BACKGROUND Mesenchymal stem cells(MSCs)are considered a promising therapy for various diseases due to their strong potential in regenerative medicine and immunomodulation.The tissue source of MSCs has gained attention...BACKGROUND Mesenchymal stem cells(MSCs)are considered a promising therapy for various diseases due to their strong potential in regenerative medicine and immunomodulation.The tissue source of MSCs has gained attention for its role in influencing their function,accessibility,and readiness for clinical use.AIM To identify the most suitable adipose source for MSC isolation and expansion for further applications.METHODS We isolated MSCs from solid adipose tissue and liposuction aspirates using the enzyme method.The MSCs were examined for their expansion using population doubling time,differentiation capacity using multilineage differentiation induction,surface markers using flow cytometry,and stability of chromosomes using the karyotyping method.Growth factors and cytokines in MSC-conditioned media were analyzed using the Luminex assay.RESULTS MSCs were isolated from solid adipose tissue and lipoaspirates and expanded from passage 0 to passage 2.All adipose-derived MSCs(AD-MSCs)exhibited the typical elongated,spindle-shaped morphology and comparable proliferation rate.They expressed positive surface markers(cluster of differentiation 73[CD73]:>97%,CD90:>98%,and CD105:>95%),and negative markers(<1%).All MSCs expressed similar levels of stemness genes(octamer-binding transcription factor 4,SRY-box 2,Krüppel-like factor,and MYC),colonyforming,and trilineage differentiation potential.Karyotyping analysis revealed normal chromosomal patterns in all samples,except one sample exhibiting a polymorphism(1qh+).Furthermore,the growth factors and cytokines of hepatocyte growth factor,vascular endothelial growth factor A,interleukin 6(IL-6),and IL-8 were detected in all AD-MSC conditioned media;but fibroblast growth factor-2 and keratinocyte growth factor were selectively expressed in conditioned media from solid or lipoaspirate AD-MSCs,respectively.CONCLUSION These findings indicate that AD-MSCs from both adipose sources possess all of the characteristic features of MSCs with source-specific secretome differences,which are suitable for further expansion and various clinical applications.展开更多
Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated...Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated with increased levels of circulato ry pro-inflammatory marke rs up to 1 year postTBI(Eagle et al.,2023).展开更多
Neuroinflammation is a key process in the pathogenesis of various neurodegenerative diseases,such as multiple sclerosis(MS),Alzheimer's disease,and traumatic brain injury.Even for disorders historically unrelated ...Neuroinflammation is a key process in the pathogenesis of various neurodegenerative diseases,such as multiple sclerosis(MS),Alzheimer's disease,and traumatic brain injury.Even for disorders historically unrelated to neuroinflammation,such as Alzheimer's disease,it is now shown to precede pathological protein aggregations.展开更多
Stem cells play a key role in tissue regeneration due to their self-renewal and multidirectional differentiation,which are continuously regulated by signals from the extracellular matrix(ECM)microenvironment.Therefore...Stem cells play a key role in tissue regeneration due to their self-renewal and multidirectional differentiation,which are continuously regulated by signals from the extracellular matrix(ECM)microenvironment.Therefore,the unique biological and physical characteristics of the ECM are important determinants of stem cell behavior.Although the acellular ECM of specific tissues and organs(such as the skin,heart,cartilage,and lung)can mimic the natural microenvironment required for stem cell differentiation,the lack of donor sources restricts their development.With the rapid development of adipose tissue engineering,decellularized adipose matrix(DAM)has attracted much attention due to its wide range of sources and good regeneration capacity.Protocols for DAM preparation involve various physical,chemical,and biological methods.Different combinations of these methods may have different impacts on the structure and composition of DAM,which in turn interfere with the growth and differentiation of stem cells.This is a narrative review about DAM.We summarize the methods for decellularizing and sterilizing adipose tissue,and the impact of these methods on the biological and physical properties of DAM.In addition,we also analyze the application of different forms of DAM with or without stem cells in tissue regeneration(such as adipose tissue),repair(such as wounds,cartilage,bone,and nerves),in vitro bionic systems,clinical trials,and other disease research.展开更多
Adipose tissue has emerged as a rich and clinically relevant source of regenerative cells.It offers a minimally invasive,abundant,and autologous reservoir for therapeutic applications.Among its cellular components,the...Adipose tissue has emerged as a rich and clinically relevant source of regenerative cells.It offers a minimally invasive,abundant,and autologous reservoir for therapeutic applications.Among its cellular components,the stromal vascular fraction(SVF)and adipose-derived stem cells(ASCs)have gained considerable attention due to their potent regenerative and immunomodulatory capacities.SVF is a heterogeneous mixture of cells,whereas ASCs constitute a more homogeneous mesenchymal stem cell-like population obtained through in vitro expansion.Together,these cell populations(SVF and ASCs)are described as“living drugs”,as they are viable and act as dynamic biological agents within the body.Unlike conventional medicines,living drugs exert therapeutic effects not only through direct differentiation but also via the secretion of bioactive molecules,including cytokines,growth factors,and extracellular vesicles.These secreted factors can modulate the surrounding microenvironment,enhance tissue repair,and regulate immune responses.Such paracrine mechanisms often play a more significant role than direct cell replacement,making living drugs versatile tools for regenerative medicine.This review provides a comprehensive overview of SVF and ASCs as living drugs.It discusses their cellular composition,mechanisms of action,methods of isolation,and the regenerative biomolecules they secrete.Furthermore,it explores current and emerging clinical applications,challenges,and future innovations.展开更多
Background Sustained lipolysis exacerbates subclinical ketosis(SCK)in dairy cows and is associated with inflammation and adipose tissue macrophage(ATM)infiltration.While ATM involvement in adipose homeostasis and infl...Background Sustained lipolysis exacerbates subclinical ketosis(SCK)in dairy cows and is associated with inflammation and adipose tissue macrophage(ATM)infiltration.While ATM involvement in adipose homeostasis and inflammation in early lactation is recognized,a comprehensive exploration of ATM polarization phenotypes in SCK cows is lacking.This study aimed to characterize ATM polarization and its link to lipolysis and inflammation in SCK cows.Results Subcutaneous adipose tissue samples were obtained from dairy cows to analyze protein expression and gene profiles.Compared with healthy cows,SCK cows had higher serum BHBA and NEFA,smaller adipocytes,and increased expression of lipolytic enzymes(LIPE,ATGL),indicating enhanced lipolysis.Decreased levels of FASN,PPARγ,p-SMAD3,and TGFβsuggested impaired adipogenesis.Inflammatory markers(TNF-α,IFN-γ,TLR4,Caspase1)and NFκB signaling activity were elevated.ATM infiltration was supported by increased CD9,CD68,TREM2,and CXCL1 expression.Protein abundance of M1 polarization markers(iNOS,CD86 and CCL2)in ATMs were associated with greater levels of NOS2,IL1B,CD86 and CCL2 mRNA expression in SCK cows;fluorescence intensity of NOS2 and CD86 also was elevated,alongside a higher proportion of CD68+/CD86+immunopositive cells within adipose tissue.ELISA further quantified increased concentrations of IL-1β and CCL2.Conversely,the abundance of ATM M2 polarization markers,including CD206,IL-10,KLF4,and Arg1,at both the protein and mRNA levels demonstrated a decline.Meanwhile,the proportion of CD68+/CD206+immune response cells was relatively low in SCK cows.Conclusions Overall,the present study indicated an augmented macrophage presence within adipose tissue during subclinical ketosis,with a predominance of pro-inflammatory macrophages(M1 ATM).This observation suggested a vicious cycle wherein macrophage infiltration and pro-inflammatory polarization coincide with enhanced lipolysis and an amplified inflammatory cascade.展开更多
