RESUMO
Obesity is associated with increased colonic inflammation, which elevates the risk of colon cancer. Although exercise exerts anti-inflammatory actions in multiple chronic diseases associated with inflammation, it is unknown whether this strategy prevents colonic inflammation in obesity. We hypothesized that voluntary exercise would suppress colonic inflammation in high-fat diet (HFD)-induced obesity by modulation of peroxisome proliferator-activated receptor (PPAR)-γ. Male C57Bl/6J mice fed either a control diet (6.5% fat, CON) or a high-fat diet (24% fat, HFD) were divided into sedentary, voluntary exercise or voluntary exercise with PPAR-γ antagonist GW9662 (10 mg/kg/day). All interventions took place for 12 weeks. Compared with CON-sedentary group, HFD-sedentary mice gained significantly more body weight and exhibited metabolic disorders. Molecular studies revealed that HFD-sedentary mice had increased expression of inflammatory mediators and activation of nuclear factor (NF)-κB in the colons, which were associated with decreased expression and activity of PPAR-γ. Voluntary exercise markedly attenuated body weight gain, improved metabolic disorders, and normalized the expression of inflammatory mediators and activation of NF-κB in the colons in HFD-mice while having no effects in CON-animals. Moreover, voluntary exercise significantly increased expression and activity of PPAR-γ in the colons in both HFD- and CON-animals. However, all of these beneficial effects induced by voluntary exercise were abolished by GW9662, which inhibited expression and activity of PPAR-γ. The results suggest that decreased PPAR-γ activity in the colon of HFD-induced obesity may facilitate the inflammatory response and colon carcinogenesis. Voluntary exercise prevents colonic inflammation in HFD-induced obesity by up-regulating PPAR-γ activity.
Assuntos
Colite/metabolismo , Colite/prevenção & controle , PPAR gama/metabolismo , Esforço Físico , Adiponectina/sangue , Anilidas/farmacologia , Animais , Peso Corporal , Colite/etiologia , Colo/efeitos dos fármacos , Colo/metabolismo , Dieta Hiperlipídica/efeitos adversos , Ingestão de Alimentos , Teste de Tolerância a Glucose , Mediadores da Inflamação/metabolismo , Insulina/sangue , Leptina/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Obesidade/complicações , Obesidade/metabolismo , Obesidade/patologia , PPAR gama/antagonistas & inibidores , Regulação para CimaRESUMO
To observe the effect of Ligusticum wallichii-containing serum on the expressions of Toll-like receptor 4 and myeloid differentiation factor 88 in hepatic stellate cells. Clean-grade SD rats were randomly divided into 5 groups and orally given L. wallichii decoction, colchicine and normal saline for 7 d to prepare L. wallichii-containing serums. Except for the blank group, all of the remaining groups were stimulated with LPS 1 mg x L(-1) for 24 h. After being intervened, the L. wallichii-containing serums were cultured in 5% CO2 incubator at 37 degrees C for 24 hours. The expression of TLR4 and MyD88 were detected by RT-PCR and Western blot. After HSC was stimulated with LPS, TLR4 and MyD88 mRNA and protein expressions were significantly higher than the blank control group (P < 0.01). After being intervened with L. wallichii-containing serum, TLR4 and MyD88 mRNA and protein expressions were notably lower than the model group (P < 0.05 or P < 0.01). In conclusion, L. wallichii-containing serum could regulate the TLR4 signaling pathway and show the anti-fibrosis effect by inhibiting the expression of TLR4 and MyD88 in LPS-induced HSCs.
