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OBJECTIVE: To develop an interference-free and rapid method to elucidate Guanxin II (GX II)'s representative vasodilator absorbed bioactive compounds (ABCs) among enormous phytochemicals. METHODS: The contents of ferulic acid, tanshinol, and hydroxysafflor yellow A (FTA) in GX II/rat serum after the oral administration of GX II (30 g/kg) were detected using ultra-performance liquid chromatography-mass spectrometry. Totally 18 rats were randomly assigned to the control group (0.9% normal saline), GX II (30 g/kg) and FTA (5, 28 and 77 mg/kg) by random number table method. Diastolic coronary flow velocity-time integral (VTI), i.e., coronary flow or coronary flow-mediated dilation (CFMD), and endothelium-intact vascular tension of isolated aortic rings were measured. After 12 h of exposure to blank medium or 0.5 mmol/L H2O2, endothelial cells (ECs) were treated with post-dose GX II of supernatant from deproteinized serum (PGSDS, 300 µL PGSDS per 1 mL of culture medium) or FTA (237, 1539, and 1510 mg/mL) for 10 min as control, H2O2, PGSDS and FTA groups. Nitric oxide (NO), vascular endothelial growth factor (VEGF), endothelin-1 (ET-1), superoxide dismutase (SOD), malondialdehyde (MDA) and phosphorylated phosphoinositide 3 kinase (p-PI3K), phosphorylated protein kinase B (p-AKT), phosphorylated endothelial nitric oxide synthase (p-eNOS) were analyzed. PGSDS was developed as a GX II proxy of ex vivo herbal crude extracts. RESULTS: PGSDS effectively eliminates false responses caused by crude GX II preparations. When doses equaled the contents in GX II/its post-dose serum, FTA accounted for 98.17% of GX II -added CFMD and 92.99% of PGSDS-reduced vascular tension. In ECs, FTA/PGSDS was found to have significant antioxidant (lower MDA and higher SOD, P<0.01) and endothelial function-protective (lower VEGF, ET-1, P<0.01) effects. The increases in aortic relaxation, endothelial NO levels and phosphorylated PI3K/Akt/eNOS protein induced by FTA/PGSDS were markedly abolished by NG-nitro-L-arginine methyl ester (L-NA, eNOS inhibitor) and wortmannin (PI3K/AKT inhibitor), respectively, indicating an endothelium-dependent vasodilation via the PI3K/AKT-eNOS pathway (P<0.01). CONCLUSION: This study provides a strategy for rapidly and precisely elucidating GX II's representative in/ex vivo cardioprotective absorbed bioactive compounds (ABCs)-FTA, suggesting its potential in advancing precision ethnomedicine.
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Endotélio Vascular , Vasodilatação , Animais , Vasodilatação/efeitos dos fármacos , Masculino , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/metabolismo , Ratos Sprague-Dawley , Ratos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Óxido Nítrico/metabolismo , Vasodilatadores/farmacologia , Vasodilatadores/farmacocinética , Ácidos Cumáricos/farmacologia , Ácidos Cumáricos/farmacocinética , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismoRESUMO
Background: Adriamycin (doxorubicin) is an important traditional drug that exhibits cytotoxicity in Diffuse Large B-cell Lymphoma (DLBCL). Doxorubicin affects the DLBCL cells at all stages of their cell cycle. Combined with our previous results, this study discovered that the overexpression of hsa-miR-28-5p inhibited the proliferation, promoted apoptosis, and triggered cell cycle arrest at the S-phase in DLBCL cells. However, the effect of (Homo sapiens, hsa)-microRNA (miR)-28-5p on doxorubicin sensitivity in DLBCL has not been investigated. This study aims to reveal the effects of hsa-miR-28-5p on doxorubicin sensitivity at the level of DLBCL cells. Methods: To determine the optimal concentration of doxorubicin, different concentrations of doxorubicin were used to treat DLBCL cells. CCK-8 assay was used to detect the proliferation of DLBCL cells. The hsa-miR-28-5p-mimic NC and hsa-miR-28-5p mimic were transfected to doxorubicin-mediated DLBCL cells. Simultaneously, blank control groups were set up. The cells were cultured and transfected for 24 h. Next, each group was administered with different concentrations of doxorubicin and cultured again for 24 h to observe the effects of hsa-miR-28-5p on doxorubicin sensitivity at different times. The proliferation, early apoptosis, and late apoptosis in DLBCL cells were determined using soft agar colony-forming assay, mitochondrial membrane potential assay, and caspase-3 activity assay, respectively. The apoptosis and cell cycle were explored using Annexin V-PE/7-AAD and PI/RNase staining buffer, respectively. We speculated that PD-L1 might be involved in the effect of hsa-miR-28-5p on the sensitivity of adriamycin (doxorubicin) in the DLBCL cells. Hence, we performed immunohistochemistry (IHC) to determine PD-L1 expression within formalin-fixed paraffin-embedded (FFPE) samples from 52 DLBCL cases. Results: The optimal concentration of doxorubicin targeting DLBCL cells was found to be 3.028 µmol/l. The effect of doxorubicin on DLBCL cells was time- and