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1.
J Ethnopharmacol ; 251: 112554, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31923541

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is tightly associated with inflammation response and oxidative stress. As a folk medicine applied in treatment of diarrhea, Bruguiera gymnorrhiza also possesses anti-inflammatory and anti-oxidative activities, which indicated that B. gymnorrhiza may exert anti-colitis effect. AIM OF THE STUDY: To investigate effect and mechanism of B. gymnorrhiza on experimental UC. MATERIALS AND METHODS: Aqueous extract of B. gymnorrhiza leaves (ABL) was used for investigation in the present study. Murine UC was established through access to 3% dextran sulfate sodium (DSS) for 7 days. Meanwhile, mice accepted treatment with ABL (25, 50, 100 mg/kg) or sulfasalazine (200 mg/kg) once daily. On the last day, disease activity index (DAI) including body weight loss, fecal character and degree of bloody diarrhea was evaluated, colon segments were obtained for length measurement and further analysis and feces were collected for intestinal microbiota analysis. RESULTS: ABL ameliorated DAI scores, colon length shortening and histopathological damage in DSS-induced colitis mice obviously. SOD activity, levels of MDA and GSH altered by colitis were restored remarkably after ABL treatment. ABL inhibited increases in levels of colonic COX-2, iNOS, TNF-α, IL-6, IL-1ß, IL-4, IL-10 and IL-11 in colitis mice. Moreover, ABL prominently suppressed NF-κB p65 and IκB phosphorylation and down-regulated mRNA levels of COX-2, iNOS, TNF-α, IL-6 and IL-1ß elevated by colitis. As shown in microbiota analysis, ABL modulated composition of intestinal microbiota of colitis mice. CONCLUSION: ABL exhibited protective effect against DSS-induced ulcerative colitis through suppressing NF-κB activation and modulating intestinal microbiota.

2.
Mol Cell Endocrinol ; 472: 107-116, 2018 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-29203371

RESUMO

Small fiber neuropathy (SFN) is a common complication in diabetes, and is characterized by decreased intraepidermal nerve fiber density (IENFD). Semaphorin 3A (Sema3A), which is produced by keratinocytes, has a chemorepulsive effect on intraepidermal nerve fibers. mTOR signaling can mediate local protein synthesis that is critical for growth of axons and dendrites. Therefore, this study aimed to investigate whether Sema3A is up-regulated in diabetic keratinocytes via the mTOR-mediated p70 S6K and 4E-BP1 signaling pathways, and furthermore whether it is involved in the pathogenesis of diabetic SFN. IENFD, expression of Sema3A, and mTOR signaling, were evaluated in the skin of diabetic patients with SFN as well as control subjects. Sema3A and mTOR signaling were also assessed in HaCaT cells which had been treated with high glucose (HG) or recombinant Sema3A (rSema3A) in the presence or absence of rapamycin. Small fiber dysfunction was evaluated by examining IENFD and using behavioral tests in control and streptozotocin-induced diabetic rats treated with or without rapamycin. We found that higher Sema3A expression and over-activation of mTOR signaling, was accompanied by reduced IENFD in the skin of diabetic patients compared with control subjects. The expression of Sema3A, and mTOR signaling were up-regulated in HaCaT cells incubated with HG or rSema3A, and this could be attenuated by rapamycin. Hyperalgesia, reduced IENFD, and up-regulated Sema3A and mTOR signaling were also detected in diabetic rats. These effects were ameliorated by rapamycin treatment. Our data indicate that HG up-regulates Sema3A expression by activating mTOR signaling in diabetic keratinocytes. This pathway may therefore play a critical role in diabetic SFN.


Assuntos
Neuropatias Diabéticas/tratamento farmacológico , Glucose/toxicidade , Queratinócitos/metabolismo , Semaforina-3A/metabolismo , Transdução de Sinais , Neuropatia de Pequenas Fibras/tratamento farmacológico , Serina-Treonina Quinases TOR/metabolismo , Regulação para Cima/efeitos dos fármacos , Animais , Glicemia/metabolismo , Estudos de Casos e Controles , Linhagem Celular , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Neuropatias Diabéticas/sangue , Neuropatias Diabéticas/patologia , Feminino , Humanos , Hiperalgesia/patologia , Queratinócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Ratos Sprague-Dawley , Sirolimo/farmacologia , Pele/inervação , Pele/patologia , Neuropatia de Pequenas Fibras/sangue , Neuropatia de Pequenas Fibras/patologia
3.
Zhongguo Dang Dai Er Ke Za Zhi ; 19(4): 463-469, 2017 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-28407837

