Effect of Brassica rapa var. rapifera on Insulin Resistance and Inflammatory Analysis of Visceral Adipose Tissue of Obese Wistar Rats Under Glucolipotoxicity Condition / Efecto de Brassica rapa var. rapifera sobre la Resistencia a la Insulina y el Análisis Inflamatorio del Tejido Adiposo Visceral de Ratas Wistar Obesas en Condiciones de Glucolipotoxicidad

SUMMARY: Obesity-related pathophysiologies such as insulin resistance and the metabolic syndrome show a markedly increased risk for type 2 diabetes and atherosclerotic cardiovascular disease. This risk appears to be linked to alterations in adipose tissue function, leading to chronic inflammation and the dysregulation of adipocyte-derived factors. Brassica rapa have been used in traditional medicine for the treatment of several diseases, including diabetes. This study aimed to investigate the effect of nutritional stress induced by a high-fat and high-sucrose diet on the pathophysiology of visceral adipose tissue and the therapeutic effect of Brassica rapa in male Wistar rats. We subjected experimental rats to a high-fat (10 %) high-sucrose (20 %)/per day for 11 months and treated them for 20 days with aqueous extract Br (AEBr) at 200 mg/kg at the end of the experiment. At the time of sacrifice, we monitored plasma and tissue biochemical parameters as well as the morpho-histopathology of visceral adipose tissue. We found AEBr corrected metabolic parameters and inflammatory markers in homogenized visceral adipose tissue and reduced hypertrophy, hyperplasia, and lipid droplets. These results suggest that AEBr enhances anti-diabetic, anti-inflammatory and a protective effect on adipose tissue morphology in type 2 diabetes and obesity.

La fisiopatología relacionadas con la obesidad, como la resistencia a la insulina y el síndrome metabólico, muestran un riesgo notablemente mayor de diabetes tipo 2 y enfermedad cardiovascular aterosclerótica. Este riesgo parece estar relacionado con alteraciones en la función del tejido adiposo, lo que lleva a una inflamación crónica y a la desregulación de los factores derivados de los adipocitos. Brassica rapa se ha utilizado en la medicina tradicional para el tratamiento de varias enfermedades, incluida la diabetes. Este estudio tuvo como objetivo investigar el efecto del estrés nutricional inducido por una dieta rica en grasas y sacarosa sobre la fisiopatología del tejido adiposo visceral y el efecto terapéutico de Brassica rapa en ratas Wistar macho. Sometimos a ratas experimentales a una dieta rica en grasas (10 %) y alta en sacarosa (20 %)/por día durante 11 meses y las tratamos durante 20 días con extracto acuoso de Br (AEBr) a 200 mg/kg al final del experimento. En el momento del sacrificio, monitoreamos los parámetros bioquímicos plasmáticos y tisulares, así como la morfohistopatología del tejido adiposo visceral. Encontramos parámetros metabólicos corregidos por AEBr y marcadores inflamatorios en tejido adiposo visceral homogeneizado y reducción de hipertrofia, hiperplasia y gotitas de lípidos. Estos resultados sugieren que AEBr mejora el efecto antidiabético, antiinflamatorio y protector sobre la morfología del tejido adiposo en la diabetes tipo 2 y la obesidad.

Adiponectin restores the obesity-induced impaired immunomodulatory function of mesenchymal stromal cells via glycolytic reprogramming

Obesity has been known to negatively modulate the life-span and immunosuppressive potential of mesenchymal stromal cells (MSC). However, it remains unclear what drives the compromised potency of obese MSC. In this study, we examined the involvement of adiponectin, an adipose tissue-derived hormone, in obesity-induced impaired therapeutic function of MSC. Diet-induced obesity leads to a decrease in serum adiponectin, accompanied by impairment of survival and immunomodulatory effects of adipose-derived MSC (ADSC). Interestingly, priming with globular adiponectin (gAcrp) improved the immunomodulatory potential of obese ADSC. Similar effects were also observed in lean ADSC. In addition, gAcrp potentiated the therapeutic effectiveness of ADSC in a mouse model of DSS-induced colitis. Mechanistically, while obesity inhibited the glycolytic capacity of MSC, gAcrp treatment induced a metabolic shift toward glycolysis through activation of adiponectin receptor type 1/p38 MAPK/hypoxia inducible factor-1α axis. These findings suggest that activation of adiponectin signaling is a promising strategy for enhancing the therapeutic efficacy of MSC against immune-mediated disorders.

Research progress on dedifferentiated fat cells and their application in oral and maxillofacial bone tissue engineering / 口腔疾病防治

@#The identification of suitable seed cells represents a critical scientific problem to be solved in the field of oral and maxillofacial bone tissue regeneration. The application of adipose-derived stem cells (ASCs) in tissue and organ repair and regeneration has been studied extensively. In recent years, dedifferentiated fat (DFAT) cells have also shown broad application prospects in the field of bone tissue engineering. DFAT cells express stem cell-related markers and have the potential to differentiate into adipocytes, osteoblasts, chondrocytes, nerve cells, cardiomyocytes and endothelial cells. In addition, DFAT cells also have the advantages of minimally invasive acquisition, strong proliferation and high homogeneity. Currently, all studies involving the application of DFAT cells in scaffold-based and scaffold-free bone tissue engineering can confirm their effectiveness in promoting bone regeneration. However, cytological research still faces some challenges, including relatively low cell culture purity, unclear phenotypic characteristics and undefined dedifferentiation mechanisms. It is believed that with the continuous development and improvement of isolation, culture, identification and directional induction of osteogenic differentiation methods, DFAT cells are expected to become excellent seed cells in the field of oral and maxillofacial bone tissue engineering in the future.

