Background Brown adipose tissue(BAT)is known to be capable of non-shivering thermogenesis under cold stimulation,which is related to the mortality of animals.In the previous study,we observed that goat BAT is mainly l...Background Brown adipose tissue(BAT)is known to be capable of non-shivering thermogenesis under cold stimulation,which is related to the mortality of animals.In the previous study,we observed that goat BAT is mainly located around the kidney at birth,and changes to white adipose tissue(WAT)in the perirenal adipose tissue of goats within one month after birth.However,the regulatory factors underlying this change is remain unclear.In this study,we systematically studied the perirenal adipose tissue of goat kids in histological,cytological,and accompanying molecular level changes from 0 to 28 d after birth.Results Our study found a higher mortality rate in winter-born goat kids,with goat birthing data statistics.Then we used thermal imaging revealing high temperature in goat hips at postnatal 0 d and gradually decrease during 28 d.This is consistent with the region of perirenal BAT deposition and highlights its critical role in energy expenditure and body temperature regulation in goat kids.Additionally,we found a series of changes of BAT during the first 28 d after birth,such as whitening,larger lipid droplets,decreased mitochondrial numbers,and down-regulation of key thermogenesis-related genes(UCP1,DIO2,UCP2,CIDEA,PPARGC1a,C/EBPb,and C/EBPa).Then,we used RNA-seq found specific marker genes for goat adipose tissue and identified 12 new marker genes for BAT and 10 new marker genes for WAT of goats.Furthermore,12 candidate genes were found to potentially regulate goat BAT thermogenesis.The mechanism of the change of this biological phenomenon does not involve a large-scale death of brown adipocytes and subsequent proliferation of white adipocytes.While apoptosis may play a limited role,it is largely not critical in this transition process.Conclusions We concluded that perirenal BAT plays a crucial role in thermoregulation in newborn goat kids,with notable species differences in the expression of adipose tissue marker genes,and we highlighted some potential marker genes for goat BAT and WAT.Additionally,the change from BAT to WAT does not involve a large-scale death of brown adipocytes and subsequent proliferation of white adipocytes.展开更多
Background:Visceral adipose tissue(VAT)has been linked to the severe acute pancreatitis(SAP)prognosis,although the underlying mechanism remains unclear.It has been reported that pyroptosis worsens SAP.The present stud...Background:Visceral adipose tissue(VAT)has been linked to the severe acute pancreatitis(SAP)prognosis,although the underlying mechanism remains unclear.It has been reported that pyroptosis worsens SAP.The present study aimed to verify whether mesenteric adipose tissue(MAT,a component of VAT)can cause secondary intestinal injury through the pyroptotic pathway.Methods:Thirty-six male Sprague Dawley(SD)rats were divided into six different groups.Twelve rats were randomly divided into the SAP and control groups.We monitored the changes of MAT and B lymphocytes infiltration in MAT of SAP rats.Twelve SAP rats were injected with MAT B lymphocytes or phosphate buffer solution(PBS).The remaining twelve SAP rats were first injected with MAT B lymphocytes,and then with MCC950(NLRP3 inhibitor)or PBS.We collected blood and tissue samples from pancreas,gut and MAT for analysis.Results:Compared to the control rats,the SAP group showed inflammation in MAT,including higher expression of tumor necrosis factor(TNF-α)and interleukin-6(IL-6),lower expression of IL-10,and histological changes.Flow cytometry analysis revealed B lymphocytes infiltration in MAT but not T lymphocytes and macrophages.The SAP rats also exhibited intestinal injury,characterized by lower expression of zonula occludens-1(ZO-1)and occludin,higher levels of lipopolysaccharide and diamine oxidase,and pathological changes.The expression of NLRP3 and n-GSDMD,which are responsible for pyroptosis,was increased in the intestine of SAP rats.The injection of MAT B lymphocytes into SAP rats exacerbated the inflammation in MAT.The upregulation of pyroptosis reduced tight junction in the intestine,which contributed to the SAP progression,including higher inflammatory indicators and worse histological changes.The administration of MCC950 to SAP+MAT B rats downregulated pyroptosis,which subsequently improved the intestinal barrier and ameliorated inflammatory response of SAP.Conclusions:In SAP,MAT B lymphocytes aggravated local inflammation,and promoted the injury to the intestine through the enteric pyroptotic pathway.展开更多
BACKGROUND The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass(DJB)surgery is not clear.AIM To study the morphological and functional changes in adipose tissue after DJB and explore the poten...BACKGROUND The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass(DJB)surgery is not clear.AIM To study the morphological and functional changes in adipose tissue after DJB and explore the potential mechanisms contributing to postoperative insulin sensitivity improvement of adipose tissue in a diabetic male rat model.METHODS DJB and sham surgery was performed in a-high-fat-diet/streptozotocin-induced diabetic rat model.All adipose tissue was weighed and observed under microscope.Use inguinal fat to represent subcutaneous adipose tissue(SAT)and mesangial fat to represent visceral adipose tissue.RNA-sequencing was utilized to evaluate gene expression alterations adipocytes.The hematoxylin and eosin staining,reverse transcription-quantitative polymerase chain reaction,western blot,and enzyme-linked immunosorbent assay were used to study the changes.Insulin resistance was evaluated by immunofluorescence.RESULTS After DJB,whole body blood glucose metabolism and insulin sensitivity in adipose tissue improved.Fat cell volume in both visceral adipose tissue(VAT)and SAT increased.Compared to SAT,VAT showed more significantly functional alterations after DJB and KEGG analysis indicated growth hormone(GH)pathway and downstream adiponectin secretion were involved in metabolic regulation.The circulating GH and adiponectin levels and GH receptor and adiponectin levels in VAT increased.Cytological experiment showed that GH stimulated adiponectin secretion and improve insulin sensitivity.CONCLUSION GH improves insulin resistance in VAT in male diabetic rats after receiving DJB,possibly by increasing adiponectin secretion.展开更多
BACKGROUND Evidence suggests inflammatory mesenteric fat is involved in post-operative recurrence(POR)of Crohn’s disease(CD).However,its prognostic value is INTRODUCTION Crohn’s disease(CD)is a debilitating chronic ...BACKGROUND Evidence suggests inflammatory mesenteric fat is involved in post-operative recurrence(POR)of Crohn’s disease(CD).However,its prognostic value is INTRODUCTION Crohn’s disease(CD)is a debilitating chronic immune-mediated inflammatory disease(IMID)of the gastrointestinal tract that is increasing in incidence and prevalence globally[1].CD patients often undergo surgery for disease-related complic-ations and/or medically refractory disease.Unfortunately,surgery is not curative,and many patients develop post-operative recurrence(POR)of CD with a significant proportion eventually requiring additional surgeries.With advances in early detection and therapeutics,the contemporary 10-year risk of surgery has improved from 50%to 26%,but the risk of recurrent surgery has remained unchanged at 30%,suggesting a need to improve post-operative management strategies[2].Presently,there are two accepted strategies to mitigate POR,but each have potential limitations.Firstly,patients start early post-operative pharmacologic prophylaxis within 4-6 wk after surgery.This strategy can potentially overtreat a subset of patient who may not develop long-term disease recurrence off therapy.Consequently,these patients are at risk of medication-related adverse events and the direct and indirect costs associated with therapy with little or no benefit[3].The second strategy is performing early colonoscopy within 6-12 months after surgery and escalating therapy based on FOOTNOTES Author contributions:Gu P is the guarantor of the article and was involved in concept and design,data collection,statistical analysis,drafting of manuscript,and final approval of manuscript;Dube S and Choi SY were involved in statistical analysis,drafting of the manuscript,and final approval of manuscript;Gellada N,Win S,Lee YJ and Yang S were involved in the data collection,drafting of the manuscript,and final approval of manuscript;Haritunians T and Li D were involved in data analysis and interpretation,drafting of manuscript and final approval of manuscript;Melmed GY,Yarur AJ,Fleshner P,Kallman C and Devkota S were involved in study concept and design,data interpretation,drafting of manuscript and final approval of manuscript;Vasiliauskas EA,Bonthala N,Syal G,Ziring D and Targan SR were involved in data interpretation,drafting of manuscript and final approval of manuscript;Rabizadeh S was involved in study concept and design,drafting of manuscript and final approval of manuscript;McGovern DPB was involved in concept and design,statistical analysis,drafting of manuscript and final approval of manuscript.展开更多