concentration-dependent. hsa-miR-28-5p mimic + doxorubicin remarkably decreased proliferation of DLBCL. DLBCL cell apoptosis rate was the highest in hsa-miR-28-5p mimic + doxorubicin group. Apart from that, hsa-miR-28-5p mimic plus doxorubicin had the best effect in promoting DLBCL cell apoptosis. After the intervention of hsa-miR-28-5p mimic + doxorubicin on DLBCL cells, the cell cycle was arrested in the S-phase and DNA synthesis was blocked. hsa-miR-28-5p mimic + doxorubicin could regulate the cycle of DLBCL cells. As a result, overexpression of hsa-miR-28-5p combined with doxorubicin is possibly involved in the development of DLBCL by affecting the proliferation, apoptosis, and cycle of DLBCL cells. PD-L1 showed an association with the prognosis of DLBCL patients. Combining with the literature, this suggested hsa-miR-28-5p may influence DLBCL occurrence and therapeutic effect by regulating the PD-L1 level. Conclusion: The combination of hsa-miR-28-5p mimic and doxorubicin may be considered more effective in inhibiting growth, arresting the cell cycle, and promoting cell apoptosis of DLBCL cells compared to using doxorubicin alone. The effects of doxorubicin on DLBCL cells were found to be time- and concentration-dependent. The overexpression of hsa-miR-28-5p enhanced the effect of doxorubicin on DLBCL cells, which may be attributed to the regulation of PD-L1 levels.
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Several studies reported the relative antidepressant effects of Fructus Aurantii (FRA) with repeated treatment, the rapid antidepressant effects of FRA and the underlying mechanisms remained unclear. We, therefore, examined the rapid antidepressant actions of FRA in behavioral tests in mice and tested the underlying molecular mechanisms. We found FRA, like ketamine, reversed the behavioral deficits both in lipopolysaccharide(LPS)-induced and learned helplessness (LH) models at 1 day after a single administration. FRA was also capable of increasing the expressions of protein kinase A/cAMP-response element-binding protein/brain-derived neurotrophic factor (PKA/CREB/BDNF) signaling in hippocampus. Consistent with ketamine, FRA up-regulated the expressions of GABAergic receptor (GAD67) and glutamatergic receptor 1 (GluR1) in mouse hippocampus both exposed to LPS and LH. Moreover, synaptic proteins such as postsynaptic density-95 (PSD95) and synapsin1 were also up-regulated by a single dose of FRA both in LH and LPS models, like ketamine. Finally, metadoxine (an antagonist of CREB) inhibited the antidepressant effects of FRA in tail suspension test (TST) and forced swimming test (FST) in LPS-induced mice, which also blocked the phosphorylation of CREB and the expressions of neurotransmitters and synaptic molecules. Therefore, FRA had rapid antidepressant effects, which depended on PKA/CREB/BDNF pathway, subsequently regulated the downstream synaptic transmission.
Assuntos
Antidepressivos/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Depressão/tratamento farmacológico , Transmissão Sináptica/efeitos dos fármacos , Animais , Encéfalo/metabolismo , Proteínas de Transporte/metabolismo , Citrus/química , Frutas/química , Elevação dos Membros Posteriores , Hipocampo/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Fosforilação/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Natação , Regulação para Cima/efeitos dos fármacosRESUMO
The burden of depression is enormous, and numerous studies have found that major depressive disorder (MDD) induces cardiovascular disorders (CVD) and functional dyspepsia (FD). Excitingly, meranzin hydrate (MH), an absorbed bioactive compound of Aurantii Fructus Immaturus, reverses psychosocial stress-induced mood disorders, gastrointestinal dysfunction and cardiac disease. Pharmacological methods have repeatedly failed in antidepressant development over the past few decades, but repairing aberrant neural circuits might be a reasonable strategy. This article aimed to explore antidepressant-like effects and potential mechanisms of MH in a rat model of unpredictable chronic mild stress (UCMS). Utilizing blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI), we sought to find reliable neurocircuits or a dominant brain region revealing the multiple effects of MH. The results show that compared with UCMS rats, MH (10 mg/kg/day for 1 week i.g.)-treated rats exhibited decreased depression-like behaviour; increased expression of brain-derived neurotrophic factor (BDNF) in the hippocampal dentate gyrus; and normalized levels of adrenocorticotropic hormone (ACTH), corticosterone (CORT), and acylated ghrelin (AG). Additionally, the UCMS-induced rise in BOLD activation in the reward system was attenuated after MH treatment. A literature search shown that nucleus accumbens (NAc) and hypothalamus of the reward system might reveal multiple effects of MH on MDD-FD-CVD comorbidity. Further research will focus on the role of these two brain regions in treating depression associated with comorbidities.