Effect and Mechanism of Total Saponins from Panax Japonicus on White Adipose Tissue Browning/Brown Adipose Tissue Activation in High-fat Diet-induced Mice / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of total saponins from Panax japonicus （TSPJ） on white adipose tissue （WAT） browning/brown adipose tissue （BAT） activation in C57BL6/J male mice fed on a high-fat diet （HFD）. MethodThirty-two C57BL6/J male mice （8-week-old） were randomly divided into a normal group， a model group， a low-dose TSPJ group， and a high-dose TSPJ group. The mice in the low-dose and high-dose TSPJ groups were given TSPJ for four months by gavage at 25， 75 mg·kg-1·d-1， respectively， and those in the other groups were given 0.5% sodium carboxymethyl cellulose （CMC-Na） accordingly. After four months of feeding， all mice were placed at 4 ℃ for acute cold exposure， and the core body temperature was monitored. Subsequently， all mice were sacrificed， and BAT and inguinal WAT （iWAT） were separated rapidly to detect the corresponding indexes. Hematoxylin-eosin （HE） staining was used to observe the morphological changes in each group. The effect of TSPJ on the mRNA expression of uncoupling protein 1 （UCP1）， fatty acid-binding protein 4 （FABP4）， cytochrome C （CytC）， PR domain-containing protein 16 （PRDM16）， elongation of very long chain fatty acids protein 3 （ELOVL3）， peroxisome proliferator-activated receptor γ （PPARγ）， and peroxisome proliferator-activated receptor-γ coactivator-1α （PGC-1α） in iWAT and BAT was detected by Real-time polymerase chain reaction （Real-time PCR）. Western blot was also used to detect the protein expression of UCP1， PRDM16， PPARγ， and PGC-1α in BAT and iWAT of each group. The effect of TSPJ on UCP1 expression in BAT and iWAT was detected by immunohistochemistry. Result① Compared with the model group， TSPJ could decrease the body weight and proportions of iWAT and BAT in the HFD-induced mice （P<0.05， P<0.01）. ② The body temperature of mice in the model group decreased compared with that in the normal group in the acute cold exposure tolerance test （P<0.05）. The body temperature in the high-dose TSPJ group increased compared with that in the model group （P<0.01）. ③ Compared with the normal group， the model group showed increased adipocyte diameter in iWAT and BAT and decreased number of adipocytes per unit area. Compared with the model group， the TSPJ groups showed significantly reduced cell diameter and increased number of cells per unit area， especially in the high-dose TSPJ group. ④ Compared with the normal group， the model group showed decreased mRNA expression of FABP4， UCP1， CytC， PRDM16， ELOVL3， PGC-1α， and PPARγ in adipose tissues of mice （P<0.05， P<0.01）. Compared with the model group， after intervention with TSPJ， the mRNA expression was significantly up-regulated （P<0.05， P<0.01）. ⑤ Compared with the normal group， the model group showed decreased protein expression of UCP1， PRDM16， PPARγ， and PGC-1α in adipose tissues of mice （P<0.05， P<0.01）. Compared with the model group， after intervention with TSPJ， the protein expression increased significantly （P<0.05， P<0.01）. ConclusionTSPJ could induce the browning of iWAT/BAT activation and enhance adaptive thermogenesis in obese mice induced by HFD. The underlying mechanism may be attributed to the activation of the PPARγ/PGC-1α signaling pathway.

Injection of freshly collected adipose tissue for the treatment complex cryptoglandular anal fistula: case report

Introduction: Perianal fistula is a common colorectal disease which is caused mainly by cryptoglandular disease. Although most cases are treated successfully by surgery, management of complex perianal fistulas (CPAF) remains a challenge with limited results in recurrence and sometimes associated with fecal incontinence. The CPAF treatment with autologous adipose-derived mesenchymal stem cells (ASCs) had become a research hotspot. The technique started to be used in the treatment of Crohn's disease (CD) fistulas, where the studies showed safe and goods result from the procedure. Cultured ASCs have been used but this approach requires the preceding collection of adipose tissue, time for isolation of ASCs and subsequent in vitro expansion, need for laboratory facilities, and expertise in cell culturing. These factors have been getting over by using the commercially available alternative, allogenic ASCs. Treatment with allogeneic ASCs has shown good results in patients with CD fistulas, however with the disadvantage of being expensive. Objective: To show that the injection with freshly collected adipose tissue is an alternative to treatment with autologous or allogenic ASCs with several advantages. Methods: In this case report, we show our first experience in the treatment of CPAF with the application of collected adipose tissue in a tertiary referral hospital from Belo Horizonte, Brazil. Results The patient had a good postoperative recuperation with a complete fistula healing after 8 months without adverse effects. Conclusion: Injection with freshly collected adipose tissue is a promising and apparently safe sphincter-sparing technique in the treatment of CPAF. (AU)

The Relationship Between Carcinoembryonic Antigen and Epicardial Adipose Tissue

Abstract Background: Inflammation, which is associated with an unhealthy lifestyle, plays a critical role in the development of both cardiometabolic diseases (CMD) and cancer. Carcinoembryonic antigen (CEA) is a tumor marker which also has proinflammatory properties. Recent studies have reported CEA to be associated with atherosclerosis, metabolic syndrome, and visceral adiposity. Epicardial adipose tissue (EAT) can exhibit highly inflammatory and pathogenic properties, and is a known risk factor for CMD. However, its relationship with CEA is still unknown. Objectives: This study aimed to investigate the possible association of CEA with EAT. Methods: A total of 134 Caucasian (males = 56, females = 78) individuals, aged (22-83 years), who were admitted for routine health control, were enrolled in this cross-sectional study. CEA was measured with chemiluminescent microparticle immunoassay (CMIA). EAT was measured by transthoracic echocardiography, and the visceral fat rating (VFR) was assessed by a body composition analyzing machine. The p-value <0.05 was considered statistically significant. Results: CEA levels were categorized as tertiles: T1, 0.5-1.04; T2, 1.06-1.69; and T3, ≥1.7 ng/ml. The mean age, weight, VFR, EAT, and fasting glucose, as well as the median of systolic blood pressure (SBP), creatinine, and AST increased with the increasing CEA tertiles. CEA was significantly associated with EAT (r = 0.55, P<0.001) and VFR (r = 0.36, P<0.001). Multivariate linear regression analysis confirmed that gender, age, and EAT were the significant independent variables associated with CEA. Conclusion: Individuals with increased EAT have higher levels of CEA, suggesting that this biomarker is most likely produced by EAT; however, additional investigations are required to improve the present work.

