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1.
BMC Psychiatry ; 21(1): 485, 2021 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-34607584

RESUMO

BACKGROUND: The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) are the most commonly used scales to detect mild cognitive impairment (MCI) in population-based epidemiologic studies. However, their comparison on which is best suited to assess cognition is scarce in samples from multiple regions of China. METHODS: We conducted a cross-sectional analysis of 4923 adults aged ≥55 years from the Community-based Cohort Study on Nervous System Diseases. Objective cognition was assessed by Chinese versions of MMSE and MoCA, and total score and subscores of cognitive domains were calculated for each. Education-specific cutoffs of total score were used to diagnose MCI. Demographic and health-related characteristics were collected by questionnaires. Correlation and agreement for MCI between MMSE and MoCA were analyzed; group differences in cognition were evaluated; and multiple logistic regression model was used to clarify risk factors for MCI. RESULTS: The overall MCI prevalence was 28.6% for MMSE and 36.2% for MoCA. MMSE had good correlation with MoCA (Spearman correlation coefficient = 0.8374, p < 0.0001) and moderate agreement for detecting MCI with Kappa value of 0.5973 (p < 0.0001). Ceiling effect for MCI was less frequent using MoCA versus MMSE according to the distribution of total score. Percentage of relative standard deviation, the measure of inter-individual variance, for MoCA (26.9%) was greater than for MMSE (19.0%) overall (p < 0.0001). Increasing age (MMSE: OR = 2.073 for ≥75 years; MoCA: OR = 1.869 for≥75 years), female (OR = 1.280 for MMSE; OR = 1.163 for MoCA), living in county town (OR = 1.386 and 1.862 for MMSE and MoCA, respectively) or village (OR = 2.579 and 2.721 for MMSE and MoCA, respectively), smoking (OR = 1.373 and 1.288 for MMSE and MoCA, respectively), hypertension (MMSE: OR = 1.278; MoCA: OR = 1.208) and depression (MMSE: OR = 1.465; MoCA: OR = 1.350) were independently associated with greater likelihood of MCI compared to corresponding reference group in both scales (all p < 0.05). CONCLUSIONS: MoCA is a better measure of cognitive function due to lack of ceiling effect and with good detection of cognitive heterogeneity. MCI prevalence is higher using MoCA compared to MMSE. Both tools identify concordantly modifiable factors for MCI, which provide important evidence for establishing intervention measures.


Assuntos
Disfunção Cognitiva , Idoso , China/epidemiologia , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Entrevista Psiquiátrica Padronizada , Testes de Estado Mental e Demência , Pessoa de Meia-Idade , Testes Neuropsicológicos
2.
Nano Lett ; 20(9): 6272-6280, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32787161

RESUMO

Although immunogenic cell death (ICD)-based chemoimmunotherapy elicits an immune response, it always focuses on eliminating "seeds" (tumor cells) but neglects "soil" (tumor microenvironment, TME), leading to tumor growth and metastasis. Herein, a type of detachable core-shell nanoplatform (DOX@HA-MMP-2-DEAP/CXB) is developed, which could swell in the acidic TME because of the protonation of the 3-diethylaminopropyl isothiocyanate (DEAP) inner core for celecoxib (CXB) release, while hyaluronic acid@doxorubicine (HA@DOX) prodrug in the outer shell could release by the cleavage of matrix metalloproteinase-2 (MMP-2) peptide. HA@DOX targets tumor cells precisely for triggering ICD. And CXB acts on multiple immune cells to remodulate TME, such as increasing the infiltration of dendritic cells (DCs) and T cells, decreasing the infiltration of the immunosuppressive cells, and eliminating the physical barriers between T cells and tumor cells. For comparison, HA-DOCA/DOX/CXB traditional nanoparticles are constructed. And DOX@HA-MMP-2-DEAP/CXB performs an impressive antitumor effect, which shows potential in enhancing the effect of chemoimmunotherapy.


Assuntos
Metaloproteinase 2 da Matriz , Nanopartículas , Morte Celular , Doxorrubicina , Imunoterapia , Inoculação de Neoplasia , Neoplasias/terapia , Microambiente Tumoral
3.
ACS Appl Mater Interfaces ; 12(1): 580-590, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31809020

RESUMO

Performance declination of nanofiltration (NF) membranes caused by concentration polarization (CP) and membrane fouling has severely restricted their practical application in many fields. This work reports the construction of a novel interlayer between the substrate and the selective layer of conventional composite membranes by coordinating regulation of carbon quantum dots (CQDs) and polydopamine (PDA). Unlike traditional methods that treat CP and fouling separately, the new strategy grants the membrane with dual functions at one time. First, the insertion of the PDA-CQDs layer reformulates the interfacial polymerization process that reduces the solute transport resistance and mitigates the CP issue. Second, the sandwiched photoactive CQDs can degrade organic molecules adsorbed on the membrane surface under visible light, which is promising for low-cost fouling remediation. This study may offer valuable insights into the preparation of durable self-cleaning NF membranes for the effective treatment of complex wastewater in various industries.

4.
Adv Healthc Mater ; 9(1): e1901335, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31762228

RESUMO

Sonodynamic therapy (SDT) shows tremendous potential to induce immunogenic cell death (ICD) and activate antitumor immunity. However, it can aggravate hypoxia and release platelet (PLT)-associated danger-associated molecular patterns (DAMPs), which impede therapeutic efficacy and promote tumor metastasis. In order to solve these problems, a biomimetic decoy (designated as Lipo-Ce6/TPZ@MH ) is constructed to reverse the drawbacks of SDT by loading sonosensitizer chlorin e6 (Ce6) and hypoxia-activated tirapazamine (TPZ) in the red blood cells-PLTs hybrid membrane (MH )-camouflaged pH-sensitive liposome. After administration, the decoy exhibits enhanced cancer accumulation and retention abilities due to the immune escape and specific targeting behaviors by biomimetic surface coating. Upon local ultrasound, Ce6 produces toxic reactive oxygen species for SDT, and the resulting hypoxia microenvironment activates TPZ, which can realize a high-effective synergistic therapy. Meanwhile, DAMPs-mediated tumor metastasis is significantly inhibited, because the decoy retains platelet binding functions but is incapable of platelet-mediated metastasis. In addition, ICD-mediated strong antitumor immunities further prevent the growth and metastasis of the residual tumors left behind after synergistic treatment. Taken together, this study highlights the potential of using this cascade therapeutic therapy plus biomemitic decoy in one nanosystