Adipokines and their role in acute pancreatitis.

Acute pancreatitis (AP) is characterized by an inflammatory response that leads to edema and haemorrhaging of pancreatic tissue. In severe cases, it can even result in the necrosis of pancreatic tissue following activation within the pancreas. Adipokines are biologically active molecules released by adipose tissue that have a wide-ranging impact on health and disease. Adipokines are cytokines produced not only in white adipose tissue but also in the fat surrounding the pancreas, and they play a role in the body's inflammatory response. The presence of increased adipose tissue, often associated with obesity, has been linked to a heightened systemic inflammatory response in cases of AP. According to the literature, there are many adipokines. This article summarizes the role of adipokines in AP. Adipokines could be promising biomarkers for both diagnostic and new therapeutic treatment strategies in AP. However, a deeper knowledge of the signaling pathways of adipokines and their potential therapeutic role in AP is necessary.

Adiponectin, Interleukin-18 (IL-18), and Visceral Adipose Tissue in Filipino Americans: Biomarkers and Risk of Type 2 Diabetes.

Introduction: Filipino Americans (FAs) are at high risk for developing type 2 diabetes despite other Asian phenotypes. Evidence suggests that pro-inflammatory interleukin-18 (IL-18) and anti-inflammatory adiponectin biomarkers associated with visceral adipose tissue (VAT) may explain this risk. Objectives: This study aimed to quantify the biomarkers in relation to standard ranges of VAT or typical circulating concentration ranges reported in the literature of IL-18 and adiponectin, examine relationships of these markers, and determine if they were different among those participants without diabetes, prediabetes, and diabetes. Methods: A cross-sectional study was used to enroll FAs without diabetes, prediabetes, or diabetes. VAT was measured using the InBody 570© Body Composition Analyzer. Blood samples were obtained to assess plasma concentrations of IL-18 and adiponectin using enzyme-linked immunosorbent assay. All analyses were conducted using a 5% type I error rate. Mean ±SD and percentages were used to describe the sample and data where appropriate. Pearson's correlations (R) were calculated to determine the relationships between VAT and IL-18 in each group. Analysis of variance was used to determine differences in VAT, IL-18, and adiponectin among groups. Further, nonparametric procedures examined the differences in adiponectin among those within groups. Results: Seventy-five participants were enrolled. Biomarkers above the typical concentration range were observed for VAT, IL-18, and adiponectin. Adiponectin significantly differed among groups with lower values in the diabetes group vs. the nondiabetes group. Conclusions: The findings indicate that while inflammation-related biomarkers, such as adiponectin, correlate with VAT and may serve as indicators of increased risk of type 2 diabetes in FAs, correlation alone does not establish causality.

Exploring the interplay between epicardial fat, coronary artery calcium score, and nonalcoholic fatty liver disease through non-ECG-gated chest computed tomography: A cross-sectional study.

Background and Aims: This study examines the relationships between epicardial adipose tissue (EAT), nonalcoholic fatty liver disease (NAFLD), and coronary artery calcium score (CACS) using non-ECG-gated CT scans. It aims to determine the effectiveness of EAT measurements and NAFLD as predictors for coronary artery disease (CAD). Methods: This cross-sectional study was conducted at a specialized center, focusing on individuals who underwent non-ECG-gated chest CT scans without contrast. We evaluated EAT thickness and density in three areas: the right atrioventricular groove, the free wall of the right ventricle, and the central area of the right anterior interventricular groove. Additionally, we measured CACS and determined the presence of NAFLD by comparing liver-to-spleen density ratios. Statistical analyses, including regression models, were performed using SPSS (version 26). Results: In this study, we enrolled 365 participants, including 203 males with an average age of 47 ± 17.93 years. EAT thickness was 6.28 ± 1.62 mm, and EAT density was -96.07 ± 12.47 Hounsfield units (HU). The mean CACS was 22.27 ± 79.01, and the mean liver density was 50.01 ± 10.76 HU. A significant positive correlation was observed between EAT thickness and CACS (r = 0.208, p < 0.001). EAT density showed a significant negative correlation with CACS (r = -0.155, p = 0.003). No correlation was found between NAFLD and CACS. Univariate logistic regression analysis identified significant predictors of increased CACS, including EAT thickness (OR: 1.803), EAT density (OR: 0.671), diabetes mellitus (DM) (OR: 5.921), and hypertension (HTN) (OR: 7.414). Multivariate analysis confirmed the significance of EAT thickness (OR: 0.682), DM (OR: 3.66), and HTN (OR: 2.79) as predictors of elevated CACS. Conclusion: Our findings demonstrate that increased EAT thickness and decreased density are associated with higher CACS. Also, both DM and HTN significantly contribute to increased CACS. These results support the inclusion of EAT measurements in cardiovascular risk assessment models to enhance diagnostic accuracy.

