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<p><b>OBJECTIVE</b>To observe the effect of Compound Zhajin Granule (CZG) on Toll-like re-ceptor 4 (TLR4) signaling pathway in high-fructose corn syrup induced NASH mice.</p><p><b>METHODS</b>Thirty 6-week-old male C3H mice were divided into the high fat and high fructose (HFHFr) group (n = 20) and the control group (n = 10) according to body weight. Mice in the HFHFr group ate high fat diet and drank 20% fructose water, while those in the control group ate common diet and drank common water. After 8 weeks mice in the HFHFr group were divided into two group according to body weight, the HFHFr group and the CZG group, 10 in each group. Mice in the CZG group were fed with high fat forage and 20% fructose water, and administered with 50 mL/kg 12. 8% CZG (prepared by hawthorn, Radix Curcumae, Alisma Orientale, Fritillaria Thunbergii, Silybum Marianum, peach seed in the ratio of 3:1.5:1.5:2:1.5:2:1) by gastrogavage. Mice in the HFHFr group were fed in the same way and daily administered with equal volume of distilled water by gastrogavage. Sixteen weeks later all mice were sacrificed. Body weight, liver wet weight, liver function, and lipid metabolism were detected. Pathological changes of liver tissues were assessed by HE staining, oil red O staining, and Masson staining. Expressions of TLR4, myeloid differentiation factor 88 (MyD88), tumor necrosis factor-alpha (TNF-α) were detected using immunohistochemical staining and real-time fluorescent quantitative PCR.</p><p><b>RESULTS</b>Body weight, alanine aminotransferase (ALT), aspartate aminotransferase (AST) were obviously lower in the CZG group than in the HFHFr group (P < 0.05); oil red O stained area and density were decreased more in the CZG group than in the control group. HE staining showed ballooning inflammation was reduced more in the CZG group than in the HFHFr group. Masson staining was negative. Positive rates of TLR4 and MyD88 and mRNA expressions were significantly lower in the CZG group than in the HFHFr group (all P < 0.05).</p><p><b>CONCLUSION</b>CZG could significantly inhibit TLR4 signaling pathway of liver in NASH mice.</p>
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Animais , Masculino , Camundongos , Alanina Transaminase , Metabolismo , Aspartato Aminotransferases , Metabolismo , Dieta Hiperlipídica , Medicamentos de Ervas Chinesas , Farmacologia , Frutose , Inflamação , Metabolismo dos Lipídeos , Camundongos Endogâmicos C3H , Fator 88 de Diferenciação Mieloide , Metabolismo , Hepatopatia Gordurosa não Alcoólica , Tratamento Farmacológico , Transdução de Sinais , Receptor 4 Toll-Like , Metabolismo , Fator de Necrose Tumoral alfa , MetabolismoRESUMO
<p><b>OBJECTIVE</b>To investigate the expression of F4/80, NF-kappaB, p-AKT, AKT in the liver of nonalcoholic fatty liver disease (NAFLD) mice. To determine the role of Kupffer cells (KCs) in the development of NASH (non-alcoholic steatohepatitis), and understand the pathogenic mechanism of NASH.</p><p><b>METHODS</b>Five C3H/HeN mice fed with normal diet were served as controls, while fifteen fed with high fat, high fructose, high fat combined fructose diet respectively for 16 weeks were as NAFLD mice models. The liver inflammation and hepatic damage were examined, and the expression of F4/80, NF-Kb, p-AKT, AKT and the content of lipid in the liver were also detected.</p><p><b>RESULTS</b>Chronic intake of high fat and 30% fructose solution caused a significant increase in hepatic steatosis in animals in comparison to water controls. Liver F4/80 and NF-kappaB were significantly higher in high fat and high fat combined fructose diet fed mice than that in controls (P < 0.01, P < 0.01), F4/80 protein were higher in high fat diet treated mice than those in fructose and high fat combined fructose groups (P < 0.01, P < 0.01). Markers of insulin resistance (e. g, hepatic phospho-AKT, AKT) were only altered in fructose-fed or high fat combined fructose animals (P < 0.01, P < 0.01).</p><p><b>CONCLUSION</b>High fat and fructose diet may induce NAFLD in C3H/HeN mice. Kupffer cells and signal pathway proteins were activated, and they may play key roles in the initiation and progression of NASH.</p>
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Animais , Feminino , Humanos , Masculino , Camundongos , Dieta Hiperlipídica , Fígado Gorduroso , Alergia e Imunologia , Metabolismo , Frutose , Células de Kupffer , Alergia e Imunologia , Metabolismo dos Lipídeos , Fígado , Alergia e Imunologia , Metabolismo , Camundongos Endogâmicos C3H , NF-kappa B , Alergia e Imunologia , Hepatopatia Gordurosa não Alcoólica , Proteína Oncogênica v-akt , Alergia e Imunologia , Transdução de SinaisRESUMO
<p><b>OBJECTIVE</b>To investigate the effect of RNA interfering TLR4 signal pathway on phagocytosis of Kupffer cells.</p><p><b>METHODS</b>RAW2647 mice mononuclear macrophage leukemia cells were observed. The tested group was interfered by Tlr4-mus-1567 RNA which had the best result confirmed by QPCR, cells interfered by Negative Control RNA as NC group, and normal cell as control. We perform the phagocytosis test on each group.</p><p><b>RESULTS</b>The tested group has lower phagocytes percentage than control (17.67% +/- 3.51% vs 32.00% +/- 3.00%, P < 0.01), and lower phagocytic index (46.33% +/- 7.51% vs 82.00% +/- 6.08%, P < 0.01).</p><p><b>CONCLUSIONS</b>Decreased phagocytic activity was observed on Kupffer cells by RNA interference.</p>
