Association of the DNA Methylation of Obesity-Related Genes with the Dietary Nutrient Intake in Children.

The occurrence of obesity stems from both genetic and external influences. Despite thorough research and attempts to address it through various means such as dietary changes, physical activity, education, and medications, a lasting solution to this widespread problem remains elusive. Nutrients play a crucial role in various cellular processes, including the regulation of gene expression. One of the mechanisms by which nutrients can affect gene expression is through DNA methylation. This modification can alter the accessibility of DNA to transcription factors and other regulatory proteins, thereby influencing gene expression. Nutrients such as folate and vitamin B12 are involved in the one-carbon metabolism pathway, which provides the methyl groups necessary for DNA methylation. Studies have shown that the inadequate intake of these nutrients can lead to alterations in DNA methylation patterns. For this study, we aim to understand the differences in the association of the dietary intake between normal weight and overweight/obese children and between European American and African American children with the DNA methylation of the three genes NRF1, FTO, and LEPR. The research discovered a significant association between the nutritional intake of 6-10-years-old children, particularly the methyl donors present in their diet, and the methylation of the NRF1, FTO, and LEPR genes. Additionally, the study emphasizes the significance of considering health inequalities, particularly family income and maternal education, when investigating the epigenetic impact of methyl donors in diet and gene methylation.

Novel Differentially Methylated Regions Identified by Genome-Wide DNA Methylation Analyses Contribute to Racial Disparities in Childhood Obesity.

The magnitude of the childhood obesity epidemic and its effects on public health has accelerated the pursuit of practical preventative measures. Epigenetics is one subject that holds a lot of promise, despite being relatively new. The study of potentially heritable variations in gene expression that do not require modifications to the underlying DNA sequence is known as epigenetics. Here, we used Illumina MethylationEPIC BeadChip Array to identify differentially methylated regions in DNA isolated from saliva between normal weight (NW) and overweight/obese (OW/OB) children and between European American (EA) and African American (AA) children. A total of 3133 target IDs (associated with 2313 genes) were differentially methylated (p < 0.05) between NW and OW/OB children. In OW/OB children, 792 target IDs were hypermethylated and 2341 were hypomethylated compared to NW. Similarly, in the racial groups EA and AA, a total of 1239 target IDs corresponding to 739 genes were significantly differentially methylated in which 643 target IDs were hypermethylated and 596 were hypomethylated in the AA compared to EA participants. Along with this, the study identified novel genes that could contribute to the epigenetic regulation of childhood obesity.

Potential Role of Oxidative Stress in the Production of Volatile Organic Compounds in Obesity.

Obesity is associated with numerous health issues such as sleep disorders, asthma, hepatic dysfunction, cancer, renal dysfunction, diabetes, cardiovascular complications, and infertility. Previous research has shown that the distribution of excess body fat, rather than excess body weight, determines obesity-related risk factors. It is widely accepted that abdominal fat is a serious risk factor for illnesses associated with obesity and the accumulation of visceral fat promotes the release of pro-oxidants, pro-inflammatory, and reactive oxygen species (ROS). The metabolic process in the human body produces several volatile organic compounds (VOCs) via urine, saliva, breath, blood, skin secretions, milk, and feces. Several studies have shown that VOCs are released by the interaction of ROS with underlying cellular components leading to increased protein oxidation, lipid peroxidation, or DNA damage. These VOCs released via oxidative stress in obese individuals may serves as a biomarker for obesity-related metabolic alterations and disease. In this review, we focus on the relationship between oxidative stress and VOCs in obesity.

Racial Disparities in Methylation of NRF1, FTO, and LEPR Gene in Childhood Obesity.

Childhood obesity has affected the health of millions of children around the world despite vigorous efforts by health experts. The obesity epidemic in the United States has disproportionately afflicted certain racial and ethnic minority groups. African American children are more likely than other children to have obesity-related risk factors such as hyperlipidemia, diabetes, cardiovascular disease, and coronavirus disease (COVID-19). For the reduction in obesity-related health inequalities to be successful, it is essential to identify the variables affecting various groups. A notable advancement in epigenetic biology has been made over the past decade. Epigenetic changes like DNA methylation impact on many genes associated with obesity. Here, we evaluated the DNA methylation levels of the genes NRF1, FTO, and LEPR from the saliva of children using real-time quantitative PCR-based multiplex MethyLight technology. ALU was used as a reference gene, and the Percent of Methylated Reference (PMR) was calculated for each sample. European American children showed a significant increase in PMR of NRF1 and FTO in overweight/obese participants compared to normal weight, but not in African American children. After adjusting for maternal education and annual family income by regression analysis, the PMR of NRF1 and FTO was significantly associated with BMI z-score only in European American children. While for the gene LEPR, African American children had higher methylation in normal weight participants as compared to overweight/obese and no methylation difference in European American children. The PMR of LEPR was significantly negative associated with the obesity measures only in African American children. These findings contribute to a race-specific link between NRF1, FTO, and LEPR gene methylation and childhood obesity.

Salivary Neurotrophins Brain-Derived Neurotrophic Factor and Nerve Growth Factor Associated with Childhood Obesity: A Multiplex Magnetic Luminescence Analysis.

Obesity is linked with higher inflammatory markers and is characterized by chronic low-grade inflammation. Neurotrophins brain-derived neurotrophic factor (BDNF) and ß-nerve growth factor (ß-NGF), in addition to their neuronal functions, act on several immune cells and have been recently designated as metabokines due to their regulatory role in energy homeostasis and food intake. The current study evaluates the salivary BDNF and ß-NGF and their association with anthropometric measurement, blood pressure, and salivary insulin in children. Anthropometric measurements and saliva samples were obtained from 76 children, aged 6-10 years. Multiplex analysis was carried out for the salivary analysis of BDNF, NGF, and insulin by human magnetic Luminex performance assay. Statistical analysis was performed to analyze the best fit diagnostic value for biomarkers and the relationship of the neurotrophic levels of BDNF and NGF with obesity measures and blood pressure. Salivary BDNF and ß-NGF showed a significantly higher concentration in obese children than normal-weight children. Both neurotrophins are positively associated with obesity anthropometric measures, blood pressure, and salivary insulin. Multinominal regression analysis reported a significant association between salivary BDNF, ß-NGF, insulin, and systolic pressure adjusted for age, gender, income, and maternal education. The salivary concentration of BDNF and NGF was higher in obese children, and it is positively associated with anthropometric measures, suggesting that neurotrophins can be used as a non-invasive predictor of obesity-related complications in children.

Multiplexed measurements of salivary fetuin-A, insulin, and adiponectin as potential non-invasive biomarkers in childhood obesity.

BACKGROUND: Obesity increases the risk of developing insulin resistance, diabetes, and cardiovascular disease. The current study is designed to evaluate the association of salivary fetuin-A, insulin, and adiponectin with the obesity measures in children. METHODS: Seventy-six children aged 6-10 years participated in the study. Anthropometric measurements were recorded, and saliva was collected from the participants. Based on the Center for Disease Control and Prevention (CDC), the participants were classified into normal weight (NW), overweight (OW), and obese (OB). Multiplex analysis for salivary markers fetuin-A, insulin, and adiponectin was performed using Luminex performance assay. The diagnostic value of the salivary marker was identified by receiver operating characteristics (ROC) curve, the correlation between obesity measures and markers were performed by regression analysis. RESULTS: Salivary fetuin-A and insulin were significantly increased in OW and OB in comparison to NW. Adiponectin was significantly decreased in the OB compared to NW and OW groups. Fetuin-A and insulin had the highest area under the curve with the best diagnostic value of a biomarker than adiponectin. Fetuin-A and insulin showed a positive association with obesity measures and among the parameters, but adiponectin was inversely associated. CONCLUSIONS: Salivary fetuin-A, insulin, and adiponectin levels are associated with the obesity in elementary school-aged children.

High Olfactory Receptor-Rich 11q11 Copy Number in Girls and African American Children.

Copy number variants (CNVs) provide numerous genetic differences between individuals, and they have been linked with multiple human diseases. Obesity is one of the highly heritable complex disorders, which is associated with copy number variance (CNV). A recent report shows that the 11q11 gene, a novel olfactory receptor, and its copy number variants are involved in the early onset of obesity. In the current study, we analyzed the 11q11 gene copy number variance (CNV) based on gender in White/European American (EA) and African American (AA) normal weight and overweight/obese children. Sixty-nine boys and fifty-eight girls between the ages of 6 and 10 years belonging to either EA or AA ethnicity were involved in this study. As per World Health Organization (WHO) guidelines, each participant's body weight and height were recorded. DNA was extracted from saliva, and the copy number variants for the 11q11 gene were measured using digital PCR. The descriptive analysis of the 11q11 copy number showed significantly more copies in girls compared to boys; similarly, AA participants had significantly increased CNV compared to EA. The normal weight (NW) and overweight/obese (OW/OB) girls were significantly less likely to belong to the low copy number variant (LCNV) group of 11q11 compared to boys; similarly, NW and OW/OB AA children were significantly less likely to belong to the LCNV group. The AA girls in LCNV had significantly higher BMI z-scores. Our findings suggest that the 11q11 copy number in children is race and gender-specific.

Ethnic variability associating gut and oral microbiome with obesity in children.

Obesity is a growing worldwide problem that generally starts in the early years of life and affects minorities more often than Whites. Thus, there is an urgency to determine factors that can be used as targets as indicators of obesity. In this study, we attempt to generate a profile of gut and oral microbial clades predictive of disease status in African American (AA) and European American (EA) children. 16S rDNA sequencing of the gut and saliva microbial profiles were correlated with salivary amylase, socioeconomic factors (e.g., education and family income), and obesity in both ethnic populations. Gut and oral microbial diversity between AA and EA children showed significant differences in alpha-, beta-, and taxa-level diversity. While gut microbial diversity between obese and non-obese was not evident in EA children, the abundance of gut Klebsiella and Magasphaera was associated with obesity in AA children. In contrast, an abundance of oral Aggregatibacter and Eikenella in obese EA children was observed. These observations suggest an ethnicity-specific association with gut and oral microbial profiles. Socioeconomic factors influenced microbiota in obesity, which were ethnicity dependent, suggesting that specific approaches to confront obesity are required for both populations.

Engineered resveratrol-loaded fibrous scaffolds promotes functional cardiac repair and regeneration through Thioredoxin-1 mediated VEGF pathway.

Despite recent advancements, mortality due to coronary heart disease (CHD) remains high. Recently, the use of tissue-engineered grafts and scaffolds has emerged as a candidate for supporting the myocardium after an ischemic event. Resveratrol is a naturally occurring plant-based non-flavonoid polyphenolic compound found in many natural foods, including grapes and red wine. We embedded resveratrol in a polycaprolactone (PCL) scaffold and evaluated the cardio-therapeutic effects in a murine model of myocardial infarction (MI), with animals being grouped into Sham (S), Myocardial Infarction (MI), MI + PCL, and MI + PCL-Resveratrol (MI + PCL-R). After 4 and 8 weeks, echocardiography was performed to assess ejection fraction (EF) and fractional shortening (FS), which was followed by immunohistochemistry and immunofluorescence analysis at 8 weeks. The MI + PCL-R group showed a significant improvement in EF and FS compared with the MI + PCL group at 4 and 8-weeks post-surgery. PCL-R scaffolds treated hearts revealed decreased inflammatory cell infiltration, improved collagen extracellular matrix (ECM) secretion and blood vessel network formation following MI. The immunofluorescence analysis revealed resveratrol-loaded scaffolds promote increased expression of cTnT, Cx-43, Trx-1, and VEGF proteins. This study reports resveratrol-mediated rescue of ischemic myocardium when delivered through a biodegradable polymeric scaffold system after MI.

Telomere Length as a Biomarker for Race-Related Health Disparities.