Assuntos
Antidepressivos/farmacologia , Cumarínicos/farmacologia , Giro Denteado/efeitos dos fármacos , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Recompensa , Estresse Psicológico/tratamento farmacológico , Animais , Antidepressivos/administração & dosagem , Comportamento Animal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/efeitos dos fármacos , Cumarínicos/administração & dosagem , Giro Denteado/metabolismo , Modelos Animais de Doenças , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Ratos , Ratos WistarRESUMO
OBJECTIVE: To analyze the research hotspot and frontier of severe coronavirus disease 2019 (COVID-19) in China and abroad. METHODS: The CiteSpace software was used to visually analyze the relevant research of severe COVID-19 published by CNKI and Web of Science databases from January 30th to April 20th in 2020. The analysis content included the author of the literature, the publishing institutions, and high-frequency keywords. RESULTS: There were 389 Chinese literatures and 59 English literatures included. Analysis using CiteSpace software showed that there were four large teams in China currently concerning about the research on severe COVID-19. The co-authoring of each team was relatively close, but the teams were lack of cooperation. The main issuing institutions were affiliated hospitals of colleges and universities, but colleges and enterprises had less participation. The authors of English-language publications mainly had five research teams, some of whom had co-authored relationships. The country with the most enormous volume of English-language publications was China, followed by the United States and Canada. The Chinese keyword co-occurrence, clustering and highlighted words analysis showed that the main research areas of severe COVID-19 included clinical features, traditional Chinese medicine treatment, medical imaging, integrated traditional Chinese and Western medicine treatment and so on; nucleic acid detection, clinical features and diagnosis, plague theory and etiology mechanism, traditional Chinese medicine and integrated Chinese and Western medicine treatment, severe COVID-19 combined with diabetes and prognosis research will become future research trends; keyword cluster analysis showed that severe COVID-19, combined chronic underlying diseases, CT imaging characteristics will also become new trends in the field of research. Co-occurrence analysis of keywords in English literatures showed that the main research areas of severe COVID-19 included the names of novel coronavirus, pandemic diseases, infectious diseases, medical supplies distribution, and indicators related to myocardial damage. CONCLUSIONS: Researchers in China and abroad have different concerns about severe COVID-19. Domestic research focuses on the diagnosis and treatment of severe cases, while foreign countries attach importance to epidemic response and prevention.
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Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , COVID-19 , China , Humanos , SARS-CoV-2 , Estados UnidosRESUMO
Many studies have reported a positive association between lower socioeconomic status (SES) and higher head and neck cancer (HNC) risk. Fewer studies have examined the impact of SES on the association between alcohol or cigarette use and HNC risk. The current case-control study (1104 HNC cases and 1363 controls) investigated the influence of education, a SES indicator, on the association between HNC and the use of alcohol, cigarettes, or betel quids in Taiwan, a country with universal health care. Our results showed a larger increase in HNC risk associated with alcohol among those with lower educational level (odds ratio [OR] = 2.07; 95% confidence interval [CI], 1.53-2.80) than those with higher educational level (OR = 1.38; 95% CI, 1.04-1.85) (heterogeneity-P = .03). Educational level had an influence on the association between alcohol use and HNC risk among those with genetic susceptibility (ALDH2-deficient) to the carcinogenic effect of alcohol. The association between cigarette or betel quid use and HNC risk was similar between the high and low educational groups. National policies and social interventions have led to the decline in the prevalence of cigarette and betel quid users in Taiwan. In contrast, due to the lack of adequate alcohol control policies, alcohol consumption in Taiwan has continued to rise. A higher impact of alcohol on HNC risk among lower SES individuals even with universal health care could be the result of insufficient alcohol control policies in Taiwan.
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Neoplasias de Cabeça e Pescoço/epidemiologia , Disparidades nos Níveis de Saúde , Estilo de Vida , Carcinoma de Células Escamosas de Cabeça e Pescoço/epidemiologia , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/epidemiologia , Aldeído-Desidrogenase Mitocondrial/deficiência , Aldeído-Desidrogenase Mitocondrial/genética , Compostos de Cálcio/administração & dosagem , Compostos de Cálcio/efeitos adversos , Estudos de Casos e Controles , Escolaridade , Feminino , Predisposição Genética para Doença , Neoplasias de Cabeça e Pescoço/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Óxidos/administração & dosagem , Óxidos/efeitos adversos , Piper/efeitos adversos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/efeitos adversos , Polimorfismo de Nucleotídeo Único , Prevalência , Fatores de Risco , Fumar/efeitos adversos , Fumar/epidemiologia , Classe Social , Carcinoma de Células Escamosas de Cabeça e Pescoço/etiologia , Taiwan/epidemiologia , Assistência de Saúde UniversalRESUMO
BACKGROUND: Currently, few herbal pharmacokinetic (PK) parameters have been applied successfully for therapeutic monitoring because of the complexity of consistency when there are multiple chemicals and efficacies. PURPOSE: The present study aims to evaluate the herbal PK properties by investigating the PK parameters of the 8 absorbed bioactive compounds (ABCs), which can represent its parent herbal holistic efficacy, to achieve a PK therapeutic monitoring of herbs. METHOD: First, we tested the hypothesis that the antidepressant and prokinetic effects and related anti-inflammation and anti-oxidation activity (APIO) by Fructus aurantii-Magnolia Bark (FM) formula are related to 8 compounds according to the absorbable evidence and the determined contents. Subsequently, stable and representative APIO from 8ABCs allowed us to develop a sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of 8 compounds following the oral administration of FM decoction (20â¯g/kg) in rats. RESULT: 8 compounds either including Meranzin hydrate (MH) or MH alone almost identically (8 compounds: 91.62-108.82%)or nearly(MH: 65.38-88.41%) replicated the parent formula FM in terms of efficacy for inducing APIO. CONCLUSION: This unifying strategy shows how multi-herb formulas pharmacokinetic therapeutic monitoring can be achieved by the method we established.
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Anti-Inflamatórios/farmacocinética , Antidepressivos/farmacocinética , Antioxidantes/farmacocinética , Medicamentos de Ervas Chinesas/química , Magnolia/química , Casca de Planta/química , Animais , Cromatografia Líquida de Alta Pressão/métodos , Cumarínicos/farmacocinética , Medicamentos de Ervas Chinesas/farmacocinética , Frutas/química , Cinética , Masculino , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem/métodosRESUMO
Currently, with the satisfaction of people's material life, sports, like yoga and tai chi, have become essential activities in people's daily life. For most yoga amateurs, they could only learn yoga by self-study, like mechanically imitating from yoga video. They could not know whether they performed standardly without feedback and guidance. In this paper, we proposed a full-body posture modeling and quantitative evaluation method to recognize and evaluate yoga postures to provide guidance to the learner. Back propagation artificial neural network (BP-ANN) was adopted as the first classifier to divide yoga postures into different categories, and fuzzy C-means (FCM) was utilized as the second classifier to classify the postures in a category. The posture data on each body part was regarded as a multidimensional Gaussian variable to build a Bayesian network. The conditional probability of the Gaussian variable corresponding to each body part relative to the Gaussian variable corresponding to the connected body part was used as criterion to quantitatively evaluate the standard degree of body parts. The angular differences between nonstandard parts and the standard model could be calculated to provide guidance with an easily-accepted language, such as "lift up your left arm", "straighten your right forearm". To evaluate our method, a wearable device with 11 inertial measurement units (IMUs) fixed onto the body was designed to measure yoga posture data with quaternion format, and the posture database with a total of 211,643 data frames and 1831 posture instances was collected from 11 subjects. Both the posture recognition test and evaluation test were conducted. In the recognition test, 30% data was randomly picked from the database to train BP-ANN and FCM classifiers, and the recognition accuracy of the remaining 70% data was 95.39%, which is highly competitive with previous posture recognition approaches. In the evaluation test, 30% data were picked randomly from subject three, subject four, and subject six, to train the Bayesian network. The probabilities of nonstandard parts were almost all smaller than 0.3, while the probabilities of standard parts were almost all greater than 0.5, and thus the nonstandard parts of body posture could be effectively separated and picked for guidance. We also tested separately the trainers' yoga posture performance in the condition of without and with guidance provided by our proposed method. The results showed that with guidance, the joint angle errors significantly decreased.
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Monitorização Ambulatorial/instrumentação , Postura/fisiologia , Adulto , Algoritmos , Braço/fisiologia , Teorema de Bayes , Fenômenos Biomecânicos/fisiologia , Estudos de Avaliação como Assunto , Retroalimentação , Feminino , Humanos , Masculino , Movimento/fisiologia , Redes Neurais de Computação , Dispositivos Eletrônicos Vestíveis , Yoga , Adulto JovemRESUMO
OBJECTIVES: Vascular smooth muscle cell (VSMC) proliferation is a crucial cause of vascular neointima hyperplasia and restenosis, thus limiting the long-term efficacy of percutaneous vascular intervention. We explored the role of wild-type p53-induced phosphatase 1 (Wip1), a potent regulator of tumorigenesis and atherosclerosis, in VSMC proliferation and neointima hyperplasia. METHODS AND RESULTS: Animal model of vascular restenosis was established in wild type C57BL/6J and VSMC-specific Tuberous Sclerosis 1 (TSC1)-knockdown mice by wire injury. We observed increased protein levels of Wip1, phospho (p)-S6 Ribosomal Protein (S6), p-4EBP1 but decreased p-adenosine 5'-monophosphate-activated protein kinase (AMPK)α both in carotid artery at day 28 after injury and in VSMCs after 48âh of platelet derived growth factor-BB (PDGF-BB) treatment. By using hematoxylin-eosin staining, Ki-67 immunohistochemical staining, cell counting kit-8 assay and Ki-67 immunofluorescence staining, we found Wip1 antagonist GSK2830371 (GSK) or mammalian target of rapamycin complex 1 (mTORC1) inhibitor rapamycin both obviously reversed the neointima formation and VSMC proliferation induced by wire injury and PDGF-BB, respectively. GSK also reversed the increase in mRNA level of Collagen I after wire injury. However, GSK had no obvious effects on VSMC migration induced by PDGF-BB. Simultaneously, TSC1 knockdown as well as AMPK inhibition by Compound C abolished the vascular protective and anti-proliferative effects of Wip1 inhibition. Additionally, suppression of AMPK also reversed the declined mTORC1 activity by GSK. CONCLUSION: Wip1 promotes VSMC proliferation and neointima hyperplasia after wire injury via affecting AMPK/mTORC1 pathway.
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Aminopiridinas/uso terapêutico , Dipeptídeos/uso terapêutico , Miócitos de Músculo Liso/efeitos dos fármacos , Neointima/prevenção & controle , Proteína Fosfatase 2C/metabolismo , Lesões do Sistema Vascular/enzimologia , Proteínas Quinases Ativadas por AMP/metabolismo , Aminopiridinas/farmacologia , Animais , Becaplermina , Artéria Carótida Primitiva/patologia , Proliferação de Células/efeitos dos fármacos , Dipeptídeos/farmacologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Hiperplasia , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Músculo Liso Vascular , Neointima/etiologia , Proteína Fosfatase 2C/antagonistas & inibidores , Proteína Supressora de Tumor p53/metabolismo , Lesões do Sistema Vascular/complicaçõesRESUMO
The comorbidity of coronary heart disease (CHD) and depression in patients is extremely prevalent, with a rate from 20 to 50%, while depression-like behaviors exist in a larger percentage of patients. Therefore, the study of comorbidities is particularly urgent. Chaihu-Shugan-San (CSS), a classical traditional Chinese medicine formula, has been used to treat CHD with depression for hundreds of years. However, the mechanism of its action on comorbidities remains unclear. Here, we focused on the behavioral changes in ApoE-/- mice fed a high-fat diet (HFD) and elucidated the mechanism of CSS and its main absorbed component, meranzin hydrate (MH), as an anti-atherosclerosis and anti-depression agent. In the present study, mice were fed an HFD for 16 weeks and were intragastrically administered high and low doses of CSS and MH. Depressive-like behaviors were evaluated by the sucrose preference test, the open-field test, the light-dark test and the tail-suspension test, after which atherosclerotic plaques, plasma lipids, inflammatory cytokine levels and the expression of BDNF/TrkB were measured. We demonstrated that the atherosclerosis model group exhibited significant depressant behaviors. Moreover, CSS inhibited depressive-like behavioral changes, reduced atherosclerotic plaque areas, plasma total cholesterol, triglycerides, LDL-cholesterol levels and inflammatory cytokines including TNF-α, IL-1ß, and IL-6 in plasma and hippocampi, increased the protein and mRNA expression of BDNF and TrkB in the aorta and the hippocampus. Interestingly, MH, the main component in CSS that is absorbed in the plasma and hippocampus, exerted effects similar to those of CSS. In addition, MH increased the protein and mRNA expression of BDNF and TrkB in human umbilical vein endothelial cells (HUVECs) induced by LPS. Collectively, these results suggest that MH represents the CSS decoction, induces anti-atherosclerosis effects and improves depression-like behaviors in HFD-fed ApoE-/- mice. Moreover, the regulation of proinflammatory factors and BDNF-TrkB signaling are possibly involved in this process. Our findings indicate that MH is a potential phytochemical compound for the prevention of the comorbidity of atherosclerosis and depression.
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Aterosclerose/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Cumarínicos/farmacologia , Glicoproteínas de Membrana/metabolismo , Extratos Vegetais/farmacologia , Proteínas Tirosina Quinases/metabolismo , Animais , Anti-Inflamatórios , Fator Neurotrófico Derivado do Encéfalo/genética , Cumarínicos/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Knockout para ApoE , Extratos Vegetais/administração & dosagem , Proteínas Tirosina Quinases/genética , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVE: To survey the current status of clinical studies on patent Traditional Chinese Medicine (TCM) for idiopathic male infertility in China. METHODS: Using the keywords "oligospermia", "azoospermia", "asthenozoospermia", "infertility" and "sperm", we searched China National Knowledge Internet (CNKI), Wanfang Database and SinoMed for randomized clinical trials (RCT), cohort studies, case-control studies and case series studies focusing on the treatment of male idiopathic infertility using TCM from January 2001 to May 2017. Two individual reviewers screened the literature, extracted the information separately, recorded the titles, authors, related institutions and regions, journals and years of publication, medication studied, and outcomes. The collected data was analyzed using Microsoft Excel and SPSS. RESULTS: Totally, 307 publications were included in this study, including 243 RCTs (79%), 57 case series studies (19%) and 7 retrospective cohort studies (2%). Fifty one patent TCM and in 146 journals were involved. The number of publications gradully increased from 2001 to 2017. The authors were from 243 institutions in 29 provinces, independent municipalities or autonomous regions, mostly in Guangdong, Guangxi, Henan, Beijing and Jiangsu. Majority of the studies focused on the evaluation of the efficacy and safety of the drugs, among which the most studied medication Wuziyanzong Pills (114/307, 37.13%), Fufangxuanju Capsules, Shengjing Capsules, Huangjingzanyu Capsules, and Liuweidihuang Pills. Chinese Journal of Andrology had the highest number of publications. CONCLUSIONS: A rapid progress has been achieved in China in the studies of patent TCM for the treatment of male infertility. However, limitatiors stiu exist, ragarding inbalance among regions, low sample sizes, low quality of studies, poor involvement of phamacisis.
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Bibliometria , Medicamentos de Ervas Chinesas , Infertilidade Masculina , Medicina Tradicional Chinesa , Oligospermia , China , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Infertilidade Masculina/terapia , Masculino , Oligospermia/terapia , Estudos RetrospectivosRESUMO
OBJECTIVE: To explore the effect of Qingyi Granule (QYG) on high mobility group box-1 (HMGB1) expressions in liver and renal tissues of severe acute pancreatitis (SAP) rats. METHODS: Fifty-four Sprague-Dawley (SD) rats were divided into the sham-operation (SO) group, the SAP group, and the QYG group according to random digits table. Rats in the SAP group were induced by injecting 5% sodium taurocholate (STC). Liver and renal pathological changes were observed by HE staining. Serum contents of amylase (AMS), MDA, IL-1, and HMGB1 were detected by ELISA. HMGB1 protein expressions in liver and renal tissues were tested by immunohistochemistry. HMGB1 mRNA expressions in liver and renal tissues were detected by reversed transcription PCR. RESULTS: The pathological scores, serum levels of AMS, MDA, IL-1 and HMGB1, and protein and mRNA HMGB1 expressions in liver and renal tissues were increased more obviously in the SAP group than in the SO group (P < 0.05, P < 0.01). All of them could be down-regulated by QYG intervention, with the most significant effect seen at 72 h (P < 0.05, P < 0.01) in a time-effect relationship. CONCLUSIONS: HMGB1 participated in SAP complicated liver and renal injuries. QYG could effectively inhibit HMGB1 expressions, thereby attenuating SAP complicated liver and renal injuries.
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Medicamentos de Ervas Chinesas/farmacologia , Proteína HMGB1/metabolismo , Pancreatite/tratamento farmacológico , Amilases , Animais , Medicamentos de Ervas Chinesas/uso terapêutico , Interleucina-1 , Rim/metabolismo , Fígado/metabolismo , Pancreatite/metabolismo , RNA Mensageiro , Ratos , Ratos Sprague-Dawley , Ácido TaurocólicoRESUMO
Cancer metastasis and drug resistance are important malignant tumor phenotypes that cause roughly 90% mortality in human cancers. Current therapeutic strategies, however, face substantial challenges partially due to a lack of applicable pre-clinical models and drug-screening platforms. Notably, microscale and three-dimensional (3D) tissue culture platforms capable of mimicking in vivo microenvironments to replicate physiological conditions have become vital tools in a wide range of cellular and clinical studies. Here, we present a microfluidic device capable of mimicking a configurable tumor microenvironment to study in vivo-like cancer cell migration as well as screening of inhibitors on both parental tumors and migratory cells. In addition, a novel evaporation-based paper pump was demonstrated to achieve adaptable and sustainable concentration gradients for up to 6 days in this model. This straightforward modeling approach allows for fast patterning of a wide variety of cell types in 3D and may be further integrated into biological assays. We also demonstrated cell migration from tumor spheroids induced by an epidermal growth factor (EGF) gradient and exhibited lowered expression of an epithelial marker (EpCAM) compared with parental cells, indicative of partial epithelial-mesenchymal transition (EMT) in this process. Importantly, pseudopodia protrusions from the migratory cells - critical during cancer metastasis - were demonstrated. Insights gained from this work offer new opportunities to achieve active control of in vitro tumor microenvironments on-demand, and may be amenable towards tailored clinical applications.
Assuntos
Modelos Biológicos , Antígenos de Neoplasias/metabolismo , Moléculas de Adesão Celular/metabolismo , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Fator de Crescimento Epidérmico/farmacologia , Molécula de Adesão da Célula Epitelial , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Células MCF-7 , Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Paclitaxel/farmacologia , RNA Mensageiro/metabolismo , Esferoides Celulares/citologia , Esferoides Celulares/efeitos dos fármacos , Microambiente TumoralRESUMO
BACKGROUND: The current study evaluated the association between tea consumption and head and neck cancer (HNC) in Taiwan, where tea is a major agricultural product and a popular beverage. METHODS: Interviews regarding tea consumption (frequency, duration, and types) were conducted with 396 HNC cases and 413 controls. Unconditional logistic regression was performed to estimate the odds ratio (OR) and 95% confidence interval (CI) of HNC risk associated with tea drinking, adjusted for sex, age, education, cigarette smoking, betel quid chewing, and alcohol drinking. RESULTS: A reduced HNC risk associated with tea drinking (OR for every cup per dayâ=â0.96, 95% CI: 0.93-0.99; OR for â§5 cups per dayâ=â0.60, 95% CI: 0.39-0.94) was observed. The association was especially significant for pharyngeal cancer (OR for every cup per dayâ=â0.93, 95% CI: 0.88-0.98; OR for â§5 cups per dayâ=â0.32, 95% CI: 0.16-0.66). A significant inverse association between HNC and tea consumption was observed particularly for green tea. CONCLUSIONS: This study suggests that tea drinking may reduce the risk of HNC. The anticancer property of tea, if proven, may offer a natural chemopreventive measure to reduce the occurrence of HNC.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias de Cabeça e Pescoço/prevenção & controle , Chá , Quimioprevenção , Feminino , Neoplasias de Cabeça e Pescoço/epidemiologia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Medição de Risco , Taiwan/epidemiologiaRESUMO
The characteristics of high-voltage light-emitting diodes (HVLEDs) consisting of a 64-cell LED array were investigated by employing various LED structures. Two types of HVLED were examined: a standard HVLED with a single roughened indium tin oxide (ITO) surface grown on a sapphire substrate and a thin-film HVLED (TF-HVLED) with a roughened n-GaN and ITO double side transferred to a mirror/silicon substrate. At an injection current of 24 mA, the output powers of the HVLEDs fabricated using a sapphire substrate and those fabricated using a mirror/silicon substrate were 170 and 216 mW, respectively. Because the TF-HVLED exhibited improved thermal dissipation and light extraction, it produced a greater output power than the HVLED fabricated using the sapphire substrate did.
Assuntos
Óxido de Alumínio/química , Gálio/química , Lentes , Iluminação/instrumentação , Nanopartículas Metálicas/química , Semicondutores , Óxido de Alumínio/efeitos da radiação , Transferência de Energia , Desenho de Equipamento , Análise de Falha de Equipamento , Luz , Espalhamento de RadiaçãoRESUMO
OBJECTIVE: To observe the effects of Qingyi Granule (QYG) on the changes of total protein expressions in the pancreatic tissue of rats with severe acute pancreatitis (SAP) induced by sodium taurocholate (STC). METHODS: SAP was induced by retrograded injecting 5% STC from the gut-pancreatic duct in 36 Sprague-Dawley (SD)rats. Then they were randomly divided into the SAP group and the QYG treatment group (abbreviated as the QYG group), 18 in each group. After successful modeling, rats in the QYG group were administered with QYG water solution (W: W = 1:1) once with an interval of 12 h (1 mL/100 g), while rats in the SAP group were administered with normal saline. The medication was performed four times. The total proteins were extracted from the pancreatic tissue of all rats to perform two-dimensional electrophoresis, fluorescent staining, and atlas analysis. The protein dots with differential expressions more than four times between each other in 48 h gel pictures were chosen and used for MALDI-TOF/TOF mass chromatographic analysis and biological information analysis. RESULTS: The 5% STC induced SAP model rats had typical pathological changes in the pancreatic tissue. The proteomics changes of the pancreatic tissue were analyzed by gel image manipulation software. Twenty two disparate points were detected between two groups at 48 h, 5 points of the protein were up-regulated and 17 points were down-regulated of the total after QYG intervention. Nine protein spots expressed differently more than 4 times and stably at 48 h, 7 kinds of proteins have been identified by mass chromatographic analysis and Data Base Retrieval, and they were Serpinb1a 39 kDa protein, Serpinb1a 43 kDa protein, Prdx4 Prx IV, Clps, gamma-actin (Actg1), Eprs and Hadhsc. Those proteins were involved in signal transmit during the process of SAP pancreas--pathological injury analyzed from their functions. CONCLUSIONS: Proteomics can well reflect the effects of QYG on differential expression proteins in the pancreatic tissue of rats with SAP. Studying differential expression proteins may provide a new theoretical basis and molecule target for QYG treating SAP.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Pâncreas/metabolismo , Pancreatite/metabolismo , Pancreatite/prevenção & controle , Animais , Modelos Animais de Doenças , Pancreatite/induzido quimicamente , Proteoma , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Meprobamate tablets contain microcrystalline cellulose, a potent embolic agent that has been shown to cause gangrene in animal studies. Microvascular embolization caused by microcrystalline cellulose can contribute to the ischemic process. OBJECTIVE: We report a case of acute hand ischemia after accidental intra-arterial injection of crushed meprobamate powder in a 23-year-old male drug abuser. CASE REPORT: The distal tips of the patient's right thumb, index finger, ring finger, and little finger continued to develop gangrene despite medical therapy with heparinization, low molecular-weight dextran infusion, corticosteroid administration, and hyperbaric oxygen therapy. CONCLUSION: We believe this is the first case of acute limb ischemia caused by intra-arterial injection of meprobamate powder documented in humans. Emergency physicians should be aware that accidental intra-arterial injection of crushed oral drug formulations is potentially limb threatening and prompt recognition of similar clinical scenarios is of vital importance.