BACKGROUND Obesity has become a serious public health issue,significantly elevating the risk of various complications.It is a well-established contributor to Heart failure with preserved ejection fraction(HFpEF).Evalu...BACKGROUND Obesity has become a serious public health issue,significantly elevating the risk of various complications.It is a well-established contributor to Heart failure with preserved ejection fraction(HFpEF).Evaluating HFpEF in obesity is crucial.Epicardial adipose tissue(EAT)has emerged as a valuable tool for validating prognostic biomarkers and guiding treatment targets.Hence,assessing EAT is of paramount importance.Cardiovascular magnetic resonance(CMR)imaging is acknowledged as the gold standard for analyzing cardiac function and mor-phology.We hope to use CMR to assess EAT as a bioimaging marker to evaluate HFpEF in obese patients.AIM To assess the diagnostic utility of CMR for evaluating heart failure with preserved ejection fraction[HFpEF;left ventricular(LV)ejection fraction≥50%]by measuring the epicardial adipose tissue(EAT)volumes and EAT mass in obese patients.METHODS Sixty-two obese patients were divided into two groups for a case-control study based on whether or not they had heart failure with HFpEF.The two groups were defined as HFpEF+and HFpEF-.LV geometry,global systolic function,EAT volumes and EAT mass of all subjects were obtained using cine magnetic resonance sequences.RESULTS Forty-five patients of HFpEF-group and seventeen patients of HFpEF+group were included.LV mass index(g/m2)of HFpEF+group was higher than HFpEF-group(P<0.05).In HFpEF+group,EAT volumes,EAT volume index,EAT mass,EAT mass index and the ratio of EAT/[left atrial(LA)left-right(LR)diameter]were higher compared to HFpEF-group(P<0.05).In multivariate analysis,Higher EAT/LA LR diameter ratio was associated with higher odds ratio of HFpEF.CONCLUSION EAT/LA LR diameter ratio is highly associated with HFpEF in obese patients.It is plausible that there may be utility in CMR for assessing obese patients for HFpEF using EAT/LA LR diameter ratio as a diagnostic biomarker.Further prospective studies,are needed to validate these proof-of-concept findings.展开更多
Obesity is one of the most serious global health problems,with an incidence that increases yearly and coincides with the development of cancer.Adipose tissue macrophages(ATMs)are particularly important in this context...Obesity is one of the most serious global health problems,with an incidence that increases yearly and coincides with the development of cancer.Adipose tissue macrophages(ATMs)are particularly important in this context and contribute to linking obesity-related inflammation and tumor progression.However,the functions of ATMs on the progression of obesity-associated cancer remain unclear.In this review,we describe the origins,phenotypes,and functions of ATMs.Subsequently,we summarize the potential mechanisms on the reprogramming of ATMs in the obesity-associated microenvironment,including the direct exchange of dysfunctional metabolites,inordinate cytokines and other signaling mediators,transfer of extracellular vesicle cargo,and variations in the gut microbiota and its metabolites.A better understanding of the properties and functions of ATMs under conditions of obesity will lead to the development of new therapeutic interventions for obesity-related cancer.展开更多
The relationship between metabolic derangements and fatty liver development are undeniable,since more than 75% of patients with type 2 diabetes mellitus present with fatty liver.There is also significant epidemiologic...The relationship between metabolic derangements and fatty liver development are undeniable,since more than 75% of patients with type 2 diabetes mellitus present with fatty liver.There is also significant epidemiological association between insulin resistance(IR)and metabolic(dysfunction)-associated fatty liver disease(MAFLD).For little more than 2 years,the nomenclature of fatty liver of non-alcoholic origin has been intended to change to MAFLD by multiple groups.While a myriad of reasons for which MAFLD is thought to be of metabolic origin could be exposed,the bottom line relies on the role of IR as an initiator and perpetuator of this disease.There is a reciprocal role in MAFLD development and IR as well as serum glucose concentrations,where increased circulating glucose and insulin result in increased de novo lipogenesis by sterol regulatory elementbinding protein-1c induced lipogenic enzyme stimulation;therefore,increased endogenous production of triglycerides.The same effect is achieved through impaired suppression of adipose tissue(AT)lipolysis in insulin-resistant states,increasing fatty acid influx into the liver.The complementary reciprocal situation occurs when liver steatosis alters hepatokine secretion,modifying fatty acid metabolism as well as IR in a variety of tissues,including skeletal muscle,AT,and the liver.The aim of this review is to discuss the importance of IR and AT interactions in metabolic altered states as perhaps the most important factor in MAFLD pathogenesis.展开更多
BACKGROUND Osteoarthritis(OA)is the most prevalent form of degenerative whole-joint disease.Before the final option of knee replacement,arthroscopic surgery was the most widely used joint-preserving surgical treatment...BACKGROUND Osteoarthritis(OA)is the most prevalent form of degenerative whole-joint disease.Before the final option of knee replacement,arthroscopic surgery was the most widely used joint-preserving surgical treatment.Emerging regenerative therapies,such as those involving platelet-rich plasma,mesenchymal stem cells,and microfragmented adipose tissue(MFAT),have been pushed to the forefront of treatment to prevent the progression of OA.Currently,MFAT has been successfully applied to treat different types of orthopedic diseases.AIM To assess the efficacy and safety of MFAT with arthroscopic surgery in patients with knee OA(KOA).METHODS A randomized,multicenter study was conducted between June 2017 and November 2022 in 10 hospitals in Zhejiang,China.Overall,302 patients diagnosed with KOA(Kellgren-Lawrence grades 2-3)were randomized to the MFAT group(n=151,were administered MFAT following arthroscopic surgery),or the control group(n=151,were administered hyaluronic acid following arthroscopic surgery).The study outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)score,the visual analog scale(VAS)score,the Lequesne index score,the Whole-Organ Magnetic Resonance Imaging Score(WORMS),and safety over a 24-mo period from baseline.RESULTS The changes in the WOMAC score(including the three subscale scores),VAS pain score,and Lequesne index score at the 24-mo mark were significantly different in the MFAT and control groups,as well as when comparing values at the posttreatment visit and those at baseline(P<0.001).The MFAT group consistently demonstrated significant decreases in the WOMAC pain scores and VAS scores at all follow-ups compared to the control group(P<0.05).Furthermore,the WOMAC stiffness score,WOMAC function score,and Lequesne index score differed significantly between the groups at 12 and 24 mo(P<0.05).However,no signicant between-group differences were observed in the WORMS at 24 mo(P=0.367).No serious adverse events occurred in both groups.CONCLUSION The MFAT injection combined with arthroscopic surgery treatment group showed better mid-term clinical outcomes compared to the control group,suggesting its efficacy as a therapeutic approach for patients with KOA.展开更多
Obesity is associated with several diseases,including mental health.Adipose tissue is distributed around the internal organs,acting in the regulation of metabolism by storing and releasing fatty acids and adipokine in...Obesity is associated with several diseases,including mental health.Adipose tissue is distributed around the internal organs,acting in the regulation of metabolism by storing and releasing fatty acids and adipokine in the tissues.Excessive nutritional intake results in hypertrophy and proliferation of adipocytes,leading to local hypoxia in adipose tissue and changes in these adipokine releases.This leads to the recruitment of immune cells to adipose tissue and the release of pro-inflammatory cytokines.The presence of high levels of free fatty acids and inflammatory molecules interfere with intracellular insulin signaling,which can generate a neuroinflammatory process.In this review,we provide an up-to-date discussion of how excessive obesity can lead to possible cognitive dysfunction.We also address the idea that obesity-associated systemic inflammation leads to neuroinflammation in the brain,particularly the hypothalamus and hippocampus,and that this is partially responsible for these negative cognitive outcomes.In addition,we discuss some clinical models and animal studies for obesity and clarify the mechanism of action of anti-obesity drugs in the central nervous system.展开更多
Background High-grain(HG)diets affect lipid metabolism in the liver and mammary tissue of dairy cows,but its effects on muscle and adipose tissue have not been wide evaluated.Thus,the aim of this study is to clarify t...Background High-grain(HG)diets affect lipid metabolism in the liver and mammary tissue of dairy cows,but its effects on muscle and adipose tissue have not been wide evaluated.Thus,the aim of this study is to clarify this issue.Methods Twelve Holstein cows were randomly divided into two groups:conventional diet group(CON,n=6)and the HG diet group(n=6).On day 7 of week 4,rumen fluid was sampled to measure pH,milk was sampled to meas-ure components,and blood was sampled to measure biochemical parameters and fatty acid composition.After the experiment,cows were slaughtered to collect muscle and adipose tissue for fatty acid composition and transcriptome analysis.Results HG feeding decreased the ruminal pH,milk’s fat content and long-chain fatty acid proportion(P<0.05)and increased the proportion of short-and medium-chain fatty acids in the milk(P<0.05)as compared with CON diets.The concentrations of blood cholesterol,low-density lipoprotein,and polyunsaturated fatty acids in the HG cows were lower than those in CON cows(P<0.05).In muscle tissue,HG feeding tended to increase the triacylglycerol(TG)concentration(P<0.10).Transcriptome analysis revealed changes in the biosynthesis of the unsaturated fatty acids pathway,the regulation of lipolysis in the adipocytes pathway,and the PPAR signalling pathway.In adipose tissue,HG feeding increased the concentration of TG and decreased the concentration of C18:1 cis9(P<0.05).At the transcrip-tome level,the fatty acid biosynthesis pathway,linoleic acid metabolism pathway,and PPAR signalling pathway were activated.Conclusion HG feeding leads to subacute rumen acidosis and a decreased milk fat content.The fatty acid profiles in the milk and plasma of dairy cows were changed by HG feeding.In muscle and adipose tissue,HG feeding increased TG concentration and up-regulated the expression of genes related to adipogenesis,while down-regulated the expression of genes related to lipid transport.These results complement our knowledge of the fatty acid composi-tion of muscle and adipose tissue in dairy cows and expand our understanding of the mechanisms by which HG diets affect lipid metabolism in muscle and adipose tissue.展开更多
The world is experiencing reflections of the intersection of two pandemics:Obesity and coronavirus disease 2019.The prevalence of obesity has tripled since 1975 worldwide,representing substantial public health costs d...The world is experiencing reflections of the intersection of two pandemics:Obesity and coronavirus disease 2019.The prevalence of obesity has tripled since 1975 worldwide,representing substantial public health costs due to its comorbidities.The adipose tissue is the initial site of obesity impairments.During excessive energy intake,it undergoes hyperplasia and hypertrophy until overt inflammation and insulin resistance turn adipocytes into dysfunctional cells that send lipotoxic signals to other organs.The pancreas is one of the organs most affected by obesity.Once lipotoxicity becomes chronic,there is an increase in insulin secretion by pancreatic beta cells,a surrogate for type 2 diabetes mellitus(T2DM).These alterations threaten the survival of the pancreatic islets,which tend to become dysfunctional,reaching exhaustion in the long term.As for the liver,lipotoxicity favors lipogenesis and impairs beta-oxidation,resulting in hepatic steatosis.This silent disease affects around 30%of the worldwide population and can evolve into end-stage liver disease.Although therapy for hepatic steatosis remains to be defined,peroxisome proliferator-activated receptors(PPARs)activation copes with T2DM management.Peroxisome PPARs are transcription factors found at the intersection of several metabolic pathways,leading to insulin resistance relief,improved thermogenesis,and expressive hepatic steatosis mitigation by increasing mitochondrial beta-oxidation.This review aimed to update the potential of PPAR agonists as targets to treat metabolic diseases,focusing on adipose tissue plasticity and hepatic and pancreatic remodeling.展开更多
Heart failure with preserved ejection fraction(HFpEF)is a heterogeneous syndrome with various comorbidities,multiple cardiac and extracardiac pathophysiologic abnormalities,and diverse phenotypic presentations.Since H...Heart failure with preserved ejection fraction(HFpEF)is a heterogeneous syndrome with various comorbidities,multiple cardiac and extracardiac pathophysiologic abnormalities,and diverse phenotypic presentations.Since HFpEF is a heterogeneous disease with different phenotypes,individualized treatment is required.HFpEF with type 2 diabetes mellitus(T2DM)represents a specific phenotype of HFpEF,with about 45%-50% of HFpEF patients suffering from T2DM.Systemic inflammation associated with dysregulated glucose metabolism is a critical pathological mechanism of HFpEF with T2DM,which is intimately related to the expansion and dysfunction(inflammation and hypermetabolic activity)of epicardial adipose tissue(EAT).EAT is well established as a very active endocrine organ that can regulate the pathophysiological processes of HFpEF with T2DM through the paracrine and endocrine mechanisms.Therefore,suppressing abnormal EAT expansion may be a promising therapeutic strategy for HFpEF with T2DM.Although there is no treatment specifically for EAT,lifestyle management,bariatric surgery,and some pharmaceutical interventions(anti-cytokine drugs,statins,proprotein convertase subtilisin/kexin type 9 inhibitors,metformin,glucagon-like peptide-1 receptor agonists,and especially sodium-glucose cotransporter-2 inhibitors)have been shown to attenuate the inflammatory response or expansion of EAT.Importantly,these treatments may be beneficial in improving the clinical symptoms or prognosis of patients with HFpEF.Accordingly,well-designed randomized controlled trials are needed to validate the efficacy of current therapies.In addition,more novel and effective therapies targeting EAT are needed in the future.展开更多
Objective: To evaluate the efficacy based on clinical symptom and on magnetic resonance image of platelet-rich plasma therapy in combination with mesenchymal stem cells from autologous adipose tissue for knee osteoart...Objective: To evaluate the efficacy based on clinical symptom and on magnetic resonance image of platelet-rich plasma therapy in combination with mesenchymal stem cells from autologous adipose tissue for knee osteoarthritis treatment. Patients and Method: 30 patients including 26 females and 4 males;correspondingly, 60 knee joints were diagnosed with osteoarthritis with stages II - III of Kellgren and Lawrence, their mean age was 58.63 ± 11.11. All were injected with autologous platelet-rich plasma that was extracted by PRP set, APC 30 PRP PRCEDURE PRAK and autologously extracted mesenchymal stem cells from abdominal adipose tissue using the ADI-25-01 ADIPOSEPRCEDURE PRAK of USA. Results: After 12 months: the pain level according to VAS score at the right knee joint was decreased from 6.0 ± 1.28 before treatment to 1.9 ± 0.3;VAS score at the left knee joint was decreased from 6.43 ± 1.19 to 2.25 ± 0.43. Total Lequene score at right knee joint was decreased from 16.04 ± 1.57 before treatment to 4.31 ± 1.04, at left knee joint was decreased from 17.52 ± 1.74 before treatment to 5.15 ± 1.48. Total WOMAC score at right knee joint was decreased from 55.93 ± 5.56 to 10.37 ± 1.56;at left knee joint was decreased from 53.97 ± 5.57 to 10.07 ± 1.59. There were 86.77% joints with cartilage thickness change and the patellar cartilage thickness was increased from 1.56 ± 0.09 mm before treatment to 1.65 ± 0.09 mm. Conclusion: The treatment of knee osteoarthritis by platelet-rich plasma therapyin combination with mesenchymal stem cells from autologous adipose tissue is effective in reducing pain, improving patient's mobility and walking function, reforming articular cartilage thickness on magnetic resonance image.展开更多
Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering(TE)and regenerative medicine.In contrast to conventional biomaterials or synthetic materials,biomimetic scaffolds bas...Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering(TE)and regenerative medicine.In contrast to conventional biomaterials or synthetic materials,biomimetic scaffolds based on natural biomaterial can offer cells a broad spectrum of biochemical and biophysical cues that mimic the in vivo extracellular matrix(ECM).Additionally,such materials have mechanical adaptability,micro-structure interconnectivity,and inherent bioactivity,making them ideal for the design of living implants for specific applications in TE and regenerative medicine.This paper provides an overview for recent progress of biomimetic natural biomaterials(BNBMs),including advances in their preparation,functionality,potential applications and future challenges.We highlight recent advances in the fabrication of BNBMs and outline general strategies for functionalizing and tailoring the BNBMs with various biological and physicochemical characteristics of native ECM.Moreover,we offer an overview of recent key advances in the functionalization and applications of versatile BNBMs for TE applications.Finally,we conclude by offering our perspective on open challenges and future developments in this rapidly-evolving field.展开更多
Knee osteoarthritis is a degenerative condition with a significant disease burden and no disease-modifying therapy.Definitive treatment ultimately requires joint replacement.Therapies capable of regenerating cartilage...Knee osteoarthritis is a degenerative condition with a significant disease burden and no disease-modifying therapy.Definitive treatment ultimately requires joint replacement.Therapies capable of regenerating cartilage could significantly reduce financial and clinical costs.The regenerative potential of mesenchymal stromal cells(MSCs)has been extensively studied in the context of knee osteoarthritis.This has yielded promising results in human studies,and is likely a product of immunomodulatory and chondroprotective biomolecules produced by MSCs in response to inflammation.Adipose-derived MSCs(ASCs)are becoming increasingly popular owing to their relative ease of isolation and high proliferative capacity.Stromal vascular fraction(SVF)and micro-fragmented adipose tissue(MFAT)are produced by the enzymatic and mechanical disruption of adipose tissue,respectively.This avoids expansion of isolated ASCs ex vivo and their composition of heterogeneous cell populations,including immune cells,may potentiate the reparative function of ASCs.In this editorial,we comment on a multicenter randomized trial regarding the efficacy of MFAT in treating knee osteoarthritis.We discuss the study’s findings in the context of emerging evidence regarding adipose-derived regenerative therapies.An underlying mechanism of action of ASCs is proposed while drawing important distinctions between the properties of isolated ASCs,SVF,and MFAT.展开更多
Adequate vascularization is a critical determinant for the successful construction and clinical implementation of complex organotypic tissue models. Currently, low cell and vessel density and insufficient vascular mat...Adequate vascularization is a critical determinant for the successful construction and clinical implementation of complex organotypic tissue models. Currently, low cell and vessel density and insufficient vascular maturation make vascularized organotypic tissue construction difficult,greatly limiting its use in tissue engineering and regenerative medicine. To address these limitations, recent studies have adopted pre-vascularized microtissue assembly for the rapid generation of functional tissue analogs with dense vascular networks and high cell density. In this article, we summarize the development of module assembly-based vascularized organotypic tissue construction and its application in tissue repair and regeneration, organ-scale tissue biomanufacturing, as well as advanced tissue modeling.展开更多
The repair of bone tissue damage is a complex process that is well-orchestrated in time and space,a focus and difficulty in orthopedic treatment.In recent years,the success of mesenchymal stem cells(MSCs)-mediated bon...The repair of bone tissue damage is a complex process that is well-orchestrated in time and space,a focus and difficulty in orthopedic treatment.In recent years,the success of mesenchymal stem cells(MSCs)-mediated bone repair in clinical trials of large-area bone defects and bone necrosis has made it a candidate in bone tissue repair engineering and regenerative medicine.MSCs are closely related to macrophages.On one hand,MSCs regulate the immune regulatory function by influencing macrophages proliferation,infiltration,and phenotype polarization,while also affecting the osteoclasts differentiation of macrophages.On the other hand,macrophages activate MSCs and mediate the multilineage differentiation of MSCs by regulating the immune microenvironment.The cross-talk between MSCs and macrophages plays a crucial role in regulating the immune system and in promoting tissue regeneration.Making full use of the relationship between MSCs and macrophages will enhance the efficacy of MSCs therapy in bone tissue repair,and will also provide a reference for further application of MSCs in other diseases.展开更多
In this paper, the main goal is to prepare silk fibroin nano-fiber, which is used for regenerated tissue applications. Silk scaffold nano-fibers made by electro-spinning technology can be used in regenerated tissue ap...In this paper, the main goal is to prepare silk fibroin nano-fiber, which is used for regenerated tissue applications. Silk scaffold nano-fibers made by electro-spinning technology can be used in regenerated tissue applications. The purpose of the research is to prepare a silk-fibroin nano-fiber solution for potential applications in tissue engineering. Using a degumming process, pure silk fibroin protein is extracted from silk cocoons. The protein solution for fibroin is purified, and the protein content is determined. The precise chemical composition, exact temperature, time, voltage, distance, ratio, and humidity all have a huge impact on degumming, solubility, and electro-spinning nano-fibers. The SEM investigates the morphology of silk fibroin nano-fibres at different magnifications. It also reveals the surface condition, fiber orientation, and fiber thickness of the silk fibroin nano-fiber. The results show that regenerated silk fibroin and nano-fiber can be used in silk fibroin scaffolds for various tissue engineering applications.展开更多
This review comprehensively explores the versatile potential of mesenchymal stem cells(MSCs)with a specific focus on adipose-derived MSCs.Ophthalmic and oculoplastic surgery,encompassing diverse procedures for ocular ...This review comprehensively explores the versatile potential of mesenchymal stem cells(MSCs)with a specific focus on adipose-derived MSCs.Ophthalmic and oculoplastic surgery,encompassing diverse procedures for ocular and periocular enhancement,demands advanced solutions for tissue restoration,functional and aesthetic refinement,and aging.Investigating immunomodulatory,regenerative,and healing capacities of MSCs,this review underscores the potential use of adipose-derived MSCs as a cost-effective alternative from bench to bedside,addressing common unmet needs in the field of reconstructive and regenerative surgery.展开更多
This review explores tissue engineering as a potential solution for reproductive health issues in women caused by genetic or acquired diseases,such as premature ovarian failure or oophorectomy.The loss of ovarian func...This review explores tissue engineering as a potential solution for reproductive health issues in women caused by genetic or acquired diseases,such as premature ovarian failure or oophorectomy.The loss of ovarian function can lead to infertility,osteoporosis,and cardiovascular disease.Hormone replacement therapy is a common treatment,but it has limitations and risks.The review focuses on two main approaches in tissue engineering:scaffold-based(3D printing,electrospinning,decellularization)and scaffold-free(stem cell transplantation,organoid cultivation).Both approaches show promise in preclinical studies for creating functional ovarian tissue.Challenges include vascularization,innervation,long-term function,and safety.Despite these challenges,tissue engineering offers a potential avenue for restoring fertility and hormone balance in women with ovarian dysfunction.展开更多
基金This work was financially supported by The National Key Research and Development Program of China(No.2022YFD1300202)The National Natural Science Foundation of China(No.32372834)+2 种基金Chongqing Modern Agricultural Industry Technology System(CQMAITS202313)the Collection,Utilization and Innovation of Germplasm Resources by Research Institutes and Enterprises of Chongqing,China(cqnyncw-kqlhtxm)the Chongqing Postgraduate Research Innovation Project(CYB22141).
文摘Background Brown adipose tissue(BAT)is known to be capable of non-shivering thermogenesis under cold stimulation,which is related to the mortality of animals.In the previous study,we observed that goat BAT is mainly located around the kidney at birth,and changes to white adipose tissue(WAT)in the perirenal adipose tissue of goats within one month after birth.However,the regulatory factors underlying this change is remain unclear.In this study,we systematically studied the perirenal adipose tissue of goat kids in histological,cytological,and accompanying molecular level changes from 0 to 28 d after birth.Results Our study found a higher mortality rate in winter-born goat kids,with goat birthing data statistics.Then we used thermal imaging revealing high temperature in goat hips at postnatal 0 d and gradually decrease during 28 d.This is consistent with the region of perirenal BAT deposition and highlights its critical role in energy expenditure and body temperature regulation in goat kids.Additionally,we found a series of changes of BAT during the first 28 d after birth,such as whitening,larger lipid droplets,decreased mitochondrial numbers,and down-regulation of key thermogenesis-related genes(UCP1,DIO2,UCP2,CIDEA,PPARGC1a,C/EBPb,and C/EBPa).Then,we used RNA-seq found specific marker genes for goat adipose tissue and identified 12 new marker genes for BAT and 10 new marker genes for WAT of goats.Furthermore,12 candidate genes were found to potentially regulate goat BAT thermogenesis.The mechanism of the change of this biological phenomenon does not involve a large-scale death of brown adipocytes and subsequent proliferation of white adipocytes.While apoptosis may play a limited role,it is largely not critical in this transition process.Conclusions We concluded that perirenal BAT plays a crucial role in thermoregulation in newborn goat kids,with notable species differences in the expression of adipose tissue marker genes,and we highlighted some potential marker genes for goat BAT and WAT.Additionally,the change from BAT to WAT does not involve a large-scale death of brown adipocytes and subsequent proliferation of white adipocytes.
基金This study was supported by a grant from Beijing Natural Science Foundation(7234399).
文摘Background:Visceral adipose tissue(VAT)has been linked to the severe acute pancreatitis(SAP)prognosis,although the underlying mechanism remains unclear.It has been reported that pyroptosis worsens SAP.The present study aimed to verify whether mesenteric adipose tissue(MAT,a component of VAT)can cause secondary intestinal injury through the pyroptotic pathway.Methods:Thirty-six male Sprague Dawley(SD)rats were divided into six different groups.Twelve rats were randomly divided into the SAP and control groups.We monitored the changes of MAT and B lymphocytes infiltration in MAT of SAP rats.Twelve SAP rats were injected with MAT B lymphocytes or phosphate buffer solution(PBS).The remaining twelve SAP rats were first injected with MAT B lymphocytes,and then with MCC950(NLRP3 inhibitor)or PBS.We collected blood and tissue samples from pancreas,gut and MAT for analysis.Results:Compared to the control rats,the SAP group showed inflammation in MAT,including higher expression of tumor necrosis factor(TNF-α)and interleukin-6(IL-6),lower expression of IL-10,and histological changes.Flow cytometry analysis revealed B lymphocytes infiltration in MAT but not T lymphocytes and macrophages.The SAP rats also exhibited intestinal injury,characterized by lower expression of zonula occludens-1(ZO-1)and occludin,higher levels of lipopolysaccharide and diamine oxidase,and pathological changes.The expression of NLRP3 and n-GSDMD,which are responsible for pyroptosis,was increased in the intestine of SAP rats.The injection of MAT B lymphocytes into SAP rats exacerbated the inflammation in MAT.The upregulation of pyroptosis reduced tight junction in the intestine,which contributed to the SAP progression,including higher inflammatory indicators and worse histological changes.The administration of MCC950 to SAP+MAT B rats downregulated pyroptosis,which subsequently improved the intestinal barrier and ameliorated inflammatory response of SAP.Conclusions:In SAP,MAT B lymphocytes aggravated local inflammation,and promoted the injury to the intestine through the enteric pyroptotic pathway.
基金Supported by National Natural Science Foundation of China(General Program),No.82070852 and No.82270901.
文摘BACKGROUND The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass(DJB)surgery is not clear.AIM To study the morphological and functional changes in adipose tissue after DJB and explore the potential mechanisms contributing to postoperative insulin sensitivity improvement of adipose tissue in a diabetic male rat model.METHODS DJB and sham surgery was performed in a-high-fat-diet/streptozotocin-induced diabetic rat model.All adipose tissue was weighed and observed under microscope.Use inguinal fat to represent subcutaneous adipose tissue(SAT)and mesangial fat to represent visceral adipose tissue.RNA-sequencing was utilized to evaluate gene expression alterations adipocytes.The hematoxylin and eosin staining,reverse transcription-quantitative polymerase chain reaction,western blot,and enzyme-linked immunosorbent assay were used to study the changes.Insulin resistance was evaluated by immunofluorescence.RESULTS After DJB,whole body blood glucose metabolism and insulin sensitivity in adipose tissue improved.Fat cell volume in both visceral adipose tissue(VAT)and SAT increased.Compared to SAT,VAT showed more significantly functional alterations after DJB and KEGG analysis indicated growth hormone(GH)pathway and downstream adiponectin secretion were involved in metabolic regulation.The circulating GH and adiponectin levels and GH receptor and adiponectin levels in VAT increased.Cytological experiment showed that GH stimulated adiponectin secretion and improve insulin sensitivity.CONCLUSION GH improves insulin resistance in VAT in male diabetic rats after receiving DJB,possibly by increasing adiponectin secretion.
基金Supported by American College of Gastroenterology,Clinical Research Award 2022,No.ACG-CR-040-2022National Institute of Diabetes and Digestive and Kidney Diseases,U01,No.2299170Helmsley Charitable Trust,No.2352240。
文摘BACKGROUND Evidence suggests inflammatory mesenteric fat is involved in post-operative recurrence(POR)of Crohn’s disease(CD).However,its prognostic value is INTRODUCTION Crohn’s disease(CD)is a debilitating chronic immune-mediated inflammatory disease(IMID)of the gastrointestinal tract that is increasing in incidence and prevalence globally[1].CD patients often undergo surgery for disease-related complic-ations and/or medically refractory disease.Unfortunately,surgery is not curative,and many patients develop post-operative recurrence(POR)of CD with a significant proportion eventually requiring additional surgeries.With advances in early detection and therapeutics,the contemporary 10-year risk of surgery has improved from 50%to 26%,but the risk of recurrent surgery has remained unchanged at 30%,suggesting a need to improve post-operative management strategies[2].Presently,there are two accepted strategies to mitigate POR,but each have potential limitations.Firstly,patients start early post-operative pharmacologic prophylaxis within 4-6 wk after surgery.This strategy can potentially overtreat a subset of patient who may not develop long-term disease recurrence off therapy.Consequently,these patients are at risk of medication-related adverse events and the direct and indirect costs associated with therapy with little or no benefit[3].The second strategy is performing early colonoscopy within 6-12 months after surgery and escalating therapy based on FOOTNOTES Author contributions:Gu P is the guarantor of the article and was involved in concept and design,data collection,statistical analysis,drafting of manuscript,and final approval of manuscript;Dube S and Choi SY were involved in statistical analysis,drafting of the manuscript,and final approval of manuscript;Gellada N,Win S,Lee YJ and Yang S were involved in the data collection,drafting of the manuscript,and final approval of manuscript;Haritunians T and Li D were involved in data analysis and interpretation,drafting of manuscript and final approval of manuscript;Melmed GY,Yarur AJ,Fleshner P,Kallman C and Devkota S were involved in study concept and design,data interpretation,drafting of manuscript and final approval of manuscript;Vasiliauskas EA,Bonthala N,Syal G,Ziring D and Targan SR were involved in data interpretation,drafting of manuscript and final approval of manuscript;Rabizadeh S was involved in study concept and design,drafting of manuscript and final approval of manuscript;McGovern DPB was involved in concept and design,statistical analysis,drafting of manuscript and final approval of manuscript.
基金National Natural Science Foundation of China,No.81873887National Natural Science Foundation of China Youth Project,No.82101981Shanghai Jiao Tong University School of Medicine Double Hundred Outstanding Person Project,No.20191904。
文摘BACKGROUND Obesity has become a serious public health issue,significantly elevating the risk of various complications.It is a well-established contributor to Heart failure with preserved ejection fraction(HFpEF).Evaluating HFpEF in obesity is crucial.Epicardial adipose tissue(EAT)has emerged as a valuable tool for validating prognostic biomarkers and guiding treatment targets.Hence,assessing EAT is of paramount importance.Cardiovascular magnetic resonance(CMR)imaging is acknowledged as the gold standard for analyzing cardiac function and mor-phology.We hope to use CMR to assess EAT as a bioimaging marker to evaluate HFpEF in obese patients.AIM To assess the diagnostic utility of CMR for evaluating heart failure with preserved ejection fraction[HFpEF;left ventricular(LV)ejection fraction≥50%]by measuring the epicardial adipose tissue(EAT)volumes and EAT mass in obese patients.METHODS Sixty-two obese patients were divided into two groups for a case-control study based on whether or not they had heart failure with HFpEF.The two groups were defined as HFpEF+and HFpEF-.LV geometry,global systolic function,EAT volumes and EAT mass of all subjects were obtained using cine magnetic resonance sequences.RESULTS Forty-five patients of HFpEF-group and seventeen patients of HFpEF+group were included.LV mass index(g/m2)of HFpEF+group was higher than HFpEF-group(P<0.05).In HFpEF+group,EAT volumes,EAT volume index,EAT mass,EAT mass index and the ratio of EAT/[left atrial(LA)left-right(LR)diameter]were higher compared to HFpEF-group(P<0.05).In multivariate analysis,Higher EAT/LA LR diameter ratio was associated with higher odds ratio of HFpEF.CONCLUSION EAT/LA LR diameter ratio is highly associated with HFpEF in obese patients.It is plausible that there may be utility in CMR for assessing obese patients for HFpEF using EAT/LA LR diameter ratio as a diagnostic biomarker.Further prospective studies,are needed to validate these proof-of-concept findings.
基金supported by the Fundamental Research Funds for the Central Universities(2042021kf0102,2042021kf0083)supported by two National Natural Science Foundation of China(NSFC)Grants(81903166,82203629)+1 种基金a Natural Science Foundation of Hubei(2018CKB916)sponsored by Shanghai Pujiang Program(22PJD054).
文摘Obesity is one of the most serious global health problems,with an incidence that increases yearly and coincides with the development of cancer.Adipose tissue macrophages(ATMs)are particularly important in this context and contribute to linking obesity-related inflammation and tumor progression.However,the functions of ATMs on the progression of obesity-associated cancer remain unclear.In this review,we describe the origins,phenotypes,and functions of ATMs.Subsequently,we summarize the potential mechanisms on the reprogramming of ATMs in the obesity-associated microenvironment,including the direct exchange of dysfunctional metabolites,inordinate cytokines and other signaling mediators,transfer of extracellular vesicle cargo,and variations in the gut microbiota and its metabolites.A better understanding of the properties and functions of ATMs under conditions of obesity will lead to the development of new therapeutic interventions for obesity-related cancer.
文摘The relationship between metabolic derangements and fatty liver development are undeniable,since more than 75% of patients with type 2 diabetes mellitus present with fatty liver.There is also significant epidemiological association between insulin resistance(IR)and metabolic(dysfunction)-associated fatty liver disease(MAFLD).For little more than 2 years,the nomenclature of fatty liver of non-alcoholic origin has been intended to change to MAFLD by multiple groups.While a myriad of reasons for which MAFLD is thought to be of metabolic origin could be exposed,the bottom line relies on the role of IR as an initiator and perpetuator of this disease.There is a reciprocal role in MAFLD development and IR as well as serum glucose concentrations,where increased circulating glucose and insulin result in increased de novo lipogenesis by sterol regulatory elementbinding protein-1c induced lipogenic enzyme stimulation;therefore,increased endogenous production of triglycerides.The same effect is achieved through impaired suppression of adipose tissue(AT)lipolysis in insulin-resistant states,increasing fatty acid influx into the liver.The complementary reciprocal situation occurs when liver steatosis alters hepatokine secretion,modifying fatty acid metabolism as well as IR in a variety of tissues,including skeletal muscle,AT,and the liver.The aim of this review is to discuss the importance of IR and AT interactions in metabolic altered states as perhaps the most important factor in MAFLD pathogenesis.
基金the National Natural Science Foundation of China,No.82274547the Major Program of the National Natural Science Foundation of Zhejiang Province,No.LD22C060002+1 种基金the State Administration of Traditional Chinese Medicine of Zhejiang Province,No.GZY-ZJ-KJ-23064the Zhejiang Provincial Research Foundation for Basic Public Welfare Research,No.LGF20H270005.
文摘BACKGROUND Osteoarthritis(OA)is the most prevalent form of degenerative whole-joint disease.Before the final option of knee replacement,arthroscopic surgery was the most widely used joint-preserving surgical treatment.Emerging regenerative therapies,such as those involving platelet-rich plasma,mesenchymal stem cells,and microfragmented adipose tissue(MFAT),have been pushed to the forefront of treatment to prevent the progression of OA.Currently,MFAT has been successfully applied to treat different types of orthopedic diseases.AIM To assess the efficacy and safety of MFAT with arthroscopic surgery in patients with knee OA(KOA).METHODS A randomized,multicenter study was conducted between June 2017 and November 2022 in 10 hospitals in Zhejiang,China.Overall,302 patients diagnosed with KOA(Kellgren-Lawrence grades 2-3)were randomized to the MFAT group(n=151,were administered MFAT following arthroscopic surgery),or the control group(n=151,were administered hyaluronic acid following arthroscopic surgery).The study outcomes were changes in the Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)score,the visual analog scale(VAS)score,the Lequesne index score,the Whole-Organ Magnetic Resonance Imaging Score(WORMS),and safety over a 24-mo period from baseline.RESULTS The changes in the WOMAC score(including the three subscale scores),VAS pain score,and Lequesne index score at the 24-mo mark were significantly different in the MFAT and control groups,as well as when comparing values at the posttreatment visit and those at baseline(P<0.001).The MFAT group consistently demonstrated significant decreases in the WOMAC pain scores and VAS scores at all follow-ups compared to the control group(P<0.05).Furthermore,the WOMAC stiffness score,WOMAC function score,and Lequesne index score differed significantly between the groups at 12 and 24 mo(P<0.05).However,no signicant between-group differences were observed in the WORMS at 24 mo(P=0.367).No serious adverse events occurred in both groups.CONCLUSION The MFAT injection combined with arthroscopic surgery treatment group showed better mid-term clinical outcomes compared to the control group,suggesting its efficacy as a therapeutic approach for patients with KOA.
基金supported by the Brazilian funding agencies CNPq,and FUNDECT (to LM)
文摘Obesity is associated with several diseases,including mental health.Adipose tissue is distributed around the internal organs,acting in the regulation of metabolism by storing and releasing fatty acids and adipokine in the tissues.Excessive nutritional intake results in hypertrophy and proliferation of adipocytes,leading to local hypoxia in adipose tissue and changes in these adipokine releases.This leads to the recruitment of immune cells to adipose tissue and the release of pro-inflammatory cytokines.The presence of high levels of free fatty acids and inflammatory molecules interfere with intracellular insulin signaling,which can generate a neuroinflammatory process.In this review,we provide an up-to-date discussion of how excessive obesity can lead to possible cognitive dysfunction.We also address the idea that obesity-associated systemic inflammation leads to neuroinflammation in the brain,particularly the hypothalamus and hippocampus,and that this is partially responsible for these negative cognitive outcomes.In addition,we discuss some clinical models and animal studies for obesity and clarify the mechanism of action of anti-obesity drugs in the central nervous system.
基金funded by the National Key R&D Program of China(2022YFD1301001)the Natural Science Foundation of China(32072755).
文摘Background High-grain(HG)diets affect lipid metabolism in the liver and mammary tissue of dairy cows,but its effects on muscle and adipose tissue have not been wide evaluated.Thus,the aim of this study is to clarify this issue.Methods Twelve Holstein cows were randomly divided into two groups:conventional diet group(CON,n=6)and the HG diet group(n=6).On day 7 of week 4,rumen fluid was sampled to measure pH,milk was sampled to meas-ure components,and blood was sampled to measure biochemical parameters and fatty acid composition.After the experiment,cows were slaughtered to collect muscle and adipose tissue for fatty acid composition and transcriptome analysis.Results HG feeding decreased the ruminal pH,milk’s fat content and long-chain fatty acid proportion(P<0.05)and increased the proportion of short-and medium-chain fatty acids in the milk(P<0.05)as compared with CON diets.The concentrations of blood cholesterol,low-density lipoprotein,and polyunsaturated fatty acids in the HG cows were lower than those in CON cows(P<0.05).In muscle tissue,HG feeding tended to increase the triacylglycerol(TG)concentration(P<0.10).Transcriptome analysis revealed changes in the biosynthesis of the unsaturated fatty acids pathway,the regulation of lipolysis in the adipocytes pathway,and the PPAR signalling pathway.In adipose tissue,HG feeding increased the concentration of TG and decreased the concentration of C18:1 cis9(P<0.05).At the transcrip-tome level,the fatty acid biosynthesis pathway,linoleic acid metabolism pathway,and PPAR signalling pathway were activated.Conclusion HG feeding leads to subacute rumen acidosis and a decreased milk fat content.The fatty acid profiles in the milk and plasma of dairy cows were changed by HG feeding.In muscle and adipose tissue,HG feeding increased TG concentration and up-regulated the expression of genes related to adipogenesis,while down-regulated the expression of genes related to lipid transport.These results complement our knowledge of the fatty acid composi-tion of muscle and adipose tissue in dairy cows and expand our understanding of the mechanisms by which HG diets affect lipid metabolism in muscle and adipose tissue.
基金the Conselho Nacional de Desenvolvimento Científico e Tecnológico(Brazil),No.303785/2020-9Fundação Carlos Chagas Filho de AmparoàPesquisa do Estado do Rio de Janeiro,No.E-26/200.984/2022 for V.S-M.
文摘The world is experiencing reflections of the intersection of two pandemics:Obesity and coronavirus disease 2019.The prevalence of obesity has tripled since 1975 worldwide,representing substantial public health costs due to its comorbidities.The adipose tissue is the initial site of obesity impairments.During excessive energy intake,it undergoes hyperplasia and hypertrophy until overt inflammation and insulin resistance turn adipocytes into dysfunctional cells that send lipotoxic signals to other organs.The pancreas is one of the organs most affected by obesity.Once lipotoxicity becomes chronic,there is an increase in insulin secretion by pancreatic beta cells,a surrogate for type 2 diabetes mellitus(T2DM).These alterations threaten the survival of the pancreatic islets,which tend to become dysfunctional,reaching exhaustion in the long term.As for the liver,lipotoxicity favors lipogenesis and impairs beta-oxidation,resulting in hepatic steatosis.This silent disease affects around 30%of the worldwide population and can evolve into end-stage liver disease.Although therapy for hepatic steatosis remains to be defined,peroxisome proliferator-activated receptors(PPARs)activation copes with T2DM management.Peroxisome PPARs are transcription factors found at the intersection of several metabolic pathways,leading to insulin resistance relief,improved thermogenesis,and expressive hepatic steatosis mitigation by increasing mitochondrial beta-oxidation.This review aimed to update the potential of PPAR agonists as targets to treat metabolic diseases,focusing on adipose tissue plasticity and hepatic and pancreatic remodeling.
文摘Heart failure with preserved ejection fraction(HFpEF)is a heterogeneous syndrome with various comorbidities,multiple cardiac and extracardiac pathophysiologic abnormalities,and diverse phenotypic presentations.Since HFpEF is a heterogeneous disease with different phenotypes,individualized treatment is required.HFpEF with type 2 diabetes mellitus(T2DM)represents a specific phenotype of HFpEF,with about 45%-50% of HFpEF patients suffering from T2DM.Systemic inflammation associated with dysregulated glucose metabolism is a critical pathological mechanism of HFpEF with T2DM,which is intimately related to the expansion and dysfunction(inflammation and hypermetabolic activity)of epicardial adipose tissue(EAT).EAT is well established as a very active endocrine organ that can regulate the pathophysiological processes of HFpEF with T2DM through the paracrine and endocrine mechanisms.Therefore,suppressing abnormal EAT expansion may be a promising therapeutic strategy for HFpEF with T2DM.Although there is no treatment specifically for EAT,lifestyle management,bariatric surgery,and some pharmaceutical interventions(anti-cytokine drugs,statins,proprotein convertase subtilisin/kexin type 9 inhibitors,metformin,glucagon-like peptide-1 receptor agonists,and especially sodium-glucose cotransporter-2 inhibitors)have been shown to attenuate the inflammatory response or expansion of EAT.Importantly,these treatments may be beneficial in improving the clinical symptoms or prognosis of patients with HFpEF.Accordingly,well-designed randomized controlled trials are needed to validate the efficacy of current therapies.In addition,more novel and effective therapies targeting EAT are needed in the future.
文摘Objective: To evaluate the efficacy based on clinical symptom and on magnetic resonance image of platelet-rich plasma therapy in combination with mesenchymal stem cells from autologous adipose tissue for knee osteoarthritis treatment. Patients and Method: 30 patients including 26 females and 4 males;correspondingly, 60 knee joints were diagnosed with osteoarthritis with stages II - III of Kellgren and Lawrence, their mean age was 58.63 ± 11.11. All were injected with autologous platelet-rich plasma that was extracted by PRP set, APC 30 PRP PRCEDURE PRAK and autologously extracted mesenchymal stem cells from abdominal adipose tissue using the ADI-25-01 ADIPOSEPRCEDURE PRAK of USA. Results: After 12 months: the pain level according to VAS score at the right knee joint was decreased from 6.0 ± 1.28 before treatment to 1.9 ± 0.3;VAS score at the left knee joint was decreased from 6.43 ± 1.19 to 2.25 ± 0.43. Total Lequene score at right knee joint was decreased from 16.04 ± 1.57 before treatment to 4.31 ± 1.04, at left knee joint was decreased from 17.52 ± 1.74 before treatment to 5.15 ± 1.48. Total WOMAC score at right knee joint was decreased from 55.93 ± 5.56 to 10.37 ± 1.56;at left knee joint was decreased from 53.97 ± 5.57 to 10.07 ± 1.59. There were 86.77% joints with cartilage thickness change and the patellar cartilage thickness was increased from 1.56 ± 0.09 mm before treatment to 1.65 ± 0.09 mm. Conclusion: The treatment of knee osteoarthritis by platelet-rich plasma therapyin combination with mesenchymal stem cells from autologous adipose tissue is effective in reducing pain, improving patient's mobility and walking function, reforming articular cartilage thickness on magnetic resonance image.