Complicaciones Asociadas a la Remoción Estética del Cuerpo Adiposo de la Boca (de Bichat) - Revisión Narrativa / Complications Associated with Aesthetic Removal of the Buccal Adipose Body (Bichat's fat-pad) - Narrative Review

El cuerpo adiposo de la boca (CAB) es un componente adiposo multilobulado bien delimitado, localizado de manera bilateral en la región facial íntimamente relacionado a estructuras nerviosas y vasculares. La remoción de CAB es un procedimiento ampliamente estudiado en el campo de la cirugía maxilofacial, utilizado principalmente para cubrir defectos. Su influencia en la estética facial ha iniciado una popularización de la remoción de la extensión bucal de CAB para obtener un rostro más estilizado, intervención difundida como poco invasiva y sin complicaciones. El objetivo de este estudio fue recopilar y evaluar estudios que reporten y evalúen complicaciones asociadas a la remoción por razones estéticas de CAB. Se revisó la evidencia en las bases de datos Medline vía PubMed, Epistemonikos, Scopus y Google Scholar, utilizando términos predefinidos, seleccionando estudios primarios de reportes de casos. Se incluyeron 7 artículos con un total de 10 pacientes; de estos, ocho pacientes se realizaron este procedimiento en Brasil, uno en Estados Unidos y uno en Chile. La distribución de la población fue de 3:7 entre hombres y mujeres con edad promedio de 35 años y un rango entre los 23 a los 49 años. En relación a las complicaciones reportadas, 100 % de los pacientes presentaron asimetría facial, un 80 % presentó edema facial, 30 % manifestaron sialocele, Trismus 20 %, 40 % presentó hematoma, 20 % compromiso del estado general, 20 % presentaron disfagia, en los casos de hipoestesia, parestesia, absceso, seroma, parálisis facial, odinofagia, fiebre se expresaron en 10 % de la población estudiada. En todos los estudios se describió una reintervención quirúrgica posterior a la remoción estética del cuerpo adiposo de bichat. La escasa literatura y la baja calidad de esta, no permite estimar el porcentaje real de posibles complicaciones, tampoco es posible determinar sus resultados a largo plazo ya que no existe en la evidencia un seguimiento apropiado para estos pacientes.

The buccal adipose body (BAB) is a well- defined multilobulated adipose component, located bilaterally in the facial region, closely related to nervous and vascular structures. BAB removal is a widely studied procedure in the field of maxillofacial surgery, used mainly to cover defects. Its influence on facial aesthetics has started to popularize the removal of the BAB buccal extension to obtain a more stylized face, an intervention widely known as minimally invasive and without complications. The objective of this study was to collect and evaluate studies that report and evaluate complications associated with the removal of BAB for cosmetic reasons. The evidence was reviewed in the Medline databases via PubMed, Epistemonikos, Scopus, and Google Scholar, using predefined terms, selecting primary studies from case reports. 7 articles with a total of 10 patients were included; Of these, eight patients underwent this procedure in Brazil, one in the United States, and one in Chile. The distribution of the population was 3:7 between men and women with an average age of 35 years and a range between 23 to 49 years. In relation to the reported complications, 100 % of the patients presented facial asymmetry, 80 % presented facial edema, 30 % manifested sialocele, trismus 20 %, 40 % presented hematoma, 20 % compromised general state, 20 % presented dysphagia, in the cases of hypoesthesia, paresthesia, abscess, seroma, facial paralysis, odynophagia, fever were expressed in 10 % of the studied population. All the studies described a surgical reintervention after cosmetic removal of the bichat adipose body. The scarce literature and its low quality do not allow estimating the real percentage of possible complications, nor is it possible to determine their long-term results since there is no evidence of appropriate follow-up for these patients.

Complications in liposuction: systematic review / Complicações em lipoaspiração: revisão sistemática

Liposuction is among the most performed plastic surgery procedures in Brazil. According to data from the International Society of Aesthetic Plastic Surgery (ISAPS), 231,604 liposuctions were performed, 15.5% of all aesthetic procedures in the country in 2019. Adopting liposuction as a single procedure or adjunct to other cosmetic procedures stimulated its technical evolution from simple fat aspiration to more sophisticated body shaping. Thus, this review aimed to systematically evaluate the published data regarding the complications found in liposuction. A review was conducted using PubMed, SciELO, LILACS, Cochrane Library, SCOPUS, Web of Science, and gray literature databases, published between 2016 and 2021, using the descriptors "Liposuction" and "Complications." A total of 187 articles were found in the searched databases, of which 16 were selected according to the outcome "to assess safety through the prevalence of complications in liposuction as a single procedure and associated with other procedures such as abdominoplasty and fat grafting." We found a mortality rate ranging from 0 to 0.06 among all procedures and a predominance of venous thromboembolism, hematoma, seroma, and hyperpigmentation concerning all complications, being more common when liposuction is associated with other procedures. Therefore, through this review, it was possible to verify that liposuction as a single procedure has lower complication rates when compared to liposuction combined with other procedures.

A lipoaspiração está entre os procedimentos da cirurgia plástica mais realizados no Brasil. Segundo dados da International Society of Aesthetic Plastic Surgery (ISAPS), foram totalizadas 231.604 lipoaspirações, 15,5% dentre todos os procedimentos estéticos realizados no país em 2019. A adoção da lipoaspiração como procedimento único ou coadjuvante a outros procedimentos cosméticos estimulou sua evolução técnica da simples aspiração de gordura para uma modelagem corporal mais sofisticada. Desse modo, esta revisão objetivou avaliar sistematicamente os dados publicados em relação às complicações encontradas na lipoaspiração. Foi realizada uma revisão utilizando os bancos de dados PubMed, SciELO, LILACS, Cochrane Library, SCOPUS, Web of Science e grey literature, publicados entre os anos de 2016 e 2021, através dos descritores "Liposuction" and "Complications". Foram encontrados 187 artigos nas bases de dados pesquisadas, dos quais 16 foram selecionados de acordo com o desfecho "avaliar a segurança através da prevalência de complicações na lipoaspiração como procedimento único e a associada a outros procedimentos como abdominoplastia e lipoenxertia". Encontramos uma taxa de mortalidade que varia de 0 a 0,06 dentre todos os procedimentos e um predomínio de tromboembolismo venoso, hematoma, seroma e hiperpigmentação em relação a todas as complicações, sendo mais encontradas quando a lipoaspiração é associada a outros procedimentos. Logo, por meio desta revisão foi possível constatar que a lipoaspiração como procedimento único apresenta menores taxas de complicações quando comparada à lipoaspiração combinada com outros procedimentos.

The effects of fat graft and platelet-rich fibrin combination after epineurectomy in rats

SUMMARY OBJECTIVE: One of the most important factors that adversely affects the outcome of peripheral nerve surgery is the formation of epineural and extraneural scar tissue after surgery. Many surgical methods and pharmacological and chemical agents have been used to prevent the formation of epineural scar tissue, but satisfactory results have not been achieved in clinical applications. The purpose of this study was to investigate the combined effect of fat graft and platelet-rich fibrin on the formation of epineural scar tissue and on nerve healing in the mature rat model. METHODS: A total of 24 female Sprague-Dawley rats were used. A circumferential segment of epineurium was excised from both bilateral sciatic nerves. The epineurectomized right nerve segment was wrapped with a combination of fat graft and platelet-rich fibrin (experimental group), while the left nerve segment did not receive any surgical procedure other than the epineurectomy (sham group). Notably, 12 randomly selected rats were sacrificed in the fourth week for histopathological examination of early results. The other 12 rats were sacrificed in the eighth week for late results. RESULTS: The formation of fibrosis, inflammation, and myelin degeneration were less common in the experimental group, while nerve regeneration was found to be higher at both 4 and 8 weeks. CONCLUSION: The intraoperative application of a combination of fat graft and platelet-rich fibrin appears to be effective on nerve healing after surgery at both the early and late periods.

Experimental study of subcutaneous adipose-derived stem cells inhibiting orthodontic root resorption / 中国修复重建外科杂志

OBJECTIVE@#To investigate the effect of human subcutaneous adipose-derived stem cells (hADSCs) local transplantation on orthodontically induced root resorption (OIRR) and provide theoretical and experimental basis for the clinical application of hADSCs to inhibit OIRR.@*METHODS@#Forty 8-week-old male Sprague Dawley rats were randomly divided into experimental group and control group, with 20 rats in each group, to establish the first molar mesial orthodontic tooth movement (OTM) model of rat right maxillary. The rats in the experimental group were injected with 25 μL of cell suspension containing 2.5×10 5 hADSCs on the 1st, 4th, 8th, and 12th day of modeling, while the rats in the control group were injected with 25 μL of PBS. The rat maxillary models were obtained before and after 7 and 14 days of force application, and 10 rats in each group were killed and sampled after 7 and 14 days of force application. The OTM distance was measured by stereomicroscope, the root morphology of the pressure side was observed by scanning electron microscope and the root resorption area ratio was measured. The root resorption and periodontal tissue remodeling of the pressure side were observed by HE staining and the root resorption index was calculated. The number of cementoclast and osteoclast in the periodontal tissue on the pressure side was counted by tartrate resistant acid phosphatase staining.@*RESULTS@#The TOM distance of both groups increased with the extension of the force application time, and there was no significant difference ( P<0.05). There was no significant difference in OTM distance between the experimental group and the control group after 7 and 14 days of force application ( P>0.05). Scanning electron microscope observation showed that small and shallow scattered resorption lacunae were observed on the root surface of the experimental group and the control group after 7 days of force application, and there was no significant difference in the root resorption area ratio between the two groups ( P>0.05); after 14 days of application, the root resorption lacunae deepened and became larger in both groups, and the root resorption area ratio in the experimental group was significantly lower than that in the control group ( P<0.05). The range and depth of root absorption in the experimental group were smaller and shallower than those in the control group, and the root absorption index in the experimental group was significantly lower than that in the control group after 14 days of force application ( P<0.05). The number of cementoclast in the experimental group was significantly lower than that in the control group after 7 and 14 days of force application ( P<0.05); the number of osteoclasts in the experimental group was significantly lower than that in the control group after 14 days of force application ( P<0.05).@*CONCLUSION@#Local transplantation of hADSCs may reduce the area and depth of root resorption by reducing the number of cementoclasts and osteoclasts during OTM in rats, thereby inhibiting orthodontic-derived root resorption.

