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1.
Biomed Pharmacother ; 134: 111122, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33341052

RESUMO

Brucea javanica oil (BJO), one of the main products of Brucea javanica, has been widely used in treating different kinds of malignant tumors. Quassinoids are the major category of anticancer phytochemicals of B. javanica. However, current researches on the anti-cancer effect of BJO mainly focused on oleic acid and linoleic acid, the common major components of dietary edible oils, essential and characteristic components of B. javanica like quassinoids potentially involved remained unexplored. In the current investigation, we developed an efficient HPLC method to detect brusatol, a characteristic quassinoid, and comparatively scrutinized the anti-hepatocellular carcinoma (anti-HCC) effect of BJO, brusatol-free BJO (BF-BJO), and brusatol-enriched BJO (BE-BJO) against hepatoma 22 (H22) in mice. High-performance liquid chromatography (HPLC) was utilized to identify the components in BJO. BE-BJO was extracted with 95 % ethanol. The anti-tumor effect of BJO, BF-BJO and BE-BJO was comparatively investigated, and the potential underlying mechanism was explored in H22 ascites tumor-bearing mice. The results indicated that BJO and BE-BJO significantly prolonged the survival time of H22 ascites tumor-bearing mice, while BF-BJO exhibited no obvious effect. BJO and BE-BJO exhibited pronounced anti-HCC activity by suppressing the growth of implanted hepatoma H22 in mice, including ascending weight, abdominal circumference, ascites volume and cancer cell viability, with a relatively wide margin of safety. BJO and BE-BJO significantly induced H22 cell apoptosis by upregulating the miRNA-29b gene level and p53 expression. Furthermore, BJO and BE-BJO treatment substantially downregulated Bcl-2 and mitochondrial Cytochrome C protein expression, and upregulated expression levels of Bax, Bad, cytosol Cytochrome C, caspase-3 (cleaved), caspase­9 (cleaved), PARP and PARP (cleaved) to induce H22 cells apoptosis. Brusatol was detected in BJO and found to be one of its major active anti-HCC components, rather than fatty acids including oleic acid and linoleic acid. The anti-HCC effect of BJO and BE-BJO was intimately associated with the activation of miRNA-29b, p53-associated apoptosis and mitochondrial-related pathways. Our study gained novel insight into the material basis of BJO in the treatment of HCC, and laid a foundation for a novel specific standard for the quality evaluation of BJO and its commercial products in terms of its anti-cancer application.

2.
Exp Ther Med ; 20(5): 62, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32952652

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, irreversible interstitial lung disease, with no effective cure. Polydatin is a resveratrol glucoside with strong antioxidant, anti-inflammatory and anti-apoptotic properties, which is used for treating health-related disorders such as cardiac disabilities, various types of carcinoma, hepatitis and hepatic fibrosis. The present study aimed to investigate the protective effect of polydatin against bleomycin-induced IPF and the possible underlying mechanism. A549 cells were treated with transforming growth factor-ß1 (TGF-ß1) and polydatin to observe phenotypic transformation and the related gene expression was detected. Sprague-Dawley rats were divided into seven groups and intratracheally infused with bleomycin to establish a pulmonary fibrosis model (the sham control group received saline). The rats were given pirfenidone (50 mg/kg), resveratrol (40 mg/kg) and polydatin (10, 40 and 160 mg/kg) for 28 days. The results demonstrated that polydatin had low toxicity to A549 cells and inhibited TGF-ß1-induced phenotypic transformation as determined by MTS assay or observed using a light microscope. It also decreased the gene expression levels of α-smooth muscle actin and collagen I and increased the gene expression levels of epithelial cell cadherin in vitro and in vivo by reverse transcription-quantitative PCR. Furthermore, polydatin ameliorated the pathological damage and fiber production in lung tissues found by hematoxylin and eosin staining and Masson trichrome staining. Polydatin administration markedly reduced the levels of hydroxyproline, tumor necrosis factor-α, interleukin (IL)-6, IL-13, myeloperoxidase and malondialdehyde and promoted total superoxide dismutase activity in lung tissues as determined using ELISA kits or biochemical reagent kits. It inhibited TGF-ß1 expression and phosphorylation of Smad 2 and 3 and ERK-1 and -2 in vivo as determined by western blot assays. These results suggest that polydatin protects against IPF via its anti-inflammatory, antioxidant and antifibrotic activities, and the mechanism may be associated with its regulatory effect on the TGF-ß pathway.

