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Mol Immunol ; 105: 76-85, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30496979


Activation of NLRP3 inflammasomes is crucial in the pathological process of Ulcerative colitis (UC), which could be negatively regulated by PINK1/Parkin-driven mitophagy. Palmatine is a herb derived isoquinoline alkaloid with potent anti-inflammatory and anti-bacteria activities. In present study, we evaluated the effect of palmatine on dextran sulfate sodium (DSS)-induced mice colitis and examined whether its effect is exerted by promoting mitophagy-mediated NLRP3 inflammasome inactivation. The result showed that palmatine (40, 100 mg/kg) significantly prevented bodyweight loss and colonic shortening in DSS mice, and reduced the disease activity index and histopathologic score. The levels of MPO, IL-1ß, TNF-α and the number of F4/80+ cells in colon of DSS mice were remarkably decreased by palmatine. Moreover, palmatine suppressed NLRP3 inflammasomes activation, but enhanced the expression of the mitophagy-related proteins involving LC3, PINK1 and Parkin in colonic tissue of DSS mice. These effects was consistent with the in vitro data revealing that palmatine inhibited the activation of NLRP3 inflammasomes, while promoted the expression and mitochondrial recruitment of PINK1 and Parkin in THP-1 cell differentiated macrophages. Furthermore, the effect of palmatine on THP-1 cells was neutralized by a mitophagy inhibitor Cyclosporin A (CsA) and PINK1-siRNA. In parallel, CsA significantly attenuated the therapeutic effect of palmatine in DSS mice, illustrating that the anti-colitis effect of palmatine is closely related to mitophagy. Taken together, the current results demonstrated that palmatine protected mice against DSS-induced colitis by facilitating PINK1/Parkin-driven mitophagy and thus inactivating NLRP3 inflammasomes in macrophage.

Colite , Sulfato de Dextrana/toxicidade , Inflamassomos/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Ácido Palmítico/farmacologia , Animais , Colite/induzido quimicamente , Colite/imunologia , Colite/patologia , Colite/prevenção & controle , Ciclosporina/farmacologia , Modelos Animais de Doenças , Humanos , Masculino , Camundongos Endogâmicos BALB C , Proteínas Quinases/imunologia , Células THP-1 , Ubiquitina-Proteína Ligases/imunologia
Zhen Ci Yan Jiu ; 43(6): 380-3, 2018 Jun 25.
Artigo em Chinês | MEDLINE | ID: mdl-30091545


OBJECTIVE: To observe the clinical effectiveness of acupoint catgut embedding and surface electromyogram biofeedback therapy (sEMGBF) in the treatment of stroke patients complicated with shoulder-hand syndrome (SHS). METHODS: A total of 90 stroke patients with SHS were randomly divided into acupoint catgut embedment (ACE), sEMGBF and ACE+sEMGBF (combined treatment) groups (n=30 cases/group). The catgut embedment was performed at Jianliao (LI 14), Jianyu (LI 15), Quchi (LI 11), Waiguan (TE 5) on the affected side, once every 3 weeks, twice altogether. The electromyographic biofeedback therapy (30-50 Hz, pulse duration 200 µs, 6 s-on and 10 s-off, appropriate strength) was applied to the skin area co-vering the deltoid muscle, flexor muscle of wrist and wrist extensor for 20 min, once per day, 5 times/week, for 6 weeks. The total effective rate was assessed by using Liao's and Zhu's methods (1996), the pain severity assessed using visual analogue scale (VAS), and Fugl-Meyer assessment (FMA, 66-points) scale and the patients' activities of daily living function (ADL, 100-points) were also scored. RESULTS: Before treatment, the VAS, FMA and ADL points of the three groups were not significantly different (P>0.05). After the treatment, the total effective rate (93.33%), FMA and ADL scores of the combined treatment group were significantly higher than those of the ACE and sEMGBF groups (P<0.05), while the VAS score of the combined treatment group was significantly lower than those of the ACE and sEMGBF groups (P<0.05). The total effective rates, FMA and ADL scores of the ACE and sEMGBF groups were comparable (P>0.05). The VAS score of the ACE group was markedly lower than that of the sEMGBF group (P<0.05). CONCLUSION: The combined administration of ACE and sEMGBF has a better therapeutic effect for stroke patients complicated with SHS relevant to simple ACE and simple sEMGBF therapy in improving the upper limb function, relieving pain, and enhancing the daily life quality.

Acidente Vascular Cerebral , Atividades Cotidianas , Pontos de Acupuntura , Biorretroalimentação Psicológica , Categute , Eletromiografia , Humanos , Ombro , Resultado do Tratamento , Punho
Sheng Li Xue Bao ; 69(5): 532-540, 2017 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-29063102


Numerous studies have demonstrated that estrogens may exert multifaceted effects on the cardiovascular system via activating the classical nuclear receptors ERα or ERß and the novel G protein coupled estrogen receptor (Gper). However, some studies have reported inconsistent cardiovascular phenotypes in Gper-deficient mice. The current study was aimed to reveal the effects of genetic deletion of Gper on the arterial blood pressure (ABP) and heart rate in rats. Gper-deficient Sprague-Dawley rats were generated by utilizing the CRISPR-Cas9 gene-editing technique. ABP of 10-week old male (n = 6) and 12-week old female (n = 6) Gper-deficient rats and age-matched wild type (WT) rats (6 females and 6 males) were measured under awake and restrained conditions through the non-invasive tail-cuff method daily for 8 (females) or 9 days (males). In the male WT rats, ABP and heart rate were slightly higher in day 1 to 4 than those in day 5 to 9, indicative of stress-related sympathoexcitation in the first few days and gradual adaptation to the restrained stress in later days. Gper-deficient rats had significantly higher ABP initially (male: day 1 to day 5; female: day 1 to day 3) and similar ABP in later days of measurement compared with the WT rats. The heart rate of male Gper-deficient rats was consistently higher than that of the male WT rats from day 1 to day 8. Both male and female Gper-deficient rats appeared to show slower body weight gain than the WT counterparts during the study period. Under anesthesia, ABP of Gper-deficient rats was not significantly different from their WT counterparts. These results indicate that Gper-deficient rats may be more sensitive to stress-induced sympathoexcitation and highlight the importance of Gper in the regulation of the cardiovascular function in stressful conditions.

Hipertensão/etiologia , Receptores Estrogênicos/fisiologia , Receptores Acoplados a Proteínas-G/fisiologia , Estresse Psicológico/complicações , Animais , Feminino , Masculino , Ratos , Ratos Sprague-Dawley