelin groups. In the Preeclampsia group, edema and dilatation in the proximal and distal tubules of kidneys, perivillous fibrin deposition and increase in syncytial nodules of placenta were observed. VEGF immunoreactivity decreased and iNOS immunoreactivity increased in both kidney and placenta. In neonatal brain tissue examinations, cytotoxic edema accompanied by thinning of cortex, delayed migration and lower cell counts in the hippocampus, and increase in intercellular spaces and EGL thickening in the cerebellum were observed in the preeclampsia. Expression of NeuN, GFAP, MBP, IL-10, eNOS, nNOS and NO levels decreased, whereas expression of Iba-1 increased in the preeclampsia. In the Preeclampsia + Apelin group, these findings were similar to the Control and Apelin groups. Apelin administration was found to be beneficial for preventing the adverse consequences of preeclampsia, but further experimental and clinical studies are needed to better understand these effects.

Adipose tissue, both intricate and fundamental to physiological functions, comprises cell types, including adipocytes, pivotal in secreting bioactive peptides known as \'adipokines.\' Apelin (APLN), Visfatin (VSFTN), and Irisin (IRSN) are novel adipokines involved in regulating energy, carbohydrate, protein, and lipid metabolism. APLN acts as an endogenous ligand for G-protein-coupled receptors, VSFTN is essential in nicotinamide adenine dinucleotide (NAD) biosynthesis, and IRSN is released from skeletal muscle and adipose tissues. Their influence spans various physiological domains, including insulin resistance and sensitivity, cardiovascular functions, angiogenesis, and reproductive systems. This review focuses on the potential roles of APLN, VSFTN, and IRSN in energy regulation mechanisms related to farm animal production. Despite accumulating evidence of their significance, comprehensive understanding is still emerging, with most studies based on model organisms. Thus, there\'s a pressing need for targeted research on farm animals. Addressing these knowledge gaps could pave the way for improved health strategies, reproductive efficiency, and productivity in farm animals. Future research should focus on understanding the multifaceted interactions of these adipokines and their implications for promoting sustainable and effective animal production.

BACKGROUND: Infusion of exogenous catecholamines (i.e., norepinephrine [NE] and dobutamine) is a recommended treatment for septic shock with myocardial dysfunction. However, sustained catecholamine infusion is linked to cardiac toxicity and impaired responsiveness. Several pre-clinical and clinical studies have investigated the use of alternative vasopressors in the treatment of septic shock, with limited benefits and generally no effect on mortality. Apelin-13 (APL-13) is an endogenous positive inotrope and vasoactive peptide and has been demonstrated cardioprotective with vasomodulator and sparing life effects in animal models of septic shock. A primary objective of this study was to evaluate the NE-sparing effect of APL-13 infusion in an experimental sepsis-induced hypotension.
METHODS: For this goal, sepsis was induced by cecal ligation and puncture (CLP) in male rats and the arterial blood pressure (BP) monitored continuously via a carotid catheter. Monitoring, fluid resuscitation and experimental treatments were performed on conscious animals. Based on pilot assays, normal saline fluid resuscitation (2.5 mL/Kg/h) was initiated 3 h post-CLP and maintained up to the endpoint. Thus, titrated doses of NE, with or without fixed-doses of APL-13 or the apelin receptor antagonist F13A co-infusion were started when 20% decrease of systolic BP (SBP) from baseline was achieved, to restore SBP values ≥ 115 ± 1.5 mmHg (baseline average ± SEM).
RESULTS: A reduction in mean NE dose was observed with APL-13 but not F13A co-infusion at pre-determined treatment time of 4.5 ± 0.5 h (17.37 ± 1.74 µg/Kg/h [APL-13] vs. 25.64 ± 2.61 µg/Kg/h [Control NE] vs. 28.60 ± 4.79 µg/Kg/min [F13A], P = 0.0491). A 60% decrease in NE infusion rate over time was observed with APL-13 co-infusion, (p = 0.008 vs NE alone), while F13A co-infusion increased the NE infusion rate over time by 218% (p = 0.003 vs NE + APL-13). Associated improvements in cardiac function are likely mediated by (i) enhanced left ventricular end-diastolic volume (0.18 ± 0.02 mL [Control NE] vs. 0.30 ± 0.03 mL [APL-13], P = 0.0051), stroke volume (0.11 ± 0.01 mL [Control NE] vs. 0.21 ± 0.01 mL [APL-13], P < 0.001) and cardiac output (67.57 ± 8.63 mL/min [Control NE] vs. 112.20 ± 8.53 mL/min [APL-13], P = 0.0036), and (ii) a reduced effective arterial elastance (920.6 ± 81.4 mmHg/mL/min [Control NE] vs. 497.633.44 mmHg/mL/min. [APL-13], P = 0.0002). APL-13 administration was also associated with a decrease in lactate levels compared to animals only receiving NE (7.08 ± 0.40 [Control NE] vs. 4.78 ± 0.60 [APL-13], P < 0.01).
CONCLUSIONS: APL-13 exhibits NE-sparing benefits in the treatment of sepsis-induced shock, potentially reducing deleterious effects of prolonged exogenous catecholamine administration.