Assuntos
Células Estreladas do Fígado/efeitos dos fármacos , Ligusticum , Fator 88 de Diferenciação Mieloide/genética , Receptor 4 Toll-Like/genética , Animais , Feminino , Células Estreladas do Fígado/metabolismo , Lipopolissacarídeos/farmacologia , Cirrose Hepática Experimental/tratamento farmacológico , Fator 88 de Diferenciação Mieloide/fisiologia , Fitoterapia , RNA Mensageiro/análise , Ratos , Ratos Sprague-Dawley , Receptor 4 Toll-Like/fisiologiaRESUMO
To observe the effects of Danshen-containing serum on SuFu and DYRK2 expression in the HSCs stimulated by leptin. SD rats (n = 60) were used to make danshen-containing serum by gastric perfusion for ten days with Danshen water decoction, normal saline and colchicine. The HSCs that were cultured in vitro would be stimulated for 24 hours by leptin (100 µg x L(-1)) except blank control group, after being intervened, the drug serum in each group would be cultured at 37 degrees C in 5% incubator. The cells would be collected after 24 hours, then the effects of danshen-containing serum on the proliferation of HSCs were detected by MTT, the expression of SuFu mRNA and DYRK2 mRNA were detected by RT-PCR, the expression of SuFu and DYRK2 proteins were tested by Western blot. Compared with blank control group, the expression of DYRK2 mRNA and DYRK2 proteins were enhanced obviously after stimulated the HSCs of rats by leptin (P < 0.01), but the expression of SuFu mRNA and SuFu proteins were decreased significantly (P < 0.01). Compared with the model group, after cyclopamine group (Hh pathway inhibitor), Danshen-containing serum and colchicine were interfered, the expression of DYRK2 mRNA and DYRK2 proteins were decreased clearly (P < 0.01), but the expression of SuFu mRNA and SuFu proteins were increased significantly (P < 0.01 or P < 0.05). Compared with model group, adding purmorphamine (Hh pathway agonist) to model group and making it activate could increase the expression of DYRK2 mRNA and DYRK2 proteins, but the expression of SuFu mRNA and SuFu proteins were decreased significantly (P < 0.01). Compared with the model group, using the Danshen-containing serum to interfere the purmorphamine group could make the expression of DYRK2 mRNA and DYRK2 proteins decrease and the expression of SuFu mRNA and SuFu proteins increase significantly (P < 0.01). Danshen-containing serum would inhibition the activation and increment of HSCs by interfering the expression of SuFu and DYRK2 which were induced by leptin.
Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Células Estreladas do Fígado/efeitos dos fármacos , Cirrose Hepática/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Tirosina Quinases/genética , Proteínas Repressoras/genética , Salvia miltiorrhiza/química , Animais , Feminino , Células Estreladas do Fígado/metabolismo , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Masculino , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Tirosina Quinases/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas Repressoras/metabolismo , Quinases DyrkRESUMO
BACKGROUND: The microsurgical treatment of paraclinoid aneurysms can be challenging due to the anatomical structures that surround them. OBJECTIVE: This study compared the clinical and angiographic outcomes of unruptured paraclinoid aneurysms treated with enterprise (EP) stents and low-profile visualized intraluminal support (LVIS) stents. METHODS: A retrospective analysis of the clinical and radiological data from 133 patients with 139 unruptured paraclinoid aneurysms, who received an EP or an LVIS stent between January 2017 and June 2021 at Taizhou People's Hospital, was performed. Immediate postoperative and follow-up angiographic results were analyzed retrospectively using the Raymond-Roy occlusion classification (RROC). Any complications following the procedure and the patients' clinical outcomes were noted. RESULTS: Enterprise stents were used for stent-assisted coiling in 64 patients with 68 aneurysms and LVIS stents were used in 69 patients with 71 aneurysms. Both groups exhibited an increase in the proportion of aneurysms meeting the criteria for RROC class I, but the LVIS group demonstrated a higher rate of aneurysms meeting the class I criteria compared with the EP group, both on immediate postoperative angiography (45.1% vs. 11.8%, p< 0.001) and on follow-up angiography (94.9% vs. 80.6%, p= 0.025). Procedure-related complications were experienced by 9.4% of patients in the EP group (one coil prolapse, two parent artery occlusions, and three thromboembolic events), and 8.7% of patients in the LVIS group (three stent-related thrombosis and three thromboembolic events). There were no statistically significant differences between the two groups in relation to perioperative complications (p= 0.746) or favorable clinical outcomes (p= 0.492). CONCLUSION: A greater proportion of aneurysms in the LVIS group met the criteria for RROC class I compared with the EP group. There is no significant difference in procedural complications or clinical outcomes between EP and LVIS stents. Although no aneurysm recurrence was observed during the short follow-up period, continued monitoring is required.
Assuntos
Procedimentos Endovasculares , Aneurisma Intracraniano , Humanos , Estudos Retrospectivos , Aneurisma Intracraniano/cirurgia , Resultado do Tratamento , Angiografia Cerebral/métodos , Stents , Procedimentos Endovasculares/métodosRESUMO
OBJECTIVE: To explore the mechanism of occupational medicamentosa-like dermatitis (OMDT) induced by trichloroethylene (TCE) and some immunity indexes in workers occupationally exposed to TCE. METHODS: The blood samples from 8 cases with medicamentosa-like dermatitis in 1st, 2nd, 3rd, 4th and 5th weeks after admitting to hospital were examined for liver function, immunoglobulin and some complement indexes. Thirty nine workers occupationally exposed to TCE were investigated for urinary TCE and some immuno-complement indexes. The TCE concentrations of air in workplaces were monitored. RESULTS: C3d-CIC and C3 of patients before admission were (92.86 ± 44.80) mg/L and 0.91 ± 0.19 mg/L, respectively. C3d-CIC and C3 of patients before discharge were (52.41 ± 17.75) mg/L and (1.14 ± 0.22) mg/L, respectively. There were significant differences between admission and discharge (P < 0.05). The average TCE concentration in 4 workplaces was (351.96 ± 36.72) mg/m(3), which was higher than the occupational exposure limits (OELs). The number of workers exposed to the TCE concentration-time weighted and TCA in urine over OELs were 28.21% and 56.41% of total subjects, respectively. The serum IgG and CIC levels of patients before discharge were (10.03 ± 1.21) mg/L and 103.50 ± 29.17 mU/L, which were significantly lower than those (17.21 ± 1.85) mg/L and (227.46 ± 111.67) mU/L of patients before admission (P < 0.01). CONCLUSION: The type II and III hypersensitivity may be associated with OMDT and the organ injure induced by TCE.
Assuntos
Proteínas do Sistema Complemento/imunologia , Dermatite Ocupacional/imunologia , Exposição Ocupacional , Tricloroetileno/toxicidade , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto JovemRESUMO
OBJECTIVE: To study the methods of extraction, isolation, purification and biological activities of Arnebia euchroma glycosaminoglycans (AEG). METHODS: AEG was purified by distilled water extraction, ethanol fractionation, Sephadex column chromatography. The purity and molecular weight and concentration of AEG were measured by HPLC; We divided the experiment into Physiological Saline group and the other eight groups with different doses of AEG, established RT-PRC method to observe the anti-HPV effect after their actions on the verruca tissues. RESULTS: Using HPLC, the group of AEG was divided into two glycosaminoglycans with different molecular weight as 27336 and 1152. Bioassay results showed that AEG had anti-HPV-DNA activity, the lowest effective concentration was 0.781 mg/ml. CONCLUSION: AEG extracted by this method is a mixture with two molecular weight glycosaminoglycans, and has obvious anti-HPV effect.
Assuntos
Boraginaceae/química , Glicosaminoglicanos/isolamento & purificação , Glicosaminoglicanos/farmacologia , Papillomavirus Humano 6/efeitos dos fármacos , Plantas Medicinais/química , Cromatografia Líquida de Alta Pressão , DNA Viral/efeitos dos fármacos , DNA Viral/isolamento & purificação , Glicosaminoglicanos/química , Papillomavirus Humano 6/isolamento & purificação , Concentração de Íons de Hidrogênio , Peso Molecular , Tecnologia Farmacêutica/métodosRESUMO
Hepatocellular carcinoma (HCC) is one of the most lifethreatening diseases in the world. Members of the GTPase of the immunityassociated protein (GIMAP) family are important in regulating apoptosis in cancer cells. However, the basic mechanism of GIMAP in HCC remains to be fully elucidated. The present study was performed to investigate the dysregulation of GIMAP family members in HCC. The techniques of polymerase chain reaction analysis, immunohistochemistry and ELISA were used to analyze the expression of GIMAP5 and GIMAP6 in HCC tissues, in matched noncancerous tissue samples, and in blood samples obtained from patients with HCC and healthy subjects. It was found that the mRNA expression levels of GIMAP5 and GIMAP6 were significantly downregulated in the HCC tumor samples, compared with the levels of expression in the matched nontumor tissue samples. Similarly, the mRNA expression levels of GIMAP5 and GIMAP6 were also significantly downregulated in the blood samples from patients with HCC, compared with the expression levels in the blood from healthy subjects. At the protein level, it was found that the GIMAP5 and GIMAP6 proteins were expressed at lower levels in the tumor tissue samples, compared with the matched normal tissue samples, and their expression levels were also lower in the blood samples from patients with HCC, compared with the blood samples from the healthy subjects. These data, demonstrating the downregulation of the mRNA and protein expression levels of GIMAP5 and GIMAP6 in the tumor tissues and blood of patients with HCC, suggested the involvement of GIMAP5 and GIMAP6 in the pathogenesis of HCC, and indicate their possible use as diagnostic markers for HCC.