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Animais , Camundongos , Células de Kupffer , Alergia e Imunologia , Fagocitose , Interferência de RNA , Transdução de Sinais , Receptor 4 Toll-Like , Genética , Alergia e ImunologiaRESUMO
Objective To compare the treatment effects,dosimetry,and toxicities to organs at risk of intensity-modulated radiation therapy (IMRT) and 3-dimentional conformal radiotherapy (3DCRT) plans for cervical carcinoma patients with recurrence and metastasis. Methods 62 cervical carcinoma patients with recurrence and metastasis were analyzed retrospectively, and divided into two groups including intensitymodulated radiation therapy group (n=29) and 3-dimentional conformal radiotherapy group (n=32).Patients were performed with 6 MV-X ray.The regimen was 1.8-2.2 Gy/f,1 f/d,18-33 times in total.Prescribed dose was 40-60 Gy and median dose was 52.8 Gy. At the same time for the IMRT group 29 cases were performed with 3DCRT, which was designed using the same prescribed dose to compare radiation dose distributed in organs at risk (OAR).Results The maximum dose of the two plans showed that bladder and small intestine in IMRT plans were lower than that in 3DCRT (P<0.05), showing the IMRT's protective advantage. The maximum dose of PTV in IMRT plans were significantly higher than 3DCRT (P<0.05). In the group of IMRT plans, the overall 1-,2-,and 3-year survival rates were 65.5 %(19/29), 42.1%(8/19), and 25.0 %(2/8),respectively,the median survival time was 19 months,of 28 deaths,21 patients died of tumor progression,7 patients died of distant metastases.In the group of 3DCRT plans,the overall 1-,2-,and 3-year survival rates were 60.6 %(20/33),35.0 %(7/20),and 14.3 %(1/7),respectively,the median survival time was 17 months,of 32 deaths, 24 patients died of tumor progression, 8 patients died of distant metastasis. There were no significant differences in overall 1-, 2-, and 3-year survival rates between the two groups (P>0.05). The incidence rate of toxicity in the IMRT plans was significantly lower than that in the 3DCRT plans, especially for patients with Ⅰ level and Ⅱ level.Conclusion The treatment effects of the IMRT plans are better than the 3DCRT plans for cervical carcinoma patients with recurrence and metastasis. IMRT plans can improve radiation dose in tumors and reduce the dose distributed in normal issue and reduce the incidence of the side effect.
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<p><b>OBJECTIVE</b>To investigate chronic stress induced tissue action potential and pathological changes of thoracic spinal cord 1 - 5 nerves and heart in SD rats.</p><p><b>METHODS</b>SD rats (weighing 180 - 250 g) were randomly divided into depressive group and control group (n = 10 each). Depressive model (unpredicted chronic mild stress) was established according to Gronli's protocol. The heart rhythm, tissue field action potential duration (FAPD) of thoracic spinal cord 1 - 5 nerves, atrium and ventricle were mapped by microelectrode arrays (MEA) technique. Heart was sectioned and stained with Massion and HE for pathological analysis.</p><p><b>RESULTS</b>After 3 weeks chronic stress, P wave [(35.09 +/- 7.92) ms vs. (25.43 +/- 3.38) ms, P<0.05] and Q-T interval [(114.64 +/- 35.08) ms vs. (81.93 +/- 16.35) ms, P<0.01] were significantly increased, FAPD of thoracic spinal cord 1 - 5 nerves and heart was significantly prolonged, atrial field action potential duration dispersion (FAPDd) was significantly increased, atrial premature beats (n = 2) and ventricular premature beats ( n = 3) were also recorded in rats from depressive group. Moreover, increased collagen deposition was evidenced in Massion stained myocardium and increased inflammatory cell infiltration in the heart was found by both HE stain and electron microscope from depressive rats.</p><p><b>CONCLUSION</b>Chronic mild stress could activate sympathetic nerves system, promote inflammatory cell myocardial infiltration and myocardial fibrosis, induce arrhythmias by prolonging FAPD and increasing FADPd in thoracic spinal cord 1 - 5 nerves and/or heart tissue.</p>
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Animais , Ratos , Potenciais de Ação , Transtorno Depressivo , Diagnóstico , Modelos Animais de Doenças , Eletrocardiografia , Coração , Microeletrodos , Ratos Sprague-Dawley , Medula Espinal , Estresse FisiológicoRESUMO
<p><b>OBJECTIVE</b>To investigate the relationship between the radiosensitivity of hepatic carcinoma cells and their survivin expression levels.</p><p><b>METHODS</b>Hepatic carcinoma cell lines HepG2 and SMMC-7721 were irradiated with various doses of 60Co gamma-rays. The cell survival rate, expression of survivin, cell cycle profile and activity of caspase-3 were respectively detected by clonogenic assay, immunocytochemistry, flow cytometry and chromatometry.</p><p><b>RESULTS</b>The surviving fraction at 2Gy (SF2) of HepG2 and SMMC-7721 were 0.43+/-0.01 vs 0.70+/-0.02, and HepG2 had higher radiosensitivity than SMMC-7721. gamma-rays radiation up-regulated the expression of survivin. SMMC-7721 had a significantly higher expression of survivin than HepG2 (t = 2.81-5.20, P < 0.05). The activity of caspase-3 was more powerful in HepG2 than in SMMC-7721 (t = 6.05-6.72, P < 0.01).</p><p><b>CONCLUSION</b>Survivin may play a critical role in mediating radiation resistance in SMMC-7721 through its up-regulation and caspase-3 dependent manner.</p>