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BACKGROUND: Factory workers are a key population for HIV transmission in China, as they often engage in sexual risk behaviours. This study aims to evaluate sexual risk behaviours and associated factors among factory workers in Shenzhen, China. METHODS: A cross-sectional study was conducted by using multi-stage stratified cluster random sampling. Full-time workers aged ≥18years were eligible to participate in the study. A self-administered questionnaire was used to collect information. Univariate and multivariable logistic regression were applied to assess factors associated with sexual risk behaviours. RESULTS: A total of 2029 factory workers were included. Mean age was 37.2 (±4.4)years; 48.5% were men. Two-thirds (64.9%) had had vaginal intercourse. Their sexual risk behaviours included condomless sex with casual partners in the last sex episode (23.6%), multiple sex partners (11.5%) and engaging in commercial sex (8.4%), in the past year. Having HIV/AIDS knowledge (adjusted odds ratio (AOR) 0.41, 95% confidence interval (CI) 0.24-0.70) and using a condom at sexual debut (AOR 0.08, 95% CI 0.05-0.13) were factors associated with condomless sex with casual partners in the last sex episode. Males (AOR 3.03, 95% CI 1.96-4.69 and AOR 2.19, 95% CI 1.33-3.60), local workers (AOR 2.11, 95% CI 1.01-4.42 and AOR 3.42, 95% CI 1.63-7.21), being single (AOR 2.04, 95% CI 1.39-3.01 and AOR 2.49, 95% CI 1.61-3.87), having sexual debut aged Conclusions : Sexual risk behaviours were prevalent despite most participants having basic HIV/AIDS knowledge. Future workplace-based prevention programs should target factory workers and there should be a focus on enhanced sexual education to reduce HIV transmission in China.
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Síndrome da Imunodeficiência Adquirida , Infecções por HIV , Masculino , Feminino , Humanos , Adulto , Trabalho Sexual , Estudos Transversais , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , Comportamento Sexual , Parceiros Sexuais , Preservativos , Assunção de Riscos , China/epidemiologiaRESUMO
BACKGROUND: Factory workers in low- and middle-income countries (LMICs) are vulnerable to HIV transmission. Interventions are needed to prevent HIV in this population. We systematically reviewed published literature on the efficacy of various HIV interventions in reducing stigma, risk behaviors and HIV transmission among factory workers. METHODS: A systematic review was performed using predefined inclusion and exclusion criteria. Four databases (PubMed, PsycINFO, Scopus and EMBASE) were searched for relevant publications between January 1, 1990 and December 31, 2018. Two independent reviewers assessed the methodological quality of studies. RESULTS: Thirteen articles were included, with 2 randomized controlled trials and 11 cohort studies. Five interventions and their combinations were summarized. Educational intervention increased condom use and reduced the use of recreational drugs and alcohol before sex. Community intervention that proactively provide HIV counselling and testing (HCT) services could increase the detection rate of HIV and other sexually transmitted diseases (STDs). Lottery intervention increased HCT uptake and decreased HIV public stigma. Education combined with community intervention reduced the proportion of workers with casual sex and enhanced HIV knowledge. Peer education combined with community intervention increased the proportion of workers who were willing to take their partners to HCT. Policy intervention combined with peer education enhanced HIV knowledge, perceived condom accessibility and condom use with regular partners. CONCLUSIONS: Various interventions improved HIV knowledge, decreased HIV stigma and reduced HIV-related risk behaviors among factory workers in LMICs. The combination of multiple interventions tended to achieve better efficacy than a single intervention. Persistent combination interventions are essential to address HIV in this population.