Effect of Kartogenin combined with adipose-derived stem cells on tendon-bone healing after anterior cruciate ligament reconstruction / 中国修复重建外科杂志

OBJECTIVE@#To investigate the effect of Kartogenin (KGN) combined with adipose-derived stem cells (ADSCs) on tendon-bone healing after anterior cruciate ligament (ACL) reconstruction in rabbits.@*METHODS@#After the primary ADSCs were cultured by passaging, the 3rd generation cells were cultured with 10 μmol/L KGN solution for 72 hours. The supernatant of KGN-ADSCs was harvested and mixed with fibrin glue at a ratio of 1∶1; the 3rd generation ADSCs were mixed with fibrin glue as a control. Eighty adult New Zealand white rabbits were taken and randomly divided into 4 groups: saline group (group A), ADSCs group (group B), KGN-ADSCs group (group C), and sham-operated group (group D). After the ACL reconstruction model was prepared in groups A-C, the saline, the mixture of ADSCs and fibrin glue, and the mixture of supernatant of KGN-ADSCs and fibrin glue were injected into the tendon-bone interface and tendon gap, respectively. ACL was only exposed without other treatment in group D. The general conditions of the animals were observed after operation. At 6 and 12 weeks, the tendon-bone interface tissues and ACL specimens were taken and the tendon-bone healing was observed by HE staining, c-Jun N-terminal kinase (JNK) immunohistochemical staining, and TUNEL apoptosis assay. The fibroblasts were counted, and the positive expression rate of JNK protein and apoptosis index (AI) were measured. At the same time point, the tensile strength test was performed to measure the maximum load and the maximum tensile distance to observe the biomechanical properties.@*RESULTS@#Twenty-eight rabbits were excluded from the study due to incision infection or death, and finally 12, 12, 12, and 16 rabbits in groups A-D were included in the study, respectively. After operation, the tendon-bone interface of groups A and B healed poorly, while group C healed well. At 6 and 12 weeks, the number of fibroblasts and positive expression rate of JNK protein in group C were significantly higher than those of groups A, B, and D (P<0.05). Compared with 6 weeks, the number of fibroblasts gradually decreased and the positive expression rate of JNK protein and AI decreased in group C at 12 weeks after operation, with significant differences (P<0.05). Biomechanical tests showed that the maximum loads at 6 and 12 weeks after operation in group C were higher than in groups A and B, but lower than those in group D, while the maximum tensile distance results were opposite, but the differences between groups were significant (P<0.05).@*CONCLUSION@#After ACL reconstruction, local injection of a mixture of KGN-ADSCs and fibrin glue can promote the tendon-bone healing and enhance the mechanical strength and tensile resistance of the tendon-bone interface.

Effect and mechanism of Zexie Decoction in promoting white adipose tissue browning/brown adipose tissue activation based on GLP-1R/cAMP/PKA/CREB pathway / 中国中药杂志

This study investigated the mechanism of Zexie Decoction(ZXD) in promoting white adipose tissue browning/brown adipose tissue activation based on the GLP-1R/cAMP/PKA/CREB pathway. A hyperlipidemia model was induced by a western diet(WD) in mice, and the mice were divided into a control group, a model group(WD), and low-, medium-, and high-dose ZXD groups. An adipogenesis model was induced in 3T3-L1 cells in vitro, and with forskolin(FSK) used as a positive control, low-, medium-, and high-dose ZXD groups were set up. Immunohistochemistry and immunofluorescence results showed that compared with the WD group, ZXD promoted the expression of UCP1 in white and brown adipose tissues, and also upregulated UCP1, CPT1β, PPARα, and other genes in the cells. Western blot analysis showed a dose-dependent increase in the protein expression of PGC-1α, UCP1, and PPARα with ZXD treatment, indicating that ZXD could promote the white adipose tissue browning/brown adipose tissue activation. Hematoxylin-eosin(HE) staining results showed that after ZXD treatment, white and brown adipocytes were significantly reduced in size, and the mRNA expression of ATGL, HSL, MGL, and PLIN1 was significantly upregulated as compared with the results in the WD group. Oil red O staining and biochemical assays indicated that ZXD improved lipid accumulation and promoted lipolysis. Immunohistochemistry and immunofluorescence staining for p-CREB revealed that ZXD reversed the decreased expression of p-CREB caused by WD. In vitro intervention with ZXD increased the protein expression of CREB, p-CREB, and p-PKA substrate, and increased the mRNA level of CREB. ELISA detected an increase in intracellular cAMP concentration with ZXD treatment. Molecular docking analysis showed that multiple active components in Alismatis Rhizoma and Atractylodis Macrocephalae Rhizoma could form stable hydrogen bond interactions with GLP-1R. In conclusion, ZXD promotes white adipose tissue browning/brown adipose tissue activation both in vivo and in vitro, and its mechanism of action may be related to the GLP-1R/cAMP/PKA/CREB pathway.

Aucubin combined with ADSCs-exos protects TBHP-induced nucleus pulposus cells via TLR4/NF-κB pathway / 中国中药杂志

This paper aims to investigate the effects and mechanisms of adipose-derived stem cells-exosomes(ADSCs-exos) toge-ther with aucubin in protecting human-derived nucleus pulposus cells(NPCs) from inflammatory injury, senescence, and apoptosis. The tert-butyl hydroperoxide(TBHP)-induced NPCs were assigned into normal, model, aucubin, ADSCs-exos, and aucubin+ADSCs-exos groups. The cell viability was examined by cell counting kit-8(CCK-8), cell proliferation by EdU staining, cell senescence by senescence-associated-β-galactosidase(SA-β-Gal), and cell cycle and apoptosis by flow cytometry. Enzyme-linked immunosorbent assay was employed to examine the expression of interleukin-1β(IL-1β), IL-10, and tumor necrosis factor-α(TNF-α). Real-time fluorescence quantitative PCR and Western blot were employed to determine the mRNA and protein levels of aggregated proteoglycan(aggrecan), type Ⅱ collagen alpha 1(COL2A1), Toll-like receptor 4(TLR4), and nuclear factor-kappa B(NF-κB). The results showed that compared with the model group, the aucubin or ADSCs-exos group showed enhanced viability and proliferation of NPCs, decreased proportion of G_0/G_1 phase cells, increased proportion of S phase cells, reduced apoptosis and proportion of cells in senescence, lowered IL-1β and TNF-α levels, elevated IL-10 level, down-regulated mRNA and protein levels of TLR4 and NF-κB, and up-regulated mRNA and protein levels of aggrecan and COL2A1. Compared with the aucubin or ADSCs-exos group, the aucubin+ADSCs-exos combination further increased the viability and proliferation of NPCs, decreased the proportion of G_0/G_1 phase cells, increased the proportion of S phase cells, reduced the apoptosis and proportion of cells in senescence, lowered the IL-1β and TNF-α levels, elevated the IL-10 level, down-regulated the mRNA and protein levels of TLR4 and NF-κB, and up-regulated the mRNA and protein levels of aggrecan and COL2A1. In summary, both aucubin and ADSCs-exos could exert protective effects by inhibiting inflammatory responses, reducing apoptosis and senescence of NPCs, improving cell viability and proliferation as well as extracellular matrix synthesis, which may be associated with the inhibition of TLR4/NF-κB signaling pathway activation. The combination of both plays a synergistic role in the protective effects.