3.
BMC Infect Dis ; 20(1): 455, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600260

RESUMO

BACKGROUND: Men who have sex with men (MSM) bear a high burden of syphilis infection. Expanding syphilis testing to improve timely diagnosis and treatment is critical to improve syphilis control. However, syphilis testing rates remain low among MSM, particularly in low- and middle-income countries. We describe the protocol for a randomised controlled trial (RCT) to assess whether provision of syphilis self-testing services can increase the uptake of syphilis testing among MSM in China. METHODS: Four hundred forty-four high-risk MSM will be recruited online and randomized in a 1:1:1 ratio to (1) standard syphilis self-testing arm; (2) a self-testing arm program enhanced with crowdsourcing and a lottery-based incentive, and (3) a standard of care (control). Self-testing services include a free syphilis self-test kit through the mail at monthly intervals. Participants in the lottery incentive arm will additionally receive health promotion materials generated from an open crowdsourcing contest and be given a lottery draw with a 10% chance to win 100 RMB (approximately 15 US Dollars) upon confirmed completion of syphilis testing. Syphilis self-test kits have step-by-step instructions and an instructional video. This is a non-blinded, open-label, parallel RCT. Participants in each arm will be followed-up at three and 6 months through WeChat (a social media app like Facebook messenger). Confirmation of syphilis self-test use will be determined by requiring participants to submit a photo of the used test kit to study staff via secure data messaging. Both self-testing and facility-based testing will be ascertained by sending a secure photographic image of the completed kit through an existing digital platform. The primary outcome is the proportion of participants who tested for syphilis in the past 3 months. DISCUSSION: Findings from this study will provide much needed insight on the impact of syphilis self-testing on promoting routine syphilis screening among MSM. The findings will also contribute to our understanding of the safety, effectiveness and acceptability of syphilis self-testing. These findings will have important implications for self-testing policy, both in China and internationally. TRIAL REGISTRATION: ChiCTR1900022409 (10 April, 2019).


Assuntos
Testes Diagnósticos de Rotina/métodos , Promoção da Saúde/métodos , Homossexualidade Masculina , Imunoensaio/métodos , Programas de Rastreamento/métodos , Minorias Sexuais e de Gênero , Sorodiagnóstico da Sífilis/métodos , Sífilis/diagnóstico , Treponema pallidum/imunologia , Sorodiagnóstico da AIDS/métodos , China , Crowdsourcing/métodos , Testes Diagnósticos de Rotina/efeitos adversos , Seguimentos , Infecções por HIV/diagnóstico , Infecções por HIV/virologia , HIV-1/imunologia , HIV-2/imunologia , Humanos , Masculino , Programas de Rastreamento/efeitos adversos , Motivação , Mídias Sociais , Sífilis/microbiologia , Sorodiagnóstico da Sífilis/efeitos adversos
4.
Biomed Pharmacother ; 127: 110115, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32244196

RESUMO

Patchouli alcohol (PA), a tricyclic sesquiterpene, is the major chemical component of patchouli oil. This study investigated the antidepressant-like effect and mechanism of PA in chronic unpredictable mild stress (CUMS). Our results showed that PA markedly attenuated CUMS-induced depressant-like behaviors, including an effective increase of sucrose preference and spontaneous exploratory capacity, as well as reduction of immobility time. In addition, PA markedly attenuated CUMS-induced mTOR, p70S6K, and 4E-BP-1 phosphorylation reduction in the hippocampus. Furthermore, PA reversed CUMS-induced increases in LC3-II and p62 levels and CUMS-induced decrease in PSD-95 and SYN-I levels. These results indicated that the antidepressant-like effect of PA was correlated with the activation of the mTOR signaling pathway. Moreover, behavioral experimental results showed that the antidepressant-like effect of PA was blocked by rapamycin (autophagy inducer and mTOR inhibitor) and chloroquine (autophagic flux inhibitor). These results suggest that PA exerted antidepressant-like effect in CUMS rats through inhibiting autophagy, repairing synapse, and restoring autophagic flux in the hippocampus by activating the mTOR signaling pathway. The results render PA a promising antidepressant agent worthy of further development into a pharmaceutical drug for the treatment of depression.