Gymnema sylvestre (GS) and berberine (BBR) are natural products that have demonstrated therapeutic potential for the management of obesity and its comorbidities, as effective and safe alternatives to synthetic drugs. Although their anti-obesogenic and antidiabetic properties have been widely studied, comparative research on their impact on the gene expression of adipokines, such as resistin (Res), omentin (Ome), visfatin (Vis) and apelin (Ap), has not been reported.
METHODS: We performed a comparative study in 50 adult Mexican patients with obesity treated with GS or BBR for 3 months. The baseline and final biochemical parameters, body composition, blood pressure, gene expression of Res, Ome, Vis, and Ap, and safety parameters were evaluated.
RESULTS: BBR significantly decreased (p < 0.05) body weight, blood pressure and Vis and Ap gene expression and increased Ome, while GS decreased fasting glucose and Res gene expression (p < 0.05). A comparative analysis of the final measurements revealed a lower gene expression of Ap and Vis (p < 0.05) in patients treated with BBR than in those treated with GS. The most frequent adverse effects in both groups were gastrointestinal symptoms, which attenuated during the first month of treatment.
CONCLUSIONS: In patients with obesity, BBR has a better effect on body composition, blood pressure, and the gene expression of adipokines related to metabolic risk, while GS has a better effect on fasting glucose and adipokines related to insulin resistance, with minimal side effects.

Demyelination due to autoreactive T cells and inflammation in the central nervous system are principal features of multiple sclerosis (MS), a chronic and highly disabling human disease affecting brain and spinal cord. Here, we show that treatment with apelin, a secreted peptide ligand for the G protein-coupled receptor APJ/Aplnr, is protective in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Apelin reduces immune cell entry into the brain, delays the onset and reduces the severity of EAE. Apelin affects the trafficking of leukocytes through the lung by modulating the expression of cell adhesion molecules that mediate leukocyte recruitment. In addition, apelin induces the internalization and desensitization of its receptor in endothelial cells (ECs). Accordingly, protection against EAE major outcomes of apelin treatment are phenocopied by loss of APJ/Aplnr function, achieved by EC-specific gene inactivation in mice or knockdown experiments in cultured primary endothelial cells. Our findings highlight the importance of the lung-brain axis in neuroinflammation and indicate that apelin targets the transendothelial migration of immune cells into the lung during acute inflammation.

BACKGROUND: Diabetic nephropathy is a major secondary cause of end-stage renal disease. Apelin plays an important role in the development of DN. Understanding the exact mechanism of Apelin can help expand the means of treating DN.
METHODS: Male C57BL/6 mice was used and STZ treatment was implemented for DN model establishment. Lentivirus systems including Lv-sh-RUNX3 and Lv-Apelin were obtained to knockdown RUNX3 and overexpress Apelin, respectively. A total of 36 mice were divided into 6 groups (n = 6 in each group): control, DN, DN + LV-Vector, DN + Lv-Apelin, DN + LV-Apelin + LV-sh-NC and DN + Lv-Apelin + Lv-sh-RUNX3 group. In vitro studies were performed using mesangial cells. Cell viability and proliferation was assessed through CCK8 and EDU analysis. Hematoxylin and eosin staining as well as Masson staining was implemented for histological evaluation. RT-qPCR was conducted for measuring relative mRNA levels, and protein expression was detected by western blotting. The interaction between SIRT1 and FOXO were verified by co-immunoprecipitations, and relations between RUNX3 and Apelin were demonstrated by dual luciferase report and chromatin immunoprecipitation.
RESULTS: The DN group exhibited significantly lower Apelin expression compared to control (p < 0.05). Apelin overexpression markedly improved blood glucose, renal function indicators, ameliorated renal fibrosis and reduced fibrotic factor expression (p < 0.05) in the DN group, accompanied by elevated sirt1 levels and diminished acetylated FOXO1/FOXO3a (p < 0.05). However, RUNX3 knockdown combined with Apelin overexpression abrogated these beneficial effects, leading to impaired renal function, exacerbated fibrosis, increased fibrotic factor expression and acetylated FOXO1/FOXO3a versus Apelin overexpression alone (p < 0.05). In mesangial cells under high glucose, Apelin overexpression significantly inhibited cell proliferation and fibrotic factor production (p < 0.05). Conversely, RUNX3 interference enhanced cell proliferation and the secretion of fibrotic factors. (p < 0.05). Remarkably, combining Apelin overexpression with RUNX3 interference reversed the proliferation and fibrosis induced by RUNX3 interference (p < 0.05). Mechanistic studies revealed RUNX3 binds to the Apelin promoter, with the 467-489 bp site1 as the primary binding region, and SIRT1 physically interacts with FOXO1 and FOXO3a in mesangial cells.
CONCLUSIONS: RUNX3 activated Apelin and regulated the SIRT1/FOXO signaling pathway, resulting in the suppressed cell proliferation and fibrosis in diabetic nephropathy. Apelin is a promising endogenous therapeutic target for anti-renal injury and anti-fibrosis in diabetic nephropathy. RUNX3 may serve as an endogenous intervention target for diseases related to Apelin deficiency.

Cancer is the leading cause of death worldwide, and the number of cancer-related deaths is expected to increase. Common types of cancer include skin, breast, lung, prostate, and colorectal cancers. While clinical research has improved cancer therapies, these treatments often come with significant side effects such as chronic fatigue, hair loss, and nausea. In addition, cancer treatments can cause long-term cardiovascular complications. Doxorubicin (DOX) therapy is one example, which can lead to decreased left ventricle (LV) echocardiography (ECHO) parameters, increased oxidative stress in cellular level, and even cardiac fibrosis. The apelinergic system, specifically apelin and its receptor, together, has shown properties that could potentially protect the heart and mitigate the damages caused by DOX anti-cancer treatment. Studies have suggested that stimulating the apelinergic system may have therapeutic benefits for heart damage induced by DOX. Further research in chronic preclinical models is needed to confirm this hypothesis and understand the mechanism of action for the apelinergic system. This review aims to collect and present data on the effects of the apelinergic system on doxorubicin-induced cardiotoxicity.