Effect of obesity induced by high-fat diet and adipose exosomes on knee post-traumatic osteoarthritis caused by destabilization of medial meniscus surgery in young mice / 药学学报

Obesity is an important risk factor related to osteoarthritis, but it′s role in post-traumatic osteoarthritis on young people need to further study. The internal mechanism except the mechanical loading may be associated with adipose exosomes. To examine the effect of obesity induced by high fat diet and adipose exosomes on knee post-traumatic osteoarthritis caused by destabilization of medial meniscus (DMM) surgery in young mice, 20 6-week-old C57BL/6J mice were randomly assigned to the control diet group (CD, n = 5), the DMM group (n = 5), the high fat diet group (HFD, n = 5) and the HFD plus DMM group (HFD+DMM, n = 5). The CD and DMM group were fed with a control diet, and the HFD and HFD+DMM group were fed with a high fat diet. We did the DMM surgery and the sham surgery on the mice when it was 10 weeks old. Extract obese and normal adipose exosomes, identify exosomes in vitro, and proceed fluorescence imaging in vivo using DiR staining. DMM+HFD-Exo group and DMM+CD-Exo group were injected the exosomes from the tail vain once a week (100 μL per shot with a concentration of 1 μg·μL-1). Second, 15 6-week-old C57BL/6J mice were randomly assigned to the DMM group (n = 5), the DMM plus obese adipose exosomes group (DMM+HFD-Exo, n = 5), and the DMM plus control diet adipose exosomes group (DMM+CD-Exo, n = 5). Animal welfare and experimental process are in accordance with the regulations of the Experimental Animal Ethics Committee of Nanjing University (IACUC-D2204005). All mice were sacrificed at the age of 18 weeks, the knee joints of the mice were harvested and fixed. We used micro CT to examine the samples and measured the bone volume/tissue volume, trabecular thickness, trabecular number and trabecular separation. Then the samples were decalcified and embedded in paraffin, and 4 μm thickness sections were stained with H&E and safranin O/fast green to observe the histological changes of the knee joint. The results showed compared with the control diet group, high fat diet induced obesity can aggravate the pathological changes of the post-traumatic osteoarthritis caused by DMM surgery, which shows in having a higher Mankin score. The surface of knee articular cartilage in the HFD+DMM group was rough, and the subchondral bone has an increase in bone sclerosis. Compared with the DMM group, obese adipose exosomes can exacerbate the pathological changes of the knee articular cartilage, while not influencing the subchondral bone. In conclusion, high fat diet induced obesity can aggravate the post-traumatic osteoarthritis caused by DMM surgery in young mice. The obese adipose exosomes mainly affect the surface of the knee articular cartilage.

Effect of facial filling with autologous fat particles on facial contour reshaping / 中华医学美学美容杂志

Objective:To explore the effect of facial filling with autologous fat particles on the facial contour remodeling of patients with facial rejuvenation needs and its influence on the facial skin indicators of patients.Methods:From February 2019 to February 2020, 225 female patients, aged 25-52 years, with an average age of (42.5±5.2) years, received facial rejuvenation treatment in Zhengzhou Mylai Medical Beauty Hospital. They were divided into observation group (PPDO serrated line lifting combined with autologous fat granule filling), control group 1 (PPDO serrated line lifting alone) and control group 2 (simple autologous fat granule filling alone), with 75 cases in each group. After 6 months of follow-up, facial skin indexes, contour remodeling effect and adverse reactions after treatment were compared among the three groups.Results:At the last follow-up, the facial skin elasticity and moisture scores of the observation group (63.45±10.11, 56.71±9.38) were significantly higher than those of control group 1 (51.11±9.23, 43.69±7.65) and control group 2 (52.35±9.51, 42.47±7.53). The facial spots and lipid scores (41.31±7.24, 42.18±7.46) were significantly lower than those in control group 1 (48.67±9.15, 53.49±9.45) and control group 2 (48.26±9.21, 53.55±9.53) ( F=37.39, 68.98, 17.42, 40.91, P<0.001). At the last follow-up, the lower surface width of observation group (11.35±0.63) was lower than that of control group 1 (12.21±0.85) and control group 2 (12.38±0.65). The contour ratio of the lower part of the face (0.63±0.17) was higher than that of control group 1 (0.56±0.15) and control group 2 (0.57±0.15) ( F=44.49, 4.36, P<0.05). The change level of the ratio of lower facial area (0.12±0.03) was higher than that of control group 1 (0.07±0.02) and control group 2 (0.08±0.04) ( F=54.31, P<0.001). Conclusions:For patients who need facial rejuvenation treatment, the use of autologous fat granule facial filling therapy has good clinical effects, which can significantly improve the patient's facial skin elasticity, moisture, spots, and oil. The patient's facial contour reshaping effect is better, and the aesthetic score is significantly improved, and does not increase the risk of adverse reactions.

Exosomal lncRNA ZEB1-AS1 secreted from mesenchymal stem cells attenuates diabetic nephropathy by regulating miR-142-5p/PTEN axis / 中华内分泌代谢杂志

Objective:To explore the role of an exosomal long non-coding RNA zinc finger E-box-bingding homeobox 1 antisense 1(ZEB1-AS1) from adipose-derived MSC(adMSC) and its action mechanism in DN.Methods:DN rat model and high glucose(HG)-induced glomerular mesangial cell(GMCs) model treated with exosomal ZEB1-AS1 from adMSC were used for biochemical analysis and inflammation/oxidative stress assessment. The binding relationships among ZEB1-AS1, microRNA(miR)-142-5p, and phosphatase and tensin homolog deleted on chromosome 10(PTEN) were confirmed by dual luciferase reporter assay. Western blotting was used for the measurement of PTEN protein level.Results:adMSC-secreted exosomal ZEB1-AS1 reduced the levels of blood glucose, serum creatinine, 24 h urinary protein, kidney weight, fibrosis, and inflammatory cell infiltrations in DN rats. Meanwhile, both in DN rats and HG-induced GMCs, the levels of tumor necrosis factor(TNF)-α, interleukin(IL)-6, and IL-1β were inhibited, but glutathione peroxidase(GPx), superoxide dismutase(SOD), catalase(CAT), and glutathione(GSH) were promoted by exosomal ZEB1-AS1 treatment. Additionally, miR-142-5p was identified to bind to ZEB1-AS1, while miR-142-5p further targeted PTEN. miR-142-5p overexpression or PTEN silencing reversed the inhibiting effects of exosomal ZEB1-AS1 on inflammatory cytokine levels and the promoting effects on the concentrations of antioxidant enzymes.Conclusion:Exosomal ZEB1-AS1 from adMSC prevents DN progression by controlling inflammation and oxidative stress via the miR-142-5p/PTEN pathway, suggesting that ZEB1-AS1 may serve as a potential and effective therapeutic target for treating DN.

Changes in metabolic capacity and gene expression of brown adipose tissue in the first and third trimester of pregnancy / 中华内分泌代谢杂志

Objective:To explore gene expression and metabolic capacity changes of brown adipose tissue(BAT)during different gestation periods.Methods:A normal pregnancy model was established using C57BL/6J mice, while infertile mice of the same age were served as the control group. The morphological alteration of BAT during pregnancy as well as the gene expression of uncoupling protein 1(UCP1) and other fat browning and mitochondrial marker genes were detected. Moreover, BATs from early and late gestation were selected to screen differentially expressed genes in relation to pregnancy progressing by RNA sequencing(RNA-seq), and gene ontology(GO) and Kyoto gene and gene sequencing(KEGG)were performed.Results:With pregnancy progressing, the size of BAT lipid droplets was substantially enlarged, UCP1 protein expression was decreased( P<0.01), and the fat browning marker genes(Ucp1, Dio2, and Pgc1α)and the mitochondrial marker gene CytC were downregulated( P<0.001). Additionally, a total of 1 298 distinct genes were identified by RNA-seq, 906 of which were upregulated and 392 were downregulated at later stage of pregnancy. GO and KEGG analyses revealed that the differentially expressed genes were mainly enriched in bioregulatory functional pathways such as lipid metabolism, sex steroid hormones, and inflammatory factors. Conclusion:BAT in mice showed larger lipid droplets and reduced thermogenic and metabolic capacity during late gestation, and BAT gene expression was significantly different in different periods of gestation, so reduced metabolic capacity of BAT may contribute to metabolic abnormality during pregnancy.

The study of the whole bladder acellular matrix prepared by the perfusion decellularization system combined with the adipose-derived stem cells to construct the tissue engineering bladder / 中华泌尿外科杂志

Objective:To prepare the whole bladder acellular matrix (BAM) using the self-designed perfusion decellularization system, and evaluate the feasibility of constructing the tissue engineering bladder with the adipose-derived stem cells (ADSCs).Methods:This study was conducted from October 2020 to April 2021. The self-designed perfusion decellularization system was used, and four different decellularization protocols (group A, group B, group C and group D) were formulated, according to the flow direction of the perfusate and the action time of different decellularization solutions. Among them, the urethral orifice of the bladder tissue was used as the outflow tract of the perfusion fluid in groups A and B. The top of the bladder was cut off and used as the outflow tract of the perfusion fluid in groups C and D. In groups A and C, 1% Triton X-100 was treated for 6 h, and 1% sodium dodecyl sulfate (SDS) was treated for 2 h. In groups B and D, 1% Triton X-100 was treated for 7 h, and 1% sodium dodecyl sulfate (SDS) was treated for 1 h. In addition, the tissue in the normal bladder group was directly obtained from the natural bladder tissue, which did not require perfusion, cryopreservation and thawing. The fast and efficient decellularization protocol was screened out through HE, DAPI, Masson trichrome and Alcian Blue staining and quantitative analyses to prepare the whole bladder scaffold. The prepared BAM was used as the scaffold material, and the ADSCs were used as the seeding cells to construct the tissue engineering bladder. HE and DAPI staining were used to observe the distribution of ADSCs on the BAM.Results:HE and DAPI staining showed that there was no obvious nuclear residue in the group C. Masson trichrome and Alcian Blue staining showed that the collagen structure and glycosaminoglycan were well preserved in the group C. There was no significant difference in bladder wall thickness between the group C and the normal bladder group [(975.44±158.62)μm vs.(1 064.49±168.52)μm, P > 0.05]. The DNA content in the group C [(43.59 ±4.59) ng/mg] was lower than that in the normal bladder group, group A, group B and group D [(532.50±26.69), (135.17±6.99), (182.49±13.69) and(84.00±4.38)ng/mg], and the difference was statistically significant ( P<0.05). The collagen content [(10.98 ± 0.29)μg/mg] and glycosaminoglycan content [(2.30±0.18)μg/mg] in group C were not significantly different with those in the normal bladder group [(11.69±0.49) and (2.36±0.09)μg/mg, P>0.05]. Scanning electron microscopy showed that a large number of pore structures could be observed on the surface of the prepared BAM in groups A-D and were facilitated to cell adhesion. The isolated and cultured ADSCs were identified by flow cytometry to confirm the positive expression of CD90 and CD29, and the negative expression of CD45 and CD106. Live/dead staining and CCK-8 detection confirmed that the prepared BAM in the group C had no cytotoxicity. HE and DAPI staining showed that a large number of ADSCs were distributed on the surface and inside of the tissue engineering bladder. Conclusions:The whole bladder shape BAM prepared by the self-designed perfusion decellularization system could be used as the scaffold material for bladder tissue engineering, and the constructed tissue engineering bladder could be used for bladder repair and reconstruction.

Impact of the fat mass index on early functional recovery after total knee arthroplasty / 中华骨科杂志

Objective:To investigate the effect of fat mass index (FMI) on early recovery after total knee arthroplasty (TKA).Methods:Patients who underwent primary unilateral TKA in Xi'an Honghui Hospital from July 2020 to July 2021 were retrospectively analyzed. The preoperative body composition was measured by dual energy X-ray absorptiometry and the FMI was calculated. Patients were divided into normal group (male: 3.0-6.0 kg/m 2; female: 5.0-9.0 kg/m 2), overweight group (male: 6.1-9.0 kg/m 2; female: 9.1-13.0 kg/m 2), and obese group (male: >9 kg/m 2; female: >13 kg/m 2) according to level of FMI, and the operation time, blood loss, and incidence of postoperative complications were collected. Multifactorial analysis of the effect of FMI on early recovery after TKA was performed using a generalized linear model. Draw the receiver operating characteristics (ROC) curve of BMI and FMI on the predicted effect of postoperative Western Ontario and McMaster Universities (WOMAC) osteoarthritis index scores and Knee Society Score (KSS) to compare the effect of FMI with BMI on early recovery after TKA. Results:A total of 100 patients were included in the study, 24 males and 76 females, aged 65.0±8.2 years (range, 42-81 years). There were 15 cases in normal group, 55 cases in overweight group and 30 cases in obese group. All patients successfully completed the operation and were followed up for 3.15±0.72 months (range, 2.8-3.2 months). The WOMAC scores of the obese group at 2 weeks, 1 and 2 months postoperative were 34.57±3.68, 22.03±2.79, and 15.77±2.96, which were greater than those of the normal group (28.73 ±2.58, 19.07±2.71, 12.27±3.10), as well as the overweight group (30.05±4.09, 19.33±2.42, 14.84±2.42), with statistically significant differences ( P<0.05). The KSS scores of the obese group at postoperative 1 and 2 months were 68.83±5.52 and 81.17±4.49, which were lower than those of the normal group (77.33±5.63, 87.33±4.17), as well as the overweight group (72.64±5.43, 83.73 ±5.02), with statistically significant differences ( P<0.05). The WOMAC score, KSS score, and postoperative complications at 2 months postoperatively were selected as outcome indicators to plot the ROC curve, and the ROC curve for the WOMAC score at 2 months postoperatively showed an area under the curve corresponding to FMI of 0.744 (95% CI: 0.54, 0.82), which was greater than that of BMI [0.624 (95% CI: 0.51, 0.74)], and the difference was statistically significant ( Z=2.19, P=0.021). The ROC curve for the KSS score at 2 months postoperatively showed an area under the curve corresponding to FMI of 0.718 (95% CI: 0.62, 0.82), which was greater than that of BMI [0.612 (95% CI: 0.52, 0.74)], with a statistically significant difference ( Z=2.58, P=0.016). The ROC curve for postoperative complications showed an area under the curve of 0.639 (95% CI: 0.41, 0.88) for FMI and 0.605 (95% CI: 0.37, 0.84) for BMI, with no statistically significant difference ( Z=0.48, P=0.632). Conclusion:The greater the FMI the poorer the early functional recovery after initial TKA, and FMI is more valuable than BMI in predicting the early functional recovery.

Relationship between abnormal imaging findings of adipose tissue around primary colon cancer and prognosis / 中华放射学杂志

Objective:To explore the relationship between the abnormal adipose tissue around the primary tumor of colon cancer and the prognosis.Methods:From January 2015 to December 2017, 448 patients with colon cancer in Peking University Cancer Hospital were retrospectively and consecutively collected. The scores were assigned to the severity, horizontal and vertical ranges of peritumoral adipose tissue (PAT) abnormalities, and the cumulative scores were calculated to establish the PAT grades from 1 to 3. We defined a score of 0 or 1 as PAT grade 1, a score of 2 as PAT grade 2, a score of 3 as PAT grade 3. The patients were followed up, and the overall survival (OS) and metastasis-free survival (MFS) were recorded. The Kaplan-Meier curve, log-rank test and Cox regression analysis were used to evaluate its impact on prognosis, and the hazard ratio (HR) and 95% confidence interval (CI) were calculated.Results:Among the 448 patients, patients with PAT grade 1, 2, and 3 accounted for 70.1% (314/448), 18.1% (81/448), and 11.8% (53/448), respectively. The Kaplan-Meier survival curve showed that patients with PAT grade 1 had the best OS, patients with grade 3 had the worst OS, and patients with grade 2 were in between, and the difference was statistically significant (χ 2=27.38, P<0.001). There were statistically significant differences between the grades in pairs ( P<0.05). There was no significant difference in MFS between different PAT grades (χ 2=2.85, P=0.240). The results of Cox regression analysis showed that PAT grade was an independent factor affecting the OS. Compared with PAT grade 1, the risk of death in patients with PAT grade 2 and 3 was significantly increased (HR 2.563, 95%CI 1.181-5.561; HR 2.269, 95%CI 1.005-5.121; P=0.034). PAT grade was not an independent factor of MFS ( P=0.253). Conclusion:The PAT grade established based on the degree and scope of abnormal PAT in colon cancer is an independent factor for poor prognosis of colon cancer.