5.
Clin Infect Dis ; 70(10): 2178-2186, 2020 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-31260513

RESUMO

BACKGROUND: Syphilis self-testing may help expand syphilis testing among men who have sex with men (MSM). China has rapidly scaled up human immunodeficiency virus (HIV) self-testing, creating an opportunity for integrated syphilis self-testing. However, there is a limited literature on implementing syphilis self-testing. METHODS: A cross-sectional online survey was conducted among Chinese MSM in 2018. Participants completed a survey instrument including sociodemographic characteristics, sexual behaviors, syphilis self-testing, and HIV self-testing history. Multivariable logistic regression was conducted to identify correlates of syphilis self-testing. We also recorded potential harms associated with syphilis self-testing. RESULTS: Six hundred ninety-nine MSM from 89 cities in 21 provinces in China completed the study. A total of 361/699 (51.7%) men tested for syphilis, of whom 174/699 (24.9%) men used syphilis self-testing. Among 174 who had self-tested, 90 (51.7%) reported that the self-test was their first syphilis test and 161 (92.5%) reported that they undertook syphilis self-testing together with HIV self-testing. After adjusting for covariates, syphilis self-testing was correlated with disclosure of sexual orientation to family or friends (adjusted odds ratio [aOR], 1.90; 95% confidence interval [CI], 1.32-2.73), reporting 2-5 male sexual partners (aOR, 1.81; 95% CI, 1.04-3.16), HIV self-testing (aOR, 39.90; 95% CI, 17.00-93.61), and never tested for syphilis in the hospital (aOR, 2.96; 95% CI, 1.86-4.72). Self-reported harms associated with syphilis self-testing were minimal. CONCLUSIONS: Scaling up syphilis self-testing could complement facility-based testing in China among MSM. Self-testing may increase first-time testing and has limited harms. Our findings suggest that syphilis self-testing could be integrated into HIV self-testing services.

6.
Sex Transm Infect ; 96(5): 355-357, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-31653680

RESUMO

BACKGROUND: Individuals with risk-loving attitudes may be more likely to participate in high-risk sex and gambling. We investigated whether a lottery-based financial incentive to have a negative syphilis test may attract Chinese men who have sex with men (MSM) who practised risky sexual behaviours. METHODS: In July 2018, a national online cross-sectional survey was conducted in China. We collected information on willingness to participate in a lottery-based financial incentive where men were eligible if they tested negative for syphilis, and the minimum prize that would attract them to participate. We used a validated risk attitude scale which asked about the willingness to take risks in six domains, ranging from 0 (avoids taking risk) to 10 (fully prepared to take risks). To avoid multicollinearity, we used principal components analysis to create a 'risk attitude index'. Bivariable and multivariable logistic regression explored factors associated with willingness to test negative for syphilis. RESULTS: 699 MSM enrolled with a median age of 26 years (IQR: 23-30). 70% self-identified as gay and 52% reported ever testing for syphilis. 64% stated they were likely or very likely to test for syphilis linked with a lottery-based incentive. The median desired amount for the lottery had an expected value of ¥10 (US$1.50, IQR: ¥5-¥30). Men who had greater odds of willingness to participate in the lottery-based incentive were those scoring highest on the risk attitude index (adjusted OR (AOR) 2.6, 95% CI 1.5 to 4.3), those reporting more than one sexual partner in the last 3 months (AOR 1.7, 95% CI 1.2 to 2.4), those who had not used condoms during their last sex (AOR 1.5, 95% CI 1.0 to 2.2) and those who ever had group sex (AOR 1.5, 95% CI 1.0 to 2.2). CONCLUSION: Chinese MSM with higher risk attitudes and who reported riskier sexual behaviours indicated greater interest in the concept of a lottery-based incentive for syphilis testing. A lottery-based incentive may be a promising strategy for promoting condom use among risk-loving men.


Assuntos
Atitude Frente a Saúde , Motivação , Minorias Sexuais e de Gênero/estatística & dados numéricos , Sífilis/diagnóstico , Sexo sem Proteção/estatística & dados numéricos , Adulto , Bissexualidade , China , Preservativos/estatística & dados numéricos , Estudos Transversais , Homossexualidade Masculina , Humanos , Masculino , Razão de Chances , Comportamento Sexual/psicologia , Comportamento Sexual/estatística & dados numéricos , Minorias Sexuais e de Gênero/psicologia , Inquéritos e Questionários , Sexo sem Proteção/psicologia , Adulto Jovem
7.
BMC Health Serv Res ; 19(1): 995, 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31878946

RESUMO

BACKGROUND: The number of Chinese migrants in Sub-Saharan Africa (SSA) is increasing, which is part of the south-south migration. The healthcare seeking challenges for Chinese migrants in Africa are different from local people and other global migrants. The aim of this study is to explore utilization of local health services and barriers to health services access among Chinese migrants in Kenya. METHODS: Thirteen in-depth interviews (IDIs) and six focus group discussions (FGDs) were conducted among Chinese migrants (n = 32) and healthcare-related stakeholders (n = 3) in Nairobi and Kisumu, Kenya. Data was collected, transcribed, translated, and analyzed for themes. RESULTS: Chinese migrants in Kenya preferred self-treatment by taking medicines from China. When ailments did not improve, they then sought care at clinics providing Traditional Chinese Medicine (TCM) or received treatment at Kenyan private healthcare facilities. Returning to China for care was also an option depending on the perceived severity of disease. The main supply-side barriers to local healthcare utilization by Chinese migrants were language and lack of health insurance. The main demand-side barriers included ignorance of available healthcare services and distrust of local medical care. CONCLUSIONS: Providing information on quality healthcare services in Kenya, which includes Chinese language translation assistance, may improve utilization of local healthcare facilities by Chinese migrants in the country.


Assuntos
Utilização de Instalações e Serviços/estatística & dados numéricos , Migrantes/psicologia , Adulto , China/etnologia , Feminino , Acesso aos Serviços de Saúde , Humanos , Quênia , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Migrantes/estatística & dados numéricos
8.
Biomed Pharmacother ; 117: 109135, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31226634

RESUMO

Cisplatin is one of the most frequently used chemotherapeutic agents for treatment of a wide range of cancer types. Nevertheless, the intrinsic or acquired resistance to cisplatin remains a major obstacle for cancer therapy. There are a number of factors contributing to the onset of this phenotype resistance. Signal transducers and activators of transcription 3 (STAT3) is constitutively activated in many cancer types, and such hyperactivation is associated with a poor clinical prognosis. In addition, STAT3 inhibitors have shown the ability to enhance the anti-tumor efficacy of cisplatin. In this review, we summarized the current knowledge of the STAT3 pathway in cancer treatment and its contribution to cisplatin resistance. Moreover, this review focuses on targeting STAT3 inhibition to overcome cisplatin resistance.


Assuntos
Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Fator de Transcrição STAT3/antagonistas & inibidores , Animais , Cisplatino/uso terapêutico , Humanos , Modelos Biológicos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fator de Transcrição STAT3/metabolismo
9.
PLoS Med ; 16(4): e1002785, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31013275

RESUMO

BACKGROUND: Schizophrenia is a leading cause of disability, and a shift from facility- to community-based care has been proposed to meet the resource challenges of mental healthcare in low- and middle-income countries. We hypothesized that the addition of mobile texting would improve schizophrenia care in a resource-poor community setting compared with a community-based free-medicine program alone. METHODS AND FINDINGS: In this 2-arm randomized controlled trial, 278 community-dwelling villagers (patient participants) were randomly selected from people with schizophrenia from 9 townships of Hunan, China, and were randomized 1:1 into 2 groups. The program participants were recruited between May 1, 2015, and August 31, 2015, and the intervention and follow-up took place between December 15, 2015, and July 1, 2016. Baseline characteristics of the 2 groups were similar. The patients were on average 46 years of age, had 7 years of education, had a duration of schizophrenia of 18 years with minimal to mild symptoms and nearly one-fifth loss of functioning, and were mostly living with family (95%) and had low incomes. Both the intervention and the control groups received a nationwide community-based mental health program that provided free antipsychotic medications. The patient participants in the intervention group also received LEAN (Lay health supporters, E-platform, Award, and iNtegration), a program that featured recruitment of a lay health supporter and text messages for medication reminders, health education, monitoring of early signs of relapses, and facilitated linkage to primary healthcare. The primary outcome was medication adherence (proportion of dosages taken) assessed by 2 unannounced home-based pill counts 30 days apart at the 6-month endpoint. The secondary and other outcomes included patient symptoms, functioning, relapses, re-hospitalizations, death for any reason, wandering away without notifying anyone, violence against others, damaging goods, and suicide. Intent-to-treat analysis was used. Missing data were handled with multiple imputations. In total, 271 out of 278 patient participants were successfully followed up for outcome assessment. Medication adherence was 0.48 in the control group and 0.61 in the intervention group (adjusted mean difference [AMD] 0.12 [95% CI 0.03 to 0.22]; p = 0.013; effect size 0.38). Among secondary and other outcomes we noted substantial reduction in the risk of relapse (26 [21.7%] of 120 interventional participants versus 40 [34.2%] of 117 controls; relative risk 0.63 [95% CI 0.42 to 0.97]; number needed to treat [NNT] 8.0) and re-hospitalization (9 [7.3%] of 123 interventional participants versus 25 [20.5%] of 122 controls; relative risk 0.36 [95% CI 0.17 to 0.73]; NNT 7.6). The program showed no statistical difference in all other outcomes. During the course of the program, 2 participants in the intervention group and 1 in the control group died. The limitations of the study include its lack of a full economic analysis, lack of individual tailoring of the text messages, the relatively short 6-month follow-up, and the generalizability constraint of the Chinese context. CONCLUSIONS: The addition of texting to patients and their lay health supporters in a resource-poor community setting was more effective than a free-medicine program alone in improving medication adherence and reducing relapses and re-hospitalizations. Future studies may test the effectiveness of customization of the texting to individual patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-ICR-15006053.