Interplay of FXN expression and lipolysis in white adipocytes plays a critical role in insulin sensitivity in Friedreich's ataxia mouse model.

Frataxin (FXN) is required for iron-sulfur cluster biogenesis, and its loss causes the early-onset neurodegenerative disease Friedreich ataxia (FRDA). Loss of FXN is a susceptibility factor in the development of diabetes, a common metabolic complication after myocardial hypertrophy in patients with FRDA. The underlying mechanism of FXN deficient-induced hyperglycemia in FRDA is, however, poorly understood. In this study, we confirmed that the FXN deficiency mouse model YG8R develops insulin resistance in elder individuals by disturbing lipid metabolic homeostasis in adipose tissues. Evaluation of lipolysis, lipogenesis, and fatty acid ß-oxidation showed that lipolysis is most severely affected in white adipose tissues. Consistently, FXN deficiency significantly decreased expression of lipolytic genes encoding adipose triglyceride lipase (Atgl) and hormone-sensitive lipase (Hsl) resulting in adipocyte enlargement and inflammation. Lipolysis induction by fasting or cold exposure remarkably upregulated FXN expression, though FXN deficiency lessened the competency of lipolysis compared with the control or wild type mice. Moreover, we found that the impairment of lipolysis was present at a young age, a few months earlier than hyperglycemia and insulin resistance. Forskolin, an activator of lipolysis, or pioglitazone, an agonist of PPARγ, improved insulin sensitivity in FXN-deficient adipocytes or mice. We uncovered the interplay between FXN expression and lipolysis and found that impairment of lipolysis, particularly the white adipocytes, is an early event, likely, as a primary cause for insulin resistance in FRDA patients at later age.

Methylene blue reduces monoamine oxidase expression and oxidative stress in human cardiovascular adipose tissue.

Cardiovascular diseases represent the major cause of morbidity mainly due to chronic heart failure. Epicardial (EAT) and perivascular adipose tissues (PVAT) are considered major contributors to the pathogenesis of cardiometabolic pathologies. Monoamine oxidases (MAOs) are mitochondrial enzymes recognized as sources of reactive oxygen species (ROS) in cardiometabolic pathologies. Methylene blue (MB) is one of the oldest protective agents, yet no data are available about its effects on adipose tissue. The present pilot study was aimed at assessing the effects of MB: (i) on MAO expression and (ii) oxidative stress in EAT and PVAT harvested from patients with heart failure subjected to cardiac surgery (n = 25). Adipose tissue samples were incubated with MB (0.1 µM/24 h) and used for the assessment of MAO gene and protein expression (qPCS and immune fluorescence) and ROS production (confocal microscopy and spectrophotometry). The human cardiovascular adipose tissues contain both MAO isoforms, predominantly MAO-A. Incubation with MB reduced MAOs expression and oxidative stress; co-incubation with serotonin, the MAO-A substrate, further augmented ROS generation, an effect partially reversed by MB. In conclusion, MAO-A is the major isoform expressed in EAT and PVAT and contribute to local oxidative stress; both effects can be mitigated by methylene blue.

Quantitative assessment of morphological changes in lipid droplets and lipid-mito interactions with aging in brown adipose.

The physical characteristics of brown adipose tissue (BAT) are defined by the presence of multilocular lipid droplets (LDs) within the brown adipocytes and a high abundance of iron-containing mitochondria, which give it its characteristic color. Normal mitochondrial function is, in part, regulated by organelle-to-organelle contacts. For example, the contact sites that mediate mitochondria-LD interactions are thought to have various physiological roles, such as the synthesis and metabolism of lipids. Aging is associated with mitochondrial dysfunction, and previous studies show that there are changes in mitochondrial structure and the proteins that modulate organelle contact sites. However, how mitochondria-LD interactions change with aging has yet to be fully clarified. Therefore, we sought to define age-related changes in LD morphology and mitochondria-lipid interactions in BAT. We examined the three-dimensional morphology of mitochondria and LDs in young (3-month) and aged (2-year) murine BAT using serial block face-scanning electron microscopy and the Amira program for segmentation, analysis, and quantification. Our analyses showed reductions in LD volume, area, and perimeter in aged samples in comparison to young samples. Additionally, we observed changes in LD appearance and type in aged samples compared to young samples. Notably, we found differences in mitochondrial interactions with LDs, which could implicate that these contacts may be important for energetics in aging. Upon further investigation, we also found changes in mitochondrial and cristae structure for the mitochondria interacting with LDs. Overall, these data define the nature of LD morphology and organelle-organelle contacts during aging and provide insight into LD contact site changes that interconnect biogerontology with mitochondrial function, metabolism, and bioactivity in aged BAT.

Aging human abdominal subcutaneous white adipose tissue at single cell resolution.

White adipose tissue (WAT) is a robust energy storage and endocrine organ critical for maintaining metabolic health as we age. Our aim was to identify cell-specific transcriptional aberrations that occur in WAT with aging. We leveraged full-length snRNA-Seq and histology to characterize the cellular landscape of human abdominal subcutaneous WAT in a prospective cohort of 10 younger (≤30 years) and 10 older individuals (≥65 years) balanced for sex and body mass index (BMI). The older group had greater cholesterol, very-low-density lipoprotein, triglycerides, thyroid stimulating hormone, and aspartate transaminase compared to the younger group (p < 0.05). We highlight that aging WAT is associated with adipocyte hypertrophy, increased proportions of lipid-associated macrophages and mast cells, an upregulation of immune responses linked to fibrosis in pre-adipocyte, adipocyte, and vascular populations, and highlight CXCL14 as a biomarker of these processes. We show that older WAT has elevated levels of senescence marker p16 in adipocytes and identify the adipocyte subpopulation driving this senescence profile. We confirm that these transcriptional and phenotypical changes occur without overt fibrosis and in older individuals that have comparable WAT insulin sensitivity to the younger individuals.

Cross-talks between perivascular adipose tissue and neighbors: multifaceted nature of nereids.

Perivascular adipose tissue (PVAT) is a unique fat depot surrounding blood vessels and plays a vital role in the progression of vascular remodeling and dysfunction. PVAT exhibits remarkable differences in structure, phenotype, origin, and secretome across anatomical locations. The proximity of PVAT to neighboring vascular beds favors a niche for bidirectional communication between adipocytes and vascular smooth muscle cells, endothelial cells, and immune cells. In this review, we update our understanding of PVAT's regional differences and provide a comprehensive exploration of how these differences impact cross-talks between PVAT and the vascular wall. Different PVAT depots show different degrees of vasoprotective function and resilience to pathological changes such as obesity and vasculopathies, shaping multifaceted interactions between PVAT depots and adjacent vasculatures. The depot-specific resilience may lead to innovative strategies to manage cardiometabolic disorders.

CD36 restricts lipid-associated macrophages accumulation in white adipose tissues during atherogenesis.

Visceral white adipose tissues (WAT) regulate systemic lipid metabolism and inflammation. Dysfunctional WAT drive chronic inflammation and facilitate atherosclerosis. Adipose tissue-associated macrophages (ATM) are the predominant immune cells in WAT, but their heterogeneity and phenotypes are poorly defined during atherogenesis. The scavenger receptor CD36 mediates ATM crosstalk with other adipose tissue cells, driving chronic inflammation. Here, we combined the single-cell RNA sequencing technique with cell metabolic and functional assays on major WAT ATM subpopulations using a diet-induced atherosclerosis mouse model (Apoe-null). We also examined the role of CD36 using Apoe/Cd36 double-null mice. Based on transcriptomics data and differential gene expression analysis, we identified a previously undefined group of ATM displaying low viability and high lipid metabolism and labeled them as "unhealthy macrophages". Their phenotypes suggest a subpopulation of ATM under lipid stress. We also identified lipid-associated macrophages (LAM), which were previously described in obesity. Interestingly, LAM increased 8.4-fold in Apoe/Cd36 double-null mice on an atherogenic diet, but not in Apoe-null mice. The increase in LAM was accompanied by more ATM lipid uptake, reduced adipocyte hypertrophy, and less inflammation. In conclusion, CD36 mediates a delicate balance between lipid metabolism and inflammation in visceral adipose tissues. Under atherogenic conditions, CD36 deficiency reduces inflammation and increases lipid metabolism in WAT by promoting LAM accumulation.