Disparities between the races have been well documented in health and disease in the USA. Recent studies show that telomere length, a marker of aging, is associated with obesity and obesity-related diseases, such as heart disease and diabetes. The current study aimed to evaluate the connection between telomere length ratio, blood pressure, and childhood obesity. The telomere length ratio was measured in 127 children from both European American (EA) and African American (AA) children, aged 6-10 years old. AA children had a significantly high relative telomere to the single copy gene (T/S) ratio compared to EA children. There was no significant difference in the T/S ratio between normal weight (NW) and overweight/obese (OW/OB) groups of either race. Blood pressure was significantly elevated in AA children with respect to EA children. Hierarchical regression analysis adjusted for race, gender, and age expressed a significant relationship between the T/S ratio and diastolic pressure. Low T/S ratio participants showed a significant increase in systolic pressure, while a high T/S ratio group showed an increase in diastolic pressure and heart rate of AA children. In conclusion, our findings show that AA children have high T/S ratio compared to EA children. The high T/S ratio is negatively associated with diastolic pressure.

Eating Behaviors in Relation to Child Weight Status and Maternal Education.

BACKGROUND: The eating behavior of children is important to maintain a healthy weight. This current study explored the differences in children's eating behaviors and their relation to weight status and maternal education level, using the child eating behavior questionnaire (CEBQ). METHODS: The study recruited 169 participants aged between six and ten years. Multinomial logistic regression was conducted to examine the association between the CEBQ factors and children's body weight status. The association between the CEBQ scores and maternal educational levels was examined using a one-way analysis of variance (ANOVA). RESULTS: The multinomial logistic regression findings indicate that children in the obese group exhibited a significant increase in food responsiveness, enjoyment of food, emotional overeating, and a decrease in satiety responsiveness compared to normal weight children. The one-way ANOVA showed a significant difference in subscales under the food approach (food responsiveness, desire to drink, emotional overeating) and food avoidance (satiety responsiveness) based upon the child's weight status. The three subscales under the food approach category were significantly dependent upon the maternal education but did not have a significant association with food avoidance. CONCLUSIONS: The results suggest that the increase in food responsiveness and emotional overeating in obese children is influenced by maternal education.

Environmental contaminants and male infertility: Effects and mechanisms.

The escalating prevalence of male infertility and decreasing trend in sperm quality have been correlated with rapid industrialisation and the associated discharge of an excess of synthetic substances into the environment. Humans are inevitably exposed to these ubiquitously distributed environmental contaminants, which possess the ability to intervene with the growth and function of male reproductive organs. Several epidemiological reports have correlated the blood and seminal levels of environmental contaminants with poor sperm quality. Numerous in vivo and in vitro studies have been conducted to investigate the effect of various environmental contaminants on spermatogenesis, steroidogenesis, Sertoli cells, blood-testis barrier, epididymis and sperm functions. The reported reprotoxic effects include alterations in the spermatogenic cycle, increased germ cell apoptosis, inhibition of steroidogenesis, decreased Leydig cell viability, impairment of Sertoli cell structure and function, altered expression of steroid receptors, increased permeability of blood-testis barrier, induction of peroxidative and epigenetic alterations in spermatozoa resulting in poor sperm quality and function. In light of recent scientific reports, this review discusses the effects of environmental contaminants on the male reproductive function and the possible mechanisms of action.

Salivary Amylase Gene Copy Number Is Associated with the Obesity and Inflammatory Markers in Children.

BACKGROUND: We have recently shown that the copy number of salivary amylase (AMY1) gene was significantly decreased, and the obesity-related salivary biomarkers resistin, MCP-1, TNF-α, IL-6, and CRP were significantly increased in overweight/obese children compared to normal weight. This study aimed to evaluate the association of AMY1 copy number variant (CNV) with obesity and inflammatory markers. Seventy-six participants aged between 6 and 10 years have participated, and the saliva samples were collected along with the anthropometric measurements. METHODS: AMY1 copy number was analyzed by 3D digital PCR, and obesity-related biomarkers were performed with a Bioplex multiplex analyzer. RESULTS: The mean AMY1 copy number was higher in normal weight (7.90 ± 0.38) compared to the overweight/obese group (6.20 ± 0.29). The association of AMY1 CNV with obesity and inflammatory markers showed significant negative correlation [CRP, ß = -0.238 (p < 0.05); resistin, ß = -0.25 (p < 0.05); MCP-1, ß = -0.304 (p < 0.01)] except for complement factor D, TNF α and IL-6. The anti-inflammatory cytokine, IL-10 reported a positive correlation with AMY1 copy number with a ß = 0.268 (p < 0.05). The multivariable model adjusted with age and gender depicted a similar correlation with obesity markers. CONCLUSION: Our results report that AMY1 CNV is associated with obesity and inflammatory biomarkers in children's saliva sample.

