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2.
Cell Death Dis ; 10(9): 637, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31474764

RESUMO

Prostate cancer (PCa) is the second leading cause of cancer death in men. PCa progression can be associated with obesity. Signal transducer and activator of transcription-3 (STAT3) plays a crucial role in PCa growth. However, whether STAT3 plays a role in high-fat diet (HFD)-associated PCa growth is unknown. Our data show that HFD feeding increases tumor size, STAT3 phosphorylation, and palmitic acid (PA) level in the xenograft tissues of the PCa-bearing xenograft mouse model. In vitro studies show that PA increases STAT3 expression and phosphorylation (STAT3-Y705) in PCa. Computational modeling suggests strong and stable binding between PA and unphosphorylated STAT3 at R593 and N538. The binding changes STAT3 structure and activity. Functional studies show that both STAT3 mutants (R583A and N538A) and STAT3 dominant negative significantly reduce PA-enhanced STAT3 phosphorylation, PA-increased PCa cell proliferation, migration, and invasion. In the xenograft mouse models, the HFD-increased tumor growth and STAT3 phosphorylation in tumors are reversed by STAT3 inhibition. Our study not only demonstrates the regulatory role of PA/STAT3 axis in HFD-associated PCa growth but also suggests a novel mechanism of how STAT3 is activated by PA. Our data suggest STAT3 as a therapeutic target for the treatment of HFD-associated PCa.

3.
J Ethnopharmacol ; 240: 111937, 2019 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-31075381

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Atopic dermatitis (AD), a disorder prevalent during childhood and adulthood, seriously affects the patient's quality of life. Although Huang-Lian-Jie-Du-Tang (HLJDT) has shown anti-inflammatory effects in previous studies, its effects and mechanism of action underlying AD disorder are still largely unknown. OBJECTIVE: This study explored the anti-inflammatory and immunomodulatory effects of HLJDT on the AD-like dermal disorder, induced in vitro by lipopolysaccharide (LPS)-triggered inflammation, and in vivo by 2,4-dinitrochlorobenzene (DNCB). MATERIALS AND METHODS: In vivo HLJDT effects were investigated by determining the severity of dermatitis, which consisted of observing signs of skin lesions, visually and through haematoxylin and eosin (HE) staining, in mouse ears and dorsal skin, measuring serum levels of interleukin (IL)-1α, IL-1ß, IL-2, IL-4, IL-5, IL-6, interferon (IFN)-γ, the tumour necrosis factor (TNF)-α, and determining the splenic index, number of splenic CD4+/CD8+ T-lymphocytes, as well as the phosphorylation levels of mitogen-activated protein kinases (including MAPKs-p38, ERK, and JNK), IκB-α, and nuclear factor kappa B (NF-κB) (p65) within dermal lesions. Morphological changes in LPS-induced inflammation were observed under a microscope, and ELISA and qPCR assays were used to measure IL-1α, IL-1ß, IL-6, and TNF-α expression levels. The protein expression levels of P-ERK/ERK, P-p38/p38, P-JNK/JNK, P-IKß-α, and P-p65 were measured through western blotting. Additionally, p65 expression was assessed by immunofluorescence, and LPS binding to RAW264.7 cell membrane was studied with laser confocal microscopy. RESULTS: HLJDT could remarkably mitigate DNCB-induced AD-like lesion symptoms, alleviating inflammatory mediator infiltration in mouse ears and dorsal skin tissue, down-regulating serum expression levels of IL-1α, IL-1ß, IL-2, IL-4, IL-5, IL-6, IFN-γ, and TNF-α, normalising the splenic CD4+/CD8+ T-lymphocyte ratio, and inactivating MAPKs (including p38, ERK, and JNK), IκB-α, and NF-κB (p65) in dorsal skin. Furthermore, HLJDT inhibited LPS-induced differentiation of RAW264.7 cells, as evidenced by the decreased protein and mRNA expression of IL-1α, IL-1ß, IL-6, and TNF-α. Additionally, it decreased ERK, p38, JNK, IKß-α, and p65 phosphorylation levels in the MAPKs/NF-κB pathway, inhibited p65 nuclear translocation, and reduced LPS binding to the RAW264.7 cell membrane. CONCLUSIONS: HLJDT significantly improved AD-like symptoms via inhibition of the MAPKs/NF-κB pathway. Therefore, administration of HLJDT might be a potential treatment for AD in the clinical setting.


Assuntos
Anti-Inflamatórios/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Relação CD4-CD8 , Citocinas/imunologia , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/imunologia , Dinitroclorobenzeno , Medicamentos de Ervas Chinesas/farmacologia , Fatores Imunológicos/farmacologia , Lipopolissacarídeos , Masculino , Camundongos , Proteínas Quinases Ativadas por Mitógeno/imunologia , NF-kappa B/imunologia , Células RAW 264.7 , Pele/efeitos dos fármacos , Pele/imunologia
4.
Front Biosci (Landmark Ed) ; 24: 1477-1486, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31136992

RESUMO

Diabetic nephropathy (DN) is one of the most serious complications of diabetes mellitus, for which no effective treatment currently exists. We tested the hypothesis that Qi-dan-di-huang (QDDH) might have therapuetic effects in an experimental rat model of DN. The levels of I kappa KinaseAlpha and Beta, p-p65, p-IκB alpha, TGF-ß1 and Alpha-SMA were significantly increased in kidneys in DN. QDDH decoction only partially reversed the increased Ikappa KinaseAlpha/Beta, p-p65, p-IKappaB alpha, TGF-Beta1 and alpha-SMA in the kidneys in DN. However, treatment of diabetic rats with QDDH decoction significantly inhibited the production and release of inflammatory cytokines IL-6, IL-1 beta and TNF-alpha into the serum. QDDH decoction also significantly improved the physiologic and biochemical indicators of DN, reduced glycogen and protein deposition in DN and prevented renal fibrosis. Together, the data show that QDDH decoction exerts a protective effect on kidneys in diabetic rats and reverses the inflammatory milieu of the serum in DN.


Assuntos
Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Citocinas/sangue , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/metabolismo , Fibrose , Glicogênio/metabolismo , Humanos , Mediadores da Inflamação/sangue , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Ratos Sprague-Dawley
5.
BMC Public Health ; 19(1): 330, 2019 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-30898160

RESUMO

BACKGROUND: Sub-health status is defined as declines in vitality, physiological function and capacity for adaptation, but without the presence of clinical or sub-clinical disease. We have developed and evaluated a comprehensive questionnaire, the Sub-Health Self-Rating Scale (SSS), to assess sub-health status in university students. METHOD: The items for the draft questionnaire were discussed in focus groups. The WHOQOL-BREF was selected as the validity reference. From a professional perspective and large sample evaluation, the scale ultimately consisted of 58 items. The reliability and validity of the SSS was examined in undergraduate students and 1000 questionnaires were randomly selected from the samples for expert evaluation. RESULTS: Cronbach's α of the total scale was 0.942. The dimensions of physiological, psychological and social had high reliability: 0.915, 0.856 and 0.850, respectively. Based on scree plot and related theories, there were 10 factors to be extracted. The correlation coefficient between the total scale and sub-scale was high. The dimensions of physiological, psychological and social had high correlations with the total scale: 0.929, 0.803 and 0.774, respectively. The sub-health cut-off point of the total scale was 72; for the physiological field, it was 72; for the psychological field, it was 60; and the social field, it was 56. The fit between the expert evaluation method and the scale method was 0.758. The lower the score, the worse the health condition. CONCLUSION: We established and evaluated a valid instrument (SSS) that encompasses physiological, psychological and social factors to investigate sub-health status. It is short and easy to complete, and therefore suitable for use with undergraduate students.


Assuntos
Autoavaliação Diagnóstica , Estudantes/psicologia , Inquéritos e Questionários , Adolescente , Adulto , China , Feminino , Nível de Saúde , Humanos , Masculino , Reprodutibilidade dos Testes , Estudantes/estatística & dados numéricos , Universidades , Adulto Jovem
6.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(2): 227-234, 2019 02 28.
Artigo em Chinês | MEDLINE | ID: mdl-30890513

RESUMO

OBJECTIVE: To identify the main active components in Shenbing decoction Ⅲ and their targets and explore the mechanism by which Shenbing decoction Ⅲ alleviates proteinuria in chronic kidney disease (CKD) based on network pharmacology. METHODS: The active components of Shenbing decoction Ⅲ and their potential targets, along with the oral bioavailability and drug-like properties of each component were searched in the TCMSP database. The proteinuria-related targets were searched in the GeneCards database. The active component-target network was constructed using Cytoscape software, and the acquired information of the targets from ClueGO was used for enrichment analysis of the gene pathways. RESULTS: A total of 102 active components were identified from Shenbing decoction Ⅲ. These active components acted on 126 targets, among which 69 were related to proteinuria. Enrichment analysis revealed fluid shear stress- and atherosclerosisrelated pathways as the highly significant pathways in proteinuria associated with CKD. CONCLUSIONS: We preliminarily validated the prescription of Shenbing decoction Ⅲ and obtained scientific evidence that supported its use for treatment of proteinuria in CKD. The findings in this study provide a theoretical basis for further study of the mechanism of Shenbing decoction Ⅲ in the treatment of proteinuria in CKD.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Proteinúria/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Disponibilidade Biológica , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinética , Humanos , Proteinúria/etiologia , Proteinúria/metabolismo , Insuficiência Renal Crônica/metabolismo
7.
J Cell Biochem ; 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30916806

RESUMO

microRNA-21 (miRNA-21) is a well-characterized oncogenic miRNA in human cancers. In the present study, we found that miRNA-21 was upregulated, while long noncoding RNA Mortal Obligate RNA Transcript (lncRNA MORT), which has been reported to be silenced in 16 types of cancers, was downregulated in tumor tissues than in adjacent healthy tissues of patients with ovarian carcinoma. Expression of lncRNA MORT in tumor tissues was found to be significantly affected by tumor size but not by tumor metastasis. Expression levels of lncRNA MORT and miRNA-21 were significantly and inversely correlated in both tumor tissues and adjacent healthy tissues. Overexpression of lncRNA MORT inhibited miRNA-21, while miRNA-21 overexpression failed to significantly affect lncRNA MORT expression. Overexpression of lncRNA MORT inhibited, while miRNA-21 overexpression promoted the proliferation of cells of ovarian cancer cell lines. In addition, miRNA-21 overexpression partially reversed the inhibitory effects of lncRNA MORT overexpression on cancer cell proliferation. However, overexpression of lncRNA MORT showed no significant effects on cancer cell migration and invasion. Therefore, lncRNA MORT was downregulated in ovarian carcinoma and lncRNA MORT overexpression inhibited cancer cell proliferation, possibly by downregulating miRNA-21.

8.
Artigo em Inglês | MEDLINE | ID: mdl-30425748

RESUMO

Qi-deficiency (QX) is thought to promote the body's susceptibility to disease, but the underlying mechanism through which this occurs is not clear. We surveyed the traditional Chinese medicine constitution (TCMC) of healthy college students to identify those that were PH (balanced TCMC constitution) and QX (unbalanced TCMC constitution). We then used high-throughput sequencing of the 16SrRNA V3-4 region in fecal microbiota samples to identify differences between those obtained from PH and QX individuals. Our results demonstrated that the alpha diversity of QX samples was significantly lower than that of PH samples (p < 0.05) and that beta diversity was remarkably different in QX and PH samples. Four and 122 bacterial taxa were significantly overrepresented in QX and PH groups, respectively. The genera Sphingobium, Clostridium, and Comamonas were enriched in the QX group and had a certain pathogenic role. The QX group also showed a statistically significant lack of probiotics and anti-inflammatory bacteria such as Bifidobacterium and Bdellovibrio. The functional potential of QX bacterial taxa was reduced in fatty acid metabolism and butanoate metabolism. We contend that the imbalanced intestinal microbiota in QX and the following functional changes in metabolism influence immunity and energy metabolism, which could increase susceptibility to disease.

10.
Brain Res Bull ; 142: 107-115, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29969645

RESUMO

BACKGROUND: Depression is a heterogeneous disorder, but the exact neuronal mechanisms causing the disease have not yet been discovered. METHODS/MATERIALS: We have established a chronic unpredictable mild stress (CUMS) mouse model to explore the blood oxygen level-dependent (BOLD) activity in the hippocampus, prefrontal cortex (PFC), and basolateral amygdala (BLA) using amplitude of low-frequency fluctuations (ALFF) in functional magnetic resonance imaging (fMRI). We initially studied the relationship between brain-derived neurotrophic factor (BDNF) expression and BOLD activity using BDNFtm1Krj/J mice. RESULTS: We found that CUMS induced depressive-like behaviours and stimulated changes in brain regions expressing a different BDNF level, which was decreased in the hippocampus and PFC but increased in the BLA. In contrast, the BOLD activity was elevated in the hippocampus and PFC but reduced in the BLA after CUMS exposure, indicating that the BDNF level negatively correlated with the BOLD activity in the WT CUMS-exposed mice. Moreover, the depressive-like behaviours and region-specific BOLD activity in BDNFtm1Krj/J mice were consistent with those in WT CUMS-exposed mice. CONCLUSION: We surmised that critical neural circuitry connects the hippocampus, PFC and BLA in mice, which was regulated by BDNF to protect against depression. These findings suggested a potential central role of BDNF expression in functional changes in the brain.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/metabolismo , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Transtorno Depressivo/diagnóstico por imagem , Transtorno Depressivo/fisiopatologia , Animais , Mapeamento Encefálico , Circulação Cerebrovascular/fisiologia , Modelos Animais de Doenças , Expressão Gênica , Imagem por Ressonância Magnética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Vias Neurais/diagnóstico por imagem , Vias Neurais/fisiopatologia , Neurogênese/fisiologia , Oxigênio/sangue , Distribuição Aleatória , Estresse Psicológico/diagnóstico por imagem , Estresse Psicológico/fisiopatologia
11.
Am J Transl Res ; 10(6): 1750-1761, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30018716

RESUMO

OBJECTIVE: To evaluate the protective effect of catalpol against diabetic nephropathy in db/db mouse. METHODS: 8 week old C57BLKS/J db/db mice (type 2 diabetic mouse model) were divided into three groups to feed for 16 weeks on chow diet with or without catalpol supplementation. Their food intake, water consumption, body weight, and fasting glucose levels were recorded every 4 weeks. At the end of study, urine and blood samples were examined for several metabolic variables, and kidneys were harvested for structural characterization and microarray analysis. RESULTS: Catalpol efficiently lowers the fasting glucose and the 24 h urinary albumin excretion rate. Catalpol significantly lowers serum triglycerides, increases high-density lipoproteins, and improves serum creatinine and urea nitrogen. Catalpol-fed mice preserve their kidney structure and renal function better than chow fed db/db mice. Microarray data indicates that lipid metabolism is a potential target of catalpol in exerting protective effect. CONCLUSION: Catalpol has a renal protective effect in diabetic db/db mice.

12.
Oncotarget ; 9(24): 17133-17140, 2018 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-29682210

RESUMO

Background: Accumulating evidence suggests that early menarche is associated with adult obesity, which in turn may increase the risk of insulin resistance and hyperglycemia. However, the relation of menarcheal age with gestational diabetes mellitus (GDM) remains inconsistent across studies. The objective of this meta-analysis was to evaluate the association between age at menarche and GDM risk. Materials and Methods: We searched Medline (PubMed), Embase, Web of Knowledge and the Cochrane library through the end of May 2017. We pooled summary relative risks (RR) with 95% confidence intervals (CIs). Stata 12.0 software was used to analyse the data. Results: Five prospective studies were eligible for inclusion. The results of meta-analysis showed that women in the early menarcheal age group (at < 12 years of age) had a higher risk of GDM compared with those in the "not early" menarcheal age group (at ≥ 13 years of age) (pooled RR = 1.31, 95% CI: 1.05, 1.56) with moderate heterogeneity (I2 = 47.5%, P = 0.107). However, there was no obvious protection of late menarche (at ≥ 15 years of age) versus median menarche (at 13 years of age) (pooled RR = 1.12, 95% CI: 0.92, 1.32; I2 = 0%). Conclusions: The findings support an association between earlier age at menarche and increased risk of GDM. Age at menarche may help identify women with increased risk of developing GDM. However, considering the potential limitations in this study, further larger prospective studies are warranted to verify our findings.

13.
Int Immunopharmacol ; 55: 174-182, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29268189

RESUMO

In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLSs) play an essential role in cartilage destruction. Aggressive migration and invasion by FLSs significantly affect RA pathology. Kaempferol has been shown to inhibit cancer cell migration and invasion. However, the effects of kaempferol on RA FLSs have not been investigated. Our study aimed to determine the effects of kaempferol on RA both in vitro and in vivo. In vitro, cell migration and invasion were measured using scratch assays and the Boyden chamber method, respectively. The cytoskeletal reorganization of RA FLSs was evaluated by immunofluorescence staining. Matrix metalloproteinase (MMP) levels were measured by real-time PCR, and protein expression levels were measured by western blotting. In vivo, the effects of kaempferol were evaluated in mice with CIA. The results showed that kaempferol reduced migration, invasion and MMP expression in RA FLSs. In addition, we demonstrated that kaempferol inhibited reorganization of the actin cytoskeleton during cell migration. Moreover, kaempferol dramatically suppressed tumor necrosis factor (TNF)-α-induced MAPK activation without affecting the expression of TNF-α receptors. We also demonstrated that kaempferol attenuated the severity of arthritis in mice with CIA. Taken together, these results suggested that kaempferol inhibits the migration and invasion of FLSs in RA by blocking MAPK pathway activation without affecting the expression of TNF-α receptors.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Fibroblastos/fisiologia , Quempferóis/uso terapêutico , Sinoviócitos/fisiologia , Actinas/metabolismo , Adulto , Idoso , Animais , Artrite Experimental , Movimento Celular , Células Cultivadas , Citoesqueleto/metabolismo , Feminino , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Camundongos Endogâmicos DBA , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/metabolismo
14.
Brain Res Bull ; 139: 197-202, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29253606

RESUMO

BACKGROUND AND OBJECTIVE: Xiao Yao San (XYS) is a traditional Chinese medicine used to treat depression; however, the mechanism underlying its antidepressant properties remains unclear. The objective of the present study was to investigate the effects and action mechanisms of XYS on interferon-α-induced depression in mice. METHOD: Mice were divided into six groups: control; model; low-, medium-, and high-dose XYS; and escitalopram-treated group. Except for the control mice, all groups of mice were injected with interferon (IFN)-α to establish the depression model. XYS and escitalopram were then administered to the respective mice daily for 21 days. Sucrose preference test (SPT), forced swim test (FST), and tail suspension test (TST) were used to measure behavioral indices. High-performance liquid chromatography (HPLC) was used to measure serotonin (5-HT) concentrations, while western blots were used to examine indoleamine-2,3-dioxygenase 1 (IDO1) expression in the dorsal raphe nucleus (DRN). The number of microglia in the DRN was observed using immunofluorescence. RESULTS: Compared with that of the control group, the model group showed a significant decrease in sucrose consumption (P < 0.05) and significant increase in the duration of immobility in the FST and TST (P  < 0.05). These parameters improved significantly after XYS or escitalopram treatment. There was also a significantly higher and lower expression of IDO1 protein and 5-HT in the mouse DRN, respectively, which were reversed by administering XYS and escitalopram (P < 0.05). Moreover, the number of microglia in the mouse DRN increased significantly and was reduced by XYS and escitalopram (P < 0.05). CONCLUSION: XYS reduced the number of microglia and expression of IDO1, which increased the levels of 5-HT in the mouse DRN and, thereby, improved the depressive behavior of mice. This may explain, at least in part, the antidepressant properties of XYS in patients.


Assuntos
Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Citalopram/farmacologia , Citalopram/uso terapêutico , Depressão/induzido quimicamente , Depressão/patologia , Modelos Animais de Doenças , Núcleo Dorsal da Rafe/efeitos dos fármacos , Núcleo Dorsal da Rafe/metabolismo , Preferências Alimentares/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/metabolismo , Elevação dos Membros Posteriores/psicologia , Fatores Imunológicos/toxicidade , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Interferon-alfa/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas dos Microfilamentos/metabolismo , Microglia/efeitos dos fármacos , Microglia/patologia , Serotonina/metabolismo , Sacarose/administração & dosagem , Natação/psicologia
15.
Virol J ; 14(1): 178, 2017 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-28915824

RESUMO

BACKGROUND: Hepatitis B virus (HBV) infection is a serious public health problem leading to cirrhosis and hepatocellular carcinoma. As the clinical utility of current therapies is limited, the development of new therapeutic approaches for the prevention and treatment of HBV infection is imperative. Fucoidan is a natural sulfated polysaccharide that extracted from different species of brown seaweed, which was reported to exhibit various bioactivities. However, it remains unclear whether fucoidan influences HBV replication or not. METHODS: The HBV-infected mouse model was established by hydrodynamic injection of HBV replicative plasmid, and the mice were treated with saline or fucoidan respectively. Besides, we also tested the inhibitory effect of fucoidan against HBV infection in HBV-transfected cell lines. RESULTS: The result showed that fucoidan from Fucus vesiculosus decreased serum HBV DNA, HBsAg and HBeAg levels and hepatic HBcAg expression in HBV-infected mice. Moreover, fucoidan treatment also suppressed intracellular HBcAg expression and the secretion of the HBV DNA as well as HBsAg and HBeAg in HBV-expressing cells. Furthermore, we proved that the inhibitory activity by fucoidan was due to the activation of the extracellular signal-regulated kinase (ERK) pathway and the subsequent production of type I interferon. Using specific inhibitor of ERK pathway abrogated the fucoidan-mediated inhibition of HBV replication. CONCLUSION: This study highlights that fucoidan might be served as an alternative therapeutic approach for the treatment of HBV infection.


Assuntos
Antivirais/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fucus/química , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/metabolismo , Hepatite B/virologia , Polissacarídeos/farmacologia , Replicação Viral/efeitos dos fármacos , Animais , Linhagem Celular , Replicação do DNA/efeitos dos fármacos , DNA Viral , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Humanos , Interferon Tipo I/biossíntese , Masculino , Camundongos , Transdução de Sinais/efeitos dos fármacos
16.
Saudi Pharm J ; 25(4): 625-632, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28579902

RESUMO

Atopic dermatitis (AD) is a common inflammatory skin disease with high rates of morbidity and is associated with erythema, pruritus, scaling of affected areas of skin. It is extremely important to introduce a therapeutic agent which has significant anti-inflammatory effect with less side-effect for treatment of AD. This study evaluated the effect of a natural compound from herbal extracts, the crude polysaccharide extracted from the white wax scale (CWPS), on AD-like mice. Repeated applications of 2,4-dinitrochlorobenzene (DNCB) were performed on ear and dorsal skin of BALB/c mice to induce AD-like symptoms and skin lesions. Oral administration of CWPS decreased serum IgE level and limited the infiltration of mast cells and eosinophils to the dermal tissues in the DNCB-induced AD mice. In addition, CWPS reduced Th1 and Th17 responses, leading to an attenuated cutaneous inflammatory response. Furthermore, in vitro study also demonstrated that CWPS limited T cell activation and cytokines (i.e. IFN-γ and IL-17) production induced by DNCB. We conclude that CWPS attenuates DNCB-induced AD-like skin lesion through modulating T cell-elicited immune responses and CD4+ T cell polarization, and could be exploited as a new therapeutic approach for AD.

17.
Artigo em Inglês | MEDLINE | ID: mdl-28264509

RESUMO

BACKGROUND: Suboptimal health status (SHS) is the intermediate health state between health and disease, it is medically undiagnosed and is also termed functional somatic syndrome. Although its clinical manifestations are complicated and various, SHS has not reached the disease status. Unhealthy lifestyle is associated with many chronic diseases and mortality. In accordance with the impact of lifestyle on health, it is intriguing to determine the association between unhealthy lifestyle and SHS risk. METHODS: We conducted a nested case-control study among healthy Chinese college students from March 2012 to September 2013, which was nested in a prospective cohort of 5676 students. We performed 1:1 incidence density sampling with matched controls for birth year, sex, grade, specialty and individual character. SHS was evaluated using the medical examination report and Sub-health Measurement Scale V1.0 (SHMS V1.0). Exposure was defined as an unhealthy lifestyle per the frequency of six behavioral dimensions from the Health-promoting Lifestyle Profile (HPLP-II). RESULTS: We matched 543 cases of SHS (42.66%) in a cohort of 1273 students during the 1.5 years mean follow-up time with controls. A significant difference (t = 9.79, p < 0.001) and a reduction in HPLP-II total score was present at 1.5 years follow-up (135.93 ± 17.65) compared to baseline (144.48 ± 18.66). A level-response effect was recorded with an increase of the total HPLP-II (every dimension was correlated with a decreased SHS risk). Compared to respondents with the least exposure (excellent level), those reporting a general HPLP-II level were approximately 2.3 times more likely to develop SHS (odd ratio = 2.333, 95% CI = 1.471 to 3.700); and those with less HPLP-II level (good level) were approximately 1.6 times more likely (1.644, 1.119-2.414) to develop SHS (p < 0.05). Our data indicated that unhealthy lifestyle behavior with respect to behavioral dimensions significantly affected SHS likelihood. Further analyses revealed a marked increase (average increased 14.73 points) in lifestyle level among those SHS regression to health after 1.5 years, with respect to the HPLP-II behavioral dimensions, in addition to the total score (t = -15.34, p < 0.001). CONCLUSIONS: SHS is highly attributable to unhealthy lifestyles, and the Int. J. Environ. Res. Public Health 2017, 14, 240 2 of 17 mitigation of modifiable lifestyle risk factors may lead to SHS regression. Increased efforts to modify unhealthy lifestyles are necessary to prevent SHS.


Assuntos
Promoção da Saúde , Nível de Saúde , Estilo de Vida , Estudantes , Adolescente , Adulto , Grupo com Ancestrais do Continente Asiático , China/epidemiologia , Feminino , Humanos , Masculino , Razão de Chances , Estudos Prospectivos , Fatores de Risco , Comportamento de Redução do Risco , Universidades , Adulto Jovem
18.
Lipids Health Dis ; 16(1): 28, 2017 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-28153015

RESUMO

BACKGROUND: The effects of short-term high fat diets on physiology are elusive and the molecular changes following fat overconsumption remain largely unknown. In this study, we aimed to evaluate exercise capacity in mice fed with a high fat diet (HFD) for 3 days and investigate the molecular mechanisms in the early response to high-fat feeding. METHODS: Exercise capacity was assessed by weight-loaded swimming test in mice fed a control diet (10 kcal% fat) or a HFD (60 kcal% fat) for 3 days. Global gene expression of ten important tissues (brain, heart, liver, spleen, lung, kidney, stomach, duodenum, skeletal muscle and blood) was analyzed using RNA Sequencing. RESULTS: A HFD for just 3 days can induce 71% decrease of exercise performance prior to substantial weight gain (P <0.01). Principle component analysis revealed that differential gene expression patterns existed in the ten tissues. Out of which, the brain, spleen and lung were demonstrated to have more pronounced transcriptional changes than other tissues. Biological process analysis for differentially expressed genes in the brain, spleen and lung showed that dysregulation of peripheral and central immune response had been implicated in the early stage of HFD exposure. Neurotransmission related genes and circulatory system process related genes were significantly down-regulated in the brain and lung, respectively. CONCLUSIONS: Our findings provide new insights for the deleterious effects of high-fat feeding, especially revealing that the lung maybe as a new important target attacked by short-term high-fat feeding.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Condicionamento Físico Animal/fisiologia , Transcriptoma , Animais , Sangue/metabolismo , Peso Corporal , Encéfalo/fisiologia , Pulmão/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Análise de Sequência de RNA , Baço/fisiologia
19.
Oncotarget ; 8(5): 8264-8282, 2017 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-28030814

RESUMO

Long-term treatment with high-dose Interferon-alpha (IFN-α) has resulted in depression in 30-50% of the patients. Paeoniflorin may ameliorate the IFN-α-induced depression; however, the underlying mechanism is less studied. Here, we investigated the prophylactic antidepressant and anti-neuroinflammatory effects of paeoniflorin on the behaviors and specific emotion-related regions of the brain in mice with IFN-α-induced depression. A series of behavior assessments were conducted to identify the depressive state after subcutaneously IFN-α injections and with or without intragastrically paeoniflorin administration in C57BL/6J mice. Levels of many inflammatory-related cytokines in serum, mPFC, vHi and amygdala were determined by cytokine array analysis. Furthermore, microglia and astrocyte activation in these three regions were evaluated by immunohistochemistry. We found that the mice which were subcutaneously injected IFN-α 15×106 IU/kg for 4 successive weeks to mimic an IFN-α-induced depression model had distinct inflammatory changes in the amygdala. Interestingly, 4-week 20 mg/kg or 40 mg/kg paeoniflorin pretreatments reversed the depressive-like behaviors and the abnormal inflammatory cytokine levels in the serum, mPFC, vHi and amygdala. These cytokines were not limited to the commonly reported IL-6, IL-1ß and TNF-α, but also IL-9, IL-10, IL-12, and MCP-1. Besides, the increased density of microglia in IFN-α-treated mice was reversed by paeoniflorin in these three brain areas. Taken together, our data suggest that paeoniflorin can reverse the long-term, high-dose IFN-α-induced depressive-like behaviors that were associated with local distinct neuroinflammation in the mPFC, vHi and particularly the amygdala. Paeoniflorin might have a preventive therapeutic potential in IFN-α-induced depression.


Assuntos
Anti-Inflamatórios/farmacologia , Antidepressivos/farmacologia , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Citocinas/metabolismo , Depressão/prevenção & controle , Encefalite/prevenção & controle , Glucosídeos/farmacologia , Mediadores da Inflamação/metabolismo , Interferon-alfa , Monoterpenos/farmacologia , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/metabolismo , Tonsila do Cerebelo/fisiopatologia , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Citocinas/sangue , Depressão/induzido quimicamente , Depressão/metabolismo , Depressão/psicologia , Modelos Animais de Doenças , Encefalite/induzido quimicamente , Encefalite/metabolismo , Encefalite/fisiopatologia , Preferências Alimentares/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Mediadores da Inflamação/sangue , Interferon alfa-2 , Masculino , Camundongos Endogâmicos C57BL , Microglia/efeitos dos fármacos , Microglia/metabolismo , Atividade Motora/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Córtex Pré-Frontal/fisiopatologia , Proteínas Recombinantes , Natação , Fatores de Tempo
20.
Nan Fang Yi Ke Da Xue Xue Bao ; 36(11): 1489-1495, 2016 Nov 20.
Artigo em Chinês | MEDLINE | ID: mdl-27881338

RESUMO

OBJECTIVE: To assess the effect of Guifu Dihuang Wan (GFDHW) in the treatment of yang deficiency and explore the underlying molecular mechanism. METHODS: Sixty-two participants without diseases were randomized into control group (n=31) and experimental group (n=31) and were given lifestyle intervention additional GFDHW treatment for a month. NMR technology was used for metabonomics analysis. RESULTS: Intervention with GFDHW resulted in significantly decreased conversion scores of yang deficiency in the experimental group compared with the control group (P<0.005). The concentrations of lactate, valine, proline, arginine and 3-hydroxybutyrate were increased in the plasma of yang-deficient subjects after lifestyle intervention. GFDHW treatment with lifestyle intervention significantly increased the concentrations of lactate, valine, proline, arginine and 3-hydroxybutyrate and also the levels of alanine, glutamine, alpha glucose, isoleucine, betaine and propylene glycol. CONCLUSION: GFDHW treatment improves yang deficiency possibly by increasing the concentrations of alanine, glutamine, alpha glucose, isoleucine, betaine and propylene glycol and promoting energy metabolism of the body.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Metabolômica , Deficiência da Energia Yang/tratamento farmacológico , Ácido 3-Hidroxibutírico/sangue , Arginina/sangue , Humanos , Ácido Láctico/sangue , Imagem por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Plasma , Valina/sangue
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