Assuntos
Carcinoma Hepatocelular/genética , GTP Fosfo-Hidrolases/biossíntese , Proteínas de Ligação ao GTP/biossíntese , Neoplasias Hepáticas/genética , Adolescente , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Feminino , Proteínas de Ligação ao GTP/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Família Multigênica , RNA Mensageiro/biossíntese , RNA Mensageiro/genéticaRESUMO
OBJECTIVE: To investigate the differentiation of bone marrow stem cells in transplanted livers and its impact on the long-term survival of rats with orthotopic liver transplantation. METHODS: Twenty-four female recipient rats with orthotopic liver transplantation were randomized into blank-control group, D-hanks solution group, bone marrow stem cells group with postoperative infusion of stem cells, and the pathological changes of the liver grafts and survival time of the rats were observed. The differentiation of the bone marrow stem cells were assessed 60 days after transplantation using in situ hybridization histochemistry for Sry gene and alpha-fetoprotein (AFP) immunohistochemistry. RESULTS: In rats with postoperative infusion of bone marrow stem cells through the portal vein, the median long-term graft survival time exceeded 180 days, significantly longer than that in the other two groups (P<0.05), and no obvious evidence of acute rejection was observed with positive Sry expression and AFP expression. CONCLUSION: Infusion of bone marrow stem cells through the portal vein following liver transplantation may alleviate acute graft rejection and promote long-term liver graft survival and AFP expression.
Assuntos
Diferenciação Celular , Sobrevivência de Enxerto , Células-Tronco Hematopoéticas/citologia , Transplante de Fígado , Animais , Feminino , Rejeição de Enxerto/prevenção & controle , Fígado/patologia , Veia Porta , Ratos , Ratos WistarRESUMO
OBJECTIVE: To introduce the eukaryotic expression vector pEGFP-C1-PDX-1 into nestin-positive cell derived from bone marrow stromal cells by nucleofection and optimize the conditions for transfection. METHODS: The recombinant plasmid was transfected into bone marrow stromal cells-derived nestin-positive cells with varied DNA quantities or the serum concentration in the medium. The expression of PDX-1 gene in the transfected cells was detected by RT-PCR. RESULTS: Satisfactory efficiency of transfection was achieved with the DNA quantity of 2-10 microg and medium serum concentration of 20%. PDX-1 expression was detected in the transfected cells by RT-PCR. CONCLUSION: The optimized transfection conditions result in enhanced efficiency of PDX-1 gene transfection into nestin-positive cells derived from bone marrow stromal cells, which may serve as the seed cells in tissue-engineering.
Assuntos
Células da Medula Óssea/metabolismo , Proteínas de Homeodomínio/genética , Células Estromais/metabolismo , Transativadores/genética , Transfecção/métodos , Vetores Genéticos , Humanos , Proteínas de Filamentos Intermediários/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Nestina , PlasmídeosRESUMO
OBJECTIVE: To investigate the protective effect of the ischemia preconditioning of the donor liver on posttransplant liver graft function in Chinese miniature pigs. METHODS: Twenty-five partially inbred Chinese miniature pigs were randomized into three groups, namely the normal control group, the ischemia-reperfusion group and ischemic preconditioning group. Biopsies of the liver graft were performed to analyze HSP70 expression by means of immunoblotting, and the changes of serum AST/ALT levels were assayed using an automated biochemical analyzer. Histopathological assessment was carried out to identify the hepatocyte injury using optical and transmission electron microscopy. RESULTS: Ischemia preconditioning resulted in a notable increase in HSP70 expression and milder injury of the hepatocyte microstructure, whereas ischemia-reperfusion caused a significant increase of serum transaminases level (P<0.01) with declined HSP70 expression and obvious microstructural changes of the liver tissue. CONCLUSION: Ischemic preconditioning can produce obvious protective effects on the donor liver, and positively regulates the expression of shock protein.