Deletion of newly described pro-survival molecule Pellino-1 increases oxidative stress, downregulates cIAP2/NF-κB cell survival pathway, reduces angiogenic response, and thereby aggravates tissue function in mouse ischemic models.

INTRODUCTION: In the present study, we aimed to explore the functional role of Pellino-1 (Peli1) in inducing neovascularization after myocardial infarction (MI) and hindlimb ischemia (HLI) using Peli1 global knockout mice (Peli1-/-). Recently we have shown that Peli1, an E3 ubiquitin ligase, induce angiogenesis and improve survivability, with decreased necrosis of ischemic skin flaps. METHODS: Peli1fl/fl and Peli1-/- mice were subjected to either permanent ligation of the left anterior descending coronary artery (LAD) or sham surgery (S). Tissues from the left ventricular risk area were collected at different time points post-MI. In addition, Peli1fl/fl and Peli1-/- mice were also subjected to permanent ligation of the right femoral artery followed by motor function scores, Doppler analysis for blood perfusion and immunohistochemical analysis. RESULTS: Global Peli1 knockout exacerbated myocardial dysfunction, 30 and 60 days after MI compared to wild type (WT) mice as measured by echocardiogram. In addition, Peli1-/- mice also showed decreased motor function scores and perfusion ratios compared with Peli1fl/fl mice 28 days after the induction of HLI. The use of Peli1 in adenoviral gene therapy following HLI in CD1 mice improved the perfusion ratio at 28 days compared to Ad.LacZ-injected mice. CONCLUSION: These results suggest new insights into the protective role of Peli1 on ischemic tissues and its influence on survival signaling.

Parental Feeding Practices in Relation to Maternal Education and Childhood Obesity.

Parental beliefs, attitudes, and feeding practices play a vital role in childhood obesity. This study aimed to assess parental perceptions, concerns about weight, feeding practices using the Child Feeding Questionnaire (CFQ), and its association with body mass index (BMI) and maternal education in elementary school children. Participants aged 6-10 years (n = 169) were recruited and anthropometric measurements were obtained. Pearson's correlation and hierarchical linear regression analysis were used to examine the association between BMI z-score and the seven factors of the CFQ. The BMI z-score was significantly associated with parental perceived child weight and concern about child weight. The BMI z-score had a significant negative association with parents pressuring children to eat. Parents of obese children reported significantly higher (p < 0.001) levels of perceived child weight (ß = 0.312) and concern (ß = 0.320) about their child's weight compared to the normal weight and overweight groups. Parents of overweight children showed considerably less (ß = -0.224; p < 0.005) pressuring towards their children to eat as compared to parents of normal weight children. Additionally, we found that the parental feeding practice (pressure to eat) was only dependent upon maternal education. The path analysis indicates that maternal education has a mediating effect on BMI z-score and pressure to eat is related to BMI z-score through maternal education. The findings demonstrate the association between the parents' perceptions, concerns, and pressure to eat with BMI z-score of elementary school-aged children. Only the parental feeding practice pressure to eat was dependent upon the maternal education.

The relationship between obesity and sleep timing behavior, television exposure, and dinnertime among elementary school-age children.

STUDY OBJECTIVES: The daily lifestyle behaviors of children have been shown to be associated with obesity. There are limited studies on the association of sleep timing behavior and body mass index (BMI), specifically in elementary school-age children. This study aimed to investigate the relationship between obesity and sleep timing patterns, television exposure time, and dinnertime among elementary school-age children. METHODS: Children (n = 169) aged 6 to 10 years who were residents of Alabama were recruited for this study. The questionnaires were used to determine the bedtime, wake-up time, television exposure time, and dinnertime of the participants. The participants were categorized into four groups depending on the bedtime and wake-up time behavior habits: early bed/early wake-up (EE); early bed/late wake-up (EL); late bed/early wake-up (LE); and late bed/late wake-up (LL) time. The BMI z-score, television exposure time, and dinnertime of these groups were compared. RESULTS: The LL group had a significantly higher BMI z-score compared to the EE group. The higher BMI z-score in the LL group may be associated with late bedtime and not late wake-up time. Approximately 71% of children with late bedtime (8:48 pm), 75% of children who watch television for more than 1 hour, and 54% of children who have dinner after 7:00 pm have obesity. CONCLUSIONS: Daily behavior habits such as late bedtime, increased television exposure, and late dinnertime are associated with obesity.

Urinary Biomarkers of Inflammation and Oxidative Stress Are Elevated in Obese Children and Correlate with a Marker of Endothelial Dysfunction.

Obesity is a state of chronic low-level inflammation closely associated with oxidative stress. Childhood obesity is associated with endothelial dysfunction, inflammation, and oxidative stress markers individually. This study was aimed at determining the association between the biomarkers of inflammation, oxidative stress, and endothelial dysfunction in urine samples of healthy, overweight, and obese children. Eighty-eight elementary school children aged between 6 and 10 years participated in this study. Anthropometric measurements were measured using WHO recommendations. The biomarkers of low-grade inflammation such as C-reactive protein (CRP), interleukin-6 (IL-6), and α-1-acid glycoprotein (AGP); oxidative stress markers such as 8-isoprostane and 8-hydroxy-2'-deoxyguanosine (8-OHdG); and endothelin-1 (ET-1) were analyzed in urine samples. The area under the curve (AUC) by the receiver operating characteristics (ROC) was analyzed to identify the best urinary biomarker in childhood obesity. Linear regression and Pearson correlation were analyzed to determine the association between the parameters. The obese participants have significantly increased levels of CRP, AGP, IL-6, and 8-isoprostane compared to normal-weight participants. The overweight participants had significantly increased levels of ET-1 and 8-OHdG but not the obese group compared to the NW group. The AUC for urinary CRP (AUC: 0.847, 95% CI: 0.765-0.930; p < 0.0001) and 8-isoprostane (AUC: 0.857, 95% CI: 0.783-0.932; p < 0.0001) showed a greater area under ROC curves compared to other inflammatory and oxidative markers. The urinary CRP and 8-isoprostane significantly correlated with the obesity measures (body mass index, waist circumference, and waist-to- height ratio) and ET-1, inflammatory, and oxidative markers. The increased urinary inflammatory markers and 8-isoprostane can serve as a noninvasive benchmark for early detection of the risk of developing cardiovascular disease.

Pro-Nerve Growth Factor Induces Activation of RhoA Kinase and Neuronal Cell Death.

We have previously shown that the expression of pro-nerve growth factor (proNGF) was significantly increased, nerve growth factor (NGF) level was decreased, and the expression of p75NTR was enhanced in Alzheimer's disease (AD) hippocampal samples. NGF regulates cell survival and differentiation by binding TrkA and p75NTR receptors. ProNGF is the precursor form of NGF, binds to p75NTR, and induces cell apoptosis. The objective of this study is to determine whether the increased p75NTR expression in AD is due to the accumulation of proNGF and Rho kinase activation. PC12 cells were stimulated with either proNGF or NGF. Pull-down assay was carried out to determine the RhoA kinase activity. We found the expression of p75NTR was enhanced by proNGF compared to NGF. The proNGF stimulation also increased the RhoA kinase activity leading to apoptosis. The expression of active RhoA kinase was found to be increased in human AD hippocampus compared to control. The addition of RhoA kinase inhibitor Y27632 not only blocked the RhoA kinase activity but also reduced the expression of p75NTR receptor and inhibited the activation of JNK and MAPK induced by proNGF. This suggests that overexpression of proNGF in AD enhances p75NTR expression and activation of RhoA, leading to neuronal cell death.

