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1.
Int J Biol Sci ; 16(1): 12-26, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31892842

RESUMO

Adverse cardiac remodeling after myocardial infarction (MI) is associated with extremely high mortality rates worldwide. Although optimized medical therapy, Preservation of lusitropic and inotropic function and protection against adverse remodeling in ventricular structure remain relatively frequent. This study demonstrated that Andrographolide (Andr) significantly ameliorated adverse cardiac remodeling induced by myocardial infarction and improves contractile function in mice with LAD ligation compared with the control group. Briefly, Andr markedly attenuated cardiac fibrosis and relieved inflammation after myocardial infarction. Specifically, Andr significantly blocked oxidative stress and the nuclear translocation of p-P65 following myocardial infarction. At the mechanistic level, antioxidant effect of Andr was achieved through strengthening antioxidative stress capacity and attributed to the activation of Nrf2/HO-1 Signaling. Consistently, H9C2 administrated with Andr showed a decreased oxidative stress caused by hypoxia precondition, but treatment with specific Nrf2 inhibitor (ML385) or the silence of Nrf2 blunted the activation of Nrf2/HO-1 Signaling and removed the protective effects of Andr in vitro. Thus, we suggest that Andr alleviates adverse cardiac remodeling following myocardial infarction through enhancing Nrf2 signaling pathway.

2.
J Pharmacol Exp Ther ; 371(2): 348-359, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31467086

RESUMO

Aucubin (AUB), which is extracted from Eucommia ulmoides Oliver seeds, has been found to possess anti-inflammatory and antiapoptotic properties. Recent studies have indicated that inflammation, oxidative stress, and apoptosis are involved in the pathophysiology of lipopolysaccharide (LPS)-induced cardiac dysfunction. Our study aimed to investigate the effect of AUB on LPS-induced acute cardiac injury. Male C57BL/6 mice were injected with LPS (one 6 mg/kg injection) to induce cardiac dysfunction without or with AUB pretreatment (20 or 80 mg/kg per day) for 1 week. We found that AUB ameliorated cardiac dysfunction, inflammation, oxidative stress, and apoptosis induced by LPS stimulation. Mechanistically, AUB inhibited LPS-induced oxidative stress by decreasing reactive oxygen species and thioredoxin interaction protein (TXNIP) levels. Moreover, AUB suppressed LPS-induced inflammation and apoptosis by reducing nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3)/apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC)/caspase-1 inflammasome formation. Overexpression of NLRP3 in cardiomyocytes attenuated the protective effects of AUB. Interestingly, NLRP3 deficiency ameliorated cardiac function and reduced the inflammatory response and oxidative stress after LPS insult in mice, whereas AUB could not further prevent LPS-induced cardiac dysfunction in NLRP3-deficient mice. In summary, AUB exerts a protective effect against LPS-induced inflammation, oxidative stress, and apoptosis in vivo and in vitro by regulating the TXNIP pathway and inactivating the NLRP3/ASC/caspase-1 inflammasome. Hence, AUB may be a promising agent against LPS-induced cardiac dysfunction. SIGNIFICANCE STATEMENT: Aucubin exerts a protective effect against lipopolysaccharide-induced cardiac dysfunction by regulating nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 inflammasome.

3.
J Cell Mol Med ; 23(9): 6466-6478, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31293067

RESUMO

Cardiac remodelling refers to a series of changes in the size, shape, wall thickness and tissue structure of the ventricle because of myocardial injury or increased pressure load. Studies have shown that cardiac remodelling plays a significant role in the development of heart failure. Zingerone, a monomer component extracted from ginger, has been proven to possess various properties including antioxidant, anti-inflammatory, anticancer and antidiabetic properties. As oxidative stress and inflammation contribute to acute and chronic myocardial injury, we explored the role of zingerone in cardiac remodelling. Mice were subjected to aortic banding (AB) or sham surgery and then received intragastric administration of zingerone or saline for 25 days. In vitro, neonatal rat cardiomyocytes (NRCMs) were treated with zingerone (50 and 250 µmol/L) when challenged with phenylephrine (PE). We observed that zingerone effectively suppressed cardiac hypertrophy, fibrosis, oxidative stress and inflammation. Mechanistically, Zingerone enhanced the nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/antioxidant response element (ARE) activation via increasing the phosphorylation of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) production. Additionally, we used Nrf2-knockout (KO) and eNOS-KO mice and found that Nrf2 or eNOS deficiency counteracts these cardioprotective effects of zingerone in vivo. Together, we concluded that zingerone may be a potent treatment for cardiac remodelling that suppresses oxidative stress via the eNOS/Nrf2 pathway.

4.
Dis Colon Rectum ; 61(2): 207-213, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29337776

RESUMO

BACKGROUND: Identifying patients with Crohn's disease with rapid disease progress or high risk of early surgery is crucial to clinical decision making. OBJECTIVE: The aim was to evaluate the correlation between the Lémann index at diagnosis and abdominal surgery in the first year after Crohn's disease diagnosis and to find the risk factors for early surgery. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted at a single tertiary hospital. PATIENTS: Patients diagnosed with Crohn's disease between 2013 and 2015 in our center were included. MAIN OUTCOME MEASURES: The outcome of interest was the need for an abdominal surgery within 1 year after the Lémann index evaluation at diagnosis. RESULTS: Of 212 eligible patients, 48 patients underwent abdominal surgery during follow-up. Lémann index was much higher in the surgery group (5.3 vs 2.6; p < 0.001). On tertiles of the Lémann index, the frequency of surgery grew (2.8%, 9.9%, and 55.7%; p < 0.001) as the Lémann index increased. The receiver operating characteristic curve was constructed taking into account the Lémann index for selecting patients with a high risk of surgery. Specificity, sensitivity, and area under receiver operating characteristic curve were 84.8%, 81.3%, and 0.89 of the Lémann Index at a cutoff level of 3.7. Patients with Lémann index ≥3.7 carried a higher risk of abdominal surgery (OR = 18.6; p < 0.001). Stricturing and penetrating disease were predictors for abdominal surgery, whereas antitumor necrosis factor treatment was associated with a significant reduction of surgical requirements. LIMITATIONS: This study was limited by its retrospective design. The ability of the Lémann index to predict the long-term risk of surgery was unknown. CONCLUSIONS: Lémann index at diagnosis is a reliable index to predict the risk of abdominal surgery in the first year after diagnosis of Crohn's disease. Patients with a high Lémann index might need closer follow-up or aggressive medical therapy. See Video Abstract at http://links.lww.com/DCR/A518.


Assuntos
Constrição Patológica/patologia , Doença de Crohn/diagnóstico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adulto , Constrição Patológica/cirurgia , Doença de Crohn/cirurgia , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Prevenção Secundária , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/uso terapêutico , Adulto Jovem
5.
Medicine (Baltimore) ; 96(23): e7113, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28591060

RESUMO

The patients with Crohn's disease (CD) are often accompanied with nutritional deficiencies. Compared with other intestinal benign disease, patients with CD have the higher risk of developing postoperative complications following intestinal resection. The aim of this study was to investigate the risk factors for postoperative infectious complications (PICs) after intestinal resection for CD, as well as search a practical preoperative nutritional index for PICs in patients with CD. A total of 122 patients who underwent intestinal resection for CD during 2011 to 2015 were retrospectively analyzed. After operation, 28 (22.95%) patients experienced PICs. Compared with the non-PICs group, the patients with PICs have the lower preoperative body mass index (BMI) (16.96 ±â€Š2.33 vs 19.53 ±â€Š2.49 kg/m, P < .001), lower albumin (ALB) (33.64 ±â€Š5.58 vs 36.55 ±â€Š5.69 g/L, P = .013), higher C-reactive protein (CRP) level (30.44 ±â€Š37.06 vs 15.99 ±â€Š33.30 mg/L, P = .052), and longer hospital stay (22.64 ±â€Š9.93 vs 8.90 ±â€Š4.32 days, P < .001). By analyzing the receiver-operating characteristic (ROC) curve, BMI have better value in predicting the occurrence of PICs than ALB. The areas under the ROC curves of BMI for PICs was 0.784 (95% confidence interval 0.690-0.878, P < .001) with an optimal diagnostic cut-off value of 17.5 kg/m. In the univariate and multivariate analysis, BMI < 17.5 kg/m (P = .001), ALB < 33.6 g/L (P = .024), CRP ≥ 10 mg/L (P = .026) were risk factors for PICs. Patients with a lower preoperative BMI (BMI < 17.5 kg/m) had a 7.35 times greater risk of PICs. Therefore, preoperative BMI could be regarded as a practical preoperative nutritional index for evaluating the nutritional preparation sufficiency before CD operations. Preoperative treatment with the aim of reducing CRP level and improving the patient's nutritional status may be helpful to reduce the rate of PICs.


Assuntos
Índice de Massa Corporal , Doenças Transmissíveis/diagnóstico , Doença de Crohn/cirurgia , Avaliação Nutricional , Complicações Pós-Operatórias/diagnóstico , Cuidados Pré-Operatórios , Adulto , Biomarcadores/sangue , Proteína C-Reativa/análise , Doenças Transmissíveis/epidemiologia , Doenças Transmissíveis/etiologia , Doença de Crohn/diagnóstico , Doença de Crohn/epidemiologia , Feminino , Humanos , Incidência , Intestinos/cirurgia , Masculino , Análise Multivariada , Complicações Pós-Operatórias/epidemiologia , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica/análise
6.
Int J Biomed Sci ; 11(2): 76-81, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26199580

RESUMO

Sleep disorder is a common condition in the general population. Conventional sedative-hypnotic drug therapy may not be appropriate for many patients suffering from only mild-to-moderate sleep disorders. SurAsleep, a nutritional supplement that has been used by patients with sleep disorders in the United States, shows promising effects in improving sleep disorders and enhancing sleep quality. However, double-blinded, randomized and controlled studies have not been performed to determine the efficacy of the supplement. We conducted this study on individuals suffering from mild-to-moderate sleep disorders in Shanghai, China. In this study, we randomly assigned 100 participants over the age of 50 years old with symptoms of sleep disorders to a 12-week treatment with either SurAsleep or placebo. The results were measured by a self-administrated questionnaire on changes in symptoms, which covered 3 phases of sleep: the falling-asleep stage, the sleeping stage and the waking-up stage. We also measured the changes after the 12-week intervention using the Pittsburgh Sleep Quality Index (PSQI), including 7 dimensions of sleeping. All symptoms, dimension-specific PSQI scores and total PSQI scores showed significant improvement after using SurAsleep. In this study, SurAsleep has shown potent effects in relieving somnipathy-related symptoms and improving sleep quality in sleep disorder patients.

7.
Nutr J ; 7: 31, 2008 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-18954461

RESUMO

BACKGROUND: Osteoarthritis-induced arthralgia is a common cause of morbidity in both men and women worldwide. AR7 Joint Complex is a nutritional supplement containing various ingredients including sternum collagen II and methylsulfonylmethane. The product has been marketed in United States for over a decade, but clinical data measuring the effectiveness of this supplement in relieving arthralgia is lacking. The goal of this study was to determine the effect of AR7 Joint Complex on osteoarthritis. METHODS: A total of 100 patients over the age of 50 who had osteoarthritis were recruited to the double-blind study and randomly assigned into either treatment or placebo control groups. The patients in the treatment group were given AR7 Joint Complex orally, 1 capsule daily for 12 weeks, while the patients in the control group were given a placebo for the same period of time. Prior to and at the end of the study, data including Quality of Life questionnaires (SF-36), visual analog scales (1 to 100 mm), and X-rays of affected joints were collected. RESULTS: A total of 89 patients completed the study: 44 from the treatment group and 45 from the control group. No significant change in X-ray results was found in either group after the study. However, there was a significant decrease in patients complaining of arthralgia and tenderness (P < 0.01) in the treatment group and there was also a significant difference between the treatment and control groups at the end of the study. In addition, for Quality of Life data, the body pain index (BP) in the treatment group was significantly improved (P < 0.05) compared to the control group. No significant toxicity was noted in either group. CONCLUSION: AR7 Joint Complex appears to have short-term effects in relieving pain in patients with osteoarthritis. Whether such an effect is long-lasting remains to be seen.


Assuntos
Artralgia/tratamento farmacológico , Suplementos Nutricionais , Articulações/efeitos dos fármacos , Osteoartrite/tratamento farmacológico , Qualidade de Vida , Anti-Inflamatórios/administração & dosagem , Artralgia/patologia , Artralgia/psicologia , Artrografia , China , Colágeno Tipo II/administração & dosagem , Dimetil Sulfóxido/administração & dosagem , Método Duplo-Cego , Feminino , Humanos , Articulações/patologia , Masculino , Pessoa de Meia-Idade , Osteoartrite/patologia , Osteoartrite/psicologia , Dor/tratamento farmacológico , Dor/psicologia , Sulfonas/administração & dosagem , Inquéritos e Questionários , Resultado do Tratamento
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