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1.
Gene ; 722: 144058, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31494240

RESUMO

PURPOSE: Adipose-derived mesenchymal stem cells (MSCs) are attractive biological agents in regenerative medicine. To optimize cell therapies, it is necessary to determine the most effective delivery method for MSCs. Therefore, we evaluated the biological properties of MSCs after exposure to various temperatures to define optimal storage conditions prior to therapeutic delivery of MSCs. DESIGN: Prospective observational study. METHODS AND MATERIALS: Adherent and non-adherent MSCs were incubated at multiple temperatures (i.e., 4, 23 and 37 °C) in Lactated Ringers (LR) solution lacking essential cell growth ingredients, or in culture media which is optimized for cell growth. Cells were assessed either after the temperature changes (4 h) or after recovery (24 h). Metabolic activity of MSCs, cell number and expression of representative mRNA biomarkers were evaluated to assess the biological effects of temperature. We monitored changes in mRNAs expression related to cytoprotective- or stress-related responses (e.g., FOS, JUN, ATF1, ATF4, EGR1, EGR2, MYC), proliferation (e.g., HIST2H4, CCNB2), and extracellular matrix production (ECM; e.g., COL3A1, COL1A1) by quantitative real time reverse-transcriptase polymerase chain reaction (RT-qPCR) analysis. RESULTS: Our study demonstrates that storing MSCs in Lactated Ringers (LR) solution for 4 h decreases cell number and metabolic activity. The number of viable MSCs decreased significantly when cultured at physiological temperature (37 °C) and severe hypothermia (4 °C), while cells grown at ambient temperature (23 °C) exhibited the least detrimental effects. There were no appreciable biological differences in mRNA markers for proliferation or ECM deposition at any of the temperatures. However, biomarkers related to cytoprotective- or stress-responses were selectively elevated depending on temperature or media type (i.e., LR versus standard media). CONCLUSION: The biological impact of nutrient-free media and temperature changes after 4 h exposure persists after a 24 h recovery period. Hence, storage temperature and media conditions should be optimized to improve effective dosing of MSCs.


Assuntos
Tecido Adiposo/citologia , Temperatura Baixa , Células-Tronco Mesenquimais/citologia , Sobrevivência Celular , Meios de Cultura , Humanos , Células-Tronco Mesenquimais/metabolismo , Nutrientes , RNA Mensageiro/metabolismo , Temperatura Ambiente
2.
Einstein (Sao Paulo) ; 18: eAO4876, 2020.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31576909

RESUMO

OBJECTIVE: To investigate the effects of sericin extracted from silkworm Bombyx mori cocoon on morphophysiological parameters in mice with obesity induced by high-fat diet. METHODS: Male C57Bl6 mice aged 9 weeks were allocated to one of two groups - Control and Obese, and fed a standard or high-fat diet for 10 weeks, respectively. Mice were then further subdivided into four groups with seven mice each, as follows: Control, Control-Sericin, Obese, and Obese-Sericin. The standard or high fat diet was given for 4 more weeks; sericin (1,000mg/kg body weight) was given orally to mice in the Control-Sericin and Obese-Sericin Groups during this period. Weight gain, food intake, fecal weight, fecal lipid content, gut motility and glucose tolerance were monitored. At the end of experimental period, plasma was collected for biochemical analysis. Samples of white adipose tissue, liver and jejunum were collected and processed for light microscopy analysis; liver fragments were used for lipid content determination. RESULTS: Obese mice experienced significantly greater weight gain and fat accumulation and had higher total cholesterol and glucose levels compared to controls. Retroperitoneal and periepididymal adipocyte hypertrophy, development of hepatic steatosis, increased cholesterol and triglyceride levels and morphometric changes in the jejunal wall were observed. CONCLUSION: Physiological changes induced by obesity were not fully reverted by sericin; however, sericin treatment restored jejunal morphometry and increased lipid excretion in feces in obese mice, suggesting potential anti-obesity effects.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Dieta Hiperlipídica , Obesidade/tratamento farmacológico , Sericinas/uso terapêutico , Tecido Adiposo/patologia , Animais , Fármacos Antiobesidade/farmacologia , Peso Corporal/efeitos dos fármacos , Colesterol/análise , Dieta Hiperlipídica/efeitos adversos , Ingestão de Alimentos/efeitos dos fármacos , Fígado Gorduroso/patologia , Trânsito Gastrointestinal/efeitos dos fármacos , Teste de Tolerância a Glucose , Fígado/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/etiologia , Obesidade/fisiopatologia , Reprodutibilidade dos Testes , Sericinas/farmacologia , Fatores de Tempo , Resultado do Tratamento , Triglicerídeos/análise , Ganho de Peso/efeitos dos fármacos
3.
Biol Res ; 52(1): 54, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31581950