RESUMO

OBJECTIVE: To study the effects of embryonic lead exposure on food intake and bowel movement in offspring rats and possible mechanisms. METHODS: Sprague-Dawley rats were given 0.1% (low-dose lead exposure group) or 0.2% (high-dose lead exposure group) lead acetate freely during pregnancy to establish an animal model of embryonic lead exposure. A blank control group was also established. The male offspring rats were enrolled in the study, and 10 male offspring rats from each group were selected to observe the changes in food intake, bowel movement, gastric emptying, intestine propulsion, and pathological inflammatory response in the gastric mucosa. Eight offspring rats were selected from each group, and electron microscopy and immunohistochemistry were used to observe the changes in the ultrastructure of jejunal microvilli and cell junction and the expression of cholecystokinin-8 (CCK-8) and motilin (MTL) in the feeding center, in order to reveal the possible mechanisms for abnormal gastrointestinal motility in offspring rats induced by embryonic lead exposure. RESULTS: Compared with the control group, the low- and high-dose lead exposure groups had a significant reduction in daily food intake, a significant increase in water content of feces, a significant reduction in fecal pellet weight, and a significant increase in small intestine propulsion (P<0.05). The high-dose lead exposure group had a significant reduction in gastric emptying ability compared with the control group (P<0.05). Compared with the control group, the lead exposure groups had significantly greater pathological inflammatory changes in the gastric mucosa (P<0.05), significant reductions in the number and length of the jejunal microvilli and the number of epithelial desmosome junctions (P<0.05), a significant increase in the macula densa gap (P<0.05), and significant increases in the expression of MTL and CCK-8 in the feeding center (P<0.05), in a dose-dependent manner. CONCLUSIONS: The degree of gastrointestinal structural injury and expression levels of MTL and CCK-8 in the feeding center are lead dose-dependent, which may be important mechanisms for changes in food intake, bowel movement, and digestive functions in offspring rats induced by embryonic lead exposure.


Assuntos
Defecação/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Feto/efeitos dos fármacos , Chumbo/toxicidade , Animais , Feminino , Esvaziamento Gástrico/efeitos dos fármacos , Jejuno/efeitos dos fármacos , Jejuno/patologia , Ratos , Ratos Sprague-Dawley
4.
Zhongguo Dang Dai Er Ke Za Zhi ; 19(3): 361-367, 2017 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-28302213

RESUMO

OBJECTIVE: To explore the effects of embryonic lead exposure on motor function and balance ability in offspring rats and the possible mechanisms. METHODS: An animal model of embryonic lead exposure was prepared with the use of pregnant Sprague-Dawley rats freely drinking 0.1% (low-dose group, LG) or 0.2% (high-dose group, HG) lead acetate solution. A normal control group (NG) was also set. The male offspring rats of these pregnant rats were included in the study, consisting of 12 rats in the NG group, 10 rats in the LG group, and 9 rats in the HG group. The offspring rats' motor function and balance ability were evaluated using body turning test and coat hanger test. Eight rats were randomly selected from each group, and immunohistochemistry and Timm's staining were employed to measure the expression of c-Fos and mossy fiber sprouting (MFS) in the hippocampus. RESULTS: The HG group had a significantly longer body turning time than the NG and LG groups (P<0.05), and the LG group had a significantly longer body turning time than the NG group (P<0.05). The HG group had a significantly lower score of balance ability than the NG and LG groups (P<0.05), and the LG group had a significantly lower score of balance ability than the NG group (P<0.05). The area percentage of c-Fos-positive neurons in the hippocampal CA1 region was significantly higher in the HG group than in the other two groups (P<0.05), and it was significantly higher in the LG group than in the NG group (P<0.05). The semi-quantitative scores of MFS in the hippocampal CA3 region and dentate gyrus were significantly higher in the HG group than in the other two groups (P<0.05), and they were significantly higher in the LG group than in the NG group (P<0.05). CONCLUSIONS: Embryonic lead exposure could impair the offspring rats' motor function and balance ability. These changes may be related to increased c-Fos expression in the hippocampal CA3 region and abnormal MFS in the hippocampal CA3 region and dentate gyrus.


Assuntos
Feto/efeitos dos fármacos , Chumbo/toxicidade , Atividade Motora/efeitos dos fármacos , Equilíbrio Postural/efeitos dos fármacos , Animais , Feminino , Hipocampo/química , Hipocampo/efeitos dos fármacos , Masculino , Fibras Musgosas Hipocampais/efeitos dos fármacos , Gravidez , Proteínas Proto-Oncogênicas c-fos/análise , Ratos , Ratos Sprague-Dawley
5.
ACS Appl Mater Interfaces ; 8(23): 14845-54, 2016 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-27229625

RESUMO

Phenylboronic acid (PBA) is a tumor-targeting molecule, but its nonspecific interaction with normal cells or other components containing cis-diol residues undoubtedly limits its potential application in tumor-targeting drug delivery. Herein, we developed fructose-coated mixed micelles via PBA-terminated polyethylene glycol monostearate (PBA-PEG-C18) and Pluronic P123 (PEG20-PPG70-PEG20) to solve this problem, as the stability of borate formed by PBA and fructose was dramatically dependent on pH. The fluorescence spectroscopic results indicated that the borate formed by PBA and fructose decomposed at a decreased pH, and better binding between PBA and sialic acid (SA) was observed at a low pH. These results implied that the fructose groups decorated on the surface of the micelles could be out-competed by SA at a low pH. In vitro uptake and cytotoxicity studies demonstrated that the fructose coating on the mixed micelles improved the endocytosis and enhanced the cytotoxicity of drug-loaded mixed micelles in HepG2 cells but reduced the cytotoxicity in normal cells. These results demonstrate that a simple decorating strategy may facilitate PBA-targeted nanoparticles for tumor-specific drug delivery.


