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Circulation Research Apr 2021Cardiovascular diseases are the leading cause of death worldwide. Overweight and obesity are strongly associated with comorbidities such as hypertension and insulin... (Review)
Review
Cardiovascular diseases are the leading cause of death worldwide. Overweight and obesity are strongly associated with comorbidities such as hypertension and insulin resistance, which collectively contribute to the development of cardiovascular diseases and resultant morbidity and mortality. Forty-two percent of adults in the United States are obese, and a total of 1.9 billion adults worldwide are overweight or obese. These alarming numbers, which continue to climb, represent a major health and economic burden. Adipose tissue is a highly dynamic organ that can be classified based on the cellular composition of different depots and their distinct anatomical localization. Massive expansion and remodeling of adipose tissue during obesity differentially affects specific adipose tissue depots and significantly contributes to vascular dysfunction and cardiovascular diseases. Visceral adipose tissue accumulation results in increased immune cell infiltration and secretion of vasoconstrictor mediators, whereas expansion of subcutaneous adipose tissue is less harmful. Therefore, fat distribution more than overall body weight is a key determinant of the risk for cardiovascular diseases. Thermogenic brown and beige adipose tissue, in contrast to white adipose tissue, is associated with beneficial effects on the vasculature. The relationship between the type of adipose tissue and its influence on vascular function becomes particularly evident in the context of the heterogenous phenotype of perivascular adipose tissue that is strongly location dependent. In this review, we address the abnormal remodeling of specific adipose tissue depots during obesity and how this critically contributes to the development of hypertension, endothelial dysfunction, and vascular stiffness. We also discuss the local and systemic roles of adipose tissue derived secreted factors and increased systemic inflammation during obesity and highlight their detrimental impact on cardiovascular health.
Topics: Adipose Tissue; Adiposity; Animals; Blood Pressure; Blood Vessels; Cardiovascular Diseases; Heart Disease Risk Factors; Homeostasis; Humans; Hypertension; Inflammation; Insulin Resistance; Intra-Abdominal Fat; Mice; Obesity; Overweight; Subcutaneous Fat; Vascular Diseases; Vascular Stiffness; Vasoconstriction
PubMed: 33793327
DOI: 10.1161/CIRCRESAHA.121.318093 -
Acta Dermato-venereologica Nov 2020A variety of applications of human adipose tissue stem cell-derived exosomes have been suggested as novel cell-free therapeutic strategies in the regenerative and... (Randomized Controlled Trial)
Randomized Controlled Trial
Combination Treatment with Human Adipose Tissue Stem Cell-derived Exosomes and Fractional CO2 Laser for Acne Scars: A 12-week Prospective, Double-blind, Randomized, Split-face Study.
A variety of applications of human adipose tissue stem cell-derived exosomes have been suggested as novel cell-free therapeutic strategies in the regenerative and aesthetic medical fields. This study evaluated the clinical efficacy and safety of adipose tissue stem cell-derived exosomes as an adjuvant therapy after application of fractional CO2 laser for acne scars. A 12-week prospective, double-blind, randomized, split-face trial was performed. A total of 25 patients received 3 consecutive treatment sessions of fractional CO2 laser to the whole face, with a follow-up evaluation. Post-laser treatment regimens were applied; for each patient, one side of the face was treated with adipose tissue stem cell-derived exosomes gel and the other side was treated with control gel. Adipose tissue stem cell-derived exosomes-treated sides had achieved a significantly greater improvement than the control sides at the final follow-up visit (percentage reduction in échelle d'évaluation clinique des cicatrices d'acné scores: 32.5 vs 19.9%, p < 0.01). Treatment-related erythema was milder, and post-treatment downtime was shorter on the applications of human adipose tissue stem cell-derived exosomes-treated side. In conclusion, the combined use of this novel material with resurfacing devices would provide synergistic effects on both the efficacy and safety of atrophic acne scar treatments.
Topics: Acne Vulgaris; Adipose Tissue; Cicatrix; Double-Blind Method; Exosomes; Humans; Lasers, Gas; Low-Level Light Therapy; Prospective Studies; Stem Cells; Treatment Outcome
PubMed: 33073298
DOI: 10.2340/00015555-3666 -
Bioengineered Dec 2021Ferroptosis is an important form of myocardial cell death in myocardial ischemia-reperfusion injury (MIRI). Naringenin (NAR), as a flavonoid, has a significant advantage...
Naringenin alleviates myocardial ischemia/reperfusion injury by regulating the nuclear factor-erythroid factor 2-related factor 2 (Nrf2) /System xc-/ glutathione peroxidase 4 (GPX4) axis to inhibit ferroptosis.
Ferroptosis is an important form of myocardial cell death in myocardial ischemia-reperfusion injury (MIRI). Naringenin (NAR), as a flavonoid, has a significant advantage in improving MIRI. But the regulatory effect and mechanism of NAR on ferroptosis in MIRI have not been reported. After the rats were given NAR and induced to form myocardial ischemia-reperfusion (MI/R) injury, Tetrazolium chloride (TTC) staining was used to detect the myocardial infarction area of rats, and Hematoxylin-eosin (H&E) staining was used to detect myocardial injury. The markers of tissue inflammation were detected by ELISA. Serum creatine kinase Serum creatin kinase (CPK), Lactate dehydrogenase (LDH), and lipid peroxide (LPO) and oxidative stress related levels were measured. In addition, iron detection kits were used to detect total iron and Fe levels in cardiac tissues, and western blot was used to detect the expression of ferroptosis-related proteins and the expression of nuclear factor-erythroid factor 2-related factor 2 (Nrf2) and glutathione peroxidase 4 (GPX4). At the cellular level, H9C2 cardiomyocytes were induced by hypoxia/reoxygenation (H/R), and ferroptosis inducer Erastin was administered to detect cell viability, ferroptosis-related indicators, oxidative stress related indicators, and expressions of Nrf2 and GPX4, to explore the mechanisms involved. NAR alleviated MI/R-induced pathological damage, inflammation and lipid peroxidation in myocardial tissue of rats. NAR adjusted the NRF2 /System xc - /GPX4 axis and improved ferroptosis. At the cellular level, ferroptosis inducer Erastin reversed the protective effect of NAR on H/R-induced H9C2 cardiomyocytes. In conclusion, NAR can alleviate MIRI by regulating the Nrf2/System xc-/GPX4 axis to inhibit ferroptosis.
Topics: Animals; Cell Survival; Cells, Cultured; Ferroptosis; Flavanones; Myocardial Reperfusion Injury; Myocardium; Myocytes, Cardiac; NF-E2-Related Factor 2; Oxidative Stress; Phospholipid Hydroperoxide Glutathione Peroxidase; Rats; Rats, Sprague-Dawley; Signal Transduction
PubMed: 34699317
DOI: 10.1080/21655979.2021.1995994 -
Proceedings of the National Academy of... Oct 2023The immune system is a complex network of cells with critical functions in health and disease. However, a comprehensive census of the cells comprising the immune system...
The immune system is a complex network of cells with critical functions in health and disease. However, a comprehensive census of the cells comprising the immune system is lacking. Here, we estimated the abundance of the primary immune cell types throughout all tissues in the human body. We conducted a literature survey and integrated data from multiplexed imaging and methylome-based deconvolution. We also considered cellular mass to determine the distribution of immune cells in terms of both number and total mass. Our results indicate that the immune system of a reference 73 kg man consists of 1.8 × 10 cells (95% CI 1.5-2.3 × 10), weighing 1.2 kg (95% CI 0.8-1.9). Lymphocytes constitute 40% of the total number of immune cells and 15% of the mass and are mainly located in the lymph nodes and spleen. Neutrophils account for similar proportions of both the number and total mass of immune cells, with most neutrophils residing in the bone marrow. Macrophages, present in most tissues, account for 10% of immune cells but contribute nearly 50% of the total cellular mass due to their large size. The quantification of immune cells within the human body presented here can serve to understand the immune function better and facilitate quantitative modeling of this vital system.
Topics: Male; Humans; Human Body; Lymphocytes; Lymph Nodes; Spleen; Macrophages
PubMed: 37871201
DOI: 10.1073/pnas.2308511120 -
Nutrients Jun 2020Protein is an important component of a healthy diet and appears to be integral to enhancing training adaptations in exercising individuals. The purpose of this narrative... (Review)
Review
Protein is an important component of a healthy diet and appears to be integral to enhancing training adaptations in exercising individuals. The purpose of this narrative review is to provide an evidence-based assessment of the current literature examining increases in dietary protein intake above the recommended dietary allowance (RDA: 0.8 g/kg/d) in conjunction with chronic exercise on body composition (i.e., muscle, fat and bone). We also highlight acute and chronic pre-sleep protein studies as well as the influence of exercise timing on body composition. Overall, a high-protein diet appears to increase muscle accretion and fat loss and may have beneficial effects on bone when combined with exercise. Pre-sleep protein is a viable strategy to help achieve total daily protein goals. Importantly, there appears to be no deleterious effects from a high-protein diet on muscle, fat or bone in exercising individuals.
Topics: Adipose Tissue; Adolescent; Adult; Body Composition; Bone and Bones; Diet, High-Protein; Dietary Proteins; Exercise; Female; Humans; Male; Muscle, Skeletal; Sleep; Time Factors; Young Adult
PubMed: 32630466
DOI: 10.3390/nu12061890 -
Frontiers in Endocrinology 2020Since the recent rediscovery of brown adipose tissue (BAT) in adult humans, this thermogenic tissue has been attracting increasing interest. The inverse relationship... (Review)
Review
Since the recent rediscovery of brown adipose tissue (BAT) in adult humans, this thermogenic tissue has been attracting increasing interest. The inverse relationship between BAT activity and body fatness suggests that BAT, because of its energy dissipating activity, is protective against body fat accumulation. Cold exposure activates and recruits BAT, resulting in increased energy expenditure and decreased body fatness. The stimulatory effects of cold exposure are mediated through transient receptor potential (TRP) channels and the sympathetic nervous system (SNS). Most TRP members also function as chemesthetic receptors for various food ingredients, and indeed, agonists of TRP vanilloid 1 such as capsaicin and its analog capsinoids mimic the effects of cold exposure to decrease body fatness through the activation and recruitment of BAT. The antiobesity effect of other food ingredients including tea catechins may be attributable, at least in part, to the activation of the TRP-SNS-BAT axis. BAT is also involved in the facultative thermogenesis induced by meal intake, referred to as diet-induced thermogenesis (DIT), which is a significant component of the total energy expenditure in our daily lives. Emerging evidence suggests a crucial role for the SNS in BAT-associated DIT, particularly during the early phase, but several gut-derived humoral factors may also participate in meal-induced BAT activation. One intriguing factor is bile acids, which activate BAT directly through Takeda G-protein receptor 5 (TGR5) in brown adipocytes. Given the apparent beneficial effects of some TRP agonists and bile acids on whole-body substrate and energy metabolism, the TRP/TGR5-BAT axis represents a promising target for combating obesity and related metabolic disorders in humans.
Topics: Adipose Tissue, Brown; Animals; Diet; Energy Metabolism; Humans; Obesity; Thermogenesis
PubMed: 32373072
DOI: 10.3389/fendo.2020.00222 -
The Journals of Gerontology. Series A,... Sep 2019There is increasing use of computed tomography (CT) in sarcopenia research using a wide variety of techniques. We performed a systematic review of the CT literature to...
BACKGROUND/OBJECTIVE
There is increasing use of computed tomography (CT) in sarcopenia research using a wide variety of techniques. We performed a systematic review of the CT literature to identify the differences between approaches used.
METHODS
A comprehensive search of PubMed from 1983 to 2017 was performed to identify studies that used CT muscle measurements to assess muscle mass and myosteatosis. The CT protocols were evaluated based on anatomic landmark(s), thresholding, muscle(s) segmented, key measurement (ie, muscle attenuation, cross-sectional area, volume), derived variables, and analysis software. From the described search, 657 articles were identified and 388 studies met inclusion criteria for this systematic review.
RESULTS
Muscle mass was more commonly assessed than myosteatosis (330 vs. 125). The most commonly assessed muscle or muscle groups were total abdominal wall musculature (142/330 and 49/125 for muscle mass and myosteatosis, respectively) and total thigh musculature (90/330 and 48/125). The most commonly used landmark in the abdomen was the L3 vertebra (123/142 and 45/49 for muscle mass and myosteatosis, respectively). Skeletal muscle index and intermuscular adipose tissue were the most commonly used measures of abdominal wall muscle mass (114/142) and myosteatosis (27/49), respectively. Cut points varied across studies. A significant majority of studies failed to report important CT technical parameters, such as use of intravenous contrast and slice thickness (94% and 63%, respectively).
CONCLUSIONS
There is considerable variation in the CT approaches used for the assessment of muscle mass and myosteatosis. There is a need to develop consensus for CT-based evaluation of sarcopenia and myosteatosis.
Topics: Adipose Tissue; Body Composition; Humans; Muscle, Skeletal; Sarcopenia; Tomography, X-Ray Computed
PubMed: 30726878
DOI: 10.1093/gerona/glz034 -
Frontiers in Endocrinology 2021Adipose tissue (e.g. white, brown and brite) plays a critical role in modulating energy metabolism. Activating brown adipose tissue (BAT) and inducing browning in white...
BACKGROUND
Adipose tissue (e.g. white, brown and brite) plays a critical role in modulating energy metabolism. Activating brown adipose tissue (BAT) and inducing browning in white adipose tissue (WAT) has been proposed to be a potential molecular target for obesity treatment. Emodin is a natural anthraquinone derivative that exhibits variety of pharmacologic effects including lowering lipids and regulating glucose utilization. However, the underlying mechanism of action is still unclear. In the present study, we investigated whether emodin could alleviate obesity promoting browning process in adipose tissue.
METHODS
C57BL/6J mice were fed with high fat diet to induce obesity. Emodin at the doses of 40 and 80 mg/kg were orally given to obesity mice for consecutive 6 weeks. Parameters including fasting blood glucose, oral glucose tolerance, blood lipids, and the ratios of subcutaneous white adipose tissue (scWAT) or BAT mass to body weight, and morphology of adipose tissue were observed. Besides, the protein expression of uncoupling protein 1 (UCP1) and prohibitin in BAT and scWAT was determined by immunohistochemistry method. Relative mRNA expression of , transmembrane protein 26 () and in scWAT was analyzed using qRT-PCR. And the protein expression of UCP1, CD36, fatty acid transporter 4 (FATP4), peroxisome proliferator-activated receptor alpha (PPARα) and prohibitin of scWAT and BAT were analyzed using western blotting. In addition, ultra-high-performance liquid chromatography with electrospray ionization tandem mass spectrometry was utilized to detect the small lipid metabolites of scWAT and BAT.
RESULTS
Emodin decreased the body weight and food intake in HFD-induced obesity mice, and it also improved the glucose tolerance and reduced the blood lipids. Emodin treatment induced beiging of WAT, and more multilocular lipid droplets were found in scWAT. Also, emodin significantly increased markers of beige adipocytes, e.g. , and mRNA in scWAT, and UCP1, CD36, FATP4, PPARα and prohibitin protein expression in scWAT and BAT. Furthermore, emodin perturbed the lipidomic profiles in scWAT and BAT of obese mice. Emodin increased total ceramides (Cers), lysophosphatidylcholines (LPCs), lyso-phosphatidylcholines oxygen (LPCs-O), and phosphatidylethanolamines oxygen (PEs-O) species concentration in scWAT. Specifically, emodin significantly up-regulated levels of Cer (34:1), LPC (18:2), LPC-(O-20:2), PC (O-40:7), PE (O-36:3), PE (O-38:6), PE (O-40:6), and sphingolipid (41:0) [SM (41:0)], and down-regulated PC (O-38:0), PE (O-40:4), PE (O-40:5) in scWAT of obesity mice. In terms of lipid matabolites of BAT, the emodin remarkably increased the total PCs levels, which was driven by significant increase of PC (30:0), PC (32:1), PC (32:2), PC (33:4) and PC (38:0) species. In addition, it also increased species of LPCs, e.g. LPC (20:0), LPC (20:1), LPC (22:0), LPC (22:1), LPC (24:0), and LPC (24:1). Especially, emodin treatment could reverse the ratio of PC/PE in HFD-induced obese mice.
CONCLUSIONS
These results indicated that emodin could ameliorate adiposity and improve metabolic disorders in obese mice. Also, emodin could promote browning in scWAT and activate the BAT activities. In addition, emodin treatment-induced changes to the scWAT and BAT lipidome were highly specific to certain molecular lipid species, indicating that changes in tissue lipid content reflects selective remodeling in scWAT and BAT of both glycerophospholipids and sphingolipids in response to emodin treatment.
Topics: Adipose Tissue, Brown; Adipose Tissue, White; Animals; Body Weight; Diet, High-Fat; Emodin; Lipid Metabolism; Lipid Metabolism Disorders; Male; Mice; Mice, Obese; Obesity; Thermogenesis
PubMed: 34040579
DOI: 10.3389/fendo.2021.618037 -
Clinical and Translational Medicine Aug 2023Breast cancer (BC) is a highly heterogeneous disease, and although immunotherapy has recently increased patient survival in a number of solid and hematologic...
BACKGROUND
Breast cancer (BC) is a highly heterogeneous disease, and although immunotherapy has recently increased patient survival in a number of solid and hematologic malignancies, most BC subtypes respond poorly to immune checkpoint blockade therapy (ICB). B cells, particularly those that congregate in tertiary lymphoid structures (TLS), play a significant role in antitumour immunity. However, B-cell heterogeneity at single-cell resolution and its clinical significance with TLS in BC need to be explored further.
METHODS
Primary tumour lesions and surrounding normal tissues were taken from 14 BC patients, totaling 124,587 cells, for single-cell transcriptome sequencing and bioinformatics analysis.
RESULTS
Based on the usual markers, the single-cell transcriptome profiles were classified into various clusters. A thorough single-cell study was conducted with a focus on tumour-infiltrating B cells (TIL-B) and tumour-associated neutrophils (TAN). TIL-B was divided into five clusters, and unusual cell types, such as follicular B cells, which are strongly related to immunotherapy efficacy, were identified. In BC, TAN and TIL-B infiltration are positively correlated, and at the same time, compared with TLS-high, TAN and TIL-B in TLS-low group are significantly positively correlated.
CONCLUSIONS
In conclusion, our study highlights the heterogeneity of B cells in BC, explains how B cells and TLS contribute significantly to antitumour immunity at both the single-cell and clinical level, and offers a straightforward marker for TLS called CD23. These results will offer more pertinent information on the applicability and effectiveness of tumour immunotherapy for BC.
Topics: Humans; Female; Breast Neoplasms; Transcriptome; Tertiary Lymphoid Structures; Neoadjuvant Therapy; Lymphocytes, Tumor-Infiltrating; Prognosis
PubMed: 37525587
DOI: 10.1002/ctm2.1346 -
Stem Cell Research & Therapy Nov 2020Mesenchymal stem cell (MSC)-derived exosomes have shown comprehensive application prospects over the years. Despite performing similar functions, exosomes from different...
BACKGROUND
Mesenchymal stem cell (MSC)-derived exosomes have shown comprehensive application prospects over the years. Despite performing similar functions, exosomes from different origins present heterogeneous characteristics and components; however, the relative study remains scarce. Lacking of a valuable reference, researchers select source cells for exosome studies mainly based on accessibility and personal preference.
METHODS
In this study, exosomes secreted by MSCs derived from different tissues were isolated, by ultracentrifugation, and proteomics analysis was performed. A total of 1014 proteins were detected using a label-free method.
RESULTS
Bioinformatics analysis revealed their shared function in the extracellular matrix receptor. Bone marrow MSC-derived exosomes showed superior regeneration ability, and adipose tissue MSC-derived exosomes played a significant role in immune regulation, whereas umbilical cord MSC-derived exosomes were more prominent in tissue damage repair.
CONCLUSIONS
This study systematically and comprehensively analyzes the human MSC-derived exosomes via proteomics, which reveals their potential applications in different fields, so as to provide a reference for researchers to select optimal source cells in future exosome-related studies.
Topics: Adipose Tissue; Bone Marrow; Bone Marrow Cells; Exosomes; Humans; Mesenchymal Stem Cells; Proteomics; Umbilical Cord
PubMed: 33246507
DOI: 10.1186/s13287-020-02032-8