RESUMO

BACKGROUND: IcarisideII (ICAII) could promote the differentiation of adipose tissue-derived stem cells (ADSCs) to Schwann cells (SCs), leading to improvement of erectile function (EF) and providing a realistic therapeutic option for the treatment of erectile dysfunction (ED). However, the underlying molecular mechanisms of ADSCs and ICAII in this process remain largely unclear. METHODS: ADSCs were treated with different concentrations of ICAII. Cell proliferation was determined by MTT assay. qRT-PCR and western blot were performed to detect expressions of SCs markers, signal transducer and activator of transcription-3 (STAT3), and microRNA-let-7i (let-7i). Luciferase reporter assay was conducted to verify the regulatory relationship between let-7i and STAT3. The detection of intracavernosal pressure (ICP) and the ratio of ICP/mean arterial pressure (MAP) were used to evaluate the EF in bilateral cavernous nerve injury (BCNI) rat models. RESULTS: ICAII promoted cell proliferation of ADSCs in a dose-dependent manner. The mRNA and protein levels of SCs markers were increased by ICAII treatment in a dose-dependent manner in ADSCs. Moreover, let-7i was significantly decreased in ICAII-treated ADSCs and upregulation of let-7i attenuated ICAII-induced promotion of SCs markers. In addition, STAT3 was a direct target of let-7i and upregulated in ICAII-treated ADSCs. Interestingly, overexpression of STAT3 abated the let-7i-mediated inhibition effect on differentiation of ADSCs to SCs and rescued the ICAII-mediated promotion effect on it. Besides, combination treatment of ADSCs and ICAII preserved the EF of BCNI rat models, which was undermined by let-7i overexpression. CONCLUSION: ICAII was effective for preserving EF by promoting the differentiation of ADSCs to SCs via modulating let-7i/STAT3 pathway.


Assuntos
Tecido Adiposo/citologia , Diferenciação Celular/efeitos dos fármacos , Disfunção Erétil/tratamento farmacológico , Flavonoides/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células de Schwann/efeitos dos fármacos , Animais , Western Blotting , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley , Transfecção
4.
Pediatr Endocrinol Rev ; 17(1): 4-16, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31599132

RESUMO

Growth hormone (GH) is a pleiotropic hormone that coordinates an array of physiological processes including growth and metabolism. GH promotes anabolic action in all tissues except adipose, where it catabolizes stored fat to release energy for the promotion of growth in other tissues. However, chronic stimulation of lipolysis by GH results in an increased flux of free fatty acids (FFAs) into systemic circulation. Hence, a sustained release of high levels of GH contributes significantly to the development of insulin resistance by antagonizing the anti-lipolytic action of insulin. The molecular pathways associated with the lipolytic effect of GH in adipose tissue however, remain elusive. Recent studies have provided molecular insights into GH-induced lipolysis and impairment of insulin signaling. This review discusses the physiological and metabolic actions of GH on adipose tissue as well as GH-mediated deregulation of the FSP27-PPARγ axis which alters adipose tissue homeostasis and contributes to the development of insulin resistance and Type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Hormônio do Crescimento Humano , Resistência à Insulina , Lipólise , Tecido Adiposo/efeitos dos fármacos , Diabetes Mellitus Tipo 2/induzido quimicamente , Diabetes Mellitus Tipo 2/fisiopatologia , Hormônio do Crescimento Humano/metabolismo , Hormônio do Crescimento Humano/farmacologia , Humanos , Lipólise/efeitos dos fármacos
5.
Wiad Lek ; 72(9 cz 2): 1834-1838, 2019.
Artigo em Polonês | MEDLINE | ID: mdl-31622275

RESUMO

The adipose and osseous tissue, although both derived from the connective tissues, perform different functions. In the common opinion, obesity might be a protective factor against bone loss and osteoporosis. The adipose tissue is a recognized major endocrine organ, producing a number of active biological substances, which affect the bone mass. Adipocyte and osteoblast are derived from the same mesenchymal stem cells. Therefore abnormal secretion of adipocytokines may play an important role not only in pathogenesis of the obesity, but also can influence the bone . It is supposed that obesity might have a protective effect on bone tissue in postmenopausal women, by increasing the load on the axial skeleton and because of its hormonal activity.


Assuntos
Tecido Adiposo/fisiopatologia , Osso e Ossos/fisiopatologia , Obesidade/patologia , Osteoporose/patologia , Adipocinas/fisiologia , Densidade Óssea , Feminino , Humanos , Células-Tronco Mesenquimais
6.
Zhonghua Shao Shang Za Zhi ; 35(9): 641-644, 2019 Sep 20.
Artigo em Chinês | MEDLINE | ID: mdl-31594181

RESUMO

Adipose stem cells (ASCs) are mesenchymal stem cells derived from adipose tissue, and they have potentials of self-renewal and multi-directional differentiation. Compared with bone marrow mesenchymal stem cells, ASCs have many advantages, such as easy access, easy cultivation, and abundant content, which are valuable seed cells in the field of repair and reconstruction. In recent years, with the deepening of the researches on differentiation, regulation, and function of ASCs, the clinical application of ASCs has gradually increased with good therapeutic effects.


Assuntos
Adipócitos/citologia , Terapia Baseada em Transplante de Células e Tecidos , Células-Tronco Mesenquimais/citologia , Engenharia Tecidual , Tecido Adiposo/citologia , Diferenciação Celular , Humanos
7.
Zhonghua Shao Shang Za Zhi ; 35(9): 645-654, 2019 Sep 20.
Artigo em Chinês | MEDLINE | ID: mdl-31594182

RESUMO

Objective: To investigate whether adipose-derived stem cells (ASCs) from allogeneic diabetic rats can promote wound healing in diabetic rats or not and the mechanism. Methods: (1) Fifty-six male Wistar rats aged 12-16 weeks were divided into diabetic group and healthy group according to the random number table (the same grouping method below), with 28 rats in each group. Rats in healthy group were not treated with any treatment. Rats in diabetic group were injected with 10 g/L streptozotocin 60 mg/kg intraperitoneally in one time to establish the diabetic model. Four rats in diabetic group and 4 rats in healthy group were selected according to the random number table, and the adipose tissue in the inguinal region was taken to culture and purify ASCs, so as to obtain healthy rat-derived ASCs (hereinafter referred to as nASCs) and diabetic rat-derived ASCs (hereinafter referred to as dASCs). The third passage of nASCs (n=3) and dASCs (n=3) were taken, and the positive expression rates of cell surface differentiation antigens CD105, CD31, CD34, and CD44 were detected with flow cytometer for defining ASCs purity. (2) The rest 24 rats in healthy group and 24 rats in diabetic group were used to make three round full-thickness skin defect wounds with a diameter of 12 mm on the back of each rat. Immediately after injury, phosphate buffer saline (PBS), nASCs of 2×10(7)/mL, and dASCs of 2×10(7)/mL each in the volume of 0.5 mL were subcutaneously injected into three wounds and their margins of each rat, respectively. On post injury day (PID) 1, 3, 7, and 12, 6 rats in each group were selected according to the random number table to calculate the wound area, and the wound tissue was stained with hematoxylin-eosin to observe the histological morphology of the wound. (3) Human ASCs (hASCs) were subcultured, and the 4th to 7th passage of cells were used for the subsequent experiments. The hASCs were divided into 7 groups, with 12 samples in each group. Cells in blank control group were cultured with mesenchymal stem cell culture medium, and cells in simple advanced glycation end products (AGEs) group, simple protein group, simple high glucose group, simple high osmotic pressure group, AGEs-high glucose combination group, and protein-high osmotic pressure combination group were cultured with mesenchymal stem cell culture medium containing a final mass concentration of 100 mg/L AGEs, 100 mg/L bovine serum albumin (BSA), 28 mmol/L D-glucose, 28 mmol/L mannitol, 100 mg/L AGEs+ 28 mmol/L D-glucose, 100 mg/L BSA+ 28 mmol/L mannitol, respectively. Cell proliferation was detected by cell counting kit 8 at post culture hour (PCH) 2 and on post culture day (PCD) 2, 4 and 6. (4) The hASCs were divided into blank control group, simple AGE group, simple high glucose group, and AGE-high glucose combination group, with 12 samples in each group, which were treated the same as corresponding groups in experiment (3). On PCD 0, 2, 4, and 6, the positive expression rates of cell surface differentiation antigens CD105, CD44, and CD45 were detected by flow cytometer to estimate their homeostasis. (5) The hASCs were divided into AGE-high glucose combination group and protein-high osmotic pressure combination group, with 9 samples in each group, which were treated the same as corresponding groups in experiment (3). On PCD 2, 4, and 6, the expression of intracellular protein was detected by cyanine 3-streptavidin double-antibody sandwich technique. Data were processed with analysis of variance for factorial design, least significant difference test, and Bonferroni correction. Results: (1) The positive expression rates of CD44 in nASCs and dASCs were both higher than 96%, the positive expression rates of CD31 and CD34 were low, and the positive expression rates of CD105 were about 40%, which basically met the purity requirements. (2) The areas of wounds treated by three methods in rats of healthy group and diabetic group were similar on PID 1 (P>0.05). In healthy group, compared with (0.682 1±0.078 9), (0.314 3±0.113 7), and (0.064 3±0.002 1) cm(2) of the PBS-treated wounds in rats, the area of nASCs-treated wounds in rats decreased significantly on PID 3, 7, and 12 [(0.464 1±0.092 6), (0.223 9±0.072 7), and (0.034 3±0.012 5) cm(2), P<0.05], the area of dASCs-treated wounds in rats decreased significantly on PID 3 and 12 [(0.514 1±0.124 1) and (0.043 7±0.032 8) cm(2), P<0.05] but was not obviously changed on PID 7 [(0.274 2±0.062 5) cm(2), P>0.05]. Compared with those of the dASCs-treated wounds of rats within the same group, the area of the nASCs-treated wounds of rats in healthy group decreased significantly on PID 3 and 7 (P<0.05) but was not obviously changed on PID 12 (P>0.05). In diabetic group, compared with (0.853 5±0.204 8), (0.670 5±0.164 8), and (0.131 4±0.074 4) cm(2) of the PBS-treated wounds in rats, the area of nASCs-treated wounds in rats decreased significantly on PID 3, 7, and 12 [(0.633 4±0.132 5), (0.331 8±0.023 5), and (0.074 2±0.003 8) cm(2), P<0.05], the area of dASCs-treated wounds in rats decreased significantly on PID 3 [(0.773 6±0.182 2) cm(2), P<0.05] but was not obviously changed on PID 7 and 12 [(0.510 6±0.192 2) and (0.114 4±0.003 1) cm(2), P>0.05]. Compared with the dASCs-treated wounds of rats within the same group, the area of the nASCs-treated wounds of rats in diabetic group was not obviously changed on PID 3 and 7 (P>0.05) but decreased significantly on PID 12 (P<0.05). There was no obvious difference in histological morphology of the wounds treated with three methods in rats of each group on PID 1. On PID 3, a small amount of microvessels were formed in the wounds treated with nASCs and dASCs of rats in both groups, but microvessel formation was almost undetected in the PBS-treated wounds. On PID 7, more small blood vessels and fibroblasts (Fbs) were observed in the wounds treated with nASCs and dASCs of rats in both groups, but the small blood vessels and Fbs were slightly less in the PBS-treated wounds. On PID 12, the wounds treated with nASCs and dASCs of rats in the two groups were covered by epithelial tissue, the granulation tissue in the PBS-treated wounds of rats in healthy group was not obvious, and the PBS-treated wounds of rats in diabetic group were not completely epithelialized. (3) Compared with those of blank control group, the cell number of hASCs in simple AGEs group decreased significantly on PCD 2, 4, and 6 (P<0.05), which increased significantly on PCD 2 and 4 in simple high glucose group (P<0.05), and that in AGEs-high glucose combination group decreased significantly on PCD 4 and 6 (P<0.05). (4) Compared with that on PCD 4 within the same group, the positive expression rate of CD105 in hASCs decreased significantly in blank control group, simple AGEs group, and AGEs-high glucose combination group on PCD 6 (P<0.05). The positive expression rate of CD44 was higher than 95%, and that of CD45 was less than 2% in hASCs of each group at each time point. (5) Detection values of 7 proteins were located in the confidence interval. The expression levels of basic fibroblast growth factor and tissue inhibitor of metalloproteinase-1 in hASCs of AGEs-high glucose combination group and protein-high osmotic pressure combination group showed increasing trend with the prolongation of culture time. The expression level of human monocyte chemoattractant protein 1 (MCP-1) in hASCs of AGEs-high glucose combination group showed increasing trend with the prolongation of culture time, while the expression level of growth-regulated oncogene (GRO) on PCD 6 was significantly higher than that on PCD 4 within the same group (P<0.05); the expression levels of MCP-1 and GRO in hASCs of protein-high osmotic pressure combination group showed decreasing trend with the prolongation of culture time. The expression level of follistatin in hASCs of protein-high osmotic pressure combination group decreased obviously on PCD 4, while that in hASCs of AGEs-high glucose combination group was significantly lower on PCD 6 than that on PCD 4 (P<0.05). The expression level of vascular endothelial growth factor (VEGF) in hASCs of protein-high osmotic pressure combination group decreased gradually with the prolongation of culture time, while that in hASCs of AGEs-high glucose combination group on PCD 4 decreased significantly as compared with that on PCD 2 (P<0.05). The expression level of urokinase-type plasminogen activator receptor in hASCs of protein-high osmotic pressure combination group on PCD 6 was significantly higher than that on PCD 4 within the same group (P<0.05) and that of AGEs-high glucose combination group on PCD 6 (P<0.05). Conclusions: Both nASCs and dASCs can promote wound healing in rats with simple defect injury, but dASCs have no significant effect on wound healing in rats with diabetes mellitus, which may be related to the inhibition of ASCs proliferation and the influence of high glucose and AGEs intervention on their homeostasis and secretory function.


Assuntos
Diabetes Mellitus Experimental/terapia , Transplante de Células-Tronco , Células-Tronco/citologia , Cicatrização , Tecido Adiposo/citologia , Animais , Células Cultivadas , Diabetes Mellitus Experimental/complicações , Humanos , Masculino , Distribuição Aleatória , Ratos , Ratos Wistar
8.
Bratisl Lek Listy ; 120(9): 686-689, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31475555

RESUMO

BACKGROUND: The lipografting is increasingly used in the field of plastic surgery. Widely used harvesting technique of fatderived stem-cells is lipoaspiration. There exist two big streams of fat harvesting for lipografting: mechanical liposuction and manual liposuction. METHODS: Two harvested specimens were compared in this prospective blind study in the means of stem-cells viability and their ability to grow in cell-cultures. Techniques to compare were: manual lipoaspiration with 50 ml syringe and WAL (water-jet assisted liposuction). RESULTS: Twenty specimens from ten patients were investigated in the tissue bank. There were no differences in the amount of live stem-cells between two groups. Also no differences were found between both harvesting techniques in the mean of cell ability to grow in cell-cultures. CONCLUSION: It can be concluded that there are no statistically significant differences in the number, vitality and viability of stem cells when comparing two ways of mesenchymal stem cell collection, both manual and machine sampling (WAL). When cultured in vitro, both samples collected from each patient also appeared to be able to multiply with no statistical differences (Tab. 2, Fig. 2, Ref. 18).