Association of salivary C-reactive protein with the obesity measures and markers in children.

OBJECTIVE: Overweight and obesity is a pro-inflammatory state. This study aimed to examine the level of the salivary obesity markers in normal weight (NW) and overweight/obese (OW/OB) children, association with the obesity measures and the interrelations between the biomarkers. SUBJECTS AND METHODS: Seventy-six children (40 normal weight and 36 overweight/obese) were recruited for this study. Body weight, height, and waist circumference measurement were obtained. The saliva sample was collected from all the participants. According to the Center for Disease Control and Prevention (CDC), the participants were classified into the normal weight or overweight/obese depending upon the body mass index (BMI) percentile ranking. The obesity panel of salivary markers resistin, C-C Motif Chemokine Ligand 2 (CCL2)/monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), complement factor D, and interleukin-10 (IL-10) were determined using human magnetic Luminex performance assay. The receiver operating characteristics (ROC) analysis was used to determine the area under the curve (AUC) to identify the best salivary biomarker in children. Linear regression and Pearson's correlation analyses to determine the association between the parameters. RESULTS: The obesity biomarkers resistin, MCP-1, TNF-α, IL-6 and CRP were significantly high in overweight/obese compared to normal weight. Salivary CRP (AUC: 0.866, 95% CI: 0.780-0.952; p<0.0001) showed superiority area under ROC curves with good discriminatory power than resistin, MCP-1, TNF-α, and IL-6. BMI z-score, WC z-score, and WHtR z-score showed a significant association (p<0.0001) with CRP. The CRP significantly (p<0.0001) correlated with resistin, CCL2/MCP-1, TNF-α, IL-6, and IL-10 by linear regression and Pearson's correlation analysis. CONCLUSION: Increased level of salivary CRP in children may be considered as a non-invasive marker for childhood obesity for detection of the risk factors for the development of metabolic dysregulation.

Evaluation of dermal tissue regeneration using resveratrol loaded fibrous matrix in a preclinical mouse model of full-thickness ischemic wound.

The complete loss of dermal tissue due to ischemia is a serious challenge facing clinicians. Frequently, the failure of wound healing is due to ischemic conditions prevailing at the site of damaged tissue. Restoration of lost vasculature at the ischemic site can be achieved by supplementing proangiogenic stimuli through an engineered scaffold mimicking dermal extracellular matrix. Towards this objective, we have developed an electrospun scaffold loaded with the pro-angiogenic molecule resveratrol. The physical and chemical changes in the polymeric scaffold before and after loading of resveratrol were characterized using field emission scanning electron microscopy (FE-SEM), Fourier-transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), coherence scanning interferometry (CSI) and X-ray diffraction (XRD). A sustained release of resveratrol from the scaffold was elucidated by UV-spectrophotometer analysis. The enhancement in cell-matrix interaction was studied using human umbilical vein endothelial cells (HUVECs) seeded on the scaffolds. The biocompatibility analysis of resveratrol loaded scaffolds was evaluated through a subcutaneous implantation study in mice. The therapeutic potential of resveratrol loaded scaffolds to accelerate tissue repair was analyzed in a full-thickness ischemic wound model in mice. Wound closure and H&E staining analysis showed rapid closure of ischemic wound area and re-epithelialization in resveratrol loaded scaffold treated groups compared to collagen and negative control groups. The immunostaining analysis further revealed the activation of thioredoxin-1 (Trx-1), heme oxygenase-1 (HO-1) mediated vascular endothelial growth factor (VEGF) signaling in resveratrol loaded scaffold treated group. The expression of Bcl-2 in healing wound edges post-treatment with resveratrol loaded scaffold confirmed the anti-apoptotic effect mediated by resveratrol. From this study, we explored a synergistic effect mediated by resveratrol and fibrous scaffolds to aid the ischemic wound healing process through effective vascularization.