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1.
Chem Biol Interact ; 388: 110832, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38101599

RESUMO

Cardiovascular disease (CVD) is the most common cause of death, environmental factors, such as arsenic, playing an important role in the progress of CVD. Vascular endothelial dysfunction (VED) is a crucial early feature for CVD, inorganic arsenic (iAs) can induce autophagy in various cells. However, the role of endothelial autophagy has rarely been studied in VED triggered by arsenic. Total of one hundred and twenty healthy male C57BL/6J mice weighing 18-22 g were randomly divided into an arsenic-exposure group and a control group for 3, 6, 9, and 12 weeks. The results showed that, independent of the exposure period, autophagy markers of p-ATG16L1 levels and Beclin 1 contents in the aortic arch endothelium increased significantly compared with those of the corresponding control group. And different exposure duration decreased NO contents in the serum significantly. Combined with the histological changes that endothelial injury aggravated gradually with the increasing exposure period, suggesting that under exposure to iAs over 9 weeks, VED was remarkably induced, and consistant high levels of endothelial autophagy may play an important role. Additionally, levels of p-AMPKα/AMPKα increased significantly and p-mTORC1/mTORC1 levels decreased remarkably in the aortic arch endothelium. Then, a NaAsO2-induced-VED in vitro model was used to explore the mechanism of arsenic-induced endothelial autophagy. Similarly, p-AMPKα/AMPKα level significantly increased, and p-mTORC1/mTORC1 level remarkably decreased induced by 30 µmol/L NaAsO2 in HUAECs. Further, an AMPK inhibitor (Compound C) pre-treatment prior to arsenic exposure reversed the increased autophagy level, and alleviated the endothelial dysfunction in HUVECs, as shown by the significant increase in the intracellular NO content and the cell vitality. Mechanistically, we revealed that AMPKα is active in autophagy of endothelial cells in arsenic-induced VED by regulating mTORC1/p70S6K/ULK1. The present study provide a new promising target for prevention and control arsenic-associated CVD.


Assuntos
Arsênio , Doenças Cardiovasculares , Camundongos , Animais , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina , Proteínas Quinases Ativadas por AMP , Células Endoteliais , Arsênio/toxicidade , Proteínas Quinases S6 Ribossômicas 70-kDa , Camundongos Endogâmicos C57BL , Autofagia
2.
Poult Sci ; 102(2): 102335, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36470031

RESUMO

Hexavalent chromium (Cr(Ⅵ)) is considered to be a common environmental pollutant, which widely exists in industrial effluents and wastes and then potentially noxious effects to the health of the poultry. Studies have reported that selenium (Se), which is one of the essential trace elements of the poultry and participates in the oxidative metabolism, can alleviate Cr(Ⅵ)-induced organ damage by inhibiting oxidative stress, but its specific molecular mechanism remains unclear. Herein, animal models of Cr(Ⅵ)- and Se-exposure were constructed using broilers to investigate the antagonistic mechanism of Se to Cr(Ⅵ)-induced hepatotoxicity. In this experiment, the four groups of broiler models were used as the research objects: control, Se, Se plus Cr, and Cr groups. Histopathology and ultrastructure liver changes were observed. Liver-somatic index, serum biochemistry, oxidative stress, Nrf2 pathway related factors, and autophagy-related genes were also determined. Overall, Se was found to ameliorate the disorganized structure, hepatic insufficiency, and oxidative damage caused by Cr(Ⅵ) exposure. Electron microscopy analysis further showed that the number of autophagosomes was obviously decreased after Se treatment compared to Cr group. Furthermore, gene and protein expression analyses illustrated that the levels of Nrf2, glutathione peroxidase 1 (GPx-1), NAD(P)H: quinone oxidoreductase 1 (NQO1), and mechanistic target of rapamycin (mTOR) in the Se&Cr group was upregulated, along with decreased expression of Beclin 1, ATG5 and LC3 compared to the Cr group. These suggest that Se can repair the oxidative lesion and autophagy induced by Cr(Ⅵ) exposure in broiler livers by upregulating the Nrf2 signaling pathway.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Selênio , Animais , Selênio/farmacologia , Selênio/metabolismo , Galinhas/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Cromo/toxicidade , Cromo/metabolismo , Estresse Oxidativo , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Doença Hepática Induzida por Substâncias e Drogas/veterinária , Transdução de Sinais
3.
Transl Cancer Res ; 11(7): 2122-2134, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35966299

RESUMO

Background: This study aims to discriminate risk factors associated with early death (died within 3 months) in metastatic small-cell lung cancer (SCLC) patients, and construct predictive nomograms to help physicians in guiding individual treatment. Methods: Surveillance, Epidemiology, and End Results (SEER) database was used to obtain records of deceased metastatic SCLC patients. The univariate and multivariate logistic regression methods were managed to identify risk factors for early death in overall patients and chemotherapy recipients. Predictive nomograms were developed and then validated by receiver operating characteristics curve (ROC) and calibration plots to verify its' precision. Results: A total of 13,229 patients were collected of which 5,832 of them encountered early death. The univariate and multivariate logistic regression analysis identified variables that were negatively associated with early death include sex, age, race, sequence, T stage, N stage, organ metastasis. Chemotherapy and radiotherapy implementation significantly decreased the odds of early death. For the chemotherapy recipients, white male patients with advanced age (over 80 years old), T4 stage, multiple organ metastasis, and without radiotherapy most likely died within 3 months. The area under the curve (AUC) of the nomograms for overall population and chemotherapy recipients' early death prediction was 0.839 and 0.653. Conclusions: Early death among metastatic SCLC patients was extremely common in clinical practice. The nomograms constructed were able to assist clinical physicians in discriminating high-risk SCLC patients for targeted intervention, and elderly white male patients diagnosed with advanced T stage and multiple organ metastasis might be exempted from systemic treatment to receive palliative care.

4.
Ecotoxicol Environ Saf ; 239: 113629, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35576799

RESUMO

Hexavalent chromium [Cr (VI)] is a common environmental pollutant. Although selenium (Se) can antagonize the toxicity of Cr (VI), the specific underlying mechanism has not been identified. To investigate this mechanism, we used potassium dichromate (K2Cr2O7) and selenium-rich yeast (SeY) to construct single Cr (VI)- and combined Se/Cr (VI)-exposed broiler models during a 42-day period. Broilers were randomly assigned to the control (C), SeY (Se), SeY + Cr (VI) (Se/Cr), and Cr (VI) (Cr) groups. The antagonistic mechanisms of Se and Cr (VI) were evaluated using histopathological evaluation, serum and tissue biochemical tests, real-time fluorescence quantitative polymerase chain reaction, and western blotting. The results suggested that Se alleviated the morphological and structural damage to renal tubules and glomeruli, while reducing the organ index, creatinine levels, and blood urea nitrogen levels in the kidneys of Cr (VI)-exposed broilers. Furthermore, Cr (VI) reduced the levels of superoxide dismutase and glutathione, and increased the levels of malondialdehyde, in broiler kidney tissues. However, Se alleviated Cr (VI)-induced oxidative stress by increasing the levels of superoxide dismutase and glutathione, and decreasing the levels of malondialdehyde, within a certain range. Compared to the C group, the levels of p38, JNK, p-p38, p-JNK, p-p38/p38, and p-JNK/JNK significantly increased, whereas those of ERK, p-ERK, and p-ERK/ERK decreased, in the Cr group. Compared to the Cr group, the levels of p38, JNK, p-p38, p-JNK, p-p38/p38, and p-JNK/JNK significantly decreased, whereas those of ERK, p-ERK, and p-ERK/ERK increased, in the Se/Cr group. Furthermore, the levels of p53, c-Myc, Bax, Cyt-c, caspase-9, and caspase-3 significantly increased, and those of Bcl-2 and Bcl-2/Bax significantly decreased, following Cr (VI) exposure, while Se restored the expression of these genes. In conclusion, our findings suggest that SeY can protect against Cr (VI)-induced dysfunction and apoptosis by regulating the mitogen-activated protein kinase pathway activated by oxidative stress in broiler kidney tissues.


Assuntos
Proteínas Quinases Ativadas por Mitógeno , Selênio , Animais , Apoptose , Galinhas/metabolismo , Cromo/toxicidade , Glutationa , Rim/metabolismo , Malondialdeído , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Selênio/metabolismo , Selênio/farmacologia , Superóxido Dismutase , Proteína X Associada a bcl-2
5.
Animals (Basel) ; 12(2)2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-35049769

RESUMO

This study was conducted to investigate the molecular mechanisms of selenium (Se) antagonism of hexavalent chromium (Cr6+)-induced toxicity. Potassium dichromate (K2Cr2O7) and selenium-enriched yeast (SeY) were used to construct the single Cr6+ and combined Se/Cr6+ exposure broiler models, and then the broilers were randomly divided into four groups (C group, Se group, Se/Cr6+ group, and Cr6+ group). After a 42-day experiment, the spleen tissues of broilers were excised and weighted. The antagonistic mechanisms of Se and Cr6+ were evaluated using histopathological assessment, serum biochemical tests, oxidative stress kits, ELISA, qPCR, and Western blotting. On the whole, there were no significant changes between the C and Se groups. The spleen organ index in the Cr6+ group was significantly decreased, but SeY increased spleen organ index to a certain extent. The levels of SOD and GSH were reduced, and the MDA content was elevated by Cr6+; however, these changes were mitigated by Se/Cr6+ exposure. Importantly, Cr6+ exposure induced a series of histopathological injuries in broiler spleen tissues, while these symptoms were significantly relieved in the Se/Cr6+group. Furthermore, Cr6+ significantly decreased the levels of T-globulin, IgA, IgM, and IgG in serum. Contrarily, dramatically more T-globulin IgA, IgM, and IgG were found in the Se/Cr6+group than in the Cr6+ group. Revealed by the results of qPCR and WB, the expressions of NF-κB, IκBα, and p-IκBα were upregulated in Cr6+ groups, while they were downregulated in Se/Cr6+ group compared to that in Cr6+ group. Besides IFN-γ and IL-2, the expressions of pro-inflammatory cytokines were significantly increased by Cr6+ exposure, but the SeY supplement relived the expression levels mediated by Cr6+ exposure. In conclusion, our findings suggest SeY has biological activity that can protect broiler spleens from immunosuppression and inflammation induced by Cr6+, and we speculate that the NF-κB signaling pathway is one of its mechanisms.

6.
Environ Res ; 186: 109506, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32315827

RESUMO

Although the harmful effects of arsenic exposure on the cardiovascular system have received great attention, there is still no effective treatment. Vascular endothelial dysfunction (VED) is the initial step of cardiovascular diseases, where pigment epithelium-derived factor (PEDF) plays an important role in maintaining endothelial function. Here, we explored the protective role of PEDF in VED induced by arsenic, and its underlying molecular mechanism, designing an in vivo rat model of arsenic exposure recovery and in vitro endothelial EA. hy926 cell-based assays. The edema of aortic endothelial cells in rats significantly improved during recovery from arsenite exposure compared with rats exposed to 10 and 50 mg/L arsenite continuously. In addition, serum levels of nitric oxide (NO), von Willebrand factor, and nitric oxide synthase (inducible and total activities) in rats, which were greatly affected by arsenite exposure, returned to levels similar to those in the control group after recovery with distilled water. The recovery from arsenite exposure was associated with increased levels of PEDF; decreased protein levels of Fas, FasL, P53, and phospho-p38; and inhibited apoptosis in aortic endothelial cells in vivo. Recombinant human PEDF treatment (100 nM) prevented the toxic effects of arsenite (50 µM) on endothelial cells in vitro by increasing NO content, decreasing reactive oxygen species (ROS) levels, and inhibiting apoptosis, as well as increasing cell viability and decreasing levels of P53 and phospho-p38. Our findings suggest that PEDF protects endothelial cells from arsenic-induced VED by increasing NO release and inhibiting apoptosis, where P53 and p38MAPK are its main targets.


Assuntos
Arsênio , Serpinas , Animais , Arsênio/toxicidade , Células Cultivadas , Células Endoteliais , Proteínas do Olho , Humanos , Fatores de Crescimento Neural , Ratos
7.
Front Oncol ; 10: 228, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32175279

RESUMO

Failure of cancer chemotherapy is mostly due to multidrug resistance (MDR). Overcoming MDR mediated by overexpression of ATP binding cassette (ABC) transporters in cancer cells remains a big challenge. In this study, we explore whether NVP-TAE684, a novel ALK inhibitor which has the potential to inhibit the function of ABC transport, could reverse ABC transporter-mediated MDR. MTT assay was carried out to determine cell viability and reversal effect of NVP-TAE684 in parental and drug resistant cells. Drug accumulation and efflux assay was performed to examine the effect of NVP-TAE684 on the cellular accumulation and efflux of chemotherapeutic drugs. The ATPase activity of ABCG2 transporter in the presence or absence of NVP-TAE684 was conducted to determine the impact of NVP-TAE684 on ATP hydrolysis. Western blot analysis and immunofluorescence assay were used to investigate protein molecules related to MDR. In addition, the interaction between NVP-TAE684 and ABCG2 transporter was investigated via in silico analysis. MTT assay showed that NVP-TAE684 significantly decreased MDR caused byABCG2-, but not ABCC1-transporter. Drug accumulation and efflux tests indicated that the effect of NVP-TAE684 in decreasing MDR was due to the inhibition of efflux function of ABCG2 transporter. However, NVP-TAE684 did not alter the expression or change the subcellular localization of ABCG2 protein. Furthermore, ATPase activity analysis indicated that NVP-TAE684 could stimulate ABCG2 ATPase activity. Molecular in silico analysis showed that NVP-TAE684 interacts with the substrate binding sites of the ABCG2 transporter. Taken together, our study indicates that NVP-TAE684 could reduce the resistance of MDR cells to chemotherapeutic agents, which provides a promising strategy to overcome MDR.

8.
Int J Mol Sci ; 21(4)2020 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-32092870

RESUMO

The overexpressing ABCB1 transporter is one of the key factors leading to multidrug resistance (MDR). Thus, many ABCB1 inhibitors have been found to be able to overcome ABCB1-mediated MDR. However, some inhibitors also work as a substrate of ABCB1, which indicates that in order to achieve an effective reversal dosage, a higher concentration is needed to overcome the pumped function of ABCB1, which may concurrently increase the toxicity. WYE-354 is an effective and specific mTOR (mammalian target of rapamycin) inhibitor, which recently has been reported to reverse ABCB1-mediated MDR. In the current study, 3-(4,5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay was carried out to determine the cell viability and reversal effect of WYE-354 in parental and drug-resistant cells. Drug accumulation was performed to examine the effect of WYE-354 on the cellular accumulation of chemotherapeutic drugs. The ATPase (adenosine triphosphatase) activity of the ABCB1 transporter in the presence or absence of WYE-354 was conducted in order to determine the impact of WYE-354 on ATP hydrolysis. Western blot analysis and immunofluorescence assay were used to investigate the protein molecules related to MDR. In addition, the interaction between the WYE-354 and ABCB1 transporter was investigated via in silico analysis. We demonstrated that WYE-354 is a substrate of ABCB1, that the overexpression of the ABCB1 transporter decreases the efficacy of WYE-354, and that the resistant WYE-354 can be reversed by an ABCB1 inhibitor at a pharmacological achievable concentration. Furthermore, WYE-354 increased the intracellular accumulation of paclitaxel in the ABCB1-mediated MDR cell line, without affecting the corresponding parental cell line, which indicated that WYE-354 could compete with other chemotherapeutic drugs for the ABCB1 transporter substrate binding site. In addition, WYE-354 received a high score in the docking analysis, indicating a strong interaction between WYE-354 and the ABCB1 transporter. The results of the ATPase analysis showed that WYE-354 could stimulate ABCB1 ATPase activity. Treatment with WYE-354 did not affect the protein expression or subcellular localization of the ABCB1. This study provides evidence that WYE-354 is a substrate of the ABCB1 transporter, implicating that WYE-354 should be avoided for use in ABCB1-mediated MDR cancer.


Assuntos
Purinas/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Subfamília B de Transportador de Cassetes de Ligação de ATP/química , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Adenosina Trifosfatases/metabolismo , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Doxorrubicina/química , Doxorrubicina/farmacologia , Resistência a Múltiplos Medicamentos/genética , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Modelos Moleculares , Simulação de Acoplamento Molecular , Paclitaxel/química , Paclitaxel/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Purinas/química , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Verapamil/farmacologia
9.
Cancers (Basel) ; 12(1)2020 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-31940916

RESUMO

Tivantinib, also known as ARQ-197, is a potent non-ATP competitive selective c-Met inhibitor currently under phase 3 clinical trial evaluation for liver and lung cancers. In this study, we explored factors that may lead to tivantinib resistance, especially in regards to its interaction with ATP-binding cassette super-family G member 2 (ABCG2). ABCG2 is one of the most important members of the ATP-binding cassette (ABC) transporter family, a group of membrane proteins that play a critical role in mediating multidrug resistance (MDR) in a variety of cancers, including those of the liver and lung. Tivantinib received a high score in docking analysis, indicating a strong interaction between tivantinib and ABCG2, and an ATPase assay indicated that tivantinib stimulated ABCG2 ATPase activity in a concentration-dependent manner. An MTT assay showed that ABCG2 overexpression significantly desensitized both the cancer cells and ABCG2 transfected-HEK293 cells to tivantinib and that this drug resistance can be reversed by ABCG2 inhibitors. Furthermore, tivantinib upregulated the protein expression of ABCG2 without altering the cell surface localization of ABCG2, leading to increased resistance to substrate drugs, such as mitoxantrone. Altogether, these data demonstrate that tivantinib is a substrate of ABCG2, and, therefore, ABCG2 overexpression may decrease its therapeutic effect. Our study provides evidence that the overexpression of ABCG2 should be monitored in clinical settings as an important risk factor for tivantinib drug resistance.

10.
Molecules ; 24(10)2019 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-31130645

RESUMO

Ginkgo tea is a kind of health food produced from Ginkgo biloba leaves. The market of Ginkgo tea encountered many difficulties because of its bad palatability and vague function statement. In this study, two kinds of glycosidase were used to improve the flavor of Ginkgo tea, and three kinds of bioactivities were selected to investigate the health care function of the tea infusion. The aroma components extracted by headspace absorb (HSA) method during the making of Ginkgo tea were analyzed by GC-MS. The flavonoids and ginkgolides released into the tea infusion were studied by HPLC. A combination of ß-glucosidase (ß-G) and α-rhamnosidase (α-R) was applied during the making of the tea. The contents of characteristic aroma components and the release of total flavonoids and ginkgolides were increased significantly by adding ß-G and α-R. The composition of flavone glycosides was changed greatly. The free radical scavenging, inhibition of inflammatory cell activation, and tumor cytotoxicity activities of the tea were demonstrably improved. According to the release of active components, Ginkgo tea can be brewed repeatedly for at least three times. The enzymes used here show potential application prospects in the making of Ginkgo tea or tea drink to get higher contents of flavonoids, ginkgolides, and aroma components.


Assuntos
Bebidas/análise , Flavonoides/metabolismo , Ginkgo biloba/química , Ginkgolídeos/metabolismo , Glicosídeo Hidrolases/metabolismo , beta-Glucosidase/metabolismo , Odorantes/análise
11.
Artigo em Inglês | MEDLINE | ID: mdl-30857143

RESUMO

The echinococcosis of humans and animals is a chronic helminthic disease caused by the larva of genus Echinococcus tapeworms. It is a globally distributed disease which is an important socioeconomic and public health problem in many low and middle-income countries. This research aimed to firstly quantitatively analyze the publications with bibliometrics software and evaluated the hot topics and emerging trends of echinococcosis research from 1980 to 2017. A total of 7688 references on echinococcosis research were retrieved from the Web of Science Core Collection database. Then the reference was analyzed with CiteSpace software to make the knowledge network maps. The largest cluster (#0) with 83 members was cystic echinococcosis, and cystic echinococcosis, mebendazole, antibody and transmission were the four keywords with the strongest citation bursts in the echinococcosis research field. Furthermore, cystic echinococcosis, chemotherapy and immunodiagnosis, management of definitive and intermediate host are the top four research hot topics and emerging trends in the echinococcosis field. This research presents an insight into the echinococcosis field and valuable visualizing information for echinococcosis researchers to detect new viewpoints on cooperative countries/institutions, potential co-workers and research frontiers.


Assuntos
Bibliometria , Pesquisa Biomédica/tendências , Equinococose , Bases de Conhecimento , Publicações , Animais , Equinococose/diagnóstico , Equinococose/imunologia , Equinococose/terapia , Humanos , Software
12.
Biol Trace Elem Res ; 190(2): 405-413, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30392020

RESUMO

Water-borne arsenicosis is caused by the consumption of excess levels of inorganic arsenic from drinking water and is a worldwide public health issue. Arsenic exposure has recently attracted extensive attention due to its damage to the cardiovascular system. Vascular endothelial dysfunction (VED) is recognized as an important cause of cardiovascular diseases. Pigment epithelium-derived factor (PEDF) plays an important role in maintaining endothelial function, and our previous studies suggested that PEDF may have role in arsenic-induced damage. In the present study, we established subchronic arsenic exposure (3 months) rat model from drinking water at doses of 0, 2 mg/L, 10 mg/L, and 50 mg/L, respectively. The results showed that the endothelial cells of the aortic arch were obviously damaged, the apoptosis rate increased, the vWF and iNOS levels increased, and the NO and TNOS levels significantly decreased in the arsenic exposure groups. Regardless of serum or aortic arch endothelium, PEDF levels in the arsenic exposure groups decreased compared to the control group. The oxidative stress level and key proteins associated with apoptosis such as Fas, FasL, P53, and p-p38 were then detected to explore the detailed mechanisms. The results showed that the P53 and p-p38 levels significantly increased in the 10 mg/L and 50 mg/L groups compared to the control group. The MDA content in the arsenic exposure groups increased markedly, whereas the SOD activity decreased significantly with the increased arsenic dose. Taken together, our study is the first to find that PEDF plays a protective role in arsenic-induced endothelial dysfunction through anti-oxidation and anti-apoptosis, and p38 and P53 may be promising target proteins.


Assuntos
Arsênio/farmacologia , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Proteínas do Olho/metabolismo , Fatores de Crescimento Neural/metabolismo , Serpinas/metabolismo , Animais , Arsênio/administração & dosagem , Arsênio/análise , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Células Endoteliais/metabolismo , Masculino , Ratos , Ratos Wistar , Relação Estrutura-Atividade
13.
PLoS One ; 13(5): e0197563, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29771951

RESUMO

Kaempferol (kae) and its glycosides are widely distributed in nature and show multiple bioactivities, yet few reports have compared them. In this paper, we report the antitumor, antioxidant and anti-inflammatory activity differences of kae, kae-7-O-glucoside (kae-7-O-glu), kae-3-O-rhamnoside (kae-3-O-rha) and kae-3-O-rutinoside (kae-3-O-rut). Kae showed the highest antiproliferation effect on the human hepatoma cell line HepG2, mouse colon cancer cell line CT26 and mouse melanoma cell line B16F1. Kae also significantly inhibited AKT phosphorylation and cleaved caspase-9, caspase-7, caspase-3 and PARP in HepG2 cells. A kae-induced increase in DPPH and ABTS radical scavenging activity, inhibition of concanavalin A (Con A)-induced activation of T cell proliferation and NO or ROS production in LPS-induced RAW 264.7 macrophage cells were also seen. Kae glycosides were used to produce kae via environment-friendly enzymatic hydrolysis. Kae-7-O-glu and kae-3-O-rut were hydrolyzed to kae by ß-glucosidase and/or α-L-rhamnosidase. This paper demonstrates the application of enzymatic catalysis to obtain highly biologically active kae. This work provides a novel and efficient preparation of high-value flavone-related products.


Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Antioxidantes/farmacologia , Glucosídeos/farmacologia , Glicosídeos/farmacologia , Quempferóis/farmacologia , Animais , Apoptose/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Avaliação Pré-Clínica de Medicamentos , Radicais Livres , Glicosídeo Hidrolases/metabolismo , Humanos , Hidrólise , Quempferóis/isolamento & purificação , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas Recombinantes/metabolismo , beta-Glucosidase/metabolismo
14.
Nat Prod Res ; 32(5): 588-591, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28431473

RESUMO

Osmanthus fragrans are well-known for their fragrance, but it is wasteful if to discard O. fragrans flower after extracting their essential oils. In this paper, we found that O. fragrans flower residues were rich in flavonoids. Six flavonoids and one phenylethanoid glycoside were isolated from the ethanol extract of O. fragrans flower residues, identified as quercetin (1), rutin (2), verbascoside (3), genistin (4), kaempferol (5), isorhamnetin (6) and naringin (7). In bioactivity study, kaempferol (IC50 = 1.43 µg/mL) showed the best anti-inflammatory activity. Isorhamnetin, quercetin, kaempferol, verbascoside and rutin (the values of IC50 were 18.30, 11.05, 16.88, 20.21 and 22.76 µg/mL, respectively) showed excellent DPPH free radical scavenging activity. Verbascoside performed relatively well at inhibiting the growth of both CT26 colonic carcinoma cells (IC50 = 46.87 µg/mL) and HepG2 hepatocarcinoma cells (IC50 = 30.58 µg/mL). In addition, quercetin and kaempferol showed strong anti-proliferation activity against HepG2 cells.


Assuntos
Flavonoides/química , Flavonoides/farmacologia , Óleos Voláteis/química , Oleaceae/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular , Fracionamento Químico , Avaliação Pré-Clínica de Medicamentos/métodos , Flores/química , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Células Hep G2 , Humanos , Concentração Inibidora 50 , Quempferóis/química , Quempferóis/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Óleos Voláteis/análise , Quercetina/química , Quercetina/farmacologia , Rutina/química , Rutina/farmacologia
15.
Microb Pathog ; 109: 200-208, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28578092

RESUMO

The lectin pathway, one of the complement cascade systems, provides the primary line of defense against invading pathogens. The serine protease of MASP-2 plays an essential role in complement activation of the lectin pathway. The C-terminal segment of MASP-2 is comprised of the CCP1-CCP2-SP domains, and is the crucial catalytic segment. However, what is the effect of CCP1-CCP2-SP domains in controlling chronic infection is unknown. In order to evaluate the potential impact of CCP1-CCP2-SP domains on tuberculosis, we constructed the human MASP-2 CCP1/2SP, CCP2SP and SP recombinant plasmids, and delivered these plasmids by DNA-DOTAP:cholesterol cationic nanolipoplexes to BCG-infected mice. After 21 days post DNA-DOTAP:chol nanolipoplexes application, we analyzed bacteria loads of pulmonary, pathology of granuloma, lymphocyte subpopulations. The C3a, C4a and MASP-2 levels in serum were measured with enzyme-linked immunosorbent assays. Compared to the control group that received GFP DNA-DOTAP:chol nanolipoplexes, MASP-2 CCP1/2SP DNA-DOTAP:chol nanolipoplexes treated group showed significantly enlarged pulmonary granulomas lesion (P < 0.05) and did not reduce bacteria loads in the lung tissue (P < 0.05). Furthermore, the levels of C3a in serum were decreased (P < 0.05), the number and percentage of PD1+ and Tim3+ cells subgroups were increased in BCG-infected mice after treated with MASP-2 CCP1/2SP DNA-DOTAP:chol nanolipoplexes (P < 0.05). But, there was no statistical difference in the serum C4a and MASP-2 level among DNA nanolipoplexes treated groups (P > 0.05). These findings provided experimental evidence that MASP-2 CCP1/2SP DNA nanolipoplexes shown the negative efficacy in controlling Mycobacterium tuberculosis infection, and displayed a potential role of down-regulating T-cell-mediated immunity in tuberculosis.


Assuntos
Carboxipeptidases/imunologia , Serina Proteases Associadas a Proteína de Ligação a Manose/imunologia , Mycobacterium bovis/imunologia , Tuberculose/imunologia , Animais , Carga Bacteriana , Linfócitos T CD4-Positivos , Linfócitos T CD8-Positivos , Células CHO , Carboxipeptidases/genética , Linhagem Celular , Cricetulus , Ensaio de Imunoadsorção Enzimática , Feminino , Proteínas de Ligação ao GTP , Expressão Gênica , Vetores Genéticos , Granuloma/imunologia , Granuloma/microbiologia , Humanos , Imunidade Celular , Lectinas/metabolismo , Lipossomos , Pulmão/microbiologia , Pulmão/patologia , Serina Proteases Associadas a Proteína de Ligação a Manose/genética , Camundongos , Mycobacterium bovis/genética , Plasmídeos/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/imunologia , D-Ala-D-Ala Carboxipeptidase Tipo Serina
16.
Se Pu ; 35(11): 1198-1203, 2017 Nov 08.
Artigo em Chinês | MEDLINE | ID: mdl-29372767

RESUMO

A novel analytical method was developed for the simultaneous determination of six fluorescent whitening agents (FWAs:FWA 135, FWA 184, FWA 185, FWA 199, FWA 378 and FWA 393) in paper and plastic food packaging materials by high performance liquid chromatography with fluorescence detection (HPLC-FLD). The sample was extracted with mixed solution of chloroform and acetonitrile (3:7, v/v), then cleaned up by HLB solid phase extraction column. Qualitative and quantitative analyses were carried out by HPLC. The sample was separated on a Phenomenex C18 column using acetonitrile and 5 mmol/L ammonium acetate aqueous solution as mobile phases. The results indicated that the linear range of FWA393 was 15-1500 µg/L and the linear ranges of the other five FWAs were 5-500 µg/L with correlation coefficients greater than 0.999. The recoveries in spiked samples were between 80.4% and 125.0% with RSDs (n=6) of 1%-13%. Furthermore, this method was applied to analyze 12 samples in the market to verify the practicality of the method. The method showed the advantages of simplicity, high recovery and good precision, and is suitable for the detection of the six fluorescent whitening agents in food packaging materials.


Assuntos
Clareadores/análise , Cromatografia Líquida de Alta Pressão , Embalagem de Alimentos , Plásticos/análise , Corantes Fluorescentes , Extração em Fase Sólida
17.
Microb Pathog ; 100: 221-228, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27725284

RESUMO

BACKGROUND: The role of MASP-2 is vital in the process of complement activation by the lectin pathway. It is generally considered that the functional activation of MASP-2 contribute to the infection disease development process. AIMS: To analyze the association between MASP-2 functional gene (rs72550870) polymorphism and the infection disease risk by a meta-analysis. METHOD: Relevant case-control studies were identified by searching Cochrane Library, PubMed, Emabase, DOAJ, CAB Abstracts, CSA, CINAHL, EBSCO, Scopus, Global Health, Index Copernicus, CA, China National Knowledge Infrastructure (CNKI) databases up to 10th January 2016. The data were extracted and the methodological quality of studies were evaluated. The STATA 12.0 software was used to perform statistical analysis. RESULTS: 9 studies were included. There was no significant association between masp-2 gene (p.D120G, rs72550870) polymorphism and the risk of infection disease under the allele model (G vs. A: OR = 0.89, 95%CI = 0.66-1.21)(P = 0.445>0.05) and the recessive model (AG + GG vs.AA: OR = 0.88, 95%CI = 0.65-1.20) (P = 0.428>0.05). CONCLUSION: This is the first comprehensive meta-analysis indicates that the MASP-2 functional gene (rs72550870) polymorphism is not associated with the infection diseases, and the key functional gene polymorphism of rs72550870 did not increase susceptibility to the infection diseases. Similarly, there were no obvious difference in subgroup analysis based on geographical areas and pathogenic microorganisms.


Assuntos
Doenças Transmissíveis/genética , Doenças Transmissíveis/imunologia , Predisposição Genética para Doença , Fatores Imunológicos/genética , Serina Proteases Associadas a Proteína de Ligação a Manose/genética , Polimorfismo Genético , China , Humanos , Medição de Risco
18.
Microb Pathog ; 99: 282-286, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27585546

RESUMO

Tuberculosis is a chronic infectious disease, which caused by Mycobacterium tuberculosis. It typically affects the functions of the lung and causes high morbidity and mortality rates worldwide. The lectin pathway, one of the complement cascade systems, provides the primary line of defense against invading pathogens. However, what is the specific effection between tuberculosis and complement is unknown. Mannose-binding lectin (MBL), a recognition subunit, binds to arrays of carbohydrates on the surfaces of pathogens, which results in the activation of MBL-associated serine protease-2 to trigger a downstream reaction cascade of complement system. The effects of human MBL-associated serine protease-2 (hMASP-2) were assessed in a rabbit-skin model by intradermal injection of 5 × 106 viable BCG bacilli. The rAd-hMASP-2 accelerated the formation of liquefaction and healing of the granuloma lesions, reduced the bacteria loads of the skin nodules. The serum levels of IL-2 and IFN-γ were significantly increasing during the granuloma and liquefaction phases in the rAd-hMASP-2 group. This study suggests that hMASP-2 can induce a protective efficacy in BCG-infected rabbit skin models, which affects both the progress of lesions and the survival of the mycobacteria within them.


Assuntos
Serina Proteases Associadas a Proteína de Ligação a Manose/metabolismo , Mycobacterium bovis/imunologia , Pele/patologia , Tuberculose Cutânea/imunologia , Tuberculose Cutânea/patologia , Úlcera/imunologia , Úlcera/patologia , Animais , Modelos Animais de Doenças , Granuloma/patologia , Humanos , Coelhos , Pele/imunologia , Tuberculose Cutânea/microbiologia , Úlcera/microbiologia , Cicatrização
19.
Microb Pathog ; 82: 15-26, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25773770

RESUMO

BACKGROUND: It is generally considered that HLA-Ⅱ genes contribute to the Helicobacter pylori (Hp) infection and disease development process. AIMS: To perform a meta-analysis to explore the relationship between HLA-Ⅱgene polymorphism and host susceptibility to Hp infection. METHODS: Relevant cohort studies, case-control studies and cross-sectional studies were identified by searching Cochrane Library, PubMed, EMBASE, Web of Science and CBM up to July 2014. The data were extracted and methodological quality of the studies were evaluated. RevMan5.0 software was used to perform statistical analysis. RESULTS: In Asian population, HLA-DQB1*0303 acted as the protective gene in Hp infection (statistically significant pooled OR = 0.54) and the susceptible genes in Hp infection involved HLA-DQB1*0401, HLA-DQA1*0103 and HLA-DQA1*0301 (statistically significant pooled OR and 95%CI were 3.34(1.93,5.77), 1.64(1.16,2.33) and 2.03(1.20,3.44) respectively). No statistically significant difference between DQB1*0303, HLA-DQA1*0103 and DQA1*0301 and Hp infection in European population (P>0.05). And no statistically significant difference (P>0.05) in the overall effect of the association between the rest of HLA-Ⅱalleles and Hp infection. CONCLUSIONS: In Asian population, the protective gene HLA-DQB1*0303 and the susceptible genes HLA-DQB1*0401, HLA-DQA1*0103 and HLA-DQA1*0301 in Hp infection were established by meta-analysis. And there was no HLA-Ⅱallele was found to associate with Hp infection among European population.


Assuntos
Resistência à Doença , Predisposição Genética para Doença , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/genética , Helicobacter pylori/imunologia , Antígenos de Histocompatibilidade Classe II/genética , Polimorfismo Genético , Ásia/epidemiologia , Europa (Continente)/epidemiologia , Frequência do Gene , Humanos
20.
Zhongguo Dang Dai Er Ke Za Zhi ; 16(6): 638-42, 2014 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-24927443

RESUMO

OBJECTIVE: To establish the Chinese Pediatric Evaluation of Disability Inventory (PEDI) norms in Chongqing, China. METHODS: PEDI (English version) was translated into Chinese and proof read by back-translation. A total of 1 140 children stratified by age were randomly selected from Chongqing and evaluated by the Chinese version of the PEDI. The obtained data were statistically analyzed. RESULTS: Of 1 140 questionnaires, 1 075 (94.3%) were valid. The data showed that the raw and scale scores of PEDI increased with age, but the standard scores did not increase with age. The raw, scale, and standard scores on self-care and social function scales were significantly lower than American PEDI norms in some age periods (P<0.05), but the raw, scale, and standard scores on mobility scale were not significantly different from American norms (P>0.05). CONCLUSIONS: The PEDI norms in Chongqing have been successfully established, and can be used to assess the daily function in children, judge the degree of daily function impairment, evaluate the effect of rehabilitation training, and make the rehabilitation plan for disabled children.


Assuntos
Avaliação da Deficiência , Pediatria , Criança , Pré-Escolar , China , Feminino , Humanos , Lactente , Masculino
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