RESUMEN
BACKGROUND: Stroke is a major cause of death or long-term disability worldwide. Many patients with stroke receive integrative therapy consisting of Western medicine (WM) and routine rehabilitation in conjunction with Chinese medicine (CM), such as acupuncture and Chinese herbal medicine. However, there is no available evidence on the effectiveness of the combined use of WM and CM interventions in stroke rehabilitation. AIMS: The purpose of this meta-analysis is to evaluate the results of all individual studies to assess the combined use of CM and WM in stroke rehabilitation compared with WM only. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines were followed. MEDLINE, EMBASE, Cochrane and China National Knowledge Infrastructure (CNKI) were searched. The included outcomes were dependency, motor function, depression and swallowing function. Subgroup analysis was performed, and publication bias was assessed using funnel plots. SUMMARY OF REVIEW: 58 studies and 6339 patients were included in the meta-analysis. Subgroup analysis revealed that combined therapy comprising both acupuncture and WM had a superior effect on improving dependency and swallowing function compared with standard WM therapy alone. Potential superiority of combined therapy comprising CM and WM in improving depression compared with standard WM therapy was also found. CONCLUSIONS: Our results indicate that the combined use of CM and WM could be more efficacious in stroke rehabilitation compared with the use of WM therapy alone. However, most studies were short in duration (2 to 4 weeks) and prone to different types of biases, which prevents making any conclusion regarding the long-term effects and raises concerns regarding true efficacy in context of high likelihood of Hawthorn bias. So, more randomised controlled trials with more rigorous design and longer duration of treatment and follow-up need to be conducted to compare WM alone versus WM and CM combined. PROSPERO REGISTRATION NUMBER: CRD42020152050.
Asunto(s)
Terapia por Acupuntura , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Terapia por Acupuntura/efectos adversos , Terapia por Acupuntura/métodos , China , Humanos , Medicina Tradicional China , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/terapia , Rehabilitación de Accidente Cerebrovascular/efectos adversosRESUMEN
Despite the benefit of statins in reducing cardiovascular risk, a sizable proportion of patients still remain at risk. Since HDL reduces CVD risk through a process that involves formation of pre-beta particles that facilitates the removal of cholesterol from the lipid-laden macrophages in the arteries, inducing pre-beta particles, may reduce the risk of CVD. A novel BET bromodomain antagonist, RVX-208, was reported to raise apoA-I and increase preß-HDL particles in non-human primates and humans. In the present study, we investigated the effect of RVX-208 on aortic lesion formation in hyperlipidemic apoE(-/-) mice. Oral treatments of apoE(-/-) mice with 150 mg/kg b.i.d RVX-208 for 12 weeks significantly reduced aortic lesion formation, accompanied by 2-fold increases in the levels of circulating HDL-C, and â¼50% decreases in LDL-C, although no significant changes in plasma apoA-I were observed. Circulating adhesion molecules as well as cytokines also showed significant reduction. Haptoglobin, a proinflammatory protein, known to bind with HDL/apoA-I, decreased >2.5-fold in the RVX-208 treated group. With a therapeutic dosing regimen in which mice were fed Western diet for 10 weeks to develop lesions followed by switching to a low fat diet and concurrent treatment with RVX-208 for 14 weeks, RVX-208 similarly reduced lesion formation by 39% in the whole aorta without significant changes in the plasma lipid parameters. RVX-208 significantly reduced the proinflammatory cytokines IP-10, MIP1(®) and MDC. These results show that the antiatherogenic activity of BET inhibitor, RVX-208, occurs via a combination of lipid changes and anti-inflammatory activities.
Asunto(s)
Enfermedades de la Aorta/prevención & control , Aterosclerosis/prevención & control , Betaína-Homocisteína S-Metiltransferasa/antagonistas & inhibidores , Hiperlipidemias/tratamiento farmacológico , Quinazolinas/uso terapéutico , Animales , Aorta/efectos de los fármacos , Aorta/metabolismo , Aorta/patología , Enfermedades de la Aorta/sangre , Enfermedades de la Aorta/etiología , Enfermedades de la Aorta/patología , Apolipoproteína A-I/sangre , Apolipoproteínas E/deficiencia , Aterosclerosis/sangre , Aterosclerosis/etiología , Aterosclerosis/patología , Línea Celular , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Citocinas/sangre , Dieta con Restricción de Grasas , Dieta Occidental/efectos adversos , Evaluación Preclínica de Medicamentos , Células Endoteliales , Perfilación de la Expresión Génica , Humanos , Hiperlipidemias/sangre , Hiperlipidemias/complicaciones , Hiperlipidemias/dietoterapia , Hiperlipidemias/genética , Inflamación/sangre , Inflamación/prevención & control , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Quinazolinas/farmacología , Quinazolinonas , ARN Mensajero/análisis , Células U937RESUMEN
CONTEXT: Black seed [Nigella sativa L. (Ranunculaceae)] has been shown in animal models to lower serum cholesterol levels. OBJECTIVES: In order to determine if extracts from black seed have any effects on high-density lipoprotein (HDL), we characterized the effects of black seed extract on apolipoprotein A-I (apo A-I) gene expression, the primary protein component of HDL. MATERIALS AND METHODS: Hepatocytes (HepG2) and intestinal cells (Caco-2) were treated with black seed extracts, and Apo A-I, peroxisome proliferator-activated receptor α (PPARα), and retinoid-x-receptor α (RXRα) were measured by Western blot analysis. Apo A-I mRNA levels were measured by quantitative real-time polymerase chain reaction and apo A-I gene transcription was measured by transient transfection of apo A-I reporter plasmids. RESULTS: Extracts from black seeds significantly increased hepatic and intestinal apo A-I secretion, as well as apo A-I mRNA and gene promoter activity. This effect required a PPARα binding site in the apo A-I gene promoter. Treatment of the extract with either heat or trypsin had no effect on its ability to induce apo A-I secretion. Treatment with black seed extract induced PPARα expression 9-fold and RXRα expression 2.5-fold. Furthermore, the addition of PPARα siRNA but not a control siRNA prevented some but not all the positive effects of black seed on apo A-I secretion. DISCUSSION: Black seed extract is a potent inducer of apo A-I gene expression, presumably by enhancing PPARα/RXRα expression. CONCLUSIONS: We conclude that black seed may have beneficial effects in treating dyslipidemia and coronary heart disease.
Asunto(s)
Apolipoproteína A-I/genética , Lipoproteínas HDL/efectos de los fármacos , Nigella sativa/química , Extractos Vegetales/farmacología , Células CACO-2 , Regulación de la Expresión Génica/efectos de los fármacos , Células Hep G2 , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Humanos , Lipoproteínas HDL/metabolismo , PPAR alfa/genética , Regiones Promotoras Genéticas/efectos de los fármacos , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptor alfa X Retinoide/genética , SemillasRESUMEN
OBJECTIVE: Chromium is a key micronutrient required for lipid and carbohydrate metabolism. Some but not all clinical trials have associated use of chromium supplements with improved insulin sensitivity and lipid profile including increased high-density lipoprotein cholesterol levels. METHODS: Because apolipoprotein A-I (apoA-I) is the principal protein of high-density lipoprotein, the molecular pathways underlying chromium-related changes in apoA-I expression were studied in a human hepatoma cell line (HepG2) transfected with full-length apoA-I promoter attached to the reporter chloramphenicol acetyl transferase gene. RESULTS: Exposure of these cells to different concentrations of chromium chloride (0, 0.5, 1.0, and 3.0 mM) resulted in a dose-dependent decrease in apoA-I promoter activity (chloramphenicol acetyl transferase activity expressed as a percentage of an internal control was 99.4 +/- 7.2% in control cells versus 87.6 +/- 5.0%, 73.4 +/- 2.3%, and 36.6 +/- 3.9%, respectively, P < 0.01). Chromium chloride at 10 mM concentration was toxic and caused death in a large number of cells. Treating HepG2 cells with other minerals known to have insulin-sensitizing effects such as magnesium (1 mM), zinc (0.2 mM), and vanadyl sulfate (0.1 mM) significantly reduced apoA-I promoter activity in the presence and absence of 100 microU/mL of insulin. Northern blot analyses showed that the apoA-I mRNA content of cells treated with 0.2 mM of chromium chloride relative to G3PDH mRNA was not significantly increased compared with controls (0.652 +/- 0.122 versus 0.745 +/- 0.143, the ratio of apoA-I to glyceraldehyde 3-phosphate dehydrogenase (G3PDH) mRNA in control and chromium-treated cells, respectively). Western blot analyses of proteins secreted in culture media indicated that neither chromium treatment of the HepG2 cells (858.0 +/- 151.4 arbitrary units) nor treatment with magnesium (1323.3 +/- 175.7) or vanadium (1102 +/- 78.7) significantly altered apoA-I concentrations compared with controls (1061.7 +/- 114.7). However treatment of HepG2 cells with 0.2 mM of zinc significantly reduced apoA-I concentrations (291.0 +/- 29.2 versus 1061.7 +/- 114.7; P < 0.001). CONCLUSIONS: Supraphysiologic concentrations of chromium and other minerals with known insulin-sensitizing activity may reduce apoA-I promoter activity in cultured cells. Whether similar changes may occur in vivo remains to be shown. However, these observations do not support the use of pharmacologic amounts of chromium supplementation to enhance the cardioprotective lipid profile.