Assuntos
Tecido Adiposo/citologia , Lipectomia/métodos , Células-Tronco Mesenquimais/citologia , Células Cultivadas , Humanos , Estudos Prospectivos
9.
J Agric Food Chem ; 67(38): 10595-10603, 2019 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-31475817

RESUMO

While ß-cryptoxanthin is hypothesized to have a preventive effect on lifestyle-related diseases, its underlying mechanisms are unknown. We investigated the effect of ß-cryptoxanthin on energy metabolism in adipose tissues and its underlying mechanism. C57BL/6J mice were fed a high-fat diet (60% kcal fat) containing 0 or 0.05% ß-cryptoxanthin for 12 weeks. ß-cryptoxanthin treatment was found to reduce body fat gain and plasma glucose level, while increasing energy expenditure. The expression of uncoupling protein (UCP) 1 was elevated in adipose tissues in the treatment group. Furthermore, the in vivo assays showed that the Ucp1 mRNA expression was higher in the ß-cryptoxanthin treatment group, an effect that disappeared upon cotreatment with a retinoic acid receptor (RAR) antagonist. In conclusion, we report that ß-cryptoxanthin reduces body fat and body weight gain and that ß-cryptoxanthin increases the expression of UCP1 via the RAR pathway.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , beta-Criptoxantina/administração & dosagem , Obesidade/tratamento farmacológico , Receptores do Ácido Retinoico/metabolismo , Proteína Desacopladora 1/genética , Animais , Metabolismo Energético/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/genética , Obesidade/metabolismo , Receptores do Ácido Retinoico/genética , Transdução de Sinais/efeitos dos fármacos , Proteína Desacopladora 1/metabolismo
11.
Acta Vet Scand ; 61(1): 42, 2019 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-31500653

RESUMO

BACKGROUND: Overweight and obesity have been adversely associated with longevity in dogs but there is scarce knowledge on the relation between body composition and lifespan. We aimed to investigate the effects of body composition, and within-dog changes over time, on survival in adult Labradors using a prospective cohort study design. The dogs had a median age of 6.5 years at study start and were kept in similar housing and management conditions throughout. The effects of the various predictors, including the effect of individual monthly-recorded change in body weight as a time varying covariate, were evaluated using survival analysis. RESULTS: All dogs were followed to end-of-life; median age at end-of-life was 14.0 years. Body composition was measured annually with dual-energy x-ray absorptiometer (DEXA) scans between 6.2 and 17.0  years. All 39 dogs had DEXA recorded at 8, 9 and 10 years of age. During the study the mean (± SD) percent of fat (PF) and lean mass (PL) was 32.8 (± 5.6) and 64.2 (± 5.5) %, respectively, with a mean lean:fat ratio (LFR) of 2.1 (± 0.6); body weight (BW) varied from 17.5 to 44.0 kg with a mean BW change of 9.9 kg (± 3.0). There was increased hazard of dying for every kg increase in BW at 10 years of age; for each additional kg of BW at 10 years, dogs had a 19% higher hazard (HR = 1.19, P = 0.004). For the change in both lean mass (LM) and LFR variables, it was protective to have a higher lean and/or lower fat mass (FM) at 10 years of age compared to 8 years of age, although the HR for change in LM was very close to 1.0. For age at study start, older dogs had an increased hazard. There was no observed effect for the potential confounders sex, coat colour and height at shoulders, or of the time-varying covariate. CONCLUSIONS: These results suggest that even rather late-life control efforts on body weight and the relationship between lean and fat mass may influence survival in dogs. Such "windows of opportunity" can be used to develop healthcare strategies that would help promote an increased healthspan in dogs.


Assuntos
Composição Corporal/fisiologia , Peso Corporal/fisiologia , Cães/fisiologia , Longevidade/fisiologia , Tecido Adiposo , Animais , Estudos Longitudinais , Análise de Sobrevida
12.
Anticancer Res ; 39(8): 4475-4478, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366547

RESUMO

Chronic inflammation is involved in the development of cancer, lifestyle-related diseases, and autoimmune diseases. It also influences the severity of these diseases. Macrophages that accumulate in tumor tissues and adipose tissues of obesity have been shown to increase expression of inflammatory cytokines, thereby inducing inflammatory changes in these tissues. The macrophage phenotype is believed to be important in mediating inflammatory changes in tissues. Recently, monocytes/macrophages activated with low-dose lipopolysaccharide (LPS) were demonstrated to suppress increased expression of monocyte chemotactic protein (MCP)-1 and inflammatory cytokines (interleukin (IL)-1 ß, IL-8, and tumor necrosis factor (TNF)-α). By suppressing the increased expression of chemotaxis-related and inflammation-related factors, monocytes/macrophages activated with low-dose LPS are considered to suppress the migration of macrophages into tissues and to regulate inflammatory changes in these tissues, respectively. The effects of macrophages activated with low-dose LPS were different from those of macrophages activated with high-dose LPS. In this review, we discuss the usefulness of monocytes/macrophages activation by low-dose LPS.


