RESUMO
Hemp seed, the dried fruit of Cannabis sativa L. (Moraceae), has been extensively documented as a folk source of food due to its nutritional and functional value. This study evaluated the antidepressant effect of hemp seed oil (HSO) during its estrogen-like effect in Perimenopausal depression (PMD) rats induced by ovariectomy combined with chronic unpredictable mild stress (OVX-CUMS). Female SD rats (SPF, 10 weeks, sham operated group, ovariectomy (OVX) model group, ovariectomy - chronic unpredictable mild stress (OVX-CUMS) group, HSO + OVX-CUMS group, fluoxetine (FLU) + OVX-CUMS group, n=8) were subjected to treatment with HSO (4.32 g/kg) or fluoxetine (10 mg/kg) for 28 days (20 mL/kg by ig). Sucrose preference test (SPT), forced swimming test (FST), open field test (OFT), estrogen receptor α (ERα) and estrogen receptor ß (ERß) expression, estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH), cortisol (CORT), adrenocorticotropic hormone (ACTH), corticotropin releasing hormone (CRH), norepinephrine (NE), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5HIAA) levels are measured to evaluate the function of the hypothalamic-pituitary-ovarian (HPO) and hypothalamic-pituitary-adrenal (HPA) axis. The results showed that OVX-CUMS significantly decrease sucrose preference rate in SPT, increase immobility time in FST and OFT, and decrease movement distance and stand-up times in OFT. HSO treatment significantly improves depression-like behaviors, upregulates the expression of ERα and ERß, improves HPO axis function by increasing E2 levels and decreasing FSH and LH levels, reverses HPA axis hyperactivation by decreasing CORT, ACTH, and CRH levels, and upregulates NE, 5-HT, and 5HIAA levels in model rats. The findings suggested that HSO could improve depression-like behavior in OVX-CUMS rats by regulating HPO/HPA axis function and neurotransmitter disturbance.
Assuntos
Cannabis , Depressão , Ratos , Feminino , Animais , Depressão/tratamento farmacológico , Depressão/prevenção & controle , Sistema Hipotálamo-Hipofisário/metabolismo , Cannabis/metabolismo , Receptor alfa de Estrogênio/metabolismo , Fluoxetina/metabolismo , Fluoxetina/farmacologia , Serotonina/metabolismo , Serotonina/farmacologia , Receptor beta de Estrogênio/metabolismo , Perimenopausa , Ratos Sprague-Dawley , Sistema Hipófise-Suprarrenal/metabolismo , Hormônio Adrenocorticotrópico/metabolismo , Hormônio Adrenocorticotrópico/farmacologia , Hormônio Foliculoestimulante/metabolismo , Hormônio Foliculoestimulante/farmacologia , Sacarose , Estresse Psicológico/tratamento farmacológico , Modelos Animais de DoençasRESUMO
Information regarding the function of Melilotus officinalis (L.) Pall. in skeletal muscles is still unknown. In this study, we explored the possible regulatory targets of M. (L.) Pall. that affects the repair patterns in chronic muscle injury. We analyzed the potential target genes and chemical composition of M. (L.) Pall. and constructed a "drug-component-disease target genes" network analysis. Five active ingredients and 87 corresponding targets were obtained. Muscle-tendon junction (MTJ) cells were used to perform receptor-ligand marker analysis using the CellphoneDB algorithm. Targets of M. (L.) Pall. were screened further for the cellular ligand-receptor protein action on MTJs. Enrichment analysis suggests that those protein-associated ligand receptors may be associated with a range of intercellular signaling pathways. Molecular docking validation was then performed. Five proteins (CCL2, VEGFA, MMP2, MET, and EGFR) may be regulated by the active ingredient luteolin and scoparone. Finally, molecular dynamics simulations revealed that luteolin can stably target binding to MMP2. M. (L.) Pall. influences skeletal muscle repair patterns by affecting the fibroblast interactions in the muscle-tendon junctions through the active ingredients luteolin and scoparone.
Assuntos
Medicamentos de Ervas Chinesas , Melilotus , Humanos , Ligantes , Luteolina , Metaloproteinase 2 da Matriz , Melilotus/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Músculo EsqueléticoRESUMO
BACKGROUND: Several epidemiology studies have explored the association between dietary B vitamins' intake and the risk of esophageal cancer (EC). However, the results remain inconclusive. Thus, we conducted a systematic review with meta-analysis to evaluate such association. METHODS: Literature retrieval was performed using PubMed (Medline), ScienceDirect, and Cochrane Library electronic databases for all studies published from database inception to December 2017. RESULTS: The meta-analysis included 19 studies and showed an overall decreased risk of EC (OR=0.77, 95% CI: 0.68-0.87) in association with multivitamin B (ie, B1, B2, B3, B5, B6, B9, and B12) dietary intake. In a subgroup analysis based on vitamin B subclass, B1, B3, B6, and B9 vitamins were associated with decreased EC risk (vitamin B1: OR=0.68, 95% CI: 0.56-0.82; vitamin B3: OR=0.70, 95% CI: 0.53-0.94; vitamin B6: OR=0.64, 95% CI: 0.49-0.83; and vitamin B9: OR=0.69, 95% CI: 0.55-0.86). By contrast, no association was detected between dietary vitamin B2 and vitamin B5 intake and EC risk (vitamin B2: OR=0.86, 95% CI: 0.64-1.16; vitamin B5: OR=0.49, 95% CI: 0.20-1.20), whereas a potential non-linear dose-response association was found between dietary vitamin B12 intake and EC risk. A statistically significant, inverse association was observed for an increase of 100 µg/day in supplemental vitamin B6 and B9 and EC risk (vitamin B6: OR=0.98, 95% CI: 0.98-0.99; vitamin B9: OR= 0.89; 95% CI: 0.86-0.94). CONCLUSION: These findings support that vitamin B may have an influence on carcinogenesis of the esophagus. Vitamin B1, B3, B6, B9 showed a decreased risk of EC, and vitamin B12 showed an increased risk of EC.
RESUMO
This study evaluated the factors impacting overall survival (OS) and time to progression (TTP) in patients with unresectable hepatocellular carcinoma (HCC) who received transarterial chemoembolization (TACE). HCC patients were grouped based on tumor vascularity and lipidiol deposition after TACE. Tumor vascularity was classified based on contrast enhancement on arterial phase baseline CT scans. Lipiodol deposition was evaluated using CT scans. The progression-free rate was significantly higher in patients with good blood supply + good lipiodol deposition compared to those with good blood supply + poor lipiodol deposition. In patients with poor lipidiol deposition, risk of death was significantly positively correlated with stage, and negatively correlated with number of TACE procedures and degree of lipidiol deposition after the first TACE. Risk of disease progression in these patients was positively correlated with tumor size, and negatively correlated with number of TACE procedures and degree of lipidiol deposition after the first TACE. Our data showed that tumor vascularity and lipiodol deposition can be used as early radiological markers to identify patients who do not respond to TACE, and who can be considered earlier for alternative combination treatment strategies. Our data also indicated that poor lipiodol retention may predict a poor TTP and OS despite the blood supply status.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica , Óleo Etiodado/uso terapêutico , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/tratamento farmacológico , Progressão da Doença , Feminino , Seguimentos , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Carga TumoralRESUMO
OBJECTIVES: The objective of this study was to evaluate the efficacy of combined therapy using Sorafenib and radiofrequency ablation (RFA) with curative intent for all detectable lesions in patients with Barcelona Clinic Liver Cancer (BCLC) Stage 0-B1 hepatocellular carcinoma (HCC). METHODS: One hundred and twenty-eight patients with HCC from 12 centers were enrolled in this retrospective study; 64 patients who received Sorafenib plus RFA (Sorafenib-RFA) were compared with a control group treated with RFA alone. The two patient groups were selected with a predefined criterion and matched in terms of their clinical and tumor characteristics at baseline. The primary end point of the study was the incidence of post-RFA HCC recurrence. Secondary end points were overall survival (OS) and treatment toxicity. RESULTS: During a median follow-up of 134.1 weeks, 49 patients died and 79 survived. The 1-, 2-, and 3-year cumulative incidences of post-RFA recurrence were 40.5%, 62.9%, and 74.5%, respectively, in the Sorafenib-RFA group, and 62.8%, 85.4%, and 92.7%, respectively, in the RFA group. The 1-, 2-, 3-, and 4-year OS rates were 85.6%, 64.0%, 58.7%, and 50.3%, respectively, in the Sorafenib-RFA group, and 80.7%, 47.2%, 30.9%, and 30.9%, respectively, in the RFA group. Thus, the Sorafenib-RFA group exhibited better survival than the RFA alone group. CONCLUSIONS: Combined therapy with Sorafenib-RFA was associated with a lower incidence of post-RFA recurrence and better OS than RFA alone in patients with BCLC Stage 0-B1 HCC. Although these findings suggest that Sorafenib and RFA is safe and effective for the treatment of early HCC, prospective and randomized controlled trials are needed to validate them.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/terapia , Ablação por Cateter/métodos , Neoplasias Hepáticas/terapia , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Adulto , Carcinoma Hepatocelular/patologia , Estudos de Coortes , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Niacinamida/uso terapêutico , Estudos Retrospectivos , Sorafenibe , Resultado do TratamentoRESUMO
Endothelial dysfunction, characterized by impairment of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) bioavailability, has been implicated in diabetic cardiovascular pathogenesis. In this study, low-molecular-weight fucoidan (LMWF), which has multiple biological activities including anti-inflammatory and anti-oxidative properties, was investigated for its protective effect against endothelial dysfunction in Goto-Kakizaki type 2 diabetic rats. LMWF (50, 100, or 200 mg/kg/day) or probucol (100 mg/kg/day) were given to diabetic rats for 12 weeks. Basal blood pressure, acetylcholine- or flow-mediated relaxation of mesenteric and paw arteries, endothelium-dependent dilation of aorta, eNOS phosphorylation, and NO production were measured using laser Doppler flowmetry, force myograph, hematoxylin and eosin staining, western blot analysis, and an NO assay. We found that LMWF robustly ameliorated the basal hypertension and impairment of endothelium-dependent relaxation in the aorta, as well as mesenteric and paw arteries in diabetic rats. In addition, the reduction in eNOS phosphorylation at Ser1177, eNOS expression, and NO production because of diabetes were partially reversed by LMWF treatment. However, probucol, a lipid-modifying drug with antioxidant properties, displayed only mild effects. Moreover, LMWF induced, in a dose-dependent manner, endothelium-dependent vasodilation and eNOS phosphorylation at Ser1177 in normal aorta, and also promoted Ser1177 phosphorylation and NO synthesis in primary cultured vasoendothelial cells. Thus, these data demonstrate for the first time that fucoidan protects vasoendothelial function and reduces basal blood pressure in type 2 diabetes rats via, at least in part, preservation of eNOS function. Fucoidan is therefore a potential candidate drug for protection of endothelium in diabetic cardiovascular complications.