Pericoronary adipose tissue(PCAT)plays an important role in the pathogenesis and progression of cardiovascular diseases due to its bidirectional communication with the coronary artery wall.In recent years,PCAT paramet...Pericoronary adipose tissue(PCAT)plays an important role in the pathogenesis and progression of cardiovascular diseases due to its bidirectional communication with the coronary artery wall.In recent years,PCAT parameters measured using coronary computed tomography have emerged as potential noninvasive imaging biomarkers for quantifying coronary artery inflammation,with significant clinical value in the early detection,disease progression assessment,treatment efficacy evaluation,and prognosis prediction of cardiovascular diseases.Furthermore,new technologies such as PCAT radiomics analysis have broadened its potential applications in evaluating coronary plaque vulnerability,predicting cardiovascular events,and improving risk stratification.This review discusses recent advances in PCAT research,focusing on its role in coronary artery disease risk identification and inflammation monitoring,and aims to offer imaging-based insights to support its future clinical use in cardiovascular disease management.展开更多
Obesity has become a global threat to health;however,the available drugs for treating obesity are limited.We investigated the anti-obesity effect of hydroxy-α-sanshool(HAS),an amide derived from the fruit of Zanthoxy...Obesity has become a global threat to health;however,the available drugs for treating obesity are limited.We investigated the anti-obesity effect of hydroxy-α-sanshool(HAS),an amide derived from the fruit of Zanthoxylum bungeanum,which promotes the management of obesity by triggering the browning of white adipose tissue(WAT)targeting the membrane receptor of transient receptor potential vanilloid 1(TRPV1).However,HAS easily undergoes configuration transformation and oxidative degradation.The short peptide CKGGRAKDC or adipose-targeting sequence(ATS)binds specifically to prohibitin on the surface of WAT cells and can be used as recognition assembly to enhance adipocyte targetability.Furthermore,mesoporous silica nanoparticles(MSNs)are widely used in drug delivery systems because of their large specific surface area and pore volume.Therefore,HAS-loaded adipose-targeted MSNs(MSNs-ATS)were developed to enhance the adipocyte targetability,safety,and efficacy of HAS,and tested on mature 3T3-L1 cells and obese mouse models.MSNs-ATS showed higher specificity for adipocyte targetability without obvious toxicity.HAS-loaded MSNs-ATS showed anti-obesity effects superior to those of HAS alone.In conclusion,we successfully developed adipocyte-targeted,HAS-loaded MSNs with good safety and anti-obesity effects.展开更多
Background Adipose tissue plays a central role in regulating whole-body metabolic health,facilitated by the variety of cell types and their wide-ranging functions.In addition,depot-specific differences in adipose tiss...Background Adipose tissue plays a central role in regulating whole-body metabolic health,facilitated by the variety of cell types and their wide-ranging functions.In addition,depot-specific differences in adipose tissue have been shown to play important roles in different disease states including obesity,diabetes,and metabolic dysfunction in human and animal models.For early postpartum dairy cattle,metabolic dysfunction,triggered by a negative energy balance,is often manifested as subclinical ketosis(SCK).However,the role that subcutaneous(SAT)and visceral(VAT)adipose tissue depots,and their diverse cellular compositions,play in the response to subclinical ketosis conditions is unclear.Results Flank SAT and omental VAT were collected via laparotomy from five non-ketotic(NK;BHB≤0.8 mmol/L)and five subclinical ketosis(SCK;1.4 mmol/L<BHB≤2.6 mmol/L)multiparous cows during early lactation.Following collection,nuclei were isolated from the tissue and subjected to single-nuclei RNA sequencing in order to investigate the transcriptional cellular heterogeneity.Distinct clusters of adipocytes(AD),adipose stem/progenitor cells(ASPC),immune cells(IMC),endothelial cells(EC),and pericyte/smooth muscle cells(PE/SMC)were identified in both adipose depots,with a greater abundance of ASPC in SAT compared to VAT.In addition,we identified a VAT-specific AD subtype characterized by higher expression of progenitor-like marker genes.While the abundance of none of the identified cell subtypes were different between SCK and NK,underlying transcriptional changes provided insight into potential effects of SCK.In general,SCK was associated with pro-lipogenic,anti-inflammatory,and pro-angiogenic transcriptional changes,possibly indicating a greater capacity for homeostatic responsiveness in SAT under conditions of enhanced negative energy balance.In contrast,SCK appeared to promote transcriptional changes indicative of impaired adipogenesis,impaired angiogenesis,and increased inflammation in VAT.Conclusions Uniquely,our study presents novel insight into the cellular heterogeneity of adipose tissue in dairy cattle with subclinical ketosis.Furthering our understanding of the role of adipose tissue in response to this form of metabolic challenge has the potential to enhance efforts aimed at limiting the incidence and impact of subclinical ketosis and improving the health and productivity of dairy cattle.展开更多
Background:Long-term exposure to light has emerged as a novel risk factor for metabolic diseases.The whitening of brown adipose tissue(BAT)may play an important role in metabolic disorders caused by long-term continuo...Background:Long-term exposure to light has emerged as a novel risk factor for metabolic diseases.The whitening of brown adipose tissue(BAT)may play an important role in metabolic disorders caused by long-term continuous light exposure.This study aimed to investigate the morphological and functional alterations in BAT under continuous light conditions and to identify traditional Chinese medicine compounds capable of reversing these changes.Methods:A metabolic disorder model was established by subjecting mice to continuous light exposure for 5 weeks.During this period,body weight,food intake,and body fat percentage were monitored.Serum levels of triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),and low density lipoprotein cholesterol(LDL-C)were measured to assess lipid metabolism.Histological changes in BAT were examined using H&E staining.The expression of the thermogenic marker uncoupling protein 1(UCP1)in BAT was determined by RT-qPCR and Western blot to evaluate thermogenic function.RNA sequencing(RNA-seq)was employed to identify differentially expressed genes(DEGs)involved in BAT whitening induced by prolonged continuous light exposure.DEGs were analyzed using the connectivity map(CMap)database to identify potential preventive and therapeutic compounds.The therapeutic efficacy of the selected compounds was subsequently evaluated using the above indicators,and key pathways were validated through western blot analysis.Results:After 5 weeks of continuous light exposure,mice exhibited increased body fat percentage and serum levels of TG,impaired mitochondrial function,reduced thermogenic capacity,and whitening of BAT.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analyses indicated that BAT whitening was primarily associated with the adenosine 5'-monophosphate-activated protein kinase(AMPK)signaling pathway,fatty acid metabolism,and circadian rhythm.Ten hub genes identified using Cytoscape were mainly related to AMPK signaling and heat shock proteins.In vivo experiments showed that cordycepin significantly attenuated the increase in body fat percentage caused by prolonged light exposure.This effect was mediated by activation of the AMPK/PGC-1α/UCP1 signaling pathway,which restored the multilocular morphology and thermogenic function of BAT.Conclusion:Cordycepin mitigates continuous light-induced BAT whitening and metabolic disturbances by activating the AMPK signaling pathway.展开更多
Epicardial adipose tissue(EAT)is an active form of visceral adipose tissue that can affect myocardial function due to shared circulation with the myocardium.Given its rapid metabolic activity,EAT is considered a poten...Epicardial adipose tissue(EAT)is an active form of visceral adipose tissue that can affect myocardial function due to shared circulation with the myocardium.Given its rapid metabolic activity,EAT is considered a potential therapeutic target for medications that modulate fat and is a potent marker of metabolic changes including those observed in diabetic cardiomyopathy.Recent investigations propose an association between EAT accumulation and chronic diseases such as type 2 diabetes mellitus(T2DM),atrial fibrillation,and heart failure with preserved ejection fraction.According to the method first described by Iacobellis et al,EAT thickness is identified as the echo-free space between the outer wall of the myocardium and the visceral layer of the pericardium,measured in the parasternal short-and long-axis views at end-systole using ultrasound.Ultrasound of EAT is a safe,cost-effective,and readily available tool for cardiometabolic risk assessment.This minireview investigates the current role of echocardiography in the assessment of EAT thickness in patients with T2DM,regardless of the presence of overt heart failure.We also discuss whether changes in EAT thickness may be used as a significant marker of disease progression and if delta EAT thickness could serve as a surrogate of effective therapy.展开更多
Aging is one of the most significant health challenges worldwide and is a primary cause of chronic diseases and physiological decline.Among the myriad changes that occur with aging,alterations in adipose tissue distri...Aging is one of the most significant health challenges worldwide and is a primary cause of chronic diseases and physiological decline.Among the myriad changes that occur with aging,alterations in adipose tissue distribution and function have gained considerable attention because of their profound impact on metabolic health and overall well-being.Subcutaneous adipose tissue(SAT)and visceral adipose tissue(VAT)are the two major depots of white adipose tissue,each with distinct roles in metabolism and health.Understanding the characteristics and underlying mechanisms of SAT and VAT is crucial for elucidating the aging process and developing strategies to promote healthy aging.This review focuses on delineating and analyzing the characteristics and intrinsic mechanisms underlying the aging of subcutaneous and visceral adipose tissue during the aging process,which can contribute to a better understanding of the aging process and enhance healthy aging.展开更多
Aesthetic medicine is a branch of medicine dedicated to improve an individual’s appearance and overall visual appeal.Conventional aesthetic treatments have limitations,including the risk of complications,allergic rea...Aesthetic medicine is a branch of medicine dedicated to improve an individual’s appearance and overall visual appeal.Conventional aesthetic treatments have limitations,including the risk of complications,allergic reactions,and temporary benefits.Adipose tissue offers a promising alternative to conventional aesthetic treatments.The regenerative properties,accessibility and versatility of adipose tissue make it an attractive option for individuals seeking natural and long-lasting aesthetic results.Adipose tissue is rich source of adipose tissue derived stem cells(ASCs),growth factors and extracellular matrix.It can restore and rejuvenate the damaged and aged tissues.Adipose tissue can be used in different formats such as pure adipose tissue grafts,stromal vascular fraction,nanofat,macrofat,microfat and as a pure population of ASCs.In addition,ASC derived exosomes offer a unique cell-free therapy advantages bioactive molecules like growth factors,cytokines,and microRNAs to stimulate collagen production,improve skin texture,and address pigmentation issues.This review highlights the multifaceted potential of adipose tissue in aesthetic medicine.It discusses its diverse applications,the biological mechanisms involved,and emerging therapeutic approaches.Moreover,this review also highlights the challenges and future direction of using adipose tissue-based therapies for aesthetic treatments.展开更多
Gut microbiota regulate the activation of adipose browning,which promote energy dissipation and combat diet-induced obesity.Pomegranate peel polyphenols(PPPs)have been shown to reduce obesity,regulate lipid metabolism...Gut microbiota regulate the activation of adipose browning,which promote energy dissipation and combat diet-induced obesity.Pomegranate peel polyphenols(PPPs)have been shown to reduce obesity,regulate lipid metabolism in adipose tissue,and modulate the composition of gut microbiota in animal fed high-fat diet(HFD).However,the role of gut microbiota in the improvement of obesity by PPPs has not been elucidated.In current study,we applied antibiotics to inhibit gut microbiota in mice fed HFD and treated with PPPs.The results showed that the inhibition of gut microbiota impair the effect of PPPs on reducing obesity and promoting adipose browning,and change the fecal metabolomic profiles in respond to PPPs.Moreover,the inhibition of gut microbiota supressed the promotive effects of PPPs on the levels of Akkermansia and microbiota-related metabolites,such as urolithin A,short-chain fatty acids(SCFAs),and bile acids(BAs),which were associated with activating adipose browning.Therefore,our results suggested that the presence of gut microbiota is essential for PPPs to ameliorate HFD-induced obesity.The related bacteria or metabolites generated by the interaction between PPPs and microbiota promote adipose browning and facilitate the beneficial effects of PPPs.展开更多
Increasing evidence of the significant clinical value of protection against ischemia/reperfusion injury has contributed to the realization of the independent importance of this approach in improving prognosis and redu...Increasing evidence of the significant clinical value of protection against ischemia/reperfusion injury has contributed to the realization of the independent importance of this approach in improving prognosis and reducing cardiovascular mortality.Extracellular vesicles(EVs)derived by adipose mesenchymal stem cells may mediate the paracrine effects of stem cells and provide regenerative and anti-inflammatory properties,which are enhanced byγ-aminobutyric acid.The protective effects on cardiac myocytes may result from the EV embarked by miR-21-5p,which is a target for thioredoxin-interacting protein,regulating the formation of thioredoxin-interacting protein-thioredoxin complexes and subsequently enhancing the antioxidant activity of thioredoxin.It has been found thatγ-aminobutyric acid governs myocardial bioenergetics through suppressing inflammation and supporting mitochondrial structure.Finally,stem cell-based cell-free therapy based on adipose-derived stem cell EVs is considered a promising approach to individualized management of ischemia-induced cardiomyopathy.展开更多
Bio-accumulation of endocrine-disrupting chemicals(EDCs)in human body may result in various adverse health effects.This study measured the levels of 16 EDCs in the visceral adipose tissue of 55 participants in China a...Bio-accumulation of endocrine-disrupting chemicals(EDCs)in human body may result in various adverse health effects.This study measured the levels of 16 EDCs in the visceral adipose tissue of 55 participants in China and investigated their association with obesity.MeP,BPP,PrP,BPA,EtP,BPE,and BPC were frequently detected in more than 50%of the adipose tissues.A positive correlation between bisphenol A and body mass index(BMI)was observed in both multivariate linear regression model(β=0.87,95%confidence interval:0.21-1.53,p=0.011)and multivariate logistic regression analysis(odds ratio=1.28,95%confidence interval:1.01-1.62,0.044).Restricted cubic spline regression analysis revealed a significant nonlinear association between bisphenol P and BMI.Weighted quantile sum regression and quantile-based g-computation revealed a slight positive trend between EDCs mixed exposure and BMI,with bisphenol A as the primary contributor to the positive correlation with BMI.Our findings suggest the extensive existence of environmental EDCs in the adipose tissue of the adult Chinese population and indicate that exposure to BPA in adipose tissue may be associated with the occurrence of obesity.展开更多
BACKGROUND Fracture is one of the most pervasive injuries in the musculoskeletal system,and there is a complex interaction between macrophages and adipose tissue-derived stem cells(ADSCs)in fracture healing.However,tw...BACKGROUND Fracture is one of the most pervasive injuries in the musculoskeletal system,and there is a complex interaction between macrophages and adipose tissue-derived stem cells(ADSCs)in fracture healing.However,two-dimensional(2D)coculture of macrophages and ADSCs can not accurately mimic the in vivo cell microenvironment.AIM To establish both 2D and 3D osteogenic coculture models to investigate the interaction between macrophages and ADSCs.METHODS After obtaining ADSCs from surgery and inducing differentiation of the THP1 cell line,we established 2D and 3D osteogenic coculture models.To assess the level of osteogenic differentiation,we used alizarin red staining and measured the relative expression levels of osteogenic differentiation markers osteocalcin,Runt-related transcription factor 2,and alkaline phosphatase through polymerase chain reaction.Verification was conducted by analyzing the expression changes of N-cadherin and the activation of the Wnt/β-catenin signaling pathway using western blotting.RESULTS In this study,it was discovered that macrophages in 3D culture inhibited osteogenic differentiation of ADSCs,contrary to the effect in 2D culture.This observation confirmed the significance of intricate intercellular connections in the 3D culture environment.Additionally,the 3D culture group exhibited significantly higher N-cadherin expression and showed reducedβ-catenin and Wnt1 protein levels compared to the 2D culture group.CONCLUSION Macrophages promoted ADSC osteogenic differentiation in 2D culture conditions but inhibited it in 3D culture.The 3D culture environment might inhibit the Wnt/β-catenin signaling pathway by upregulating N-cadherin expression,ultimately hindering the osteogenic differentiation of ADSCs.By investigating the process of osteogenesis in ADSCs,this study provides novel ideas for exploring 3D osteogenesis in ADSCs,fracture repair,and other bone trauma repair.展开更多
Background Thermogenic adipose tissue,both beige and brown,experiences whitening as animals are exposed to warmth and age,but the potential mechanisms are not fully understood.In this study,we employed singlenucleus R...Background Thermogenic adipose tissue,both beige and brown,experiences whitening as animals are exposed to warmth and age,but the potential mechanisms are not fully understood.In this study,we employed singlenucleus RNA-seq to construct a cell atlas during whitening progression and identified the characteristics of thermogenic adipocytes.Results Our histological studies and bulk transcriptome gene expression analysis confirmed that both perirenal and omental adipose tissues(pAT and oAT)exhibited progressive whitening in goats.Compared to the classic brown adipocytes in mice,goat thermogenic adipocytes were more closely related in gene expression patterns to human beige adipocytes,which was also confirmed by adipocyte type-and lineage-specific marker expression analysis.Furthermore,trajectory analysis revealed beige-and white-like adipocytes deriving from a common origin,coexisting and undergoing the transdifferentiation.In addition,differences in gene expression profiles and cell communication patterns(e.g.,FGF and CALCR signaling)between oAT and pAT suggested a lower thermogenic capacity of oAT than that of pAT.Conclusions We constructed a cell atlas of goat pAT and oAT and descripted the characteristics of thermogenic adipocytes during whitening progression.Altogether,our results make a significant contribution to the molecular and cellular mechanisms behind the whitening of thermogenic adipocytes,and providing new insights into obesity prevention in humans and cold adaptation in animals.展开更多
BACKGROUND Electroacupuncture(EA)has been recognized for its beneficial effects on glucolipid metabolism,potentially through the regulation of sensory nerve coordination.The expandability of peripancreatic adipose tis...BACKGROUND Electroacupuncture(EA)has been recognized for its beneficial effects on glucolipid metabolism,potentially through the regulation of sensory nerve coordination.The expandability of peripancreatic adipose tissue(PAT)is implicated in the transition from obesity to type 2 diabetes mellitus(T2DM).However,the specific pancreatic responses to EA require further elucidation.AIM To investigate the influence of EA on pancreatic glucolipid reduction level in a high-fat diet(HFD)rat model.METHODS To delineate the precise pathway through which EA mediates interactions bet ween PAT and islets,we assessed the expression levels of NGF,TRPV1,insulin,as well as other proteins in the pancreas and PAT.This approach enabled us to identify the acupoints that are most conducive to optimizing glycolipid metabolism.RESULTS The ST25,LI11 and ST37 groups attenuated HFD-induced obesity and insulin resistance(IR)to distinct degrees,with ST25 group having the greatest effect.EA at ST25 was found to modify the local regulatory influence of PAT on the pancreatic intrinsic nervous system.Specifically,EA at ST25 obviously activated the TRPV1-CGRP-islet beta cell pathway,contributing to the relief of glucolipid metabolic stress.The beneficial effects were abrogated following the chemical silencing of TRPV1 sensory afferents,confirming their indispensable role in EA-mediated regulation of islet and PAT function.Furthermore,in TRPV1 knockout mice,a reduction in PAT inflammation was observed,along with the recovery of islet beta cell function.EA at LI11 and ST37 demonstrated anti-inflammatory properties and helped ameliorate IR.CONCLUSION The PAT ecological niche influenced the progression from obesity to T2DM through various immunometabolic pathways.EA at ST25 could regulate glucolipid metabolism via the TRPV1-CGRP-islet beta cell pathway.展开更多
BACKGROUND Incisional hernias are a common complication of previous surgeries and remain a persistent issue in clinical practice,posing a significant burden on healthcare systems despite advances in education and tech...BACKGROUND Incisional hernias are a common complication of previous surgeries and remain a persistent issue in clinical practice,posing a significant burden on healthcare systems despite advances in education and technology.Surgical techniques,primarily involving the use of mesh to cover the abdominal wall gap,are widely used as a standard intervention strategy.AIM To examine the regeneration of the aponeurosis defect in the anterior abdominal wall in rats using regenerative mimetic factors of the extracellular matrix[ReGeneraTing Agent(RGTA)],adipose tissue micrografts(ATM),and platelet rich plasma(PRP)as regenerative agents.METHODS Regenerative agents such as RGTA,ATM,and PRP are gaining popularity.ATM involves autologous adipose tissue cells with mesenchymal stem cell markers and a high percentage of stromal vascular fraction cells.RGTAs are heparan sulfate(HS)mimetics that replace degraded HSs in damaged tissue,enhancing the quality and speed of repair.PRP is a concentrated plasma preparation containing seven fundamental proteins responsible for tissue production.An acellular dermal matrix is a biological implant free of cellular or antigenic components,making it an excellent material for reconstructive surgery.Polyglactin is a synthetic,absorbable mesh that loses 50%of its strength after fourteen days,providing initial support for new tissue regeneration before being completely absorbed.RESULTS Rats will undergo a laparotomy with a precise 2 cm by 2 cm excision of the anterior abdominal wall fascia below the umbilicus.They will be divided into sixteen groups,each receiving different combinations of regenerative factor injections into the denervated area in both non-contaminated and contaminated environments.A collagenelastin matrix will be used to join the aponeurosis edges,with an absorbable polyglactin mesh anchored over it.Samples will be taken for macroscopic,histological,and immunohistochemical evaluation of tissue regeneration.CONCLUSION Our study aims to demonstrate how these factors promote cell proliferation and healing of the denervated anterior abdominal wall,potentially reducing the frequency and complications of incisional hernias.This approach could offer a more economical and efficient treatment option compared to current costly methods.展开更多
文摘BACKGROUND Mesenchymal stem cells(MSCs)are considered a promising therapy for various diseases due to their strong potential in regenerative medicine and immunomodulation.The tissue source of MSCs has gained attention for its role in influencing their function,accessibility,and readiness for clinical use.AIM To identify the most suitable adipose source for MSC isolation and expansion for further applications.METHODS We isolated MSCs from solid adipose tissue and liposuction aspirates using the enzyme method.The MSCs were examined for their expansion using population doubling time,differentiation capacity using multilineage differentiation induction,surface markers using flow cytometry,and stability of chromosomes using the karyotyping method.Growth factors and cytokines in MSC-conditioned media were analyzed using the Luminex assay.RESULTS MSCs were isolated from solid adipose tissue and lipoaspirates and expanded from passage 0 to passage 2.All adipose-derived MSCs(AD-MSCs)exhibited the typical elongated,spindle-shaped morphology and comparable proliferation rate.They expressed positive surface markers(cluster of differentiation 73[CD73]:>97%,CD90:>98%,and CD105:>95%),and negative markers(<1%).All MSCs expressed similar levels of stemness genes(octamer-binding transcription factor 4,SRY-box 2,Krüppel-like factor,and MYC),colonyforming,and trilineage differentiation potential.Karyotyping analysis revealed normal chromosomal patterns in all samples,except one sample exhibiting a polymorphism(1qh+).Furthermore,the growth factors and cytokines of hepatocyte growth factor,vascular endothelial growth factor A,interleukin 6(IL-6),and IL-8 were detected in all AD-MSC conditioned media;but fibroblast growth factor-2 and keratinocyte growth factor were selectively expressed in conditioned media from solid or lipoaspirate AD-MSCs,respectively.CONCLUSION These findings indicate that AD-MSCs from both adipose sources possess all of the characteristic features of MSCs with source-specific secretome differences,which are suitable for further expansion and various clinical applications.
文摘Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated with increased levels of circulato ry pro-inflammatory marke rs up to 1 year postTBI(Eagle et al.,2023).
基金supported by FWO(Fonds voor Wetenschappelijk Onderzoek),grant number G07562NFWO(to BB)。
文摘Neuroinflammation is a key process in the pathogenesis of various neurodegenerative diseases,such as multiple sclerosis(MS),Alzheimer's disease,and traumatic brain injury.Even for disorders historically unrelated to neuroinflammation,such as Alzheimer's disease,it is now shown to precede pathological protein aggregations.
文摘Stem cells play a key role in tissue regeneration due to their self-renewal and multidirectional differentiation,which are continuously regulated by signals from the extracellular matrix(ECM)microenvironment.Therefore,the unique biological and physical characteristics of the ECM are important determinants of stem cell behavior.Although the acellular ECM of specific tissues and organs(such as the skin,heart,cartilage,and lung)can mimic the natural microenvironment required for stem cell differentiation,the lack of donor sources restricts their development.With the rapid development of adipose tissue engineering,decellularized adipose matrix(DAM)has attracted much attention due to its wide range of sources and good regeneration capacity.Protocols for DAM preparation involve various physical,chemical,and biological methods.Different combinations of these methods may have different impacts on the structure and composition of DAM,which in turn interfere with the growth and differentiation of stem cells.This is a narrative review about DAM.We summarize the methods for decellularizing and sterilizing adipose tissue,and the impact of these methods on the biological and physical properties of DAM.In addition,we also analyze the application of different forms of DAM with or without stem cells in tissue regeneration(such as adipose tissue),repair(such as wounds,cartilage,bone,and nerves),in vitro bionic systems,clinical trials,and other disease research.
文摘Adipose tissue has emerged as a rich and clinically relevant source of regenerative cells.It offers a minimally invasive,abundant,and autologous reservoir for therapeutic applications.Among its cellular components,the stromal vascular fraction(SVF)and adipose-derived stem cells(ASCs)have gained considerable attention due to their potent regenerative and immunomodulatory capacities.SVF is a heterogeneous mixture of cells,whereas ASCs constitute a more homogeneous mesenchymal stem cell-like population obtained through in vitro expansion.Together,these cell populations(SVF and ASCs)are described as“living drugs”,as they are viable and act as dynamic biological agents within the body.Unlike conventional medicines,living drugs exert therapeutic effects not only through direct differentiation but also via the secretion of bioactive molecules,including cytokines,growth factors,and extracellular vesicles.These secreted factors can modulate the surrounding microenvironment,enhance tissue repair,and regulate immune responses.Such paracrine mechanisms often play a more significant role than direct cell replacement,making living drugs versatile tools for regenerative medicine.This review provides a comprehensive overview of SVF and ASCs as living drugs.It discusses their cellular composition,mechanisms of action,methods of isolation,and the regenerative biomolecules they secrete.Furthermore,it explores current and emerging clinical applications,challenges,and future innovations.
基金supported by grants from National Natural Science Foundation of China(32125038)National Key Research and Development Program of China(grant number 2023YFD1801100 and 2023YFD1800804)+1 种基金the Key Research and Development Program of the Xinjiang Uygur Autonomous Region(No.2024B02016)the 2115 Talent Development Program of China Agricultural University.
文摘Background Sustained lipolysis exacerbates subclinical ketosis(SCK)in dairy cows and is associated with inflammation and adipose tissue macrophage(ATM)infiltration.While ATM involvement in adipose homeostasis and inflammation in early lactation is recognized,a comprehensive exploration of ATM polarization phenotypes in SCK cows is lacking.This study aimed to characterize ATM polarization and its link to lipolysis and inflammation in SCK cows.Results Subcutaneous adipose tissue samples were obtained from dairy cows to analyze protein expression and gene profiles.Compared with healthy cows,SCK cows had higher serum BHBA and NEFA,smaller adipocytes,and increased expression of lipolytic enzymes(LIPE,ATGL),indicating enhanced lipolysis.Decreased levels of FASN,PPARγ,p-SMAD3,and TGFβsuggested impaired adipogenesis.Inflammatory markers(TNF-α,IFN-γ,TLR4,Caspase1)and NFκB signaling activity were elevated.ATM infiltration was supported by increased CD9,CD68,TREM2,and CXCL1 expression.Protein abundance of M1 polarization markers(iNOS,CD86 and CCL2)in ATMs were associated with greater levels of NOS2,IL1B,CD86 and CCL2 mRNA expression in SCK cows;fluorescence intensity of NOS2 and CD86 also was elevated,alongside a higher proportion of CD68+/CD86+immunopositive cells within adipose tissue.ELISA further quantified increased concentrations of IL-1β and CCL2.Conversely,the abundance of ATM M2 polarization markers,including CD206,IL-10,KLF4,and Arg1,at both the protein and mRNA levels demonstrated a decline.Meanwhile,the proportion of CD68+/CD206+immune response cells was relatively low in SCK cows.Conclusions Overall,the present study indicated an augmented macrophage presence within adipose tissue during subclinical ketosis,with a predominance of pro-inflammatory macrophages(M1 ATM).This observation suggested a vicious cycle wherein macrophage infiltration and pro-inflammatory polarization coincide with enhanced lipolysis and an amplified inflammatory cascade.
基金Supported by the Health Commission of the Sichuan Province Medical Science and Technology Program,China,No.24WXXT10the Sichuan Province Science and Technology Support Program,China,No.2021YJ0242the 23rd Batch of Student Scientific Research Project Approval of Jiangsu University,China,No.Y23A164.
文摘Pericoronary adipose tissue(PCAT)plays an important role in the pathogenesis and progression of cardiovascular diseases due to its bidirectional communication with the coronary artery wall.In recent years,PCAT parameters measured using coronary computed tomography have emerged as potential noninvasive imaging biomarkers for quantifying coronary artery inflammation,with significant clinical value in the early detection,disease progression assessment,treatment efficacy evaluation,and prognosis prediction of cardiovascular diseases.Furthermore,new technologies such as PCAT radiomics analysis have broadened its potential applications in evaluating coronary plaque vulnerability,predicting cardiovascular events,and improving risk stratification.This review discusses recent advances in PCAT research,focusing on its role in coronary artery disease risk identification and inflammation monitoring,and aims to offer imaging-based insights to support its future clinical use in cardiovascular disease management.
基金supported by the Natural Science Foundation of Sichuan Province(No.2022NSFSC0720)Research Center for the Development of the Comprehensive Health Industry and Rural Revitalization of Sichuan TCM(No.DJKYB202306)State Administration of Traditional Chinese Medicine of Sichuan Province of China(No.2020HJZX001).
文摘Obesity has become a global threat to health;however,the available drugs for treating obesity are limited.We investigated the anti-obesity effect of hydroxy-α-sanshool(HAS),an amide derived from the fruit of Zanthoxylum bungeanum,which promotes the management of obesity by triggering the browning of white adipose tissue(WAT)targeting the membrane receptor of transient receptor potential vanilloid 1(TRPV1).However,HAS easily undergoes configuration transformation and oxidative degradation.The short peptide CKGGRAKDC or adipose-targeting sequence(ATS)binds specifically to prohibitin on the surface of WAT cells and can be used as recognition assembly to enhance adipocyte targetability.Furthermore,mesoporous silica nanoparticles(MSNs)are widely used in drug delivery systems because of their large specific surface area and pore volume.Therefore,HAS-loaded adipose-targeted MSNs(MSNs-ATS)were developed to enhance the adipocyte targetability,safety,and efficacy of HAS,and tested on mature 3T3-L1 cells and obese mouse models.MSNs-ATS showed higher specificity for adipocyte targetability without obvious toxicity.HAS-loaded MSNs-ATS showed anti-obesity effects superior to those of HAS alone.In conclusion,we successfully developed adipocyte-targeted,HAS-loaded MSNs with good safety and anti-obesity effects.
基金supported in part by the Agriculture and Food Research Initiative Competitive Grants#2022-67015-36319 and#2024-67034-42234 from USDA-NIFA(United States Department of Agriculture–National Institute of Food and Agriculture).
文摘Background Adipose tissue plays a central role in regulating whole-body metabolic health,facilitated by the variety of cell types and their wide-ranging functions.In addition,depot-specific differences in adipose tissue have been shown to play important roles in different disease states including obesity,diabetes,and metabolic dysfunction in human and animal models.For early postpartum dairy cattle,metabolic dysfunction,triggered by a negative energy balance,is often manifested as subclinical ketosis(SCK).However,the role that subcutaneous(SAT)and visceral(VAT)adipose tissue depots,and their diverse cellular compositions,play in the response to subclinical ketosis conditions is unclear.Results Flank SAT and omental VAT were collected via laparotomy from five non-ketotic(NK;BHB≤0.8 mmol/L)and five subclinical ketosis(SCK;1.4 mmol/L<BHB≤2.6 mmol/L)multiparous cows during early lactation.Following collection,nuclei were isolated from the tissue and subjected to single-nuclei RNA sequencing in order to investigate the transcriptional cellular heterogeneity.Distinct clusters of adipocytes(AD),adipose stem/progenitor cells(ASPC),immune cells(IMC),endothelial cells(EC),and pericyte/smooth muscle cells(PE/SMC)were identified in both adipose depots,with a greater abundance of ASPC in SAT compared to VAT.In addition,we identified a VAT-specific AD subtype characterized by higher expression of progenitor-like marker genes.While the abundance of none of the identified cell subtypes were different between SCK and NK,underlying transcriptional changes provided insight into potential effects of SCK.In general,SCK was associated with pro-lipogenic,anti-inflammatory,and pro-angiogenic transcriptional changes,possibly indicating a greater capacity for homeostatic responsiveness in SAT under conditions of enhanced negative energy balance.In contrast,SCK appeared to promote transcriptional changes indicative of impaired adipogenesis,impaired angiogenesis,and increased inflammation in VAT.Conclusions Uniquely,our study presents novel insight into the cellular heterogeneity of adipose tissue in dairy cattle with subclinical ketosis.Furthering our understanding of the role of adipose tissue in response to this form of metabolic challenge has the potential to enhance efforts aimed at limiting the incidence and impact of subclinical ketosis and improving the health and productivity of dairy cattle.
文摘Background:Long-term exposure to light has emerged as a novel risk factor for metabolic diseases.The whitening of brown adipose tissue(BAT)may play an important role in metabolic disorders caused by long-term continuous light exposure.This study aimed to investigate the morphological and functional alterations in BAT under continuous light conditions and to identify traditional Chinese medicine compounds capable of reversing these changes.Methods:A metabolic disorder model was established by subjecting mice to continuous light exposure for 5 weeks.During this period,body weight,food intake,and body fat percentage were monitored.Serum levels of triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),and low density lipoprotein cholesterol(LDL-C)were measured to assess lipid metabolism.Histological changes in BAT were examined using H&E staining.The expression of the thermogenic marker uncoupling protein 1(UCP1)in BAT was determined by RT-qPCR and Western blot to evaluate thermogenic function.RNA sequencing(RNA-seq)was employed to identify differentially expressed genes(DEGs)involved in BAT whitening induced by prolonged continuous light exposure.DEGs were analyzed using the connectivity map(CMap)database to identify potential preventive and therapeutic compounds.The therapeutic efficacy of the selected compounds was subsequently evaluated using the above indicators,and key pathways were validated through western blot analysis.Results:After 5 weeks of continuous light exposure,mice exhibited increased body fat percentage and serum levels of TG,impaired mitochondrial function,reduced thermogenic capacity,and whitening of BAT.Gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)enrichment analyses indicated that BAT whitening was primarily associated with the adenosine 5'-monophosphate-activated protein kinase(AMPK)signaling pathway,fatty acid metabolism,and circadian rhythm.Ten hub genes identified using Cytoscape were mainly related to AMPK signaling and heat shock proteins.In vivo experiments showed that cordycepin significantly attenuated the increase in body fat percentage caused by prolonged light exposure.This effect was mediated by activation of the AMPK/PGC-1α/UCP1 signaling pathway,which restored the multilocular morphology and thermogenic function of BAT.Conclusion:Cordycepin mitigates continuous light-induced BAT whitening and metabolic disturbances by activating the AMPK signaling pathway.
文摘Epicardial adipose tissue(EAT)is an active form of visceral adipose tissue that can affect myocardial function due to shared circulation with the myocardium.Given its rapid metabolic activity,EAT is considered a potential therapeutic target for medications that modulate fat and is a potent marker of metabolic changes including those observed in diabetic cardiomyopathy.Recent investigations propose an association between EAT accumulation and chronic diseases such as type 2 diabetes mellitus(T2DM),atrial fibrillation,and heart failure with preserved ejection fraction.According to the method first described by Iacobellis et al,EAT thickness is identified as the echo-free space between the outer wall of the myocardium and the visceral layer of the pericardium,measured in the parasternal short-and long-axis views at end-systole using ultrasound.Ultrasound of EAT is a safe,cost-effective,and readily available tool for cardiometabolic risk assessment.This minireview investigates the current role of echocardiography in the assessment of EAT thickness in patients with T2DM,regardless of the presence of overt heart failure.We also discuss whether changes in EAT thickness may be used as a significant marker of disease progression and if delta EAT thickness could serve as a surrogate of effective therapy.
基金the National Natural Science Foundation of China(grant no.82272289).
文摘Aging is one of the most significant health challenges worldwide and is a primary cause of chronic diseases and physiological decline.Among the myriad changes that occur with aging,alterations in adipose tissue distribution and function have gained considerable attention because of their profound impact on metabolic health and overall well-being.Subcutaneous adipose tissue(SAT)and visceral adipose tissue(VAT)are the two major depots of white adipose tissue,each with distinct roles in metabolism and health.Understanding the characteristics and underlying mechanisms of SAT and VAT is crucial for elucidating the aging process and developing strategies to promote healthy aging.This review focuses on delineating and analyzing the characteristics and intrinsic mechanisms underlying the aging of subcutaneous and visceral adipose tissue during the aging process,which can contribute to a better understanding of the aging process and enhance healthy aging.
文摘Aesthetic medicine is a branch of medicine dedicated to improve an individual’s appearance and overall visual appeal.Conventional aesthetic treatments have limitations,including the risk of complications,allergic reactions,and temporary benefits.Adipose tissue offers a promising alternative to conventional aesthetic treatments.The regenerative properties,accessibility and versatility of adipose tissue make it an attractive option for individuals seeking natural and long-lasting aesthetic results.Adipose tissue is rich source of adipose tissue derived stem cells(ASCs),growth factors and extracellular matrix.It can restore and rejuvenate the damaged and aged tissues.Adipose tissue can be used in different formats such as pure adipose tissue grafts,stromal vascular fraction,nanofat,macrofat,microfat and as a pure population of ASCs.In addition,ASC derived exosomes offer a unique cell-free therapy advantages bioactive molecules like growth factors,cytokines,and microRNAs to stimulate collagen production,improve skin texture,and address pigmentation issues.This review highlights the multifaceted potential of adipose tissue in aesthetic medicine.It discusses its diverse applications,the biological mechanisms involved,and emerging therapeutic approaches.Moreover,this review also highlights the challenges and future direction of using adipose tissue-based therapies for aesthetic treatments.
基金supported by the National Natural Science Foundation of China(32001679 and 31871801)the Science and Technology Research of Shaanxi Province(2021QFY07-03)+1 种基金supported by the Fundamental Research Funds for the Central Universities(GK202103098)the Scientific and Technological Achievements Commercialization Program of Shaanxi(2023-YDCGZH-13)。
文摘Gut microbiota regulate the activation of adipose browning,which promote energy dissipation and combat diet-induced obesity.Pomegranate peel polyphenols(PPPs)have been shown to reduce obesity,regulate lipid metabolism in adipose tissue,and modulate the composition of gut microbiota in animal fed high-fat diet(HFD).However,the role of gut microbiota in the improvement of obesity by PPPs has not been elucidated.In current study,we applied antibiotics to inhibit gut microbiota in mice fed HFD and treated with PPPs.The results showed that the inhibition of gut microbiota impair the effect of PPPs on reducing obesity and promoting adipose browning,and change the fecal metabolomic profiles in respond to PPPs.Moreover,the inhibition of gut microbiota supressed the promotive effects of PPPs on the levels of Akkermansia and microbiota-related metabolites,such as urolithin A,short-chain fatty acids(SCFAs),and bile acids(BAs),which were associated with activating adipose browning.Therefore,our results suggested that the presence of gut microbiota is essential for PPPs to ameliorate HFD-induced obesity.The related bacteria or metabolites generated by the interaction between PPPs and microbiota promote adipose browning and facilitate the beneficial effects of PPPs.
文摘Increasing evidence of the significant clinical value of protection against ischemia/reperfusion injury has contributed to the realization of the independent importance of this approach in improving prognosis and reducing cardiovascular mortality.Extracellular vesicles(EVs)derived by adipose mesenchymal stem cells may mediate the paracrine effects of stem cells and provide regenerative and anti-inflammatory properties,which are enhanced byγ-aminobutyric acid.The protective effects on cardiac myocytes may result from the EV embarked by miR-21-5p,which is a target for thioredoxin-interacting protein,regulating the formation of thioredoxin-interacting protein-thioredoxin complexes and subsequently enhancing the antioxidant activity of thioredoxin.It has been found thatγ-aminobutyric acid governs myocardial bioenergetics through suppressing inflammation and supporting mitochondrial structure.Finally,stem cell-based cell-free therapy based on adipose-derived stem cell EVs is considered a promising approach to individualized management of ischemia-induced cardiomyopathy.
基金supported by the National Natural Science Foundation of China(Nos.22125606 and 22241604)the Chinese Academy of Sciences Project of Young Scientists in Basic Research(No.YSBR-086).
文摘Bio-accumulation of endocrine-disrupting chemicals(EDCs)in human body may result in various adverse health effects.This study measured the levels of 16 EDCs in the visceral adipose tissue of 55 participants in China and investigated their association with obesity.MeP,BPP,PrP,BPA,EtP,BPE,and BPC were frequently detected in more than 50%of the adipose tissues.A positive correlation between bisphenol A and body mass index(BMI)was observed in both multivariate linear regression model(β=0.87,95%confidence interval:0.21-1.53,p=0.011)and multivariate logistic regression analysis(odds ratio=1.28,95%confidence interval:1.01-1.62,0.044).Restricted cubic spline regression analysis revealed a significant nonlinear association between bisphenol P and BMI.Weighted quantile sum regression and quantile-based g-computation revealed a slight positive trend between EDCs mixed exposure and BMI,with bisphenol A as the primary contributor to the positive correlation with BMI.Our findings suggest the extensive existence of environmental EDCs in the adipose tissue of the adult Chinese population and indicate that exposure to BPA in adipose tissue may be associated with the occurrence of obesity.
文摘BACKGROUND Fracture is one of the most pervasive injuries in the musculoskeletal system,and there is a complex interaction between macrophages and adipose tissue-derived stem cells(ADSCs)in fracture healing.However,two-dimensional(2D)coculture of macrophages and ADSCs can not accurately mimic the in vivo cell microenvironment.AIM To establish both 2D and 3D osteogenic coculture models to investigate the interaction between macrophages and ADSCs.METHODS After obtaining ADSCs from surgery and inducing differentiation of the THP1 cell line,we established 2D and 3D osteogenic coculture models.To assess the level of osteogenic differentiation,we used alizarin red staining and measured the relative expression levels of osteogenic differentiation markers osteocalcin,Runt-related transcription factor 2,and alkaline phosphatase through polymerase chain reaction.Verification was conducted by analyzing the expression changes of N-cadherin and the activation of the Wnt/β-catenin signaling pathway using western blotting.RESULTS In this study,it was discovered that macrophages in 3D culture inhibited osteogenic differentiation of ADSCs,contrary to the effect in 2D culture.This observation confirmed the significance of intricate intercellular connections in the 3D culture environment.Additionally,the 3D culture group exhibited significantly higher N-cadherin expression and showed reducedβ-catenin and Wnt1 protein levels compared to the 2D culture group.CONCLUSION Macrophages promoted ADSC osteogenic differentiation in 2D culture conditions but inhibited it in 3D culture.The 3D culture environment might inhibit the Wnt/β-catenin signaling pathway by upregulating N-cadherin expression,ultimately hindering the osteogenic differentiation of ADSCs.By investigating the process of osteogenesis in ADSCs,this study provides novel ideas for exploring 3D osteogenesis in ADSCs,fracture repair,and other bone trauma repair.
基金supported by the National Key Research and Development Programme of China(grant number 2021YFF1001000)the National Natural Science Foundation of China(grant number 32170627)+1 种基金the Postdoctoral Innovative Talents Support Program of China(grant number BX20200282)the Natural Science Foundation of Sichuan Province(grant number 23NSFSC1804).
文摘Background Thermogenic adipose tissue,both beige and brown,experiences whitening as animals are exposed to warmth and age,but the potential mechanisms are not fully understood.In this study,we employed singlenucleus RNA-seq to construct a cell atlas during whitening progression and identified the characteristics of thermogenic adipocytes.Results Our histological studies and bulk transcriptome gene expression analysis confirmed that both perirenal and omental adipose tissues(pAT and oAT)exhibited progressive whitening in goats.Compared to the classic brown adipocytes in mice,goat thermogenic adipocytes were more closely related in gene expression patterns to human beige adipocytes,which was also confirmed by adipocyte type-and lineage-specific marker expression analysis.Furthermore,trajectory analysis revealed beige-and white-like adipocytes deriving from a common origin,coexisting and undergoing the transdifferentiation.In addition,differences in gene expression profiles and cell communication patterns(e.g.,FGF and CALCR signaling)between oAT and pAT suggested a lower thermogenic capacity of oAT than that of pAT.Conclusions We constructed a cell atlas of goat pAT and oAT and descripted the characteristics of thermogenic adipocytes during whitening progression.Altogether,our results make a significant contribution to the molecular and cellular mechanisms behind the whitening of thermogenic adipocytes,and providing new insights into obesity prevention in humans and cold adaptation in animals.
基金Supported by National Natural Science Foundation of China,No.82305376,No.82374577,No.82305375,No.82074532,and No.82405567The Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD).
文摘BACKGROUND Electroacupuncture(EA)has been recognized for its beneficial effects on glucolipid metabolism,potentially through the regulation of sensory nerve coordination.The expandability of peripancreatic adipose tissue(PAT)is implicated in the transition from obesity to type 2 diabetes mellitus(T2DM).However,the specific pancreatic responses to EA require further elucidation.AIM To investigate the influence of EA on pancreatic glucolipid reduction level in a high-fat diet(HFD)rat model.METHODS To delineate the precise pathway through which EA mediates interactions bet ween PAT and islets,we assessed the expression levels of NGF,TRPV1,insulin,as well as other proteins in the pancreas and PAT.This approach enabled us to identify the acupoints that are most conducive to optimizing glycolipid metabolism.RESULTS The ST25,LI11 and ST37 groups attenuated HFD-induced obesity and insulin resistance(IR)to distinct degrees,with ST25 group having the greatest effect.EA at ST25 was found to modify the local regulatory influence of PAT on the pancreatic intrinsic nervous system.Specifically,EA at ST25 obviously activated the TRPV1-CGRP-islet beta cell pathway,contributing to the relief of glucolipid metabolic stress.The beneficial effects were abrogated following the chemical silencing of TRPV1 sensory afferents,confirming their indispensable role in EA-mediated regulation of islet and PAT function.Furthermore,in TRPV1 knockout mice,a reduction in PAT inflammation was observed,along with the recovery of islet beta cell function.EA at LI11 and ST37 demonstrated anti-inflammatory properties and helped ameliorate IR.CONCLUSION The PAT ecological niche influenced the progression from obesity to T2DM through various immunometabolic pathways.EA at ST25 could regulate glucolipid metabolism via the TRPV1-CGRP-islet beta cell pathway.
文摘BACKGROUND Incisional hernias are a common complication of previous surgeries and remain a persistent issue in clinical practice,posing a significant burden on healthcare systems despite advances in education and technology.Surgical techniques,primarily involving the use of mesh to cover the abdominal wall gap,are widely used as a standard intervention strategy.AIM To examine the regeneration of the aponeurosis defect in the anterior abdominal wall in rats using regenerative mimetic factors of the extracellular matrix[ReGeneraTing Agent(RGTA)],adipose tissue micrografts(ATM),and platelet rich plasma(PRP)as regenerative agents.METHODS Regenerative agents such as RGTA,ATM,and PRP are gaining popularity.ATM involves autologous adipose tissue cells with mesenchymal stem cell markers and a high percentage of stromal vascular fraction cells.RGTAs are heparan sulfate(HS)mimetics that replace degraded HSs in damaged tissue,enhancing the quality and speed of repair.PRP is a concentrated plasma preparation containing seven fundamental proteins responsible for tissue production.An acellular dermal matrix is a biological implant free of cellular or antigenic components,making it an excellent material for reconstructive surgery.Polyglactin is a synthetic,absorbable mesh that loses 50%of its strength after fourteen days,providing initial support for new tissue regeneration before being completely absorbed.RESULTS Rats will undergo a laparotomy with a precise 2 cm by 2 cm excision of the anterior abdominal wall fascia below the umbilicus.They will be divided into sixteen groups,each receiving different combinations of regenerative factor injections into the denervated area in both non-contaminated and contaminated environments.A collagenelastin matrix will be used to join the aponeurosis edges,with an absorbable polyglactin mesh anchored over it.Samples will be taken for macroscopic,histological,and immunohistochemical evaluation of tissue regeneration.CONCLUSION Our study aims to demonstrate how these factors promote cell proliferation and healing of the denervated anterior abdominal wall,potentially reducing the frequency and complications of incisional hernias.This approach could offer a more economical and efficient treatment option compared to current costly methods.