Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 32
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Vet Sci ; 21(3): e39, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32476313

RESUMO

BACKGROUND: There are various Helicobacter species colonizing the stomachs of animals. Although Helicobacter species usually cause asymptomatic infection in the hosts, clinical signs can occur due to gastritis associated with Helicobacter in animals. Among them, Helicobacter pylori is strongly associated with chronic gastritis, gastric ulcers, and gastric cancers. As the standard therapies used to treat H. pylori have proven insufficient, alternative options are needed to prevent and eradicate the diseases associated with this bacterium. Cheonwangbosim-dan (CBD), a traditional herbal formula that is popular in East Asia, has been commonly used for arterial or auricular flutter, neurosis, insomnia, and cardiac malfunction-induced disease. OBJECTIVES: The present study investigated the antimicrobial effect of CBD on H. pylori-infected human gastric carcinoma AGS cells and model mice. METHODS: AGS cells were infected with H. pylori and treated with a variety of concentrations of CBD or antibiotics. Mice were given 3 oral inoculations with H. pylori and then dosed with CBD (100 or 500 mg/kg) for 4 weeks or with standard antibiotics for 1 week. One week after the last treatment, gastric samples were collected and examined by histopathological analysis, real-time quantitative polymerase chain reaction, and immunoblotting. RESULTS: Our results showed that CBD treatment of AGS cells significantly reduced the H. pylori-induced elevations of interleukin-8, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2). In the animal model, CBD treatment inhibited the colonization of H. pylori and the levels of malondialdehyde, inflammation, proinflammatory cytokines, iNOS, and COX-2 in gastric tissues. CBD also decreased the phosphorylation levels of p38 mitogen-activated protein kinase family. CONCLUSIONS: This study suggests that CBD might be a prospective candidate for treating H. pylori-induced gastric injury.

2.
J Ethnopharmacol ; 235: 406-414, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-30703490

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Lithospermi radix has been prescribed in traditional folk medicine to treat diverse diseases like cancer. AIM OF THE STUDY: The present study assessed the sub-chronic oral toxicity of an aqueous extract of lithospermi radix (WLR) in Fischer 344 rats over a period of 13 weeks. MATERIALS AND METHODS: The chemical compositions of WLR were analyzed using ultra-high performance liquid chromatography (UHPLC). WLR was daily administered to Fischer 344 rats at 0, 500, 1000, and 2000 mg/kg body weights (bw) for 13 weeks via oral gavage. Changes in mortalities, body weights, and intakes of food and water were monitored during the WLR treatment period. Urine was collected and analyzed 12 h before necropsy. Organ weights, hematological parameters, and plasma biochemical parameters were determined along with histopathological examination. RESULTS: When compared with the normal control group, no remarkable toxic signs or parameter variations related with WLR treatment were observed in mortality, body weights, organ weights, food and water consumptions, urinalysis, hematological and plasma biochemical analyses, and histopathological examination. Mortalities observed in one male at 2000 mg/kg bw and three females at 1000 mg/kg bw were not related with WLR treatment because no gross findings of toxicity were observed in both morphological and histological examination. Some significant changes in clinical parameters or histological lesions observed in WLR-treated animals were not related with WLR treatment because the differences were marginal and did not show dose-dependent or directional changes. CONCLUSIONS: Based on these findings, the calculated no-observed-adverse-effect-level (NOAEL) in rats was higher than 2000 mg/kg bw.


Assuntos
Lithospermum/química , Tamanho do Órgão/efeitos dos fármacos , Extratos Vegetais/toxicidade , Testes de Toxicidade Subcrônica , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta a Droga , Feminino , Masculino , Medicina Tradicional , Nível de Efeito Adverso não Observado , Extratos Vegetais/administração & dosagem , Raízes de Plantas , Ratos , Ratos Endogâmicos F344
3.
Appl Clin Inform ; 9(4): 919-926, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30586673

RESUMO

BACKGROUND: Insulin therapy, medical nutrition therapy, and physical activity are required for the treatment of type 1 diabetes (T1D). There is a lack of studies in real-life environments that characterize patient-reported data from logs, activity trackers, and medical devices (e.g., glucose sensors) in the context of exercise. OBJECTIVE: The objective of this study was to compare data from continuous glucose monitor (CGM), wristband heart rate monitor (WHRM), and self-tracking with a smartphone application (app), iDECIDE, with regards to exercise behaviors and rate of change in glucose levels. METHODS: Participants with T1D on insulin pump therapy tracked exercise for 1 month with the smartphone app while WHRM and CGM recorded data in real time. Exercise behaviors tracked with the app were compared against WHRM. The rate of change in glucose levels, as recorded by CGM, resulting from exercise was compared between exercise events documented with the app and recorded by the WHRM. RESULTS: Twelve participants generated 277 exercise events. Tracking with the app aligned well with WHRM with respect to frequency, 3.0 (2.1) and 2.5 (1.8) days per week, respectively (p = 0.60). Duration had very high agreement, the mean duration from the app was 65.6 (55.2) and 64.8 (54.9) minutes from WHRM (p = 0.45). Intensity had a low concordance between the data sources (Cohen's kappa = 0.2). The mean rate of change of glucose during exercise was -0.27 mg/(dL*min) and was not significantly different between data sources or intensity (p = 0.21). CONCLUSION: We collated and analyzed data from three heterogeneous sources from free-living participants. Patients' perceived intensity of exercise can serve as a surrogate for exercise tracked by a WHRM when considering the glycemic impact of exercise on self-care regimens.


Assuntos
Sistemas Computacionais , Diabetes Mellitus Tipo 1/fisiopatologia , Exercício Físico , Aplicativos Móveis , Monitorização Fisiológica/instrumentação , Glicemia , Diabetes Mellitus Tipo 1/sangue , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Smartphone
4.
Biochem Biophys Res Commun ; 498(3): 566-572, 2018 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-29524408

RESUMO

TXNIP is a potent tumor suppressor with reduced expression in various types of human cancer. The prognostic and predictive power of TXNIP has been recognized in human breast cancer. The aim of this study is to investigate the clinical relevance and functional roles of TXNIP downregulation in breast cancer. We examined TXNIP expression at the protein level in tissue microarray (TMA)-based human breast cancers and its correlation with clinical parameters and molecular markers on immunohistochemistry (IHC). Compared with normal tissues, TXNIP expression was significantly decreased in human breast cancer tissues and animal mammary tumors, along with tumor progression. TXNIP was restored immediately after histone deacetylase inhibitor treatment in breast cancer cells, implying transcriptional regulation of TXNIP by histone modification. Decreased TXNIP protein levels were more common in tumors showing high proliferative activity, such as high Ki-67 labeling indexes and low p27 expression. TXNIP knockdown led to increased in vitro and in vivo breast cancer cell growth accompanied by p27 reduction and GLUT1 induction. Interestingly, estrogen receptor (ER)-positive breast cancer samples showed higher TXNIP expression compared to ER-negative samples. TXNIP expression decreased when ER signaling was activated by estradiol, while its expression increased under ER blockage by anti-estrogen fulvestrant. In addition, TXNIP knockdown in breast cancer cells caused significant reduction in the cell-growth inhibitory effect of anti-estrogen fulvestrant. In conclusion, our data demonstrated that TXNIP functions to suppress high proliferative activity and estrogen-dependent cell growth in breast cancer.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Mama/patologia , Proteínas de Transporte/genética , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Animais , Mama/metabolismo , Neoplasias da Mama/metabolismo , Proteínas de Transporte/análise , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Doenças do Cão/genética , Doenças do Cão/metabolismo , Doenças do Cão/patologia , Cães , Estrogênios/metabolismo , Feminino , Humanos , Neoplasias Mamárias Animais/genética , Neoplasias Mamárias Animais/metabolismo , Neoplasias Mamárias Animais/patologia
5.
Int Immunopharmacol ; 49: 67-76, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28551494

RESUMO

Isoimperatorin (IMP), an active natural furocoumarin, has numerous pharmacologic effects, including anti-inflammatory, analgesic, antispasmodic, and anticancer activities. This study aimed to evaluate the preventive activity of IMP in an ovalbumin (OVA)-induced murine model of asthma and to investigate its possible molecular mechanisms. Female BALB/c mice were sensitized on days 0 and 14 via intraperitoneal injection of 20µg OVA. On days 21-23 after the initial sensitization, the mice received an airway challenge with OVA (1% w/v in PBS) for 1h; meanwhile, IMP (10 or 30mg/kg once daily) was administered by gavage on days 18-23. Our results revealed that IMP significantly lowered the productions of interleukin (IL)-4, IL-5, IL-13, eotaxin, and immunoglobulin (Ig)E in bronchoalveolar lavage fluid (BALF), plasma, or lung tissues. Histological studies showed that IMP inhibited OVA-induced inflammatory cell infiltration and mucus production in the respiratory tract. In addition, pretreatment with IMP suppressed the activation of p38 mitogen-activated protein kinase (p38 MAPK), extracellular-signal-regulated kinases 1/2 (ERK1/2), and nuclear factor-κB (NF-κB). Together, these results suggest that IMP effectively inhibits airway inflammation and mucus hypersecretion by downregulating the levels of Th2 cytokines and inhibiting NF-κB and MAPK pathways.


