Alterations of DNA methylation profile in peripheral blood of children with simple obesity.

Purpose: To investigate the association between DNA methylation and childhood simple obesity. Methods: Genome-wide analysis of DNA methylation was conducted on peripheral blood samples from 41 children with simple obesity and 31 normal controls to identify differentially methylated sites (DMS). Subsequently, gene functional analysis of differentially methylated genes (DMGs) was carried out. After screening the characteristic DMGs based on specific conditions, the methylated levels of these DMS were evaluated and verified by pyrosequencing. Receiver operating characteristic (ROC) curve analysis assessed the predictive efficacy of corresponding DMGs. Finally, Pearson correlation analysis revealed the correlation between specific DMS and clinical data. Results: The overall DNA methylation level in the obesity group was significantly lower than in normal. A total of 241 DMS were identified. Functional pathway analysis revealed that DMGs were primarily involved in lipid metabolism, carbohydrate metabolism, amino acid metabolism, human diseases, among other pathways. The characteristic DMS within the genes Transcription factor A mitochondrial (TFAM) and Piezo type mechanosensitive ion channel component 1(PIEZO1) were recognized as CpG-cg05831083 and CpG-cg14926485, respectively. Furthermore, the methylation level of CpG-cg05831083 significantly correlated with body mass index (BMI) and vitamin D. Conclusions: Abnormal DNA methylation is closely related to childhood simple obesity. The altered methylation of CpG-cg05831083 and CpG-cg14926485 could potentially serve as biomarkers for childhood simple obesity. Supplementary Information: The online version contains supplementary material available at 10.1007/s13755-024-00275-w.

Quercetin Attenuates Atherosclerosis via Modulating Apelin Signaling Pathway Based on Plasma Metabolomics.

OBJECTIVE: To interpret the pharmacology of quercetin in treatment of atherosclerosis (AS). METHODS: Fourteen apolipoprotein E-deficient (ApoE-/-) mice were divided into 2 groups by a random number table: an AS model (ApoE-/-) group and a quercetin treatment group (7 in each). Seven age-matched C57 mice were used as controls (n=7). Quercetin [20 mg/(kg·d)] was administered to the quercetin group intragastrically for 8 weeks for pharmacodynamic evaluation. Besides morphological observation, the distribution of CD11b, F4/80, sirtuin 1 (Sirt1) and P21 was assayed by immunohistochemistry and immunofluorescence to evaluate macrophage infiltration and tissue senescence. Ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MSC/MS) was performed to study the pharmacology of quercetin against AS. Then, simultaneous administration of an apelin receptor antagonist (ML221) with quercetin was conducted to verify the possible targets of quercetin. Key proteins in apelin signaling pathway, such as angiotensin domain type 1 receptor-associated proteins (APJ), AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), tissue plasminogen activator (TPA), uncoupling protein 1 (UCP1) and angiotensin II receptor 1 (AT1R), were assayed by Western blot. RESULTS: Quercetin administration decreased lipid deposition in arterial lumen and improved the morphology of ApoE-/- aortas in vivo. Quercetin decreased the densities of CD11b, F4/80 and P21 in the aorta and increased the level of serum apelin and the densities of APJ and Sirt1 in the aorta in ApoE-/- mice (all P<0.05). Plasma metabolite profiling identified 118 differential metabolites and showed that quercetin affected mainly glycerophospholipids and fatty acyls. Bioinformatics analysis suggested that the apelin signaling pathway was one of the main pathways. Quercetin treatment increased the protein expressions of APJ, AMPK, PGC-1α, TPA and UCP1, while decreased the AT1R level (all P<0.05). After the apelin pathway was blocked by ML221, the effect of quercetin was abated significantly, confirming that quercetin attenuated AS by modulating the apelin signaling pathway (all P<0.05). CONCLUSION: Quercetin alleviated AS lesions by up-regulation the apelin signaling pathway.

Role of licochalcone C in cardioprotection against ischemia/reperfusion injury of isolated rat heart via antioxidant, anti-inflammatory, and anti-apoptotic activities.

AIMS: This study aimed to evaluate the protective effect of licochalcone C against myocardial ischemia/reperfusion injury in rats. MAIN METHODS: Left ventricular developed pressure (LVDP) and its maximum up/down rate (±dp/dtmax) were recorded as myocardial function. Levels of creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione/glutathione disulfide (GSH/GSSG) ratio, and tumor necrosis factor-alpha (TNF-α) were determined by using enzyme-linked immunosorbent assay. Cell morphology was observed and mitochondrial damage was assessed by HE coloration and transmission electron microscopy, respectively. Cardiomyocyte apoptosis was determined by using terminal deoxynucleotidyl transferased UTP nick-end labeling (TUNEL). KEY FINDINGS: Pretreatment with licochalcone C significantly improved the recovery of LVDP and ±dp/dtmax, and increased the levels of SOD and GSH/GSSG ratio. However, pretreatment with licochalcone C not only decreased the TUNEL-positive cell ratio and morphological changes, but also weaken the mitochondrial injury and the levels of CK, LDH, MDA, and TNF-α. SIGNIFICANCE: These results suggested an important function of licochalcone C extracted from traditional Chinese medicine in the cardioprotection via antioxidant, anti-inflammatory, and anti-apoptotic activities.

Strategies for implementing Health-Promoting Schools in a province in China.

After successful pilot projects in 10 schools (four schools with tobacco control and six schools with nutrition interventions, plus 10 control schools), Health and Education officials in Zhejiang Province, China, decided to scale up Health-Promoting Schools (HPS) systematically over the entire province, starting with an initial cohort of 51 additional schools, reaching from primary to vocational schools. Interviews with school personnel during the first phase of scaling up illuminated the key pre-implementation, implementation, and monitoring and evaluation activities. Pre-implementation activities included choosing an entry point, setting up a special HPS committee, and establishing a work plan. Implementation activities included conducting mobilization meetings, prioritizing health, popularizing the HPS concept, ensuring community cooperation and participation, acting as role models, offering training, and using new teaching and learning methods. Monitoring and evaluation activities included process, baseline, and final evaluations and changing standards of evaluation to a more holistic evaluation that schools go through to become Health-Promoting Schools. Schools also reported that they faced - and overcame - a number of challenges including understanding and integrating the HPS concept and lack of professional development and support. Results revealed that schools transitioned from a passive model of education to interactive pedagogy put priority on health and viewed it as a co-responsibility, reshaped assessment to a more holistic approach and called for more training and technical support. Participants mentioned that they gained knowledge and skills and developed a deeper understanding about health. Health impact was also demonstrated, for instance in reduced injuries and reduced smoking, and educational impact was demonstrated, for instance in improved relationships of children to parents and teachers, improved social qualities, and improved teacher satisfaction.

Strategies for implementing health-promotion schools in a province in China

After successful pilot projects in 10 schools (four schools with tobacco control and six schools with nutrition interventions, plus 10 control schools), Health and Education officials in Zhejiang Province, China, decided to scale up Health Promoting Schools (HPS) systematically over the entire province, starting with an initial cohort of 51 additional schools, reaching from primary to vocational schools. Interviews with school personnel during the first phase of scaling up illuminated the key pre implementation, implementation, and monitoring and evaluation activities. Pre implementation activities included choosing an entry point, setting up a special HPS committee, and establishing a work plan. Implementation activities included conducting mobilization meetings, prioritizing health, popularizing the HPS concept, ensuring community cooperation and participation, acting as role models, offering training, and using new teaching and learning methods. Monitoring and evaluation activities included process, baseline, and final evaluations and changing standards of evaluation to a more holistic evaluation that schools go through to become Health Promoting Schools. Schools also reported that they faced, and overcame, a number of challenges including understanding and integrating the HPS concept and lack of professional development and support. Results revealed that schools transitioned from a passive model of education to interactive pedagogy put priority on health and viewed it as a co-responsibility, reshaped assessment to a more holistic approach and called for more training and technical support. Participants mentioned that they gained knowledge and skills and developed a deeper understanding about health. Health impact was also demonstrated, for instance in reduced injuries and reduced smoking, and educational impact was demonstrated, for instance in improved relationships of children to parents and teachers, improved social qualities, and improved teacher satisfaction. (AU)