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Países em Desenvolvimento , Infecções por HIV/prevenção & controle , Instalações Industriais e de Manufatura , Saúde Ocupacional , Estudos de Coortes , Humanos , Avaliação de Programas e Projetos de Saúde , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Men who have sex with men (MSM) are disproportionately affected by HIV and other STIs worldwide. Rectal douching, which is commonly used by MSM in preparation for anal sex, may increase the risk of HIV and other STIs by injuring the rectal mucosa. Results from individual studies reporting associations between rectal douching and HIV and other STIs among MSM are inconsistent. We performed a systematic review and meta-analysis to estimate the association between rectal douching and HIV and other STIs among MSM. METHODS: We searched PubMed, Embase, Scopus and Web of Science for studies published from January 1970 to November 2018. Studies that reported ORs and 95% CIs of associations between rectal douching and infection with HIV/STIs, or reported enough data to calculate these estimates, were included. We assessed risk of bias using the Newcastle-Ottawa Scale. ORs were pooled using a random effects model. RESULTS: Twenty-eight eligible studies were identified in our review, of which 24 (20 398 participants) were included in the meta-analysis. Rectal douching was associated with increased odds of infection with HIV (OR 2.80, 95% CI 2.32 to 3.39), and any STI other than HIV (including hepatitis B virus (HBV), hepatitis C virus (HCV), chlamydia, gonorrhoea, syphilis and human papillomavirus) (OR 2.46, 95% CI 1.95 to 3.11) among MSM. For specific STIs, douching was associated with increased odds of viral hepatitis (HBV, HCV) (OR 3.29, 95% CI 2.79 to 3.87), and chlamydia or gonorrhoea (OR 3.25, 95% CI 2.02 to 5.23). These associations remained significant in studies that adjusted for potential confounders. CONCLUSION: Rectal douching may put MSM at increased risk for infection with HIV and other STIs. Longitudinal studies are needed to clarify this association, and health education materials should inform men of the potential for increased risk of infection with rectal douching.
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Infecções por HIV/prevenção & controle , Homossexualidade Masculina/estatística & dados numéricos , Infecções Sexualmente Transmissíveis/prevenção & controle , Irrigação Terapêutica , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Infecções por HIV/epidemiologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Comportamento Sexual , Infecções Sexualmente Transmissíveis/epidemiologia , Irrigação Terapêutica/efeitos adversos , Adulto JovemRESUMO
Transmission of biological information is a biochemical process of multistep cascade from genes/proteins to metabolites. However, because most metabolites reflect the terminal information of the biochemical process, it is difficult to describe the transmission process of disease information in terms of the metabolomics strategy. In this paper, by incorporating network and metabolomics methods, an integrated approach was proposed to systematically investigate and explain the molecular mechanism of renal interstitial fibrosis. Through analysis of the network, the cascade transmission process of disease information starting from genes/proteins to metabolites was putatively identified and uncovered. The results indicated that renal fibrosis was involved in metabolic pathways of glycerophospholipid metabolism, biosynthesis of unsaturated fatty acids and arachidonic acid metabolism, riboflavin metabolism, tyrosine metabolism, and sphingolipid metabolism. These pathways involve kidney disease genes such as TGF-ß1 and P2RX7. Our results showed that combining metabolomics and network analysis can provide new strategies and ideas for the interpretation of pathogenesis of disease with full consideration of "gene-protein-metabolite."
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Nefropatias/sangue , Nefropatias/urina , Metabolômica , Obstrução Ureteral/complicações , Animais , Nefropatias/etiologia , Ratos , Ratos Sprague-DawleyRESUMO
Factory workers make up a large proportion of China's internal migrants and may be highly susceptible to job and adaptation stress, negative affective states (e.g., depression and anxiety), and Internet gaming disorder (IGD). This cross-sectional study investigated the relationships between job stress, psychological adaptation, negative affective states and IGD among 1,805 factory workers recruited by stratified multi-stage sampling between October and December 2019. Structural equation modeling (SEM) was conducted to test the proposed mediation model. Among the participants, 67.3% were male and 71.7% were aged 35 years old or below. The prevalence of probable depression, probable anxiety, and IGD was 39.3, 28.7, and 7.5%. Being male, younger age, and shorter duration of living in Shenzhen were associated with higher IGD scores. Job stress was significantly associated with IGD (ß = 0.11, p = 0.01) but not with negative affective states (ß = 0.01, p = 0.77). Psychological adaptation was significantly associated with negative affective states (ß = -0.37, p < 0.001) but not with IGD (ß = 0.09, p > 0.05). Negative affective states were positively associated with IGD (ß = 0.27, p < 0.001). The indirect effect of psychological adaptation (ß = -0.10, p = 0.004) but not job stress (ß = 0.003, p = 0.77) on IGD through negative affective states was statistically significant. The observed psychological correlates and mechanisms are modifiable, and can inform the design of evidence-based prevention programs for depression, anxiety, and IGD in this population.
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[This corrects the article DOI: 10.1016/j.eclinm.2020.100351.].
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INTRODUCTION: We aimed to assess sex differences in treatment outcomes and adherence comparing men who have sex with women (MSW), men who have sex with men (MSM), and women who have sex with men (WSM), as well as men and women who inject drugs living with HIV on combination antiretroviral therapy (ART) in Guangdong, China. METHODS: We performed a retrospective observational cohort study with data from the National Free Antiretroviral Treatment Program database. We included ART-naive patients aged 18 to 80 years who had contracted HIV through sex or injecting drugs, initiated first-line ART between January 2004 and December 2016, and had at least 60 days of follow-up. Participants were followed for five years. Kaplan-Meier analysis and Cox proportional hazard models were used to evaluate all-cause mortality. Cumulative incidence function and Cox proportional hazards models accounting for competing risks were used to evaluate disease progression to AIDS. Modified Poisson regression models were used to evaluate immunological and virological responses and loss to follow-up. Repeated measures analysis was used to evaluate regular CD4+ cell count, HIV viral load monitoring, ART adherence, side effects, and interruption of ART. FINDINGS: We included 26,409 persons living with HIV. 21,779 (82·5%) people acquired HIV through sex (5118 WSM [23·5%], 8506 MSW [39·0%], 8175 MSM [37·5%]), and 4610 people (17·5%) through injection drug use (249 women [5·4%], 4361 men [94·6%]). Among those infected through sex, MSW had increased risks of all-cause mortality (adjusted hazard ratio [aHR] 1·48, 95% CI 1·20-1·83), progression to AIDS (1·27, 1·09-1·47), virological failure (adjusted incidence rates ratio [aIRR] 1·27, 95% CI 1·09-1·48), and loss to follow-up (1·22, 1·10-1·35) compared to WSM. In contrast, MSM had lower risk of all-cause mortality (aHR 0·49, 95%CI 0·32-0·76), disease progression to AIDS (0·83, 0·68-1·00), and virological failure (aIRR 0·78, 95%CI 0·65-0·94), were more likely to receive regular CD4+ cell count (1·08, 1·07-1·10) and HIV viral load monitoring (1·13, 1·12-1·15), were less likely to report missing ART doses (0·54, 0·49-0·61), interrupt ART (0·34, 0·26-0·44), or be lost to follow-up (0·56, 0·49-0·65) compared to WSM. Men who inject drugs were almost twice as likely as women who inject drugs to die (aHR 1·72, 95%CI 1·03-2·85), experience disease progression to AIDS (2·05, 1·18-3·57), virological failure (aIRR 1·81, 95%CI 1·19-2·76), report ART side effects (1·78, 1·43-2·22), and interruptions in ART (2·29, 1·50-3·50). INTERPRETATION: Our findings highlight the importance of identifying potentially at-risk MSW and promoting HIV education and testing among them. Particular attention is warranted among men who inject drugs to improve timely HIV diagnosis, drug interaction management, and retention in treatment. Additional research from rural settings is needed to assess the long-term treatment outcomes and adherence in MSM with HIV.
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Background: Coronavirus disease 2019 (COVID-19) was first identified in Wuhan, China, in December 2019 and quickly spread throughout China and the rest of the world. Many mathematical models have been developed to understand and predict the infectiousness of COVID-19. We aim to summarize these models to inform efforts to manage the current outbreak. Methods: We searched PubMed, Web of science, EMBASE, bioRxiv, medRxiv, arXiv, Preprints, and National Knowledge Infrastructure (Chinese database) for relevant studies published between 1 December 2019 and 21 February 2020. References were screened for additional publications. Crucial indicators were extracted and analysed. We also built a mathematical model for the evolution of the epidemic in Wuhan that synthesised extracted indicators. Results: Fifty-two articles involving 75 mathematical or statistical models were included in our systematic review. The overall median basic reproduction number (R0) was 3.77 [interquartile range (IQR) 2.78-5.13], which dropped to a controlled reproduction number (Rc) of 1.88 (IQR 1.41-2.24) after city lockdown. The median incubation and infectious periods were 5.90 (IQR 4.78-6.25) and 9.94 (IQR 3.93-13.50) days, respectively. The median case-fatality rate (CFR) was 2.9% (IQR 2.3-5.4%). Our mathematical model showed that, in Wuhan, the peak time of infection is likely to be March 2020 with a median size of 98,333 infected cases (range 55,225-188,284). The earliest elimination of ongoing transmission is likely to be achieved around 7 May 2020. Conclusions: Our analysis found a sustained Rc and prolonged incubation/ infectious periods, suggesting COVID-19 is highly infectious. Although interventions in China have been effective in controlling secondary transmission, sustained global efforts are needed to contain an emerging pandemic. Alternative interventions can be explored using modelling studies to better inform policymaking as the outbreak continues.
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Exogenous supplementation of antioxidants with ROS scavenging activity would be a potential therapy to cerebral ischemia-reperfusion injury in stroke. In the present study, a series of NDGA analogues with attenuation oxidative stress by directly scavenging ROS and indirectly through keap1/Nrf2/ARE pathway activation were designed and synthesized. All analogues were found to effectively remove ROS directly by DPPH radical scavenging assay, and compound 3a conferred potent protection from the oxidative injury in PC12 cells via promoting Nrf2 to translocate into nucleus and increasing expression of heme oxygenase-1(HO-1), where strongly reduced intracellular ROS level indirectly. More importantly, 3a significantly reduced brain infarction after cerebral ischemia-reperfusion injury in rats subjected to transient middle cerebral artery occlusion (MCAO). Overall, our findings shown compound 3a could serve as a promising compound for the treatment of stroke.
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Isquemia Encefálica/tratamento farmacológico , Desenho de Fármacos , Masoprocol/farmacologia , Fármacos Neuroprotetores/farmacologia , Acidente Vascular Cerebral/tratamento farmacológico , Animais , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Peróxido de Hidrogênio/antagonistas & inibidores , Peróxido de Hidrogênio/farmacologia , Masculino , Masoprocol/síntese química , Masoprocol/química , Estrutura Molecular , Fármacos Neuroprotetores/química , Células PC12 , Ratos , Ratos Sprague-Dawley , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
NF-κB is a critical target for cancer treatment due to its central role in facilitating cancer progression and desensitizing cancer cells to chemotherapeutic drugs. In this study, a series of chemically modified asymmetric curcuminoid analogs named S01-S15 were synthesized and evaluated for NF-κB inhibitory activity in gastric cancer cell lines. Cell growth inhibition assays revealed that most of these analogs effectively inhibited the growth of BGC-823, SGC-7901, and MFC cells. S06 was selected for further research. MTT assay, clonogenic assay, Hoechst 33258 staining assay, and western blotting revealed that S06 could exert anti-gastric cancer effects by downregulating NF-κB activity. Moreover, via its effects on NF-κB, S06 effectively enhanced the sensitivity of the gastric cancer cells to irinotecan. Together, this study provide a series of new curcuminoid analogs as promising cancer therapeutic agents.
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Antineoplásicos/farmacologia , Camptotecina/análogos & derivados , Curcumina/farmacologia , NF-kappa B/antagonistas & inibidores , Neoplasias Gástricas/tratamento farmacológico , Antineoplásicos/síntese química , Antineoplásicos/química , Camptotecina/química , Camptotecina/farmacologia , Proliferação de Células/efeitos dos fármacos , Curcumina/análogos & derivados , Curcumina/química , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Irinotecano , Estrutura Molecular , NF-kappa B/metabolismo , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
Rhein is a major medicinal ingredient isolated from several traditional Chinese medicines, including Rheum palmatum L., Aloe barbadensis Miller, Cassia angustifolia Vahl., and Polygonum multiflorum Thunb. Rhein has various pharmacological activities, such as anti-inflammatory, antitumor, antioxidant, antifibrosis, hepatoprotective, and nephroprotective activities. Although more than 100 articles in PubMed are involved in the pharmacological mechanism of action of rhein, only a few focus on the relationship of crosstalk among multiple pharmacological mechanisms. The mechanism of rhein involves multiple pathways which contain close interactions. From the overall perspective, the pathways which are related to the targets of rhein, are initiated by the membrane receptor. Then, MAPK and PI3K-AKT parallel signaling pathways are activated, and several downstream pathways are affected, thereby eventually regulating cell cycle and apoptosis. The therapeutic effect of rhein, as a multitarget molecule, is the synergistic and comprehensive result of the involvement of multiple pathways rather than the blocking or activation of a single signaling pathway. We review the pharmacological mechanisms of action of rhein by consulting literature published in the last 100 years in PubMed. We then summarize these pharmacological mechanisms from a comprehensive, interactive, and crosstalk perspective. In general, the molecular mechanism of action of drug must be understood from a systematic and holistic perspective, which can provide a theoretical basis for precise treatment and rational drug use.
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BACKGROUND: The selection of effect indicators in the pharmacokinetic/ pharmacodynamic study of complex diseases to describe the relationship between plasma concentration and effect indicators is difficult. PURPOSE: Three effect indicators of renal fibrosis were successfully determined. The relationship between pharmacokinetics and pharmacodynamics of rhein in rhubarb was elucidated. STUDY DESIGN: The study was a metabolomics analysis of rat plasma and pharmacokinetics/ pharmacodynamics of rhein. METHODS: A sensitive and simple ultra performance liquid chromatography-tandem triple quadrupole mass spectrometry (UPLC-MS/MS) method was applied to determine the rhein plasma concentration in the rat model of renal fibrosis and rat sham-operated group after the administration of rhubarb decoction. Then, the ultra performance liquid chromatography-Micromass quadrupole-time of flight mass spectrometry (UPLC-QTOF/MS) metabolomics method was used to screen biomarkers of renal fibrosis in rat plasma. Furthermore, the relationship between the plasma concentration of rhein and the concentration of three biomarkers directly related to renal fibrosis were analyzed. RESULTS: The three screened biomarkers could represent the effect of rhein treatment on renal fibrosis. Increasing the plasma concentration of rhein tended to restore the concentration of the three biomarkers in the model group compared with that in the sham-operated group. Evident differences in the area under the plasma concentration-time curve (AUC) of rhein were also observed under different pathological states. The results provide valuable information for the clinical application of rhubarb. CONCLUSION: Rhein intervention could recover the physiological balance in living organisms from the pharmacokinetic/pharmacodynamic levels. New information on the pharmacokinetic/pharmacodynamic study of complex diseases is provided.
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Antraquinonas/farmacocinética , Nefropatias/tratamento farmacológico , Nefropatias/patologia , Rheum/química , Animais , Biomarcadores/sangue , Cromatografia Líquida/métodos , Fibrose/tratamento farmacológico , Nefropatias/metabolismo , Masculino , Metabolômica/métodos , Ratos Sprague-Dawley , Espectrometria de Massas em TandemRESUMO
Rosavin is a bioactive antidepressant component isolated from Rhodiola rosea L. In this work, an ultra-performance liquid chromatography (UPLC) method was established for the determination of rosavin in rat plasma. The chromatographic separation was achieved on a HSS T3 column (100 mm × 2.1 mm, 1.8 µm) with a gradient mobile phase consisting of acetonitrile and water (0.1% formic acid). Plasma samples were processed with one-step protein precipitation. Rutin was chosen as internal standard and the detection wavelength was 249 nm. The pharmacokinetic parameters were analyzed using the drug and statistics software. The results showed that the established method has an excellent linearity in the range of 10-1,000 ng/mL (R(2) = 0.992) with a lower limit of quantification (10 ng/mL). The intra- and interday precision (relative standard deviation) were from 2.0 to 10.6% and the extraction recovery was 92.4-95.1%. The simple and rapid UPLC method was successfully applied to the pharmacokinetic and bioavailability study of rosavin in rats.
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Antidepressivos/sangue , Cromatografia Líquida de Alta Pressão/normas , Dissacarídeos/sangue , Espectrometria de Massas em Tandem/normas , Administração Intravenosa , Administração Oral , Animais , Antidepressivos/farmacocinética , Cromatografia Líquida de Alta Pressão/métodos , Dissacarídeos/farmacocinética , Limite de Detecção , Masculino , Variações Dependentes do Observador , Desnaturação Proteica , Ratos , Ratos Sprague-Dawley , Padrões de Referência , Reprodutibilidade dos Testes , Rutina/sangue , Espectrometria de Massas em Tandem/métodosRESUMO
Corilagin, which was isolated from several medical herbs, has been reported to exert many pharmacological activities. A simple and rapid liquid ultra-performance liquid chromatography (UPLC) coupled to photodiode array (PDA) method has been developed to quantify corilagin in rat plasma. In this study, plasma samples were prepared by ethyl acetate extraction. Separation was performed on a HSS T3 (100mm×2.1mm, 1.8µm) column by using a mobile phase of acetonitrile and water with 0.1% trifluoroacetic acid (v/v). Corilagin and internal standard epicatechin were detected at a wavelength of 266nm. The calibration curve was linear (r>0.998) over a concentration range of 0.2µg/mL to 20µg/mL with a lower quantification limit of 0.2µg/mL. Both intra and inter-day precision values were within 5.7% and extraction recovery were greater than 81.0%. Stability tests showed that corilagin and IS remained stable during the analytical procedure. The validated UPLC-PDA method was then used to analyze the pharmacokinetics of corilagin administered to rats intravenously (10mg/kg) or orally (50mg/kg). Oral bioavailability of corilagin was calculated to be 10.7%, indicating that this component is not suitable for oral administration. The results provide basis for further preclinical studies on corilagin.
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Cromatografia Líquida/métodos , Glucosídeos/sangue , Taninos Hidrolisáveis/sangue , Espectrofotometria Ultravioleta/métodos , Administração Oral , Animais , Área Sob a Curva , Disponibilidade Biológica , Glucosídeos/administração & dosagem , Glucosídeos/farmacocinética , Meia-Vida , Taninos Hidrolisáveis/administração & dosagem , Taninos Hidrolisáveis/farmacocinética , Limite de Detecção , Ratos , Ratos Sprague-Dawley , Padrões de ReferênciaRESUMO
BACKGROUND: The transcription factor nuclear factor-κB (NF-κB) is constitutively activated in a variety of human cancers, including gastric cancer. NF-κB inhibitors that selectively kill cancer cells are urgently needed for cancer treatment. Curcumin is a potent inhibitor of NF-κB activation. Unfortunately, the therapeutic potential of curcumin is limited by its relatively low potency and poor cellular bioavailability. In this study, we presented a novel NF-κB inhibitor named Da0324, a synthetic asymmetric mono-carbonyl analog of curcumin. The purpose of this study is to research the expression of NF-κB in gastric cancer and the antitumor activity and mechanism of Da0324 on human gastric cancer cells. METHODS: The expressions between gastric cancer tissues/cells and normal gastric tissues/cells of NF-κB were evaluated by Western blot. The inhibition viability of compounds on human gastric cancer cell lines SGC-7901, BGC-823, MGC-803, and normal gastric mucosa epithelial cell line GES-1 was assessed with the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay. Absorption spectrum method and high-performance liquid chromatography method detected the stability of the compound in vitro. The compound-induced changes of inducible NF-κB activation in the SGC-7901 and BGC-823 cells were examined by Western blot analysis and immunofluorescence methods. The antitumor activity of compound was performed by clonogenic assay, matrigel invasion assay, flow cytometric analysis, Western blot analysis, and Hoechst 33258 staining assay. RESULTS: High levels of p65 were found in gastric cancer tissues and cells. Da0324 displayed higher growth inhibition against several types of gastric cancer cell lines and showed relatively low toxicity to GES-1. Moreover, Da0324 was more stable than curcumin in vitro. Western blot analysis and immunofluorescence methods showed that Da0324 blocked NF-κB activation. In addition, Da0324 significantly inhibited tumor proliferation and invasion, arrested the cell cycle, and induced apoptosis in vitro. CONCLUSION: The asymmetric mono-carbonyl analog of curcumin Da0324 exhibited significantly improved antigastric cancer activity. Da0324 may be a promising NF-κB inhibitor for the selective targeting of cancer cells. However, further studies are needed in animals to validate these findings for the therapeutic use of Da0324.
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Antineoplásicos/farmacologia , Compostos de Benzilideno/farmacologia , Curcumina/análogos & derivados , Ciclopentanos/farmacologia , NF-kappa B/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Antineoplásicos/química , Compostos de Benzilideno/síntese química , Compostos de Benzilideno/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Curcumina/química , Ciclopentanos/síntese química , Ciclopentanos/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Neoplasias Gástricas/metabolismo , Relação Estrutura-AtividadeRESUMO
The cooperative material basis of the multi-component and multi-target mechanism of action of Traditional Chinese Medicine (TCM) is difficult to elucidate because of the current lack of appropriate techniques and strategies. In this paper, we focus on rhubarb treatment of renal fibrosis. Molecular docking, metabolic pathway enrichment, and network pharmacology methods were used to theoretically determine the interaction between the components of the rhubarb and disease targets related to renal fibrosis. Moreover, the methods of metabolomics, serum pharmacochemistry, histopathology and immunohistochemistry were used for the model group, the sham-operated group and the rhubarb administration group to reveal the active components and mechanisms of rhubarb. Finally, the experimental and theoretical results were integrated and comprehensively analyzed. Results indicated that anthraquinones and flavanols, such as rhein, emodin, catechin, and epicatechin, were the main active components of rhubarb. These active components play synergistic therapeutic efficacies through regulating the abnormal accumulation of the extracellular matrix, controlling the release of inflammatory factors and maintaining the balance of coagulation and fibrinolysis. Our study showed that the integration of metabolomics and network pharmacology is a powerful strategy for discovering active components of TCMs and for elucidating their mechanisms.
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Medicamentos de Ervas Chinesas/farmacologia , Nefropatias/metabolismo , Rim/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Rheum/química , Animais , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Rim/metabolismo , Rim/patologia , Masculino , Metabolômica , Análise de Componente Principal , Ratos , Ratos Sprague-DawleyRESUMO
Solasonine, a known glycoalkaloid, is a potential anti-cancer agent. In this work, a simple, sensitive and fast ultra performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantitative determination of solasonine in rat plasma. Plasma samples were processed with a protein precipitation. The separation was achieved by an ACQUITY HSS T3 (100×2.1mm, 1.8µm) column with a gradient mobile phase consisting of 0.1% formic acid and acetonitrile. Detection was carried out using positive-ion electrospray tandem mass spectrometry via multiple reaction monitoring (MRM). The validated method had an excellent linearity in the range of 0.1-500ng/mL (R(2)>0.994) with a low limit of detection (0.1ng/mL) and lower limit of quantification (0.5ng/mL). The extraction recovery was in the range of 92.4-94.9% for solasonine and 91.9% for dendrobine (internal standard, IS). The intra- and inter-day precision was below 9.8% and accuracy was from 86.0% to 94.3%. No notable matrix effect and astaticism was observed for solasonine. The method has been successfully applied to a pharmacokinetic and bioavailability study of solasonine in rats for the first time, which provides the basis for the further development and application of solasonine.
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Cromatografia Líquida de Alta Pressão/métodos , Alcaloides de Solanáceas/sangue , Espectrometria de Massas em Tandem/métodos , Animais , Disponibilidade Biológica , Limite de Detecção , Modelos Lineares , Masculino , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Alcaloides de Solanáceas/química , Alcaloides de Solanáceas/farmacocinéticaRESUMO
Curcumin and its analogues have been reported to exert anti-cancer activity against a variety of tumors. Here, we reported A501, a new curcumin analogue. The effect of A501 on cell viability was detected by MTT assay, the result showed that A501 had a better inhibiting effect on the four non-small cell lung cancer (NSCLC) cells than that of curcumin. Moreover, Colony forming experiment showed A501 significant restrained cell proliferation. Flow cytometry displayed A501 can cause G2/M arrest and induce apoptosis. Western blotting showed that A501 decreased the expression of cyclinB1, cdc-2, bcl-2, while increased the expression of p53, cleaved caspase-3 and bax. In conclusion, curcumin analogues A501 played antitumor activity by inhibiting cell proliferation and inducing apoptosis of NSCLC cells. And it was likely to be a promising starting point for the development of curcumin-based anticancer drugs.
Assuntos
Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Curcumina/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Antineoplásicos/farmacologia , Proteína Quinase CDC2 , Caspase 3/biossíntese , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Curcumina/análogos & derivados , Ciclina B1/biossíntese , Quinases Ciclina-Dependentes/biossíntese , Humanos , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Proteína Supressora de Tumor p53/biossíntese , Proteína X Associada a bcl-2/biossínteseRESUMO
A novel adsorbent of chitosan chemically modified ordered mesoporous silica was synthesized and employed as a solid phase extraction (SPE) material for flow injection (FI) micro-column preconcentration on-line coupled with inductively coupled plasma optical emission spectrometry (ICP-OES) determination of trace heavy metals V, Cu, Pb, Cd and Hg in environmental water samples. The factors affecting separation and preconcentration of target heavy metals such as pH, sample flow rate and volume, eluent concentration and volume, interfering ions were investigated. Under the optimized experimental conditions, an enrichment factor of 20 and sampling frequency of 10h(-1) were obtained. The detection limits of the method for V, Cu, Pb, Cd and Hg were 0.33, 0.30, 0.96, 0.05 and 0.93 ng mL(-1), and the relative standard deviations (RSDs) were 2.8%, 6.7%, 1.8%, 4.0% and 5.3% (n=7, C=10 ng mL(-1)), respectively. The adsorption capacities of chitosan modified ordered mesoporous silica for V, Cu, Pb, Cd, and Hg were found to be 16.3, 21.7, 22.9, 12.2 and 13.5 mg g(-1), respectively. In order to validate the developed method, a certified reference material of GSBZ50009-88 environmental water sample was analyzed and the determined values were in good agreement with the certified values. The proposed method has also been applied to the determination of trace heavy metals in natural water samples with satisfactory results.
Assuntos
Quitosana , Metais Pesados/análise , Dióxido de Silício , Análise Espectral/métodos , Poluentes Químicos da Água/análise , AdsorçãoRESUMO
A simple and sensitive method using micro-column packed with 3-(2-aminoethylamino) propyltrimethoxysilane (AAPTS) modified ordered mesoporous silica combined with inductively coupled plasma optical emission spectrometry (ICP-OES) for the speciation of inorganic arsenic (As(III) and As(V)) has been developed. The adsorption behaviors of As(III) and As(V) on AAPTS modified ordered mesoporous silica were investigated. It was found that As(V) can be selectively adsorbed on the micro-column within pH of 3-9, while As(III) could not be retained in the studied pH range and passed through the micro-column directly. Total inorganic arsenic was extracted after the oxidation of As(III) to As(V) with 50.0 micromol L(-1) KMnO(4). The assay of As(III) was based on subtracting As(V) from total As. The effect of various parameters on the separation/preconcentration of As(III) and As(V) have been investigated and the optimal experimental conditions were established. The adsorption capacity of AAPTS modified ordered mesoporous silica for As(V) was found to be 10.3 mg g(-1). The detection limit of the method for As(V) was 0.05 microg L(-1) with an enrichment factor of 100, and the relative standard deviation (R.S.D.) was 5.7% (n=7, C=1.0 microg L(-1)). In order to validate the developed method, a certified reference material GSBZ50004-88 environmental water sample was analyzed and the determined values were in good agreement with the certified values. The proposed method was successfully applied to the speciation analysis of inorganic arsenic in natural water samples.