Assuntos
Mãos/irrigação sanguínea , Hipnóticos e Sedativos/efeitos adversos , Isquemia/induzido quimicamente , Meprobamato/efeitos adversos , Doença Aguda , Adulto , Amputação Cirúrgica , Anti-Inflamatórios/uso terapêutico , Anticoagulantes/uso terapêutico , Dexametasona/uso terapêutico , Dextranos/uso terapêutico , Usuários de Drogas , Mãos/cirurgia , Humanos , Oxigenoterapia Hiperbárica , Hipnóticos e Sedativos/administração & dosagem , Injeções Intra-Arteriais/efeitos adversos , Isquemia/terapia , Masculino , Meprobamato/administração & dosagem , Pós , Abuso de Substâncias por Via Intravenosa/complicações , Adulto JovemRESUMO
Slit-channel reactors are reactors whose active surface areas are orders of magnitude higher than those of micro-reactors but have low fabrication costs relative to micro-reactors. We successfully produced biodiesel with different degrees of conversion using homogeneous catalyst in the slit-channel reactor. The reactor performance shows that percent conversion of soybean oil to biodiesel increases with channel depth, as expected, due to more efficient mixing. Shallow slit-channels require short average residence times for complete product conversion. Present results show that the slit-channel reactor provides an improved performance over traditional batch reactors using homogeneous sodium alkoxide catalyst. It is aimed to couple the reactors with solid catalysts in converting soybean oil to biodiesel and implementation method is suggested. The cost advantages resulting from the ease of fabrication of slit-channel reactors over micro-reactors and how these factors relate to the oil conversion efficiency to biodiesel are briefly noted and discussed.
Assuntos
Biocombustíveis/análise , Reatores Biológicos , Reologia/instrumentação , Reologia/métodos , Catálise , Espectroscopia de Ressonância Magnética , Hidróxido de Sódio/química , Óleo de Soja/químicaRESUMO
AIM: To explore the changes of nuclear factor-kappa B (NF-kappaB) DNA-binding activity, the expression of intercellular adhesion molecule-1 (ICAM-1) regulated by NF-kappaB at various times and to evaluate the effects of pyrrolidine dithiocarbamate (PDTC) on trinitrobenzene sulfonic acid (TNBS)-induced rat colitis. METHODS: TNBS of 0.6 mL was mixed with ethanol of 0.3 mL solution and instilled into the lumen of the rat colon. The rat models were divided into 6 groups, which were killed at 24 h, 3, 7, 14, and 21 d after enema. Colonic inflammation and damage were assessed by macroscopical and histological criteria. Activity of NF-kappaB DNA-binding was analyzed by electrophoresis mobility shift assays (EMSA). Expression of ICAM-1 was detected by in situ hybridization (ISH) and immunohistochemistry (IH). Then various doses of PDTC were injected into rat abdomen 30 min before enema with TNBS/ethanol as pretreatment. The rats were killed 4 h after enema and the colonic inflammation, myeloperoxidase (MPO) activity, malondialdehyde (MDA) level, and DNA-binding activity of NF-kappaB were assessed. Finally, PDTC was injected intraperitoneally after colitis was induced. Changes of morphology were assayed. RESULTS: During the first week, hyperemia, hemorrhage, edema and ulceration of the colonic mucosa appeared with predominant infiltration of leukocytes. Neutrophils, macrophages, lymphocytes infiltrated in mucosa and submucosa 14 d later. Fibroblasts and granuloma-like structures were also obviously seen. The binding activity of NF-kappaB began to increase at 24 h time point and reached a peak at 14 d, then decreased but still was higher than control group at 21 d (P<0.01). Levels of ICAM-1 mRNA and protein significantly elevated at 24 h and the peak was at 21 d. Pretreatment with PDTC could attenuate the development of inflammation but not by reducing NF-kappaB activity. This attenuation of inflammation had a positive relationship with the dose of PDTC. PDTC at the dose of 100 mg/kg had no therapeutic effect after colitis was induced. CONCLUSION: NF-kappaB activation is an important event that may be involved in acute and chronic inflammation development and may contribute to self-protection against early inflammation damage. NF-kappaB also regulates ICAM-1 expression during colonic inflammation. Pretreatment of PDTC may attenuate the inflammation development. But PDTC has no therapeutic effect after the colitis is induced.