基金supported by the National Natural Science Foundation of China(52003113,31900950,82102334,82002313,82072444)the National Key Research&Development Program of China(2018YFC2001502,2018YFB1105705)+6 种基金the Guangdong Basic and Applied Basic Research Foundation(2021A1515010745,2020A1515110356,2023A1515011986)the Shenzhen Fundamental Research Program(JCYJ20190808120405672)the Key Program of the National Natural Science Foundation of Zhejiang Province(LZ22C100001)the Natural Science Foundation of Shanghai(20ZR1469800)the Integration Innovation Fund of Shanghai Jiao Tong University(2021JCPT03),the Science and Technology Projects of Guangzhou City(202102020359)the Zigong Key Science and Technology Plan(2022ZCNKY07).SXC thanks the financial support under the Startup Grant of the University of Chinese Academy of Sciences(WIUCASQD2021026).HW thanks the Futian Healthcare Research Project(FTWS2022013)the financial support of China Postdoctoral Science Foundation(2021TQ0118).SL thanks the financial support of China Postdoctoral Science Foundation(2022M721490).
文摘Biomimetic materials have emerged as attractive and competitive alternatives for tissue engineering(TE)and regenerative medicine.In contrast to conventional biomaterials or synthetic materials,biomimetic scaffolds based on natural biomaterial can offer cells a broad spectrum of biochemical and biophysical cues that mimic the in vivo extracellular matrix(ECM).Additionally,such materials have mechanical adaptability,micro-structure interconnectivity,and inherent bioactivity,making them ideal for the design of living implants for specific applications in TE and regenerative medicine.This paper provides an overview for recent progress of biomimetic natural biomaterials(BNBMs),including advances in their preparation,functionality,potential applications and future challenges.We highlight recent advances in the fabrication of BNBMs and outline general strategies for functionalizing and tailoring the BNBMs with various biological and physicochemical characteristics of native ECM.Moreover,we offer an overview of recent key advances in the functionalization and applications of versatile BNBMs for TE applications.Finally,we conclude by offering our perspective on open challenges and future developments in this rapidly-evolving field.
文摘Knee osteoarthritis is a degenerative condition with a significant disease burden and no disease-modifying therapy.Definitive treatment ultimately requires joint replacement.Therapies capable of regenerating cartilage could significantly reduce financial and clinical costs.The regenerative potential of mesenchymal stromal cells(MSCs)has been extensively studied in the context of knee osteoarthritis.This has yielded promising results in human studies,and is likely a product of immunomodulatory and chondroprotective biomolecules produced by MSCs in response to inflammation.Adipose-derived MSCs(ASCs)are becoming increasingly popular owing to their relative ease of isolation and high proliferative capacity.Stromal vascular fraction(SVF)and micro-fragmented adipose tissue(MFAT)are produced by the enzymatic and mechanical disruption of adipose tissue,respectively.This avoids expansion of isolated ASCs ex vivo and their composition of heterogeneous cell populations,including immune cells,may potentiate the reparative function of ASCs.In this editorial,we comment on a multicenter randomized trial regarding the efficacy of MFAT in treating knee osteoarthritis.We discuss the study’s findings in the context of emerging evidence regarding adipose-derived regenerative therapies.An underlying mechanism of action of ASCs is proposed while drawing important distinctions between the properties of isolated ASCs,SVF,and MFAT.
文摘Adequate vascularization is a critical determinant for the successful construction and clinical implementation of complex organotypic tissue models. Currently, low cell and vessel density and insufficient vascular maturation make vascularized organotypic tissue construction difficult,greatly limiting its use in tissue engineering and regenerative medicine. To address these limitations, recent studies have adopted pre-vascularized microtissue assembly for the rapid generation of functional tissue analogs with dense vascular networks and high cell density. In this article, we summarize the development of module assembly-based vascularized organotypic tissue construction and its application in tissue repair and regeneration, organ-scale tissue biomanufacturing, as well as advanced tissue modeling.
基金Supported by the National Key Research and Development Program of China,No.2023YFC2508806Key Research and Development Project in Henan Province,No.231111310500+4 种基金Young Elite Scientists Sponsorship Program by CAST,No.2021-QNRC2-A06Scientific Research Project of Henan Zhongyuan Medical Science and Technology Innovation and Development Foundation,No.ZYYC2023ZDYouth Science Award Project of the Provincial-Level Joint Fund for Science and Technology Research and Development Project in Henan Province,No.225200810084Special Project on Training Top Talents in Traditional Chinese Medicine in Henan Province,No.2022ZYBJ242023 Hunan University of Chinese Medicine Postgraduate Innovation Project,No.2023CX64。
文摘The repair of bone tissue damage is a complex process that is well-orchestrated in time and space,a focus and difficulty in orthopedic treatment.In recent years,the success of mesenchymal stem cells(MSCs)-mediated bone repair in clinical trials of large-area bone defects and bone necrosis has made it a candidate in bone tissue repair engineering and regenerative medicine.MSCs are closely related to macrophages.On one hand,MSCs regulate the immune regulatory function by influencing macrophages proliferation,infiltration,and phenotype polarization,while also affecting the osteoclasts differentiation of macrophages.On the other hand,macrophages activate MSCs and mediate the multilineage differentiation of MSCs by regulating the immune microenvironment.The cross-talk between MSCs and macrophages plays a crucial role in regulating the immune system and in promoting tissue regeneration.Making full use of the relationship between MSCs and macrophages will enhance the efficacy of MSCs therapy in bone tissue repair,and will also provide a reference for further application of MSCs in other diseases.
文摘In this paper, the main goal is to prepare silk fibroin nano-fiber, which is used for regenerated tissue applications. Silk scaffold nano-fibers made by electro-spinning technology can be used in regenerated tissue applications. The purpose of the research is to prepare a silk-fibroin nano-fiber solution for potential applications in tissue engineering. Using a degumming process, pure silk fibroin protein is extracted from silk cocoons. The protein solution for fibroin is purified, and the protein content is determined. The precise chemical composition, exact temperature, time, voltage, distance, ratio, and humidity all have a huge impact on degumming, solubility, and electro-spinning nano-fibers. The SEM investigates the morphology of silk fibroin nano-fibres at different magnifications. It also reveals the surface condition, fiber orientation, and fiber thickness of the silk fibroin nano-fiber. The results show that regenerated silk fibroin and nano-fiber can be used in silk fibroin scaffolds for various tissue engineering applications.
文摘This review comprehensively explores the versatile potential of mesenchymal stem cells(MSCs)with a specific focus on adipose-derived MSCs.Ophthalmic and oculoplastic surgery,encompassing diverse procedures for ocular and periocular enhancement,demands advanced solutions for tissue restoration,functional and aesthetic refinement,and aging.Investigating immunomodulatory,regenerative,and healing capacities of MSCs,this review underscores the potential use of adipose-derived MSCs as a cost-effective alternative from bench to bedside,addressing common unmet needs in the field of reconstructive and regenerative surgery.
文摘This review explores tissue engineering as a potential solution for reproductive health issues in women caused by genetic or acquired diseases,such as premature ovarian failure or oophorectomy.The loss of ovarian function can lead to infertility,osteoporosis,and cardiovascular disease.Hormone replacement therapy is a common treatment,but it has limitations and risks.The review focuses on two main approaches in tissue engineering:scaffold-based(3D printing,electrospinning,decellularization)and scaffold-free(stem cell transplantation,organoid cultivation).Both approaches show promise in preclinical studies for creating functional ovarian tissue.Challenges include vascularization,innervation,long-term function,and safety.Despite these challenges,tissue engineering offers a potential avenue for restoring fertility and hormone balance in women with ovarian dysfunction.