Assuntos
Inflamação/tratamento farmacológico , Lipopolissacarídeos/uso terapêutico , Neoplasias/tratamento farmacológico , Obesidade/genética , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Quimiocina CCL2/genética , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/genética , Interleucina-1beta/genética , Interleucina-8/genética , Macrófagos/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Neoplasias/genética , Obesidade/patologia , Fator de Necrose Tumoral alfa/genética
13.
Acta Cir Bras ; 34(6): e201900605, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31432996

RESUMO

PURPOSE: To evaluate the use of adipose-derived stem cells (ADSC) in reducing the necrosis area in an experimental model of cutaneous ischemic flap in rats submitted to subcutaneous nicotine injection to simulate a smoker patient. METHODS: In an experimental study, 30 rats were enrolled and divided into two experimental groups of 15 animals all submitted to a subcutaneous nicotine injection to create ischemic cutaneous flaps on their backs. Other 10 animals were used only to obtain adipose tissue derived stem cells (ADSC). The first group (n=15) received ADSC treatment at the end of surgery while the other group, the control (n=15), received no other interventions. After euthanasia, a decal was performed on the whole area of the flap, accurately defining the transition from necrosis to healthy region. Photos of all animals were collected and evaluated by scales standardized by Paint-Autocad- 2015 software to define the area of flap necrosis in each rat. Student T test was performed to compare the groups, considering a p< 0.05 significant. Data were analyzed using SPSS IBM® 18 version. RESULTS: Through the analysis of the images by the program Paint-Autocad-2015 and the area of decal obtained by the transparent sheet, we obtained a mean of 46% necrosis of the total area of the flap in the treatment group and 69.4% in the control group. In the descriptive analysis, a mean of 3.7 cm of necrosis CI 95% (3.2 - 4.2) was evident in the treatment group whereas a mean value of 5.56 CI 95% (5.2 - 5.9) was found in control group, with p value <0.001 for this comparison. CONCLUSION: The application of adipose-derived stem cells reduces the percentage of necrosis in an experimental model of randomized cutaneous flap in rats submitted to subcutaneous nicotine injection.


Assuntos
Adipócitos/transplante , Tecido Adiposo/transplante , Cicatriz/terapia , Necrose/prevenção & controle , Nicotina/efeitos adversos , Animais , Modelos Animais de Doenças , Sobrevivência de Enxerto , Masculino , Necrose/induzido quimicamente , Nicotina/administração & dosagem , Ratos
14.
Biomed Khim ; 65(4): 339-346, 2019 Jun.
Artigo em Russo | MEDLINE | ID: mdl-31436176

RESUMO

Secretion of 21 cytokines, chemokines and growth factors (LIF, SCF, SDF-1a, SCGF-b, M-CSF, MCP-3, MIF, MIG, TRAIL, GRO-a; IL-1a, IL-2ra, IL-3, IL-12(p40), IL-16, IL-18, HGF, TNF-b, b-NGF, IFN-a2, CTACK) has been studied in vitro in the culture of human adipose-derived multipotent mesenchymal stromal cells (hAMMSCs) in conditions of its osteogenic differentiation caused by 14-day contact with calcium phosphate (CP) surface with different roughness. Bilateral X-ray amorphous CP coatings were prepared on the samples of commercially pure titanium in the anodal regime using a micro-arc method. An aqueous solution prepared from 20 wt% phosphoric acid, 6 wt% dissolved hydrohyapatite nanopowder (particle diameter 10-30 nm with single agglomerates up to 100 nm), and 9 wt% dissolved calcium carbonate was used to obtain CP coating. hAMMSCs isolated from lipoaspirate were co-cultured after 4 passages with the CP-coated samples at final concentration of 1.5´105 viable karyocytes per 1.5 mL of standard nutrition medium (without osteogenic stimulators) for 14 days (a determination of [CD45,34,14,20], CD73, CD90 и CD105 cell immunophenotype; an analysis of secretory activity) and 21 days (alizarin red S staining of culture) with medium replacement every 3-4 days. Under conditions of in vitro contact with rough CP coating hAMMSCs differentiated into osteoblasts synthesizing the mineralized bone matrix; this was accompanied by 2-3-fold increasing ratio of [CD45,34,14,20]+ hemopoietic cells. The following humoral factors of hemopoietic niches acted as the signal molecules escalating in vitro the hemopoietic base in 14 days of differentiating three-dimensional culture of hAMMSCs: either leukemia inhibitory factor (LIF) and stem cell factor (SCF) cytokines under mean index of CP roughness Ra=2.4-2.6 mm or stromal derived factor-1 (SDF-1a, CXCL12 chemokine) under Ra=3.1-4.4 mm.


Assuntos
Fosfatos de Cálcio/farmacologia , Diferenciação Celular , Células-Tronco Mesenquimais/citologia , Osteogênese , Células-Tronco Pluripotentes/citologia , Tecido Adiposo/química , Células Cultivadas , Quimiocinas/metabolismo , Citocinas/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Células Estromais/citologia
15.
APMIS ; 127(11): 727-730, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31418929

RESUMO

Aortic valve tissue excised during stenotic valve replacement surgery commonly exhibits histopathologic changes including prominent calcification of variable severity. We present briefly a case of a 78-year-old man with aortic valve stenosis and coronary artery disease undergoing aortic valve replacement and coronary artery bypass grafting. After pathologic examination of excised tissue, the aortic valve was determined to have nodular calcification and myxoid degeneration, as well as evidence of prominent, contiguous fatty infiltration of the valve's spongiosa layer. Although osseous and chondroid metaplasia have been described within excised cardiac valves, a significant constituent of adipose tissue contiguous through the length of a valve and not representing a discrete mass-forming, neoplastic lesion has been only described in isolated case reports.


Assuntos
Tecido Adiposo/patologia , Estenose da Valva Aórtica/cirurgia , Valva Aórtica/patologia , Idoso , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/patologia , Ponte de Artéria Coronária , Próteses Valvulares Cardíacas , Histologia , Humanos , Masculino
16.
Postgrad Med ; 131(7): 453-460, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31469966

RESUMO

Objectives: Recent evidence suggests an association between functional capacity and cognitive function, at least in older adults. The aim of this cross-sectional study was to examine the association between cognitive function, functional capacity, isokinetic leg strength, health-related quality of life (HRQOL), sleep quality, body fat, handgrip strength, and fatigue among a sample of MS patients. Methods: Fifty-one relapsing-remitting MS patients (age: 38.4 ± 7.1 yrs; 30 females) were recruited and agreed to participate in this study. Cognitive function was assessed by the Paced Auditory Serial Addition Test (PASAT). Functional capacity was examined using various functional tests commonly used in MS patients. Maximal voluntary unilateral leg strength was assessed using isokinetic dynamometer. Isometric handgrip strength was assessed by a dynamometer. Total body and visceral fat levels were assessed via bioelectrical impedance analyzers. Finally, the patients' HRQOL, sleep quality, and fatigue levels were evaluated using specific questionnaires. Results: A significant association was found between the PASAT score and the performance score in various functional capacity tests (p < 0.050). On the other hand, a weak but statistically significant association was found between the PASAT score and isokinetic strength of knee extensors (r = 0.319, p = 0.022) and knee flexors (r = 0.354 p = 0.011). Poor sleep quality was associated with lower performance in all the functional capacity tests examined (p < 0.05) whilst was negatively associated with the PASAT score (r = -0.334, p = 0.017). The multivariate regression analysis revealed that the performance on the TUG test was a significant predictor of cognitive function. Conclusion: Based on the results of this study, functional capacity was found to be associated with both impaired cognitive performance and low HRQOL in MS patients. In addition, an association between sleep quality and cognitive performance was revealed, confirming existing literature. Functional capacity as assessed by the TUG test emerged as the best predictor of cognitive function.


Assuntos
Cognição , Fadiga/fisiopatologia , Força da Mão/fisiologia , Esclerose Múltipla Recidivante-Remitente/fisiopatologia , Qualidade de Vida , Tecido Adiposo , Adulto , Composição Corporal , Estudos Transversais , Impedância Elétrica , Fadiga/psicologia , Feminino , Músculos Isquiotibiais , Humanos , Gordura Intra-Abdominal , Perna (Membro) , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/psicologia , Força Muscular/fisiologia , Testes Neuropsicológicos , Músculo Quadríceps , Sono , Inquéritos e Questionários , Teste de Caminhada
17.
Br J Radiol ; 92(1103): 20190300, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31430175

RESUMO

OBJECTIVE: To validate MRI fat measurement protocols using purpose built test objects and by comparison with air-displacement plethysmography (ADP) whole-body fat measurements in non-obese subjects. METHODS: Test objects of known fat concentration were used to quantify the accuracy of the MRI measurements. 10 participants with a body mass index in the range 18-30 underwent whole-body MRI using two different Dixon-based sequences (LAVA Flex and IDEAL IQ) to obtain an estimate of their whole-body fat mass. The MRI determined fat mass was compared to the fat mass determined by ADP. RESULTS: MRI test object measurements showed a high correlation to expected fat percentage (r > 0.98). The participant MRI and ADP results were highly correlated (r = 0.99) but on average (mean ± standard deviation) MRI determined a higher fat mass than ADP (3.8 ± 3.1 kg for LAVA Flex and 1.9 ± 3.2 kg for IDEAL IQ). There was no trend in the difference between MRI and ADP with total fat mass. CONCLUSION: The good agreement between MRI and ADP shows that Dixon-based MRI can be used effectively as a tool in physiological research for non-obese adults. ADVANCES IN KNOWLEDGE: This work found that for ten non-obese subjects body mass index had no effect on the MRI determination of whole-body fat mass.


Assuntos
Tecido Adiposo/anatomia & histologia , Índice de Massa Corporal , Adulto , Ar , Feminino , Humanos , Imagem por Ressonância Magnética/métodos , Masculino , Pletismografia/métodos
18.
Gynecol Oncol ; 155(1): 69-74, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31409486

RESUMO

OBJECTIVE: Adiposity has been hypothesized to interfere with the activity of bevacizumab (BEV), an anti-angiogenic agent. Measurements of adiposity, BMI, surface fat area (SFA), and visceral fat area (VFA) were investigated as prognostic of oncologic outcomes among patients treated with chemotherapy, with or without BEV, on GOG 218, a prospective phase III trial. METHOD: Pretreatment computed tomography (CT) for 1538 GOG 218 participants were analyzed. Proportional hazards models assessed association between adiposity and overall survival (OS) adjusted for other prognostic factors. The predictive value of adiposity as a function of BEV treatment was assessed in 1019 patients randomized to either chemotherapy (CT) + placebo (P) → P or CT + BEV → BEV. RESULTS: After adjusting for prognostic factors, SFA was not associated with the overall hazard of death (p = 0.981). There was a non-significant 0.1% (p = 0.062) increase in hazard of death associated with a unit increase in VFA. When comparing the treatment HRs for patients who did and did not receive BEV, there was no association with SFA (p = 0.890) or VFA (p = 0.106). A non-significant 0.8% increase in the hazard of death with unit increase in BMI (p = 0.086) was observed. BMI values were not predictive of a longer survival for patients with BEV vs placebo (p = 0.606). CONCLUSION: Measures of adiposity strongly correlated to one another but were not predictive of efficacy for BEV. VFA is a weak prognostic factor.