Relationship between epicardial adipose tissue and coronary atherosclerosis by CCTA in young adults (18-45).

Objective: Epicardial adipose tissue (EAT) is implicated in the pathogenesis and progression of coronary artery disease (CAD). Limited data exists on the interplay between EAT and atherosclerosis in young individuals. Our study aims to explore the relationship between EAT and CAD in a young cohort. Methods: All young (18-45 years) patients without prior CAD, referred for coronary computed tomography angiography (CCTA) from 2016 to 2022 were included. EAT volume and coronary artery calcium (CAC) were calculated from dedicated non-contrast scans. Coronary plaque presence, extent, and volume were quantified from CCTA. Multivariable logistic regression models for the presence of CAD, defined as any coronary atherosclerosis, were performed. Results: Overall, 712 patients (39±4.8 years, 54 % female) with 45 % Hispanic, and 21 % non-Hispanic Black were included. Patients with CAD had higher EAT volume than those without (80.80 mL ± 36.00 vs 55.16 mL ± 27.92; P < 0.001). In those with CAC=0, higher EAT was associated with the presence of CAD compared to lower EAT volume (P < 0.001). An EAT volume >76 mL was associated with higher CAC (P < 0.001), segment involvement score (P < 0.001), and quantitative total, non-calcified, and low-attenuation plaque volumes (P < 0.002). At multivariable analysis, EAT volume (per 10 mL, OR: 1.21; 95 %CI: 1.12-1.30; P < 0.0001) was independently associated with the presence of CAD. Conclusion: In a diverse cohort of young adults without history of CAD and undergoing a clinically indicated CCTA, EAT volume was independently associated with the presence of CAD. Our findings highlight EAT potential as a novel marker for CAD risk-assessment and a potential therapeutic target in young patients.

Natriuretic peptide receptor-C perturbs mitochondrial respiration in white adipose tissue.

Natriuretic peptide receptor-C (NPR-C) is highly expressed in adipose tissues, and regulates obesity related diseases, however the detailed mechanism remains unknown. In this research, we aimed to explore the potential role of NPR-C in cold exposure and high-fat/high-sugar (HF/HS) diet induced metabolic changes, especially in regulating white adipose tissue (WAT) mitochondrial function. Our findings showed that NPR-C expression, especially in epididymal WAT (eWAT), was reduced after cold exposure. Global Npr3 (gene encoding NPR-C protein) deficiency led to reduced body weight, increased WAT browning, thermogenesis, and enhanced expression of genes related to mitochondrial biogenesis. RNA-sequencing of eWAT showed that Npr3 deficiency enhanced expression of mitochondrial respiratory chain complex genes and promoted mitochondrial oxidative phosphorylation in response to cold exposure. In addition, Npr3 KO mice were able to resist obesity induced by HF/HS diet. Npr3 knockdown in stromal vascular fraction (SVF)-induced white adipocytes promoted the expression of proliferator-activated receptor gamma coactivator 1α (PGC1α), uncoupling protein 1 (UCP1) and mitochondrial respiratory chain complexes. Mechanistically, NPR-C inhibited cGMP and calcium signaling in an NPR-B-dependent manner but suppressed cAMP signaling in an NPR-B-independent manner. Moreover, Npr3 knockdown induced browning via AKT and p38 pathway activation, which were attenuated by Npr2 knockdown. Importantly, treatment with the NPR-C specific antagonist, AP-811, decreased WAT mass and increased PGC-1α, UCP1 and mitochondrial complex expression. These findings demonstrate that NPR-C deficiency enhances metabolic health by boosting energy expenditure in WAT, emphasizing the potential of NPR-C inhibition for treating obesity and related metabolic disorders.

Changes in Epicardial Adipose Tissue Assessed by Chest CT in Breast Cancer Patients Receiving Adjuvant Chemotherapy with Anthracyclines and Trastuzumab.

Background: Cardiotoxicity (CTX) induced by adjuvant chemotherapy is a significant factor that impacts the prognosis and quality of life in breast cancer (BC) patients. In this study, we aimed to investigate the changes in epicardial adipose tissue (EAT) before and after treatment in BC patients who received anthracyclines adjuvant chemotherapy protocol (AC-T) and anthracyclines combined with trastuzumabadjuvant chemotherapy protocol (AC-TH). Additionally, we assessed whether there were any differences in the changes in EAT between the two groups of patients. Our objective was to examine the effects of anthracyclines and trastuzumab on EAT and determine the potential role of EAT changes on CTX. Methods: We reviewed female BC patients who were treated with adjuvant chemotherapy protocols of AC-T and AC-TH, all of whom underwent baseline (T0) and follow-up (T1) chest computed tomography (CT) and echocardiography. A cohort of healthy women, matched in age, underwent two chest CTs. EAT was quantified on chest CT using semi-automated software. CTX was defined as a > 10% reduction in left ventricular ejection fraction (LVEF) from baseline, with an absolute value of < 53%. Results: A total of 41 BC patients were included in the study, with 23 patients in the AC-T group and 18 patients in the AC-TH group. Additionally, 22 healthy females were included as the normal group. None of the BC patients developed CTX after chemotherapy. The age did not differ significantly between the normal group and the AC-T group (p = 0.341) or the AC-TH group (p = 0.853). Similarly, the body mass index (BMI) of the normal group was comparable to that of the AC-T group (p = 0.377, 0.346) and the AC-TH group (p = 0.148, 0.119) before and after chemotherapy. The EAT volume index (mL/kg/ m 2 ) was significantly higher in both the AC-T group (5.11 ± 1.85 vs. 4.34 ± 1.55, p < 0.001) and the AC-TH group (4.53 ± 1.61 vs. 3.48 ± 1.62, p < 0.001) at T1 compared with T0. In addition, both the AC-T group (-72.95 ± 5.01 vs. -71.22 ± 3.91, p = 0.005) and the AC-TH group (-72.55 ± 5.27 vs. -68.20 ± 5.98, p < 0.001) exhibited a significant decrease in EAT radiodensity (HU) at T1 compared to T0. However, there was no significant difference observed in the normal group. At T0, no difference was seen in EAT volume index (4.34 ± 1.55 vs. 3.48 ± 1.62, p = 0.090) and radiodensity (-71.22 ± 3.91 vs. -68.20 ± 5.98, p = 0.059) between the AC-T and AC-TH groups. Similarly, at T1, there was still no significant difference observed in the EAT volume index (-5.11 ± 1.85 vs. 4.53 ± 1.61, p = 0.308) and radiodensity (-72.95 ± 5.00 vs. -72.54 ± 5.27, p = 0.802) between the two groups. Conclusions: BC patients who underwent AC-T and AC-TH adjuvant chemotherapy protocols demonstrated a significant rise in the volume index of EAT, along with a substantial reduction in its radiodensity post-chemotherapy. These findings indicate that alterations in EAT could potentially aid in identifying cardiac complications caused by chemotherapeutic agents and remind clinicians to focus on changes in EAT after adjuvant chemotherapy in BC patients to prevent the practical occurrence of CTX.

Role of gut microbial-derived metabolites and other select agents on adipocyte browning.

AIMS: Metabolic disease is a multifaceted condition characterized by the disruption of numerous metabolic parameters within the host. Its prevalence has surged significantly in recent years and it has become a prominent non-communicable disease worldwide. The effect of gut microbiota on various beige fat induction is well studied, while the mechanisms behind the link remain unclear. Given that gut microbiota-derived metabolites (meta-metabolites) secreted in the gut serve as a key mode of communication with their host through direct circulation or indirect host physiology modification, understanding the effect of meta-metabolites on adipose tissue is essential. METHODOLOGY: In our previous in-vivo studies, we observed a correlation between gut microbiota and the formation of beige fat. In this study, we further aimed to validate this correlation by treating the adipocyte cell line (3T3-L1) with meta-metabolites collected from the cecum of mice exhibiting beige adipose tissue formation. Additionally, we treated the adipocyte cell line with known beige fat inducers (L-Rhamnose and Ginsenoside) to assess meta-metabolites' efficacy on beige fat formation. KEY FINDINGS: Upon treatment with the meta-metabolites from the antibiotic-treated mice, we observed a significant increase in lipid metabolism and beige-specific gene expression. Analyzing the metabolites in these cells revealed that a set of metabolites potentially govern adipocytes, contributing to a metabolically active state. These effects were at par or even better than those of cells treated with L-Rhamnose or Ginsenoside. SIGNIFICANCE: This research sheds light on the intricate interplay between microbial metabolites and adipose tissue, offering valuable clues for understanding and potentially manipulating these processes for therapeutic purposes.

Adipose Tissue Dysfunction Following Trauma and Hypoxia Increases the Risk of Post-Surgical Adhesion: Potential for Therapeutic Interventions.

Post-surgical adhesion is a medical challenge, especially following abdominal and pelvic surgeries. This refers to the formation of fibrotic scars that form from connective tissue in the gynecological tract or abdominal cavity. Dysfunctional adipose tissue (AT) by surgical injuries and hypoxia increases the risk of post-surgical adhesion through different molecular mechanisms. Damage-associated molecular patterns (DAMPs) and Hypoxia-induced factor 1 alpha (HIF-1α) produced during surgery trauma and hypoxia induce AT dysfunction to promote inflammation, oxidative stress, metabolic alterations, and profibrotic pathways, which contribute to post-surgical adhesions. HIF-1α and DAMPs can be considered therapeutic targets to prevent AT dysfunction and diminish the formation of adhesions in obese patients undergoing abdominal or pelvic surgeries.

Physiological and metabolic functions of the ß3-adrenergic receptor and an approach to therapeutic achievements.

A specific type of beta-adrenergic receptor was discovered in the decade of 1980s and subsequently recognized as a new type of beta-adrenergic receptor, called beta3-adrenoceptor (ß3-AR). ß3-AR expresses in different tissues, including adipose tissue, gall bladder, stomach, small intestine, cardiac myocytes, urinary bladder, and brain. Structurally, ß3-AR is very similar to ß1- and ß2-AR and belongs to a G-protein coupled receptor that uses cAMP as an intracellular second messenger. Alternatively, it also activates the NO-cGMP cascade. Stimulation of the ß3-AR increases lipolysis, fatty acid oxidation, energy expenditure, and insulin action, leading to anti-obesity and anti-diabetic activity. Moreover, ß3-AR differentially regulates the myocardial contraction and relaxes the urinary bladder to balance the cardiac activity and delay the micturition reflex, respectively. In recent years, this receptor has served as an attractive target for the treatment of obesity, type 2 diabetes, congestive heart failure, and overactive bladder syndrome. Several ß3-AR agonists are in the emerging stage that can exert novel pharmacological benefits in different therapeutic areas. The present review focuses on the structure, signaling, physiological, and metabolic activities of ß3-AR. Additionally, therapeutic approaches of ß3-AR have also been considered.

Chromatin Immunoprecipitation in Adipose Tissue and Adipocytes: How to Proceed and Optimize the Protocol for Transcription Factor DNA Binding.

Chromatin immunoprecipitation (ChIP) coupled to qPCR or sequencing is a crucial experiment to determine direct transcriptional regulation under the control of specific transcriptional factors or co-regulators at loci-specific or pan-genomic levels.Here we provide a reliable method for processing ChIP from adipocytes or frozen adipose tissue collection, isolation of nuclei, cross-linking of protein-DNA complexes, chromatin shearing, immunoprecipitation, and DNA purification. We also discuss critical steps for optimizing the experiment to perform a successful ChIP in lipid-rich cells/tissues.

Chitosan based extruded nanofibrous bioscaffold for local delivery of mesenchymal stem cells to improve diabetic wound healing.

BACKGROUND: Mesenchymal stem cells (MSCs)-based treatment strategy has shown promise in bolstering the healing process of chronic wounds in diabetic patients, who are at risk of amputation and mortality. To overcome the drawbacks of suboptimal cell retention and diminished cell viability at the injury site, a novel nanofibrous biomaterial-based scaffold was developed by using a controlled extrusion of a polymeric solution to deliver the cells (human adipose-derived MSCs (ADMSCs) and placenta-derived MSCs (PLMSCs)) locally to the animal model of diabetic ulcers. METHODS: The physicochemical and biological properties of the nano-bioscaffold were characterized in terms of microscopic images, FTIR spectroscopy, tensile testing, degradation and swelling tests, contact angle measurements, MTT assay, and cell attachment evaluation. To evaluate the therapeutic efficacy, a study using an excisional wound model was conducted on diabetic rats. RESULTS: The SEM and AFM images of scaffolds revealed a network of uniform nanofibers with narrow diameters between 100-130 nm and surface roughness less than 5 nm, respectively. ADMSCs and PLMSCs had a typical spindle-shaped or fibroblast-like morphology when attached to the scaffold. Desired characteristics in terms of swelling, hydrophilicity, biodegradation rate, and biocompatibility were achieved with the CS70 formulation. The wound healing process was accelerated according to wound closure rate assay upon treatment with MSCs loaded scaffold resulting in increased re-epithelialization, neovascularization, and less inflammatory reaction. Our findings unequivocally demonstrated that the cell-loaded nano-bioscaffold exhibited more efficacy compared with its acellular counterpart. In summation, our study underscores the potential of this innovative cellular scaffold as a viable solution for enhancing the healing of diabetic ulcers. CONCLUSION: The utilization of MSCs in a nanofibrous biomaterial framework demonstrates significant promise, providing a novel avenue for advancing wound care and diabetic ulcer management.

Chinese visceral adipose index is more closely associated with risk of arterial stiffness than traditional obesity indicators: a cohort study.

BACKGROUND: The Chinese visceral adiposity index (CVAI) is a new index to evaluate visceral adipose tissue in the Chinese population. Arterial stiffness (AS) is a kind of degeneration of the large arteries, and obesity is an essential contributing factor to AS. Our study aimed to explore the longitudinal association between CVAI and the risk of AS and to compare the predictive power of CVAI, body mass index (BMI), and waist circumference (WC) for AS. METHODS: Between 2010 and 2020, a total of 14,877 participants participating in at least two brachial-ankle pulse wave velocity (baPWV) measurements from the Kailuan study were included. The Cox proportional hazard regression models were performed to evaluate the longitudinal association between CVAI and the risk of AS. The area under the receiver operating characteristic (ROC) curve was calculated to compare the predictive power of CVAI, BMI, and WC for AS. RESULTS: After adjusting for potential confounding factors, CVAI was significantly associated with the risk of AS. Compared with the first CVAI quartile, the hazard ratios (HR) and 95% CI of the second, third, and fourth quartiles were 1.30 (1.09-1.56), 1.37 (1.15-1.63), and 1.49 (1.24-1.78), respectively. The area under ROC curve of CVAI was 0.661, significantly higher than BMI (AUC: 0.582) and WC (AUC: 0.606). CONCLUSION: CVAI may be a reliable indicator to identify high-risk groups of AS in the Chinese general population, and the predictive power of CVAI for AS was better than BMI and WC.

Identification of regulatory networks and crosstalk factors in brown adipose tissue and liver of a cold-exposed cardiometabolic mouse model.

BACKGROUND: Activation of brown adipose tissue (BAT) has gained attention due to its ability to dissipate energy and counteract cardiometabolic diseases (CMDs). METHODS: This study investigated the consequences of cold exposure on the BAT and liver proteomes of an established CMD mouse model based on LDL receptor-deficient (LdlrKO) mice fed a high-fat, high-sucrose, high-cholesterol diet for 16 weeks. We analyzed energy metabolism in vivo and performed untargeted proteomics on BAT and liver of LdlrKO mice maintained at 22 °C or 5 °C for 7 days. RESULTS: We identified several dysregulated pathways, miRNAs, and transcription factors in BAT and liver of cold-exposed Ldlrko mice that have not been previously described in this context. Networks of regulatory interactions based on shared downstream targets and analysis of ligand-receptor pairs identified fibrinogen alpha chain (FGA) and fibronectin 1 (FN1) as potential crosstalk factors between BAT and liver in response to cold exposure. Importantly, genetic variations in the genes encoding FGA and FN1 have been associated with cardiometabolic-related phenotypes and traits in humans. DISCUSSION: This study describes the key factors, pathways, and regulatory networks involved in the crosstalk between BAT and the liver in a cold-exposed CMD mouse model. These findings may provide a basis for future studies aimed at testing whether molecular mediators, as well as regulatory and signaling mechanisms involved in tissue adaption upon cold exposure, could represent a target in cardiometabolic disorders.