Assuntos
Ácidos Borônicos/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Antineoplásicos/administração & dosagem , Ácidos Borônicos/química , Ácidos Borônicos/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Células Hep G2 , Humanos , Concentração de Íons de Hidrogênio , Micelas , Neoplasias/tratamento farmacológico , Polietilenoglicóis
6.
ACS Appl Mater Interfaces ; 7(28): 15148-53, 2015 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-26168166

RESUMO

Drug delivery has become an important strategy for improving the chemotherapy efficiency. Here we developed a multifunctionalized nanosized albumin-based drug-delivery system with tumor-targeting, cell-penetrating, and endolysosomal pH-responsive properties. cRGD-BSA/KALA/DOX nanoparticles were fabricated by self-assembly through electrostatic interaction between cell-penetrating peptide KALA and cRGD-BSA, with cRGD as a tumor-targeting ligand. Under endosomal/lysosomal acidic conditions, the changes in the electric charges of cRGD-BSA and KALA led to the disassembly of the nanoparticles to accelerate intracellular drug release. cRGD-BSA/KALA/DOX nanoparticles showed an enhanced inhibitory effect in the growth of αvß3-integrin-overexpressed tumor cells, indicating promising application in cancer treatments.


Assuntos
Albuminas/química , Antineoplásicos/química , Peptídeos Penetradores de Células/química , Doxorrubicina/química , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/instrumentação , Humanos , Tamanho da Partícula
7.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 41(3): 267-73, 2012 May.
Artigo em Chinês | MEDLINE | ID: mdl-22723161

RESUMO

OBJECTIVE: To screening differentially expressed genes related to adipocyte differentiation. METHODS: Total RNA extracted from the preadipocyte cell line SW872 was taken as the Driver and the total RNA from the differentiated adipocytes SW872 as the Tester. Suppression subtractive hybridization (SSH) was used to isolate the cDNA fragments of differentially expressed genes. The products of SSH were inserted into pGM-T vector to establish the subtractive library. The library was amplified through E.coli transformation and positive clones of the transformants were screened. Positive clones were sequenced. Nucleic acid similarity was subsequently analyzed by comparing with the data from GenBank. RESULTS: There were 135 white clones in the cDNA library, 64 positive clones were chosen randomly and sequenced and similarity search revealed 34 genes which expressed differentially in adipocyte differentiation. CONCLUSION: The subtracted cDNA library for differentially expressed in adipocyte differentiation has been successfully constructed and the interesting candidate genes related to adipocyte differentiation have been identified.


Assuntos
Adipócitos/citologia , Diferenciação Celular/genética , Hibridização de Ácido Nucleico/métodos , Linhagem Celular , Clonagem Molecular , Perfilação da Expressão Gênica , Biblioteca Gênica , Vetores Genéticos , Humanos , Transformação Bacteriana
8.
Zhongguo Dang Dai Er Ke Za Zhi ; 12(9): 740-3, 2010 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-20849727

RESUMO

OBJECTIVE: To study the effects of early high fat diet on sugar metaboliam, insulin sensibility and pancreatic ß cellularity in young rats. METHODS: Sixty male weaned young rats were randomly fed with high fat diet (high fat group) and normal diet (control group). The body weight, viscus fattiness and fasting plasma glucose (FPG) were measured after 3, 6 and 9 weeks. Serum insulin level was measured with radioimmunoassay. The ultrastructure of pancreas was observed under an electricmicroscope. RESULTS: The high fat group had significantly higher body weight and visceral fat weight than the control group after 3 weeks. There were no significant differences in the FPG level between the two groups at all time points. The levels of fasting insulin and HOMAIR in the high fat group were significantly higher than those in the control group after 3, 6 and 9 weeks (P<0.01). Dilation of rough endoplasmic reticulum and mild swelling of mitochondria of islet ß-cells were observed in the high fat group after 6 weeks. CONCLUSIONS: Early high fat diet may induce a reduction in insulin sensitivity and produce insulin resistance in young rats. Endoplasmic reticulum expansion in ß-cells may be an early sign of ß-cell damage due to obesity.


Assuntos
Gorduras na Dieta/efeitos adversos , Resistência à Insulina , Células Secretoras de Insulina/patologia , Animais , Glicemia/análise , Insulina , Células Secretoras de Insulina/ultraestrutura , Gordura Intra-Abdominal/patologia , Masculino , Ratos , Ratos Sprague-Dawley
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