Assuntos
Tecido Adiposo/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/patologia , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Adiposidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Bevacizumab/administração & dosagem , Carcinoma Epitelial do Ovário/diagnóstico por imagem , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade/patologia , Obesidade/fisiopatologia , Neoplasias Ovarianas/diagnóstico por imagem , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Tomografia Computadorizada por Raios X
19.
J Sports Med Phys Fitness ; 59(8): 1311-1318, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31373189

RESUMO

BACKGROUND: The purpose of this study was to examine the relationship between select physiological variables and sprint triathlon performance. METHODS: Moderately trained male triathletes (N.=15) performed two graded maximal exercise tests, on a cycle ergometer and a treadmill. Anaerobic capacity was evaluated, on a cycle ergometer and a treadmill. Within two weeks before or after the testing, all triathletes participated in a sprint triathlon race (750 m sea swim, 20 km cycle, 5 km run). RESULTS: The results showed that significant correlations exist between VO2max during cycling (r=-0.811, P<0.05) or running (r=-0.757, P<0.05) and overall triathlon performance. Stepwise multiple linear regression analysis, with triathlon performance as the dependent variable and the physiological measures during running as the independent variables, showed that VO2max (mL.min-1.kg-1), Time_CF, CHO_rate @ VT and % body fat yielded the best prediction of performance (R2=0,912). When only the physiological variables from cycling were included into the model, the results showed that VO2max (mL.min-1), VO2max (mL.min-1.kg-1) and PFmax (rpm) explained 88% of the variation in sprint triathlon performance. CONCLUSIONS: Our data indicate that overall race time for moderately trained triathletes, competing over the sprint distance can be accurately predicted from maximal laboratory tests.


Assuntos
Ciclismo/fisiologia , Corrida/fisiologia , Natação/fisiologia , Tecido Adiposo/fisiologia , Adulto , Desempenho Atlético/fisiologia , Teste de Esforço/métodos , Humanos , Modelos Lineares , Masculino , Consumo de Oxigênio/fisiologia , Fatores de Tempo
20.
Cell Prolif ; 52(5): e12669, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31380594

RESUMO

OBJECTIVES: The present study aimed to investigate whether exosomes derived from miR-375-overexpressing human adipose mesenchymal stem cells (hASCs) could enhance bone regeneration. MATERIALS AND METHODS: Exosomes enriched with miR-375 (Exo [miR-375]) were generated from hASCs stably overexpressing miR-375 after lentiviral transfection and identified with transmission electron microscopy, nanosight and western blotting. The construction efficiency of Exo (miR-375) was evaluated with qRT-PCR and incubated with human bone marrow mesenchymal stem cells (hBMSCs) to optimize the effective dosage. Then, the osteogenic capability of Exo (miR-375) was investigated with ALP and ARS assays. Furthermore, dual-luciferase reporter assay and western blotting were conducted to reveal the underlying mechanism of miR-375 in osteogenic regulation. Finally, Exo (miR-375) were embedded with hydrogel and applied to a rat model of calvarial defect, and µ-CT analysis and histological examination were conducted to evaluate the therapeutic effects of Exo (miR-375) in bone regeneration. RESULTS: miR-375 could be enriched in exosomes by overexpressing in the parent cells. Administration of Exo (miR-375) at 50 µg/mL improved the osteogenic differentiation of hBMSCs. With miR-375 absorbed by hBMSCs, insulin-like growth factor binding protein 3 (IGFBP3) was inhibited by binding to its 3'UTR, and recombinant IGFBP3 protein reduced the osteogenic effects triggered by Exo (miR-375). After incorporated with hydrogel, Exo (miR-375) displayed a slow and controlled release, and further in vivo analysis demonstrated that Exo (miR-375) enhanced the bone regenerative capacity in a rat model of calvarial defect. CONCLUSIONS: Taken together, our study demonstrated that exosomes derived from miR-375-overexpressing hASCs promoted bone regeneration.


Assuntos
Regeneração Óssea/fisiologia , Exossomos/metabolismo , MicroRNAs/metabolismo , Regiões 3' não Traduzidas , Tecido Adiposo/citologia , Animais , Regeneração Óssea/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células , Células Cultivadas , Exossomos/transplante , Humanos , Hidrogéis/química , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/química , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , Osteogênese/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/farmacologia , Crânio/patologia , Crânio/fisiologia , Fraturas Cranianas/patologia , Fraturas Cranianas/terapia
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