Assuntos
Pessoal Técnico de Saúde/organização & administração , Adesão à Medicação , Sistemas de Apoio Psicossocial , Esquizofrenia/tratamento farmacológico , Esquizofrenia/fisiopatologia , Envio de Mensagens de Texto , Adulto , Telefone Celular , China , Feminino , Recursos em Saúde , Humanos , Vida Independente/psicologia , Masculino , Adesão à Medicação/psicologia , Pessoa de Meia-Idade , Participação do Paciente , Desempenho Físico Funcional , Áreas de Pobreza , Sistemas de Alerta , População Rural , Esquizofrenia/patologia , Psicologia do Esquizofrênico
10.
Biomed Pharmacother ; 112: 108647, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30797149

RESUMO

Cisplatin remains the standard first-line chemotherapeutic agent in the treatment of many types of cancers, but its clinical application is hindered by its severe nephrotoxicity. Previous studies reported that scutellarin enhanced the anti-cancer activity of cisplatin in lung cancer cells, with no confirmation on cisplatin-induced renal damage. Here, we investigated the nephroprotective effect of scutellarin on cisplatin-induced renal injury and its underlying mechanisms. Renal function, histological change, inflammation, apoptosis, autophagy and involved pathways were investigated. Pretreatment with scutellarin prevented cisplatin-induced decline of renal function including BUN, CRE, and histological damage. Scutellarin also reduced renal inflammation by suppressing the levels of pro-inflammatory cytokine, TNF-α and IL-6. Similarly, scutellarin administration inhibited apoptosis triggered by cisplatin through reducing the expressions of Cleaved caspase-3, Cleaved PARP, p53, and the ratio of Bax/Bcl-2. Moreover, scutellarin prevented cisplatin-induced inhibition of autophagy via enhancing LC3-II/LC3-I and Atg7, and inhibition of p62. Of note, the activations of JNK, ERK, p38 and stat3 induced by cisplatin were strikingly attenuated in scutellarin-treated mice. Thus, these results provide compelling evidence that scutellarin is a novel nephroprotectant against cisplatin-induced renal toxicity.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/prevenção & controle , Apigenina/uso terapêutico , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Cisplatino/toxicidade , Glucuronatos/uso terapêutico , Lesão Renal Aguda/patologia , Animais , Apigenina/farmacologia , Apoptose/fisiologia , Autofagia/fisiologia , Glucuronatos/farmacologia , Inflamação/induzido quimicamente , Inflamação/patologia , Inflamação/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Substâncias Protetoras/farmacologia , Substâncias Protetoras/uso terapêutico , Distribuição Aleatória
11.
Int Immunopharmacol ; 62: 15-22, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29966943

RESUMO

Pogostone (PO), a major component of Pogostemon cablin, displays potent protective effects against lipopolysaccharide-induced acute lung injury (ALI) in mice. This study aimed to investigate the protective effect of PO on TNF-α-induced cell injury in human alveolar epithelial cells in vitro and its underlying mechanism. The cell viability was measured using the MTS method. The cell apoptosis was determined using flow cytometry. The activities of reactive oxygen species (ROS) were detected using a fluorescence microscope. The pro-inflammatory cytokines and antioxidant genes were assessed using reverse transcription-polymerase chain reaction. The protein expression of Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha (IκBα), and nuclear factor-kappa B (NF-κB) p65 was analyzed using the Western blot analysis. PO alleviated cell apoptosis and inhibited ROS production. It alleviated TNF-α-induced cell injury, suppressed the levels of inflammatory cytokines [interleukin (IL)-6, IL-1ß, and IL-8], and enhanced the expression of antioxidant genes (quinine oxidoreductase 1, glutamate cysteine ligase catalytic subunit, heme oxygenase-1). It increased the expression of Keap1 and promoted the activation of Nrf2. However, the phosphorylation of IκBα and the nuclear expression of NF-κB p65 decreased. The anti-inflammatory and antioxidant effects of PO were abrogated following Nrf2 and NF-κB p65 knockdown. The results indicated a protective effect of PO against TNF-α-induced cell injury in A549 cells by modulating the balance between Nrf2 and NF-κB p65 signaling pathways. They verified PO as a promising anti-inflammatory adjuvant drug for treating ALI.


Assuntos
Apoptose/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/antagonistas & inibidores , Óleos Voláteis/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Células A549 , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Células Epiteliais/imunologia , Células Epiteliais/metabolismo , Humanos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais
12.
Front Pharmacol ; 9: 615, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29962947

RESUMO

Bleomycin (BLM) is a broad spectrum anti-tumor drug and inducing pulmonary fibrosis. As an anti-tumor drug without immunosuppression, it is urgent to find a drug that reduces the side effects of BLM. Scutellarin (SCU), a flavone extracted from Erigeron breviscapus (Vant.) Hand-Mazz, has anti-inflammatory activity and ability to inhibit tumor cell growth, migration, and invasion. However, the combined role of SCU and BLM treatment in tumor is unclear. This study aimed to investigate the possible effect and related mechanisms of BLM combined with SCU in the treatment of tumor through in vivo and in vitro experiments. In vivo experiments showed that BLM combined with SCU in the treatment of mice bearing H22 ascites tumor prolonged the survival time, alleviated BLM-induced pulmonary fibrosis, reduced the production of TNF-α; IL-6, and the levels of MDA and MPO. BLM combined with SCU increased the apoptotic rate of H22 ascites cells and the levels of cleaved-caspases-3 and -8. Furthermore, BLM combined with SCU increased the protein expression of p53 and gene expression of miR-29b, and decreased the expression of TGF-ß1. In vitro experiment results showed that BLM combined with SCU inhibited the viability of H22 cells and MRC-5 cells, promoted H22 cell apoptosis, up-regulated the protein expression of p53 and down-regulated the protein expression of α-SMA and collagen-I in MRC-5 cells. These experimental results suggested that SCU could enhance the anti-tumor effect of BLM and reduce BLM-induced pulmonary fibrosis, indicating SCU as a potential adjuvant for BLM in the future.

13.
Schizophr Res ; 201: 307-314, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29807806

RESUMO

BACKGROUND: Despite the abundance of measures to assess medication adherence by persons suffering schizophrenia, few studies have evaluated their concordance and validity against a reference standard in resource-poor community settings. We explored the concordance and validity of several measures to assess antipsychotic medication adherence in a resource-poor community. METHOD: Based on a random sample of 278 villagers diagnosed with schizophrenia from Liuyang, Hunan Province, China, we used a concordance correlation coefficient (rc) and Kappa statistic to assess agreement among pill counts, refill records, clinician rating, Drug Attitude Inventory (DAI), and the Brief Adherence Rating Scale (BARS). The validity of various measures was evaluated by their concordance and sensitivity/specificity to home-based unannounced pill count (UPC) as the reference standard. RESULTS: The estimated proportion of adherent patients according to all measures (41% ~ 88%) was substantially higher than identified by UPC (35%). Concordance between any two measures was poor (rc/Kappa mostly <0.30). Validity of various measures also was poor against the UPC (rc < 0.20; Kappa <0.16), although refill records and the structured instruments (BARS) performed better than office-based pill counts and clinician impression. BARS, DAI and clinician rating were not sensitive to changes in adherence and would likely underestimate any program effect. CONCLUSION: In resource-poor community settings, most measures assessed in this study should not be used alone as they overestimated adherence, underestimated program effect, and had poor validity. A combination of UPC and several other measures may provide more insight into clinical trials and programmatic management.


Assuntos
Antipsicóticos/uso terapêutico , Adesão à Medicação , Esquizofrenia/diagnóstico , Esquizofrenia/tratamento farmacológico , Adulto , China , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , População Rural , Sensibilidade e Especificidade
14.
Phytomedicine ; 39: 111-118, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-29433672

RESUMO

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) are most widely used as effective anti-inflammatory agents. However, their clinical application brings about inevasible gastrointestinal side effects. Pogostemon cablin is a traditional herbal medicine used for the treatment of gastrointestinal diseases in China. One of its representative components, the tricyclic triterpenoid ß-patchoulone (ß-PAE) has demonstrated great anti-inflammatory activity and gastroprotective effect against ethanol-induced gastric injury, but its protective effect against gastric ulcer induced by indomethacin is still unknown. PURPOSE: To assess the protective effect of ß-PAE against ulcer produced by indomethacin and reveal the underlying pharmacological mechanism. STUDY DESIGN: We used an indomethacin-induced gastric ulcer model of rats in vivo. METHODS: Gastroprotective activity of ß-PAE (10, 20, 40 mg/kg, i.g.) was estimated via indomethacin-induced gastric ulcer model in rats. Histopathological and histochemical assessment of ulcerated tissues were performed. Protein and mRNA expression were determined by Elisa, Western blotting and qRT-PCR. RESULTS: ß-PAE could inhibit ulcer formation. Histopathological and histochemical assessment macroscopically demonstrated that ß-PAE alleviates indomethacin-induced gastric ulceration in dose-dependent manner. After administration of ß-PAE, elevated tumor necrosis factor -α level was significantly decreased and the phosphorylation of JNK and IκB was markedly inhibited. ß-PAE suppressed the levels of E-selectin, P-selectin, intercellular adhesion molecule-1, vascular cell adhesion molecule and monocyte chemoattractant protein 1, as well as myeloperoxidase. Meanwhile, ß-PAE increased cyclooxygenase enzyme activities (COX-1 and COX-2) to enhance the production of prostaglandin E2. Proangiogenic protein, vascular endothelial growth factor and its receptor fms-like tyrosine kinase-1 mRNA expression were promoted while anti-angiogenic protein, endostatin-1 and its receptor ETAR mRNA expression were decreased. CONCLUSION: ß-PAE may provide gastroprotection in indomethacin-induced gastric ulcer in rats by reducing inflammatory response and improving angiogenesis.


Assuntos
Indometacina/efeitos adversos , Substâncias Protetoras/farmacologia , Sesquiterpenos/farmacologia , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/tratamento farmacológico , Indutores da Angiogênese/farmacologia , Animais , Anti-Inflamatórios não Esteroides/efeitos adversos , Antiulcerosos/farmacologia , Dinoprostona/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Masculino , Pogostemon/química , Ratos Sprague-Dawley , Sesquiterpenos de Guaiano , Úlcera Gástrica/patologia , Fator de Necrose Tumoral alfa/metabolismo
15.
J Pharm Biomed Anal ; 146: 37-47, 2017 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-28850862

RESUMO

In this study, Liquid Chromatography (LC) separation combined with quadrupole-Time-Of-Flight Mass Spectrometry (qTOF-MS) detection was used to analyze the characteristic ions of the flavonoids from Liang-wai Gan Cao (Radix Glycyrrhizae uralensis). First, accurate mass measurement and isotope curve optimization could provide reliable molecular prediction after noise deduction, baseline calibration and "ghost peak recognition". Thus, some spectral features in the LC-MS data could be clearly explained. Secondly, the chemical structure of flavonoids was deduced by MS/MS fragment ions, and the in-silico spectra by MS-FINDER program provided strong support for overcoming the bottleneck of phytochemical identification. For a predicted formula and experimental MS/MS spectrum, the MS-FINDER program could sort the candidate compounds in the public database based on a comprehensive weighted score, and we took the first 20 reliable compounds to seek the target compound in an in-house database. Certainly, those fragmentation pathways could also be deduced and described as Retro-Diels-Alder (RDA) fragmentation reaction, losses of C4H8, C5H8, CH3, CO, CO2 and others. Accordingly, 63 flavonoids were identified, and their in-silico bioactivity were clearly disclosed by some bioinformatics tools. In this experiment, the flavonoids obtained by the four extraction processes were tested by LC-qTOF-MS. We looked for possible Q-markers from these data matrices and then quantified them; their similarities/differences were also described. The results also indicated that the Macroporous Adsorption Resins (MARs) purification is a low cost, environmentally friendly and effective approach.


Assuntos
Flavonoides/química , Glycyrrhiza uralensis/química , Extratos Vegetais/química , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos
16.
Artigo em Inglês | MEDLINE | ID: mdl-28390283

RESUMO

Chemometrics-enhanced one-dimensional/comprehensive two-dimensional gas chromatographic (GC/GC×GC) technologies, were used to explore the compositions of Chaihu Shugan San essential oils, that were extracted from the herbal formulae by different schemes. We have shown that chemometric resolution using gas chromatographic- mass spectrometry (GC-MS) could be used for the qualitative and quantitative analysis of the majority of Terpenoids or Phthalides from herb formulae and single herbs. A GC×GC system was further optimized to achieve the increased peak capacity and the enhanced signal of the hydro-distillation sample (CSSh). When hardware bottleneck resulted from very complex sample, chemometric tools were once again applied to recover the stained information in the second dimension (2D) matrix data. Heuristic evolving latent projections (HELP) could be used for two dimensional (2D) sub-matrixes Xi at n spectral detection channels, after three dimensional (3D) data splitting. For a real 3D data matrix, alternating trilinear decomposition (ATLD) algorithm could conduct regularization for an iterative trilinear decomposition procedure, by Moore-Penrose pseudoinverse computations based on singular value decomposition. After retention indices (RI) confirmation, 216 target analytes (terpenoids or phthalides) could be elucidated both in CSSh and in supercritical fluid extract (CSSs). Based on the obtained data, some potential quality markers (Q-markers) were identified which may affect the quality of the products. Finally, a "connectivity map" was plotted to describe the unique mechanisms of tradition Chinese medicine (TCM).


Assuntos
Benzofuranos/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Óleos Voláteis/química , Extratos Vegetais/química , Terpenos/análise
17.
Neural Regen Res ; 11(9): 1424-1430, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27857744

RESUMO

Our previous study used regional homogeneity analysis and found that activity in some brain areas of patients with ischemic stroke changed significantly. In the current study, we examined structural changes in these brain regions by taking structural magnetic resonance imaging scans of 11 ischemic stroke patients and 15 healthy participants, and analyzing the data using voxel-based morphometry. Compared with healthy participants, patients exhibited higher gray matter density in the left inferior occipital gyrus and right anterior white matter tract. In contrast, gray matter density in the right cerebellum, left precentral gyrus, right middle frontal gyrus, and left middle temporal gyrus was less in ischemic stroke patients. The changes of gray matter density in the middle frontal gyrus were negatively associated with the clinical rating scales of the Fugl-Meyer Motor Assessment (r = -0.609, P = 0.047) and the left middle temporal gyrus was negatively correlated with the clinical rating scales of the nervous functional deficiency scale (r = -0.737, P = 0.010). Our findings can objectively identify the functional abnormality in some brain regions of ischemic stroke patients.

18.
Biochem Biophys Res Commun ; 480(1): 139-145, 2016 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-27671201

RESUMO

Daxx is a highly conserved nuclear transcriptional factor, which has been implicated in many nuclear processes including transcription and cell cycle regulation. Our previous study demonstrated Daxx also plays a role in regulation of intracellular cholesterol content. Daxx contains several domains that are essential for interaction with a growing number of proteins. To delineate the underlying mechanism of hypocholesterolemic activity of Daxx, we constructed a set of plasmids which can be used to overexpress different fragments of Daxx and transfected to HepG2 cells. We found that the C- terminal region Daxx626-740 clearly reduced intracellular cholesterol levels and inhibited the expression of SREBPs and SCAP. In GST pull-down experiments and Double immunofluorescence assays, Daxx626-740 was demonstrated to bind directly to androgen receptor (AR). Our findings suggest that the interaction of Daxx626-740 and AR abolishes the AR-mediated activation of SCAP/SREBPs pathway, which suppresses the de novo cholesterol synthesis. Thus, C-terminal domain of Daxx acts as a potential regulator of intracellular cholesterol content in HepG2 cells.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Colesterol/biossíntese , Proteínas Nucleares/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Correpressoras , Células Hep G2 , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Chaperonas Moleculares , Proteínas Nucleares/química , Proteínas Nucleares/genética , Domínios Proteicos , Receptores Androgênicos/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/genética , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo
19.
BMC Pregnancy Childbirth ; 16(1): 183, 2016 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-27448798

RESUMO

BACKGROUND: Increasingly popular mobile health (mHealth) programs have been proposed to promote better utilization of maternal, newborn and child health services. However, women who lack access to a mobile phone are often left out of both mHealth programs and research. In this study, we determine whether household mobile phone ownership is an independent predictor of utilization of maternal and newborn health services in Timor-Leste. METHODS: The study included 581 women aged 15-49 years with a child under the age of two years from the districts of Manufahi and Ainaro in Timor-Leste. Participants were interviewed via a structured survey of knowledge, practices, and coverage of maternal and child health services, with additional questions related to ownership and utilization of mobile phones. Mobile phone ownership was the exposure variable, and the dependent variables included having at least four antenatal care visits, skilled birth attendance, health facility delivery, a postnatal checkup within 24 h, and a neonatal checkup within 24 h for their youngest child. Logistic regression models were applied to assess for associations. RESULTS: Sixty-seven percent of women reported having at least one mobile phone in the family. Women who had a mobile phone were significantly more likely to be of higher socioeconomic status and to utilize maternal and newborn health services. However, after adjusting socioeconomic factors, household mobile phone ownership was not independently associated with any of the dependent variables. CONCLUSION: Evaluations of the effects of mHealth programs on health in a population need to consider the likelihood of socioeconomic differentials indicated by mobile phone ownership.


Assuntos
Telefone Celular , Conhecimentos, Atitudes e Prática em Saúde , Serviços de Saúde Materno-Infantil/estatística & dados numéricos , Propriedade , Cuidado Pós-Natal/estatística & dados numéricos , Cuidado Pré-Natal/estatística & dados numéricos , Adolescente , Adulto , Estudos Transversais , Parto Obstétrico/estatística & dados numéricos , Feminino , Instalações de Saúde/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Gravidez , Inquéritos e Questionários , Timor-Leste , Adulto Jovem
20.
J Chromatogr Sci ; 54(6): 879-87, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26994113

RESUMO

The characteristic smell of Liang-wai Gan Cao (Glycyrrhiza uralensis) and honey-roasting products was comprehensively analyzed using gas chromatography-mass spectrometry (GC-MS). Steam distillation and headspace solid-phase microextraction (HS-SPME) were used to extract volatile organic compounds (VOCs). Multiple fibers of SPME may reflect the samples' comprehensive information to the greatest extent, depending on their chemical characters. After chemometric resolution and spectra interpretation, many aroma compounds could be identified from GC-MS data. As a result, principal component analysis was set for the differentiation of several G. uralensis samples in different regions, and some important peaks could be found. Next, VOCs' profiles of honey-roasting products suggested that the flavors could be influenced by honey and pharmaceutical technologies.


Assuntos
Cromatografia Gasosa-Espectrometria de Massas , Glycyrrhiza uralensis/química , Odorantes/análise , Compostos Orgânicos Voláteis/análise , Mel/análise , Olfato , Microextração em Fase Sólida , Compostos Orgânicos Voláteis/química
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