Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 30
Filtrar
1.
Mol Med Rep ; 23(1): 1, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33179078

RESUMO

Curcumin has a therapeutic effect on ulcerative colitis, but the underlying mechanism has yet to be elucidated. The aim of the present study was to clarify the possible mechanisms. Dextran sulfate sodium­induced colitis mice were treated with curcumin via gavage for 7 days. The effects of curcumin on disease activity index (DAI) and pathological changes of colonic tissue in mice were determined. Interleukin (IL)­6, IL­10, IL­17 and IL­23 expression levels were measured by ELISA. Flow cytometry was used to detect the ratio of mouse spleen regulatory T cells (Treg)/Th17 cells, and western blotting was used to measure the nuclear protein hypoxia inducible factor (HIF)­1α level. The results demonstrated that curcumin can significantly reduce DAI and spleen index scores and improve mucosal inflammation. Curcumin could also regulate the re­equilibration of Treg/Th17. IL­10 level in the colon was significantly increased, while inflammatory cytokines IL­6, IL­17 and IL­23 were significantly reduced following curcumin treatment. No significant difference in HIF­1α was observed between the colitis and the curcumin group. It was concluded that oral administration of curcumin can effectively treat experimental colitis by regulating the re­equilibration of Treg/Th17 and that the regulatory mechanism may be closely related to the IL­23/Th17 pathway. The results of the present study provided molecular insight into the mechanism by which curcumin treats ulcerative colitis.

2.
Biomed Pharmacother ; 131: 110524, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33152900

RESUMO

Polygonum multiflorum Thunb. (PM) is a traditional Chinese medicine, commonly used to treat a variety of diseases. However, the hepatotoxicity associated with PM hampers its clinical application and development. In this study, we refined the zebrafish hepatotoxicity model with regard to the following endpoints: liver size, liver gray value, and the area of yolk sac. The levels of alanine aminotransferase, aspartate transaminase, albumin, and microRNAs-122 were evaluated to verify the model. Subsequently, this model was used to screen different extracts, components, and constituents of PM, including 70 % EtOH extracts of PM, four fractions from macroporous resin (components A, B, C, and D), and 19 compounds from component D. We found that emodin, chrysophanol, emodin-8-O-ß-D-glucopyranoside, (cis)-emodin-emodin dianthrones, and (trans)-emodin-emodin dianthrones showed higher hepatotoxicity compared to other components in PM, whereas polyphenols showed lower hepatotoxicity. To the best of our knowledge, this study is the first to identify that dianthrones may account for the hepatotoxicity of PM. We believe that these findings will be helpful in regulating the hepatotoxicity of PM.

3.
Oncol Rep ; 44(4): 1596-1604, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32945475

RESUMO

The aim of the present study was to explore the antitumor effects of sinoporphyrin sodium (DVDMS)­mediated photodynamic therapy (PDT) and sonodynamic therapy (SDT) in glioma, and to reveal the underlying mechanisms. The uptake of DVDMS by U­118 MG cells was detected by flow cytometry (FCM). A 630­nm semiconductor laser and 1­MHz ultrasound were used to perform PDT and SDT, respectively. Cell proliferation and apoptosis were evaluated using the Cell Counting Kit­8 assay, FCM and Hoechst 33258 staining, respectively. Western blot analysis was used to detect protein expression and phosphorylation levels. BALB/c nude mice were used to establish a xenograft model of U­118 MG cells. DVDMS was injected intravenously and PDT and SDT were performed 24 h later. An in vivo imaging system was used to evaluate the fluorescence of DVDMS, to measure tumor sizes, and to evaluate the therapeutic effects. The uptake of DVDMS by U­118 MG cells was optimal after 4 h. PDT and SDT following DVDMS injection significantly inhibited the proliferation and increased apoptosis of glioma cells in vitro (P<0.05, P<0.01) respectively. In vivo, the fluorescence intensity of DVDMS was lower in the PDT and SDT groups compared with the DVDMS group, while tumor cell proliferation and weight were lower in the PDT and SDT groups than in the control group (P<0.05, P<0.01). However, there was no significant difference when laser, ultrasound or DVDMS were applied individually, compared with the control group. Hematoxylin and eosin staining suggested that both PDT and SDT induced significant apoptosis and vascular obstruction in cancer tissues. DVDMS­mediated PDT and SDT inhibited the expression levels of proliferating cell nuclear antigen (PCNA) and Bcl­xL, increased cleaved ­caspase 3 levels, and decreased the protein phosphorylation of the PI3K/AKT/mTOR signaling pathway. Changes in the expression of PCNA, and Bcl­xL and in the levels of cleaved­caspase 3 were partly reversed by N­acetyl­L­cysteine, a reactive oxygen species (ROS) scavenger. Similar results were obtained with FCM. DVDMS­mediated PDT and SDT inhibited glioma cell proliferation and induced cell apoptosis in vitro and in vivo, potentially by increasing the generation of ROS and affecting protein expression and phosphorylation levels.

4.
World J Clin Cases ; 7(8): 984-991, 2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-31119143

RESUMO

BACKGROUND: Over the past years, only few cases of follicular lymphoma diagnosed by laparoscopy have been reported in the world. Since follicular lymphoma related ascites often causes occult disease and lacks specific clinical manifestations, it is often difficult to identify the cause by routine laboratory tests and imaging methods. Diagnostic experience is not sufficient and more cases need to be accumulated for further analysis. CASE SUMMARY: Ascites due to unknown reasons often causes problems for clinical diagnosis and treatment. In this paper, we report one case with ascites in whom the reason causing ascites was not identified through routine examination. Laparoscopic examination of the celiac lesions and histological examination of the lesions were performed and the final diagnosis was peritoneal follicular lymphoma. CONCLUSION: Laparoscopic abdominal examination is of great significance for the definite diagnosis of ascites due to an unknown reason.

5.
Xenobiotica ; 49(9): 1054-1062, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30351213

RESUMO

Oxiracetam (ORT) is known as a derivative of piracetam in the family of nootropics for treating memory impairment and cognition disorders. Given the chiral toxicological concerns surrounding ORT and the absence studies of (S)-ORT, the toxicity and toxicokinetics of (S)-ORT, and comparative toxicology of oxiracetam were systematically investigated in dogs following acute and 13-week repeated oral dosing. The animal toxicity mainly manifested as loose stools in both the acute and the 13-week studies. The no-observed-adverse-effect level is proposed to be 100 mg/kg. The 13-week toxicokinetics study indicated that, in the (S)-ORT group, the time to peak concentration was delayed, elimination half-life extended, and apparent volume of distribution increased compared with the ORT group. The clearance rate increased at low- and mid-doses, but decreased in the high-dose group and was accompanied by drug accumulation. Compared with the same dose of ORT, (S)-ORT had a lower clearance rate and longer elimination half-life.


Assuntos
Pirrolidinas/farmacocinética , Pirrolidinas/toxicidade , Administração Oral , Animais , Cães , Eletrólitos/sangue , Feminino , Meia-Vida , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Mortalidade , Tamanho do Órgão/efeitos dos fármacos , Pirrolidinas/química , Estereoisomerismo , Testes de Toxicidade Aguda , Toxicocinética
6.
Chin J Integr Med ; 25(10): 743-749, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30242590

RESUMO

OBJECTIVE: To assess the genotoxicity and embryotoxicity of bicyclol methyl ether (BME), the main impurity in bicyclol. METHODS: Five concentrations of BME (0.5, 5, 50, 500 and 5000 µg/plate) were used in the Ames test to detect gene mutation. In the chromosome aberration test, Chinese hamster lung cells were used to detect chromosomal aberration of BME (15, 30, 60, 120 µg/mL) with or without S9 mixture. Embryotoxicity test was also conducted to determine any embryotoxicity of BME (7.5, 22.5, 67.5 µg/L) using zebrafish embryos. RESULTS: No significant differences were observed in the Ames test and the chromosome aberration test in the BME groups compared with the vehicle control group. The zebrafish embryos toxicity test also showed no embryo development toxicity of BME, including hatching rate, body length, pericardial area and yolk sac area. CONCLUSIONS: Bicyclol methyl ether has no genotoxicity in vitro and embryotoxicity in zebrafish embryos, and the impurity in bicyclol is qualified.


Assuntos
Compostos de Bifenilo/toxicidade , Aberrações Cromossômicas/efeitos dos fármacos , Embrião não Mamífero/efeitos dos fármacos , Éteres Metílicos/toxicidade , Animais , Cricetinae , Testes de Mutagenicidade , Peixe-Zebra
7.
J Cell Biochem ; 119(11): 9154-9167, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30145800

RESUMO

Lupus nephritis (LN) is a common and severe complication of systemic lupus erythematosus. Without intervention, LN may cause acute kidney injury and end-stage renal disease. This study aims to determine whether microRNA-485 (miR-485) affects renal tubular epithelial cells (RTECs) in LN mice via the TGF-ß-MAPK signaling pathway by targeting RhoA. Renal tissue samples were initially extracted from 15 LN and 15 normal mice. RTECs were cultivated in vitro and grouped after transfection of different mimics, inhibitors, or siRNA- RhoA. The target gene of miR-485 was confirmed by dual-luciferase reporter assay. Flow cytometry and MTT assay were applied to detect cell viability and apoptosis. It was determined that RhoA was a target gene of miR-485. We found that urine protein, creatinine, RhoA, interleukin 6 (IL-6), transforming growth factor-ß1 (TGF-ß1), and p38 mitogen-activated protein kinases (p38MAPK) were highly expressed in renal tissues of LN mice, while poor levels of miR-485 were recorded. The overexpression of miR-485 or siRNA- RhoA or the combination of miR-485 and siRNA- RhoA was demonstrated to lead to a reduction of levels of RhoA, IL-6, TGF-ß, and p38MAPK, as well as a promotion of RTECs proliferation and inhibition of RTECs apoptosis. Taken together, these findings indicated that overexpressed miR-485 downregulates RhoA which could promote cell viability and inhibit apoptosis of RTECs by regulating the RhoA-mediated TGF-ß-MAPK signaling pathway in LN mice.


Assuntos
Apoptose/fisiologia , Nefrite Lúpica/metabolismo , MicroRNAs/metabolismo , Animais , Apoptose/genética , Western Blotting , Células Cultivadas , Citometria de Fluxo , Nefrite Lúpica/genética , Sistema de Sinalização das MAP Quinases/genética , Sistema de Sinalização das MAP Quinases/fisiologia , Camundongos , MicroRNAs/genética , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Proteína rhoA de Ligação ao GTP/genética , Proteína rhoA de Ligação ao GTP/metabolismo
8.
Biomed Pharmacother ; 99: 205-213, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29334663

RESUMO

Polygonum multiflorum Thunb. has been used widely in East Asia in treatment of diseases associated with aging. However, there are many reports referred to the toxicity of P. multiflorum, especially for liver adverse reactions. The toxicity of it is caused by over dosage or by the herb itself remains unclear. The aim of this study was to study the toxicity of different extractions, components and constituents of P. multiflorum, which were assessed in zebrafish embryos. Firstly, the difference of extracting solvent to the toxicity of P. multiflorum was researched to probe the influence of usages to the safety of P. multiflorum. The toxicity of 70% EtOH extract is considerably higher than that of other extracts. Secondly, 70% EtOH extract was subjected to macroporous resin (DM-8) eluting with a gradient of water and EtOH (H2O, 25% EtOH, 40% EtOH and 95% EtOH) to give four components (A-D). The toxicity of the component (D) showed higher than the other components (A-C). Thus, the component (D) was taken more attentions to research. Lastly, study on the chemical constituents of the component (D), 27 compounds, including 7 anthraquinones (1-7), 8 stilbenes (8-15), 7 anthrones (16-22), 3 cinnamic acid amides (23-25), 2 naphthols (26-27) were isolated and assessed in zebrafish embryos. Compounds 1-3, 16-22 and 26-27 showed severe toxicity against the zebrafish embryos while other compounds, such as stilbenes, showed no obvious toxicity.


Assuntos
Embrião não Mamífero/efeitos dos fármacos , Fallopia multiflora/química , Extratos Vegetais/toxicidade , Testes de Toxicidade Aguda , Peixe-Zebra/embriologia , Animais , Notocorda/anormalidades , Notocorda/efeitos dos fármacos , Notocorda/embriologia , Extratos Vegetais/química
9.
Fish Shellfish Immunol ; 72: 309-317, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29111395

RESUMO

The present work aims to explore the time-response (from 24 h to 96 h) characteristic and identify early potential sensitive biomarkers of copper (Cu) (as copper chloride dihydrate), cadmium (Cd) (as cadmium acetate), lead (Pb) (as lead nitrate) and chromium (Cr) (as potassium dichromate) exposure in adult zebrafish, focusing on reactive oxygen species (ROS), SOD activity, lipid peroxidation and gene expression related to oxidative stress and inflammatory response. Furthermore, the survival rate decreased apparently by a concentration-dependent manner after Cu, Cr, Cd and Pb exposure, and we selected non-lethal concentrations 0.05 mg/L for Cu, 15 mg/L for Cr, 3 mg/L for Cd and 93.75µg/L for Pb to test the effect on the following biological indicators. Under non-lethal concentration, the four heavy metals have no apparent histological change in adult zebrafish gills. Similar trends in ROS production, MDA level and SOD activity were up-regulated by the four heavy metals, while MDA level responded more sensitive to Pb by time-dependent manner than the other three heavy metals. In addition, mRNA levels related to antioxidant system (SOD1, SOD2 and Nrf2) were up-regulated by non-lethal concentration Cu, Cr, Cd and Pb exposure. MDA level and SOD1 gene have a more delayed response to heavy metals. Genes related to immunotoxicity were increased significantly after heavy metals exposure at non-lethal concentrations. TNF-α and IL-1ß gene have similar sensibility to the four heavy metals, while IL-8 gene was more responsive to Cr, Cd and Pb exposure at 48 h groups and IFN-γ gene showed more sensitivity to Cu at 48 h groups than the other heavy metals. In conclusion, the present works have suggested that the IFN-γ gene may applied as early sensitive biomarker to identify Cu-induced toxicity, while MDA content and IL-8 gene may use as early sensitive biomarkers for evaluating the risk of Pb exposure. Moreover, IL-8 and IFN-γ gene were more responsive to heavy metals, which may become early sensitive and potential biomarkers for evaluating inflammatory response induced by heavy metals. This work reinforces the concept of the usefulness of gene expression assays in the evaluation of chemicals effects and helps to establish a background data as well as contributes to evaluate early environmental risk for chemicals, even predicting toxicity.


Assuntos
Brânquias/efeitos dos fármacos , Imunidade Inata , Longevidade/efeitos dos fármacos , Metais Pesados/toxicidade , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo , Animais , Biomarcadores/análise , Feminino , Brânquias/patologia , Masculino , Distribuição Aleatória , Fatores de Tempo
10.
Environ Toxicol Pharmacol ; 56: 340-349, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29102874

RESUMO

Cadmium (Cd) and lead (Pb) are naturally existing heavy metals that pose significant health risks. The present study aims to identify sensitive biomarkers for differentiating the toxicities induced by Cd and Pb and for providing clues for the early prediction of toxicity and environmental risk assessment. Indicators related to oxidative stress and inflammatory responses in zebrafish treated with Cd and Pb over time (from 24hpf to 96hpf) were compared. Furthermore, endpoints such as embryo lethality and teratogenicity were detected. Then, several related genes involved in oxidative stress and inflammatory responses characterizing both Cd and Pb exposure, along with key molecules in the MAPKs pathway, were compared at the mRNA level, allowing the selection of the most sensitive and informative biomarkers. Significant increases in reactive oxygen species (ROS) production were observed in zebrafish exposed to Cd and Pb. Cd and Pb exposure induced developmental toxicity, influencing survival rate, hatching rate, larval growth, and heart rate and causing abnormal embryonic development. Similar trends in SOD1 and SOD2 gene expression were induced by Cd and Pb, while nuclear factor erythroid-2 related factor 2 (Nrf2) gene expression responded differently to each metal. In addition, Cd and Pb induced a delayed activation of the CAT and HO-1 genes, with no apparent change in the 24hpf and 48hpf groups. Genes related to immunotoxicity were activated significantly in a time-dependent manner, and these genes exhibited different sensitivities to Cd and Pb. MAPKs pathway genes were also activated in a time-dependent manner, and the expression of these genes showed different effects under Cd and Pb treatment. In summary, the present works have identified some potential sensitive biomarkers. The Nrf2 gene is a potential biomarker to differentiate Pb-induced toxicity from that of Cd, and the IFN-γ gene may be used as a sensitive biomarker for evaluating the risk of Pb contamination. We found that the timeline of MAPKs pathway activation helped to differentiate these two metals toxicities. Furthermore, Pb induced the early activation of ERK2/3 and JNK1, while p38 MAPKs showed delayed activation with no apparent change in the 24hpf group. Cd induced an early activation of ERK2 and a delayed activation of p38a, p38b, ERK3 and JNK1, indicating that the JNK1 pathway is sensitive to Pb exposure, while the p38 pathway may be susceptible to Cd. This work contributes to sensitive biomarker identification and early environmental risk evaluation for chemicals as well as toxicity prediction.


Assuntos
Biomarcadores/metabolismo , Cádmio/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Chumbo/toxicidade , Peixe-Zebra/embriologia , Animais , Embrião não Mamífero/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismo
11.
Cell Physiol Biochem ; 44(1): 200-214, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29131032

RESUMO

BACKGROUND/AIMS: The aim of this study was to determine the anti-psoriasis effects of α-(8-quinolinoxy) zinc phthalocyanine (ZnPc-F7)-mediated photodynamic therapy (PDT) and to reveal its mechanisms. METHODS: HaCaT cells were used to observe the influence of ZnPc-F7-PDT on cell proliferation in vitro. The in vivo anti-psoriasis effects of ZnPc-F7-PDT were evaluated using a mouse vagina model, a propranolol-induced cavy psoriasis model and an imiquimod (IMQ)-induced nude mouse psoriasis model. Flow cytometry was carried out to determine T lymphocyte levels. Western blotting was performed to determine protein expression, and a reverse transcription-polymerase chain reaction test was performed to determine mRNA expression. RESULTS: The results showed that ZnPc-F7-PDT significantly inhibited the proliferation of HaCaT cells in vitro; when the light doses were fixed, changing the irradiation time or output power had little influence on the inhibition rate. ZnPc-F7-PDT significantly inhibited the hyperproliferation of mouse vaginal epithelium induced by diethylstilbestrol and improved propranolol- and IMQ-induced psoriasis-like symptoms. ZnPc-F7-PDT inhibited IMQ-induced splenomegaly and T lymphocyte abnormalities. ZnPc-F7-PDT did not appear to change T lymphocytes in the mouse vagina model. ZnPc-F7-PDT down-regulated the expression of proliferating cell nuclear antigen (PCNA), B-cell lymphoma-2 (Bcl-2), interleukin (IL)-17A mRNA and IL-17F mRNA, and up-regulated the expression of Bax. CONCLUSION: In conclusion, ZnPc-F7-PDT exhibited therapeutic effects in psoriasis both in vitro and in vivo and is a potential approach in the treatment of psoriasis. Potential mechanisms of these effects included the inhibition of hyperproliferation; regulation of PCNA, Bcl-2, Bax, IL-17A mRNA and IL-17F mRNA expression; and immune regulation.


Assuntos
Proliferação de Células/efeitos dos fármacos , Indóis/química , Compostos Organometálicos/química , Fármacos Fotossensibilizantes/uso terapêutico , Psoríase/tratamento farmacológico , Aminoquinolinas/toxicidade , Animais , Linhagem Celular , Proliferação de Células/efeitos da radiação , Modelos Animais de Doenças , Epiderme/patologia , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Feminino , Cobaias , Humanos , Imiquimode , Indóis/farmacologia , Indóis/uso terapêutico , Interleucina-17/genética , Interleucina-17/metabolismo , Lasers , Masculino , Camundongos , Camundongos Endogâmicos ICR , Camundongos Nus , Compostos Organometálicos/farmacologia , Compostos Organometálicos/uso terapêutico , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Propranolol/toxicidade , Psoríase/induzido quimicamente , Psoríase/patologia
12.
J Asian Nat Prod Res ; 19(4): 388-401, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28367640

RESUMO

Potassium 2-(1-hydroxypentyl)-benzoate (dl-PHPB) is a prodrug of 3-n-butylphthalide (dl-NBP) for treatment of cerebral ischemic stroke in China, which undergoes lactonization to form dl-NBP in plasma. And, the phase II-III clinical trial of dl-PHPB has been approved by China Food and Drug Administration (CFDA) in 2013. In this study, a toxicity and toxicokinetics evaluation of dl-PHPB was performed using beagle dogs at specially high-dose 108 mg/kg/day (65-fold higher than humans at MHRD) for 4 weeks by intravenous administration, with a 3-week recovery period. And the plasma concentrations of dl-PHPB along with its metabolite dl-NBP were determined by HPLC-UV method. The results showed that dl-PHPB was quickly metabolized into dl-NBP, and no significant accumulation was observed. A slight to moderate behavior-associated toxicity was revealed in the process of delivery; and recovered to normal at the end of administration. Changes in the blood hematological profiles included significantly increased NEUT levels and lower LYM% content. Meanwhile, a notable increase in TG content was also observed in the serum biochemical parameters at 4-week post-exposure. These findings were reversible during the recovery period. The information from these studies would be taken into consideration for the interpretation of toxicology findings and provide a reference for clinical safety assessment.


Assuntos
Benzoatos/farmacologia , Pentanos/farmacologia , Potássio/farmacologia , Animais , Benzofuranos/administração & dosagem , Benzofuranos/farmacologia , China , Cães , Feminino , Humanos , Masculino , Estrutura Molecular , Toxicocinética
13.
Sci Rep ; 7: 40030, 2017 01 09.
Artigo em Inglês | MEDLINE | ID: mdl-28067267

RESUMO

Atmospheric particle is one of the risk factors for respiratory disease; however, their injury mechanisms are poorly understood, and prevention methods are highly desirable. We constructed artificial PM2.5 (aPM2.5) particles according to the size and composition of actual PM2.5 collected in Beijing. Using these artificial particles, we created an inhalation-injury animal model. These aPM2.5 particles simulate the physical and chemical characteristics of the actual PM2.5, and inhalation of the aPM2.5 in rat results in a time-dependent change in lung suggesting a declined lung function, injury from oxidative stress and inflammation in lung. Thus, this aPM2.5-caused injury animal model may mimic that of the pulmonary injury in human exposed to airborne particles. In addition, polydatin (PD), a resveratrol glucoside that is rich in grapes and red wine, was found to significantly decrease the oxidative potential (OP) of aPM2.5 in vitro. Treating the model rats with PD prevented the lung function decline caused by aPM2.5, and reduced the level of oxidative damage in aPM2.5-exposed rats. Moreover, PD inhibited aPM2.5-induced inflammation response, as evidenced by downregulation of white blood cells in bronchoalveolar lavage fluid (BALF), inflammation-related lipids and proinflammation cytokines in lung. These results provide a practical means for self-protection against particulate air pollution.

14.
Toxicol Res (Camb) ; 6(4): 544-553, 2017 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30090523

RESUMO

Nifurtimox has been an important treatment for trypanosomiasis for many years, but new research indicates that the drug may also be an effective therapy for malignant neuroblastoma. However, there have been few published reports evaluating the toxicity of nifurtimox in different species. Therefore, to further understand its toxicity and toxicokinetic profiles, Sprague Dawley rats and beagle dogs were orally administered nifurtimox at 0, 25, 75 and 150 mg kg-1 day-1, and 0, 30, 60 and 120 mg kg-1 day-1, respectively, for 28 days, which was followed by a 28-day recovery period. Significant decreases in the body weight and food consumption were observed in rats given 75 and 150 mg kg-1 day-1, but no significant difference was observed in either body weight or food consumption in dogs. No notable gender difference was observed in the rats in our study. The mean Cmax and AUC0-t increased with the exposure time in rats, and systemic exposure on day 28 was notably higher than that on day 1 for each dosing group. In contrast, in dogs the mean Cmax and AUC0-t increased significantly in the 120 mg kg-1 day-1 group only. Other findings in rats included a dose-dependent increase in total bilirubin and urea, a significant increase in the kidney organ coefficient, a decrease in heart and thymus weights, and a decrease in the weight of testes and epididymides tissue in males administered 75 and 150 mg kg-1 day-1, with dead sperms observed in the epididymides and a loss of necrotic cells. Furthermore, the brains of rats administered 150 mg kg-1 day-1 nifurtimox revealed cerebral tissue softening. In dogs there were no treatment-related changes in organ weights during the dosing period. However, deciduous spermatoblasts were observed in the seminiferous tubules and there was a lack of long sperms in the epididymides. The findings from this study demonstrate inter-species differences in nifurtimox toxicity and toxicokinetics. These results are relevant to the evaluation of the wider clinical applications of this drug.

15.
Clin Rheumatol ; 35(12): 2901-2908, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27553386

RESUMO

Environmental factors play an important role in the development of rheumatoid arthritis (RA). Among these factors, smoking is generally considered to be an established risk factor for RA. Data regarding the impact of diet on risk of RA development is limited. This study assessed the impact of dietary patterns on RA susceptibility in Chinese populations. This was a large scale, case-control study composed of 968 patients with RA and 1037 matched healthy controls. Subjects were recruited from 18 teaching hospitals. Socio-demographic characteristics and dietary intakes 5 years prior to the onset of RA were reported by a self-administered questionnaire. Differences in quantity of consumption between cases and controls were analyzed by Student's t test. Multiple logistic regression analysis was applied to identify independent dietary risk factor(s) responsible for RA susceptibility. Compared to healthy individuals, RA patients had decreased consumption of mushrooms (P = 0.000), beans (P = 0.006), citrus (P = 0.000), poultry (P = 0.000), fish (P = 0.000), edible viscera (P = 0.018), and dairy products (P = 0.005). Multivariate analyses revealed that several dietary items may have protective effects on RA development, such as mushrooms (aOR = 0.669; 95%CI = 0.518-0.864, P = 0.002), citrus fruits (aOR = 0.990; 95%CI = 0.981-0.999, P = 0.04), and dairy products (aOR = 0.921; 95%CI 0.867-0.977, P = 0.006). Several dietary factors had independent effects on RA susceptibility. Dietary interventions may reduce the risk of RA.


Assuntos
Artrite Reumatoide/epidemiologia , Dieta , Adulto , Idoso , Artrite Reumatoide/diagnóstico , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , China/epidemiologia , Estudos Transversais , Progressão da Doença , Exposição Ambiental , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Análise de Regressão , Fatores de Risco , Fumar , Adulto Jovem
16.
Clin Rheumatol ; 34(2): 221-30, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25413735

RESUMO

The aim of this study is to investigate the remission rate of rheumatoid arthritis (RA) in China and identify its potential determinants. A multi-center cross-sectional study was conducted from July 2009 to January 2012. Data were collected by face-to-face interviews of the rheumatology outpatients in 28 tertiary hospitals in China. The remission rates were calculated in 486 RA patients according to different definitions of remission: the Disease Activity Score in 28 joints (DAS28), the Simplified Disease Activity Index (SDAI), the Clinical Disease Activity Index (CDAI), and the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean definition. Potential determinants of RA remission were assessed by univariate and multivariate analyses. The remission rates of RA from this multi-center cohort were 8.6% (DAS28), 8.4% (SDAI), 8.2% (CDAI), and 6.8% (Boolean), respectively. Favorable factors associated with remission were: low Health Assessment Questionnaire (HAQ) score, absence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP), and treatment of methotrexate (MTX) and hydroxychloroquine (HCQ). Younger age was also predictive for the DAS28 and the Boolean remission. Multivariate analyses revealed a low HAQ score, the absence of anti-CCP, and the treatment with HCQ as independent determinants of remission. The clinical remission rate of RA patients was low in China. A low HAQ score, the absence of anti-CCP, and HCQ were significant independent determinants for RA remission.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Indução de Remissão , Adulto , Idoso , Artrite Reumatoide/diagnóstico , China , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Índice de Gravidade de Doença , Resultado do Tratamento
17.
Ann Rheum Dis ; 74(6): 1078-86, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24733191

RESUMO

OBJECTIVES: To compare the efficacy and safety of Tripterygium wilfordii Hook F (TwHF) with methotrexate (MTX) in the treatment of active rheumatoid arthritis (RA). METHODS: Design: a multicentre, open-label, randomised controlled trial. All patients were assessed by trained investigators who were unaware of the therapeutic regimen. INTERVENTION: 207 patients with active RA were randomly allocated (1:1:1) to treatment with MTX 12.5 mg once a week, or TwHF 20 mg three times a day, or the two in combination. At week 12, if reduction of the 28-joint count Disease Activity Score (DAS28) was <30% in the monotherapy groups, the patient was switched to MTX+TwHF. The primary efficacy point was the proportion of patients achieving an American College of Rheumatology (ACR) 50 response at week 24. RESULTS: 174/207 (84.1%) patients completed 24 weeks of the trial. In an intention-to-treat analysis, the proportion of patients reaching the ACR50 response criteria was 46.4% (32/69), 55.1% (38/69) and 76.8% (53/69), respectively, in the MTX, TwHF and MTX+TwHF groups (TwHF vs MTX monotherapy, p=0.014; MTX+TwHF vs MTX monotherapy, p<0.001). Similar statistically significant patterns at week 24 were found for ACR20, ACR70, clinical Disease Activity Index good responses, EULAR good response, remission rate and low disease activity rate. Significant improvement in the Health Assessment Questionnaire and 36-item Short-Form Health Survey questionnaire scores from baseline to week 24 was seen in each treatment arm (p<0.05), though no significant difference was found among the treatment arms (p>0.05). The result of per-protocol analysis agreed with that seen in the intention-to-treat analysis. Seven, three and five women in the TwHF, MTX and combination groups, respectively, developed irregular menstruation (TwHF vs MTX monotherapy, p=0.216). CONCLUSIONS: TwHF monotherapy was not inferior to, and MTX+TwHF was better than, MTX monotherapy in controlling disease activity in patients with active RA. TRIAL REGISTRATION NUMBER: NCT01613079.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Metotrexato/uso terapêutico , Fitoterapia , Extratos Vegetais/uso terapêutico , Tripterygium , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Método Simples-Cego , Resultado do Tratamento
18.
Zhongguo Zhong Yao Za Zhi ; 39(14): 2716-20, 2014 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-25272502

RESUMO

OBJECTIVE: To investigate the protective effect of extracts from Cichorium endivia (CEE) in H2O2-induced HepG2 cell oxidative stress injury, and explore the antioxidant mechanism of CEE in HepG2 cells. METHOD: The viability of H2O2-induced HepG2 cells and the intracellular ROS level were measured by MTT assay and DCFH-DA fluorescence staining assay. The antioxidant-response element (ARE)-Luciferase activity was tested in HepG2 cells stably transected by ARE reporter gene. The fluorescence quantitative RT-PCR was adopted to determine the mRNA expressions of genes containing ARE sequence in HepG2 cells. RESULT: The cell viability reduced, while the ROS level increased after HepG2 cells were treated by H2O2. Different concentrations of CEE could be added to significantly improve the above results. After HepG2 cells transected by ARE reporter gene were treated with different concentrations of CEE, the intracellular ARE activity could increase in a concentration-dependent manner. In addition, the mRNA expressions of regulatory genesGCLC, GCLM and HMOX-1 containing ARE sequence in HepG2 cells were up-regulated in a concentration-dependent manner by CEE. CONCLUSION: CEE inhibited the H2O2-injured HepG2 cells by reducing the ROS level. CEE's antioxidant mechanism for HepG2 cells may be closely related to the antioxidant defense system associated with its effect of activating Nrf2-ARE pathway in HepG2 cells.


Assuntos
Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Asteraceae/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Células Hep G2 , Humanos , Peróxido de Hidrogênio/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Elementos de Resposta/genética
19.
Pharm Biol ; 51(9): 1158-64, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23763258

RESUMO

CONTEXT: The buds of Coreopsis tinctoria Nutt (Compositae) are used in the treatment of hypertension in the Uyghur folk medicine in China. OBJECTIVE: To investigate vasorelaxant properties of extracts and some flavonoids from C. tinctoria (CT) and their underlying mechanisms in isolated rat thoracic aortic rings. MATERIALS AND METHODS: Vasorelaxant effects of ethanol extracts of CT (CTA) and its flavonoids as well as water-ethanol eluates from CTA by AB-8 resins (CTAA∼CTAF) were evaluated on rat aortic rings pre-contracted with phenylephrine (PE, 1 µM) or high KCl (60 µM). We evaluated the effect of CTA, CTAD and CTAE on PE-induced contraction in a Ca²âº-free medium and a dose-effect curve of Ca²âº in pre-contracted ring with high KCl. RESULTS: Endothelial removal did not modify the effect of CTAD and CTAE (3.00 g/L) neither on PE-pre-contracted rings (164.78 ± 21.44 and 191.47 ± 16.75%) nor on KCl-pre-contracted rings (75.68 ± 10.76 and 125.14 ± 17.41%) compared with intact-endothelium rings pre-contracted with high KCl (100.49 ± 17.30 and 110.81 ± 16.33%). CTAD and CTAE (3.00 g/L) down-regulated the dose-effect curve of Ca²âº in pre-contraction with high KCl, and inhibited the pre-contraction with PE in a Ca²âº-free medium (p < 0.05). Seven flavonoids were obtained from CTAD, of which luteolin (5) and quercetin (6) were found to be the most effective relaxation in rings precontracted with PE (EC50: 0.006 and 0.039 g/L, p < 0.05) or high KCl (EC50: 0.023 and 0.045 g/L, p < 0.05). DISCUSSION AND CONCLUSION: These data demonstrated the vasorelaxant effect of CT, and its mechanism is likely due to an inhibitory effect on calcium movements through cell membranes.


Assuntos
Aorta Torácica/efeitos dos fármacos , Sinalização do Cálcio/efeitos dos fármacos , Coreopsis/química , Medicamentos de Ervas Chinesas/farmacologia , Flavonoides/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia , Animais , Anti-Hipertensivos/química , Anti-Hipertensivos/isolamento & purificação , Anti-Hipertensivos/farmacologia , China , Coreopsis/crescimento & desenvolvimento , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Endotélio Vascular/fisiologia , Etnofarmacologia , Flavonoides/química , Flavonoides/isolamento & purificação , Flores/química , Flores/crescimento & desenvolvimento , Técnicas In Vitro , Luteolina/química , Luteolina/isolamento & purificação , Luteolina/farmacologia , Masculino , Fenilefrina/antagonistas & inibidores , Fenilefrina/farmacologia , Quercetina/química , Quercetina/isolamento & purificação , Quercetina/farmacologia , Ratos , Ratos Wistar , Vasoconstritores/antagonistas & inibidores , Vasoconstritores/farmacologia , Vasodilatadores/química , Vasodilatadores/isolamento & purificação
20.
Zhonghua Bing Li Xue Za Zhi ; 41(8): 547-52, 2012 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-23157748

RESUMO

OBJECTIVE: To investigate the effects of microRNA-383 (miR-383) on PRDX3 gene expression, cell proliferation and apoptosis of human medulloblastma. METHODS: PRDX3 and miR-383 RNA expression was detected by real-time quantitative RT-PCR in human medulloblastoma tumor tissue samples, Daoy cell line and normal brain tissue samples. Western blot was used to detect protein expression of PRDX3. Synthetic miR-383 mimics were transfected into Daoy cells by lipofectamine. Using Cell Counting Kit-8 (CCK-8) method, flow cytometry was used to investigate the cell proliferation and apoptosis, cells reactive oxgen species(ROS), mitochondrial membrane potential changes in each experimental groups. RESULTS: Of 15 cases of human medulloblastoma tumor, 13 cases had miR-383 expression levels significantly lower than that of normal brain tissue, and 14 had PRDX3 mRNA expression levels significantly higher than that of normal brain tissue. The expression levels of miR-383 and PRDX3 in Daoy cells were 0.353 and 1.315 times than those of normal brain tissue, respectively. The protein expression levels of PRDX3 were higher in human medulloblatoma tumors and Daoy cells than that of normal brain tissue. Transfected miR-383 mimics increased the expression level of miR-383 after 24 h and 48 h was significantly higher than that of the control. In contrast, PRDX3 gene mRNA and protein expression levels were significantly decreased at 48 h compared with the control group. Using CCK-8 assay, the cell proliferation rate in the experimental group was significantly lower than that of the control group (P < 0.05). Annexin V-FITC assay demonstrated that early apoptosis rate of the experimental group (11.60 ± 0.30)% was significantly higher than those of the control group (2.3 ± 0.20)% and negative control group (10.37 ± 0.25)% (P = 0.000) after 48 h of transfection. The intracellular ROS levels after transfection at 24 and 48 h significantly increased than those of the control group. Mitochondrial membrane potential level at 24 h after transfection significantly decreased, comparing with the blank control group and the negative control group. CONCLUSIONS: Compared with normal brain tissue, decreased expression of miR-383 but elevated expression of PRDX3 are medulloblastoma tumour and Daoy cell lines. Up-regulation of miR-383 knockdowns the expression of PRDX3, inhibits proliferation and promotes apoptosis of Daoy cells, leading to increased intracellular ROS and decreased levels of mitochondrial membrane potential.


Assuntos
Neoplasias Cerebelares/metabolismo , Meduloblastoma/metabolismo , MicroRNAs/metabolismo , Peroxirredoxina III/metabolismo , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Cerebelares/genética , Neoplasias Cerebelares/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Meduloblastoma/genética , Meduloblastoma/patologia , Potencial da Membrana Mitocondrial , MicroRNAs/genética , Peroxirredoxina III/genética , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transfecção
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...