Assuntos
Anti-Inflamatórios/uso terapêutico , Asma/tratamento farmacológico , Furocumarinas/uso terapêutico , Pneumonia/tratamento farmacológico , Células Th2/imunologia , Alérgenos/imunologia , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Imunoglobulina E/sangue , Camundongos , Camundongos Endogâmicos BALB C , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Muco/metabolismo , NF-kappa B/metabolismo , Ovalbumina/imunologia , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
6.
Oncotarget ; 7(52): 87219-87231, 2016 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-27888617

RESUMO

Previous clinical reports have found elevated osteopontin (OPN) levels in tumor tissues to be indicative of greater malignancy in human hepatocellular carcinoma (HCC). However, the role of OPN on carcinogenesis and its underlying mechanism remain unclear. In the present study, we investigated the oncogenic role of OPN in diethylnitrosamine (DEN)-induced hepatic carcinogenesis in mice. The overall incidence of hepatic tumors at 36 weeks was significantly lower in OPN knockout (KO) mice than in wild-type (WT) mice. Apoptosis was significantly enhanced in OPN KO mice, and was accompanied by the downregulation of epidermal growth factor receptor (EGFR). In the in vitro study, OPN suppression also led to lower mRNA and protein levels of EGFR associated with the downregulation of c-Jun in Hep3B and Huh7 human HCC cells lines, which resulted in increased apoptotic cell death in both cell lines. Moreover, a positive correlation was clearly identified between the expression of OPN and EGFR in human HCC tissues. These data demonstrate that the OPN deficiency reduced the incidence of chemically induced HCC by suppressing EGFR-mediated anti-apoptotic signaling. An important implication of our findings is that OPN positively contributes to hepatic carcinogenesis.


Assuntos
Apoptose , Neoplasias Hepáticas/etiologia , Osteopontina/fisiologia , Animais , Linhagem Celular Tumoral , Dietilnitrosamina , Receptores ErbB/análise , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/fisiologia , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Osteopontina/análise , Osteopontina/antagonistas & inibidores , Transdução de Sinais/fisiologia
7.
Int Immunopharmacol ; 31: 239-47, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26773771

RESUMO

meso-Dihydroguaiaretic acid (MDGA), which is a dibenzylbutane lignin isolated from the ethyl acetate fraction of Saururus chinensis, has various biological activities, including anti-oxidative, anti-inflammatory, anti-bacterial, and neuroprotective effects. However, no report has examined the potential anti-asthmatic activity of MDGA. In this study, we evaluated the protective effects of MDGA on asthmatic responses, particularly airway inflammation and mucus hypersecretion in an ovalbumin (OVA)-induced murine model of asthma. Intragastric administration of MDGA significantly lowered the productions of interleukin (IL)-4, IL-5, IL-13, tumor necrosis-α (TNF-α), eotaxin, monocyte chemoattractant protein-1 (MCP-1), vascular cell adhesion molecule-1 (VCAM-1), and immunoglobulin (Ig)E in bronchoalveolar lavage fluid (BALF), plasma, or lung tissues. Histological studies showed that MDGA inhibited OVA-induced inflammatory cell infiltration and mucus production in the respiratory tract. Moreover, MDGA markedly attenuated the OVA-induced activations of nuclear factor kappa B (NF-κB), extracellular-signal-regulated kinases 1/2 (ERK1/2), and p38 mitogen-activated protein kinase (p38 MAPK). Together, these results suggest that MDGA effectively inhibits airway inflammation and mucus hypersecretion by downregulating the levels of T helper 2 (Th2) cytokines, chemokines, and adhesion molecules, and inhibiting the activations of NF-κB and MAPKs.


Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Guaiacol/análogos & derivados , Lignanas/uso terapêutico , Pneumonia/tratamento farmacológico , Saururaceae/imunologia , Animais , Movimento Celular/efeitos dos fármacos , Quimiocina CCL2/metabolismo , Citocinas/metabolismo , Feminino , Guaiacol/uso terapêutico , Humanos , Imunoglobulina E/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Células Th2/imunologia , Molécula 1 de Adesão de Célula Vascular/metabolismo
8.
Toxicol Appl Pharmacol ; 291: 38-45, 2016 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-26701066

RESUMO

Obesity increases the risk of chronic liver diseases, including viral hepatitis, alcohol-induced liver disease, and non-alcoholic steatohepatitis. In this study, we investigated the effects of obesity in acute hepatic failure using a murine model of thioacetamide (TA)-induced liver injury. Genetically obese ob/ob mice, together with non-obese ob/+ littermates, were subjected to a single intraperitoneal injection of TA, and examined for signs of hepatic injury. ob/ob mice showed a significantly higher survival rate, lower levels of serum alanine aminotransferase and aspartate aminotransferase, and less hepatic necrosis and apoptosis, compared with ob/+ mice. In addition, ob/ob mice exhibited significantly lower levels of malondialdehyde and significantly higher levels of glutathione and antioxidant enzyme activities compared with their ob/+ counterparts. Bioactivation analyses revealed reduced plasma clearance of TA and covalent binding of [(14)C]TA to liver macromolecules in ob/ob mice. Together, these data demonstrate that genetically obese mice are resistant to TA-induced acute liver injury through diminished bioactivation of TA and antioxidant effects.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Obesidade/genética , Tioacetamida/toxicidade , Animais , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Dose Letal Mediana , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/metabolismo , Tioacetamida/metabolismo
9.
Biol Pharm Bull ; 39(2): 221-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26632199

RESUMO

Manassantin A, a neolignan isolated from Saururus chinensis, is a major phytochemical compound that has various biological activities, including anti-inflammatory, neuroleptic, and human acyl-CoA : cholesterol acyltransferase (ACAT) inhibitory activities. In this study, we investigated the protective effects of manassantin A against ethanol-induced acute gastric injury in rats. Gastric injury was induced by intragastric administration of 5 mL/kg body weight of absolute ethanol to each rat. The positive control group and the manassantin A group were given oral doses of omeprazole (20 mg/kg) or manassantin A (15 mg/kg), respectively, 1 h prior to the administration of absolute ethanol. Our examinations revealed that manassantin A pretreatment reduced ethanol-induced hemorrhage, hyperemia, and epithelial cell loss in the gastric mucosa. Manassantin A pretreatment also attenuated the increased lipid peroxidation associated with ethanol-induced acute gastric lesions, increased the mucosal glutathione (GSH) content, and enhanced the activities of antioxidant enzymes. The levels of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1ß were clearly decreased in the manassantin A-pretreated group. In addition, manassantin A pretreatment enhanced the levels of cyclooxygenase (COX)-1, COX-2, and prostaglandin E2 (PGE2) and reduced the inducible nitric oxide synthase (iNOS) overproduction and nuclear factor kappa B (NF-κB) phosphorylation. Collectively, these results indicate that manassantin A protects the gastric mucosa from ethanol-induced acute gastric injury, and suggest that these protective effects might be associated with COX/PGE2 stimulation, inhibition of iNOS production and NF-κB activation, and improvements in the antioxidant and anti-inflammatory status.


Assuntos
Antiulcerosos/farmacologia , Lignanas/farmacologia , Gastropatias/induzido quimicamente , Animais , Antiulcerosos/química , Catalase , Etanol , Glutationa , Lignanas/química , Masculino , Malondialdeído , Estrutura Molecular , Omeprazol/farmacologia , Ratos , Ratos Sprague-Dawley , Saururaceae/química , Gastropatias/prevenção & controle , Superóxido Dismutase
10.
Carcinogenesis ; 36(12): 1550-60, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26438603

RESUMO

Several clinical studies have reported increased expression of osteopontin (OPN) in various types of human cancer, including gastric cancer. However, the precise mechanisms underlying tumor development remain unclear. In the present study, we investigated the pathogenic roles of OPN in Helicobacter pylori-induced gastric cancer development. Wild-type (WT) and OPN knockout (KO) mice were treated with N-methyl-N-nitrosourea (MNU) and infected with H.pylori. Mice were killed 50 weeks after treatment, and stomach tissues were assessed by histopathological examination, immunohistochemistry, quantitative real-time RT-PCR and western blotting. To clarify the carcinogenic effects of OPN, we also conducted an in vitro study using AGS human gastric cancer cell line and THP-1 human monocytic cell line. The overall incidence of gastric tumors was significantly decreased in OPN KO mice compared with WT mice. Apoptotic cell death was significantly enhanced in OPN KO mice and was accompanied by upregulation of signal transducer and activator of transcription 1 (STAT1) and inducible nitric oxide synthase (iNOS). In vitro study, OPN suppression also caused STAT1 upregulation and iNOS overexpression in AGS and THP-1 cells, which resulted in apoptosis of AGS cells. In addition, a negative correlation was clearly identified between expression of OPN and iNOS in human gastric cancer tissues. Our data demonstrate that loss of OPN decreases H.pylori-induced gastric carcinogenesis by suppressing proinflammatory immune response and augmenting STAT1 and iNOS-mediated apoptosis of gastric epithelial cells. An important implication of these findings is that OPN actually contributes to the development of gastric cancer.


Assuntos
Infecções por Helicobacter/genética , Osteopontina/genética , Neoplasias Gástricas/genética , Animais , Apoptose , Linhagem Celular Tumoral , Técnicas de Cocultura , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiologia , Mucosa Gástrica/patologia , Técnicas de Inativação de Genes , Infecções por Helicobacter/microbiologia , Humanos , Masculino , Metilnitrosoureia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico Sintase Tipo II/metabolismo , Osteopontina/metabolismo , Fator de Transcrição STAT1/metabolismo , Transdução de Sinais , Neoplasias Gástricas/induzido quimicamente , Neoplasias Gástricas/microbiologia
11.
Med Acupunct ; 27(3): 206-215, 2015 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-26155321

RESUMO

Background: Lymphedema is a troublesome complication affecting quality of life (QoL) in many women after breast-cancer treatment. Recent studies have suggested that acupuncture can reduce symptoms of lymphedema in breast-cancer survivors. Objectives: This was a pilot study. It was designed to assess the feasibility and the safety of acupuncture with the Saam acupuncture method for treating lymphedema in Korean patients after surgical therapy for breast cancer. Materials and Methods: This was a prospective, single-arm, observational pilot study using before and after measurements. The study was conducted at the East-West Medical Center at the Daegu Catholic University Medical Center, in Daegu, Korea. The subjects were 9 patients with breast cancer who presented with lymphedema of the upper limb ipsilateral to surgery. Saam acupuncture was administered 3 times per week for 6 consecutive weeks, for 30±5 minutes at each session.The primary outcome measure was severity of lymphedema as assessed by stages of lymphedema, a visual analogue scale (VAS), and by circumferential measurements of the upper extremity. The secondary outcome measure was QoL, which was assessed by a self-administered questionnaire using the Short Form-36 questionnaire. Results: Acupuncture reduced severity of lymphedema significantly, as assessed by the VAS (P<0.001) as well as by circumferential measurements of the upper extremity. Four weeks after the final treatment, symptoms were not aggravated. SF-36 scores remained significant for health status at the end of treatment. Conclusions: The Saam acupuncture method appeared to provide reduction of lymphedema among women after they had undergone surgery for breast cancer. A randomized, controlled prospective study with a larger sample size is required to clarify the role of acupuncture for managing lymphedema in patients with breast cancer.

12.
Trials ; 16: 246, 2015 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-26037730

RESUMO

BACKGROUND: Incomplete recovery from facial palsy results in social and physical disabilities, and the medical options for the sequelae of Bell's palsy are limited. Acupuncture is widely used for Bell's palsy patients in East Asia, but its efficacy is unclear. METHODS: We performed a randomized controlled trial including participants with the sequelae of Bell's palsy with the following two parallel arms: an acupuncture group (n = 26) and a waiting list group (n = 13). The acupuncture group received acupuncture treatments for 8 weeks, whereas the waiting list group did not receive acupuncture treatments during the 8-week period after randomization. The primary outcome measure was change in the Facial Disability Index (FDI) social and well-being subscale at week 8. We also analyzed changes in the FDI physical function subscale, the House-Brackmann score, the Sunnybrook Facial Nerve Grading system, lip mobility and stiffness at 5 and 8 weeks after randomization. An intention-to-treat analysis was applied. RESULTS: The acupuncture group exhibited greater improvements in the FDI social score (mean difference, 23.54; 95% confidence interval, 12.99 to 34.08) and better results on the FDI physical function subscale (mean difference, 21.54; 95% confidence interval, 7.62 to 35.46), Sunnybrook Facial Nerve Grading score (mean difference, 14.77; 95% confidence interval, 5.05 to 24.49), and stiffness scale (mean difference, -1.58; 95% confidence interval,-2.26 to -0.89) compared with the waiting list group after 8 weeks. No severe adverse event occurred in either group. CONCLUSION: Compared with the waiting list group, acupuncture had better therapeutic effects on the social and physical aspects of sequelae of Bell's palsy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN43104115.


Assuntos
Terapia por Acupuntura , Paralisia de Bell/terapia , Adulto , Idoso , Paralisia de Bell/fisiopatologia , Nervo Facial/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Tamanho da Amostra
13.
Lab Invest ; 95(6): 660-71, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25867766

RESUMO

Osteopontin (OPN) is a multifunctional protein that plays a role in many physiological and pathological processes, including inflammation and tumorigenesis. Here, we investigated the involvement of OPN in Helicobacter pylori (HP)-induced gastritis using OPN knockout (KO) mice and OPN knockdown (KD) cell lines. HP-infected OPN KO mice showed significantly reduced gastritis compared with wild-type (WT) mice with decreased infiltration of macrophages and a reduction in HP-induced upregulation of IL-1ß, TNF-α, and IFN-γ. HP-exposed OPN KD gastric cancer cells and macrophage-like cells showed an attenuated induction of these cytokines. We also demonstrated a reduction in the migration of monocytic and macrophage-like cells toward conditioned media harvested from HP-exposed OPN KD gastric cancer cells as well as reduced migration ability of OPN KD cells itself. In addition, HP-infected OPN KO mice showed decreased epithelial cell proliferation compared with HP-infected WT mice, in association with a reduction in MAPK pathway activation. OPN KD gastric cancer cell lines also showed lower proliferative activity and reduced MAPK activation than shRNA control cells after HP co-culture or after IL-1ß and TNF-α treatment. Taken together, these results indicate that OPN exerts a considerable influence on HP-induced gastritis by modulating the production of cytokines and contributing to macrophage infiltration. Moreover, OPN-mediated activation of the MAPK pathway in gastric epithelial cells might contribute to epithelial changes following HP infection.


Assuntos
Proliferação de Células/fisiologia , Mucosa Gástrica/metabolismo , Infecções por Helicobacter/metabolismo , Inflamação/metabolismo , Osteopontina/metabolismo , Animais , Linhagem Celular Tumoral , Citocinas , Feminino , Técnicas de Inativação de Genes , Helicobacter pylori , Humanos , Macrófagos , Camundongos , Camundongos Endogâmicos C57BL , Osteopontina/genética , Regulação para Cima
14.
Hepatology ; 60(1): 146-57, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24492981

RESUMO

UNLABELLED: Aldehyde dehydrogenase 2 (ALDH2) is the major enzyme that metabolizes acetaldehyde produced from alcohol metabolism. Approximately 40-50% of East Asians carry an inactive ALDH2 gene and exhibit acetaldehyde accumulation after alcohol consumption. However, the role of ALDH2 deficiency in the pathogenesis of alcoholic liver injury remains obscure. In the present study, wild-type and ALDH2(-/-) mice were subjected to ethanol feeding and/or carbon tetrachloride (CCl4 ) treatment, and liver injury was assessed. Compared with wild-type mice, ethanol-fed ALDH2(-/-) mice had higher levels of malondialdehyde-acetaldehyde (MAA) adduct and greater hepatic inflammation, with higher hepatic interleukin (IL)-6 expression but surprisingly lower levels of steatosis and serum alanine aminotransferase (ALT). Higher IL-6 levels were also detected in ethanol-treated precision-cut liver slices from ALDH2(-/-) mice and in Kupffer cells isolated from ethanol-fed ALDH2(-/-) mice than those levels in wild-type mice. In vitro incubation with MAA enhanced the lipopolysaccharide (LPS)-mediated stimulation of IL-6 production in Kupffer cells. In agreement with these findings, hepatic activation of the major IL-6 downstream signaling molecule signal transducer and activator of transcription 3 (STAT3) was higher in ethanol-fed ALDH2(-/-) mice than in wild-type mice. An additional deletion of hepatic STAT3 increased steatosis and hepatocellular damage in ALDH2(-/-) mice. Finally, ethanol-fed ALDH2(-/-) mice were more prone to CCl4 -induced liver inflammation and fibrosis than ethanol-fed wild-type mice. CONCLUSION: ALDH2(-/-) mice are resistant to ethanol-induced steatosis but prone to inflammation and fibrosis by way of MAA-mediated paracrine activation of IL-6 in Kupffer cells. These findings suggest that alcohol, by way of acetaldehyde and its associated adducts, stimulates hepatic inflammation and fibrosis independent from causing hepatocyte death, and that ALDH2-deficient individuals may be resistant to steatosis and blood ALT elevation, but are prone to liver inflammation and fibrosis following alcohol consumption.


Assuntos
Aldeído Desidrogenase/genética , Fígado Gorduroso Alcoólico/enzimologia , Hepatite/enzimologia , Cirrose Hepática/enzimologia , Acetaldeído/metabolismo , Aldeído Desidrogenase/sangue , Aldeído Desidrogenase/deficiência , Aldeído Desidrogenase 1 , Aldeído-Desidrogenase Mitocondrial , Animais , Intoxicação por Tetracloreto de Carbono/enzimologia , Intoxicação por Tetracloreto de Carbono/genética , Depressores do Sistema Nervoso Central/farmacocinética , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Doença Hepática Induzida por Substâncias e Drogas/genética , Citocromo P-450 CYP2E1/metabolismo , Etanol/farmacocinética , Fígado Gorduroso Alcoólico/genética , Feminino , Hepatite/genética , Isoenzimas/metabolismo , Macrófagos do Fígado/enzimologia , Cirrose Hepática/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Retinal Desidrogenase/metabolismo , Fator de Transcrição STAT3/metabolismo
15.
Hepatology ; 59(3): 1094-106, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24115096

RESUMO

UNLABELLED: Prednisolone is a corticosteroid that has been used to treat inflammatory liver diseases such as autoimmune hepatitis and alcoholic hepatitis. However, the results have been controversial, and how prednisolone affects liver disease progression remains unknown. In the current study we examined the effect of prednisolone treatment on several models of liver injury, including T/NKT cell hepatitis induced by concanavalin A (ConA) and α-galactosylceramide (α-GalCer), and hepatotoxin-mediated hepatitis induced by carbon tetrachloride (CCl4 ) and/or ethanol. Prednisolone administration attenuated ConA- and α-GalCer-induced hepatitis and systemic inflammatory responses. Treating mice with prednisolone also suppressed inflammatory responses in a model of hepatotoxin (CCl4 )-induced hepatitis, but surprisingly exacerbated liver injury and delayed liver repair. In addition, administration of prednisolone also enhanced acetaminophen-, ethanol-, or ethanol plus CCl4 -induced liver injury. Immunohistochemical and flow cytometric analyses demonstrated that prednisolone treatment inhibited hepatic macrophage and neutrophil infiltration in CCl4 -induced hepatitis and suppressed their phagocytic activities in vivo and in vitro. Macrophage and/or neutrophil depletion aggravated CCl4 -induced liver injury and impeded liver regeneration. Finally, conditional disruption of glucocorticoid receptor in macrophages and neutrophils abolished prednisolone-mediated exacerbation of hepatotoxin-induced liver injury. CONCLUSION: Prednisolone treatment prevents T/NKT cell hepatitis but exacerbates hepatotoxin-induced liver injury by inhibiting macrophage- and neutrophil-mediated phagocytic and hepatic regenerative functions. These findings may not only increase our understanding of the steroid treatment mechanism but also help us to better manage steroid therapy in liver diseases.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Células Matadoras Naturais/efeitos dos fármacos , Prednisolona/farmacologia , Linfócitos T/efeitos dos fármacos , Animais , Tetracloreto de Carbono/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/imunologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Concanavalina A/toxicidade , Modelos Animais de Doenças , Galactosilceramidas/toxicidade , Glucocorticoides/farmacologia , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/patologia , Regeneração Hepática/efeitos dos fármacos , Regeneração Hepática/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mitógenos/toxicidade , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Neutrófilos/patologia , Linfócitos T/imunologia , Linfócitos T/patologia
16.
Acupunct Med ; 32(1): 81-3, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24192146

RESUMO

We report the case of a 30-year-old woman with a right adnexal mass resembling an ovarian cyst who declined diagnostic laparoscopy and requested treatment with acupuncture. The patient was treated with Saam acupuncture for 14 weeks. After treatment, transvaginal sonography revealed disappearance of the right adnexal mass. No adverse effects of the Saam acupuncture treatment were reported.


Assuntos
Terapia por Acupuntura , Doenças dos Anexos/terapia , Cistos/terapia , Doenças dos Anexos/patologia , Adulto , Cistos/patologia , Feminino , Humanos
17.
J Vet Sci ; 14(3): 257-62, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23820201

RESUMO

Vitamin D3 up-regulated protein 1 (VDUP1) is a potent growth suppressor that inhibits tumor cell proliferation and cell cycle progression when overexpressed. In a previous study, we showed that VDUP1 knockout (KO) mice exhibited accelerated liver regeneration because such animals could effectively control the expression of cell cycle regulators that drive the G1-to-S phase progression. In the present study, we further investigated the role played by VDUP1 in initial priming of liver regeneration. To accomplish this, VDUP1 KO and wild-type (WT) mice were subjected to 70% partial hepatectomy (PH) and sacrificed at different times after surgery. The hepatic levels of TNF-α and IL-6 increased after PH, but there were no significant differences between VDUP1 KO and WT mice. Nuclear factor-κB (NF-κB), c-Jun-N-terminal kinase (JNK), and signal transducer and activator of transcription 3 (STAT-3) were activated much earlier and to a greater extent in VDUP1 KO mice after PH. A single injection of TNF-α or IL-6 caused rapid activation of JNK and STAT-3 expression in both mice, but the responses were stronger and more sustained in VDUP1 KO mice. In conclusion, our findings provide evidence that VDUP1 plays a role in initiation of liver regeneration.


Assuntos
Proteínas de Transporte/genética , Regulação da Expressão Gênica , Hepatócitos/citologia , Fígado/fisiologia , Regeneração , Tiorredoxinas/genética , Animais , Western Blotting , Proteínas de Transporte/metabolismo , Proliferação de Células , Hepatectomia , Hepatócitos/fisiologia , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Masculino , Camundongos Knockout , NF-kappa B/genética , NF-kappa B/metabolismo , Reação em Cadeia da Polimerase , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Tiorredoxinas/metabolismo
18.
J Altern Complement Med ; 19(8): 690-6, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23383974

RESUMO

OBJECTIVES: Antiestrogen therapy can cause vasomotor symptoms similar to those occurring during menopause, including hot flashes. Recent studies suggest that acupuncture is effective in reducing vasomotor symptoms in patients with breast cancer receiving tamoxifen. The purpose of this study was to assess the feasibility and safety of acupuncture for treatment of hot flashes in Korean patients with breast cancer receiving antiestrogen therapy. DESIGN: This was a prospective single-arm observational study using before and after measurements. SETTINGS/LOCATION: The study was located at the East-West Medical Center at Daegu Catholic University Medical Center, Daegu, Korea. SUBJECTS: The subjects were 10 patients with breast cancer who were undergoing antiestrogen therapy with tamoxifen or anastrozole and who were suffering from hot flashes. INTERVENTIONS: Acupuncture was administered 3 times a week for 4 consecutive weeks, for 20±5 minutes at each session. OUTCOME MEASURES: The outcome measure was severity of hot flashes assessed by visual analogue scale (VAS) and total hot flash score. RESULTS: During treatment, severity of hot flashes was reduced by 70%-95% in all patients. Acupuncture significantly alleviated severity of hot flashes assessed by a visual analogue scale (F=30.261; p<0.001) as well as the total hot flash score (F=21.698; p=0.006). Four (4) weeks after the final treatment, symptoms were not aggravated. CONCLUSIONS: Acupuncture appeared to provide effective relief from hot flashes among Korean women receiving antiestrogen therapy after surgery for breast cancer, and the effects lasted for at least 1 month after termination of treatment. A randomized controlled prospective study with a larger sample size is required to clarify the role of acupuncture in the management of hot flashes in Korean patients with breast cancer.


Assuntos
Terapia por Acupuntura , Neoplasias da Mama/tratamento farmacológico , Antagonistas de Estrogênios/efeitos adversos , Fogachos/terapia , Nitrilos/efeitos adversos , Tamoxifeno/efeitos adversos , Triazóis/efeitos adversos , Análise de Variância , Anastrozol , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , República da Coreia , Índice de Gravidade de Doença , Resultado do Tratamento
19.
J Vet Med Sci ; 75(3): 299-307, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23117827

RESUMO

Deregulated Wnt signaling pathway is implicated in many hereditary diseases and tumorigenesis including colorectal cancer, hepatocellular carcinoma and gastric cancer. In this study, to assess the relationship between chemically induced gastric tumor and canonical Wnt signaling pathway in genetically intact mice, histopathological and quantitative mRNA analyses were performed in C57BL/6J mice given drinking water containing N-methyl- N-nitrosurea (MNU). 60.5% of gastric adenoma and 27.9% of adenocarcinoma were observed 48 weeks after first administration. Also, in immunohistochemical analysis, aberrant expressions of phospho-GSK-3ß, ß-catenin, cyclin D1, c-Myc, osteopontin and COX-2 were found. In double immunofluorescent-antibody stains, ß-catenin accumulation was colocalized with other proteins. mRNA levels of cyclin D1, c-myc and COX-2 were relatively higher in adenocarcinoma. Altogether, canonical Wnt pathway was highly involved in MNU induced gastric neoplasia of C57BL/6J mice, and it could be a considerably suitable system for the study to examine the linkage between gastric tumorigenesis and the canonical Wnt pathway.


Assuntos
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Metilnitrosoureia/toxicidade , Neoplasias Gástricas/induzido quimicamente , Via de Sinalização Wnt/fisiologia , Animais , Imuno-Histoquímica , Camundongos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Neoplasias Gástricas/metabolismo
20.
Gut ; 61(1): 53-63, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21917648

RESUMO

OBJECTIVE: Vitamin D(3) upregulated protein 1 (VDUP1) is a potent tumour suppressor whose expression is dramatically reduced in various types of human cancers, including gastric cancer. However, the precise mechanisms underlying tumour development remain unclear. In the present study, the authors examined the effect of VDUP1 on Helicobacter pylori-induced gastric carcinogenesis in mice. DESIGN: Gastric cancer was generated in VDUP1 knockout (KO) and wild-type mice using a combination of N-methyl-N-nitrosourea treatment and H pylori infection. Fifty weeks after treatment, gastric tissues from both types of mice were examined by histopathology, immunohistochemistry and immunoblotting. In vitro tests on the human gastric cancer cell line, AGS, were also performed to identify the underlying mechanisms of cancer development. RESULTS: The overall incidence of gastric cancer was significantly higher in VDUP1 KO mice than in wild-type mice. Similarly, VDUP1 KO mice showed more severe chronic gastritis, glandular atrophy, foveolar hyperplasia, metaplasia and dysplasia. Although no differences in the apoptotic index were apparent, lack of VDUP1 increased the rate of gastric epithelial cell proliferation in non-cancerous stomachs, with corresponding increases in tumour necrosis factor alpha (TNFα) level, nuclear transcription factor kappa B (NF-κB) activation and cyclooxygenase-2 (COX-2) expression. An in vitro study showed that H pylori-associated cell proliferation and induction of TNFα, NF-κB and COX-2 were inhibited in cells transfected with VDUP1. In addition, overexpression of VDUP1 in AGS cells suppressed TNFα-induced NF-κB activation and COX-2 expression. CONCLUSION: Our data show that VDUP1 negatively regulates H pylori-associated gastric carcinogenesis, in part by disrupting cell growth and inhibiting the induction of TNFα, NF-κB and COX-2. These findings provide important insights into the role of VDUP1 in H pylori-associated tumourigenesis.


Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas de Transporte/metabolismo , Infecções por Helicobacter/complicações , Helicobacter pylori , Neoplasias Gástricas/etiologia , Tiorredoxinas/metabolismo , Animais , Biomarcadores Tumorais/fisiologia , Proteínas de Transporte/fisiologia , Processos de Crescimento Celular/fisiologia , Linhagem Celular Tumoral , Ciclo-Oxigenase 2/metabolismo , Humanos , Metilnitrosoureia/efeitos adversos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/metabolismo , Distribuição Aleatória , Neoplasias Gástricas/metabolismo , Tiorredoxinas/fisiologia , Análise Serial de Tecidos , Fator de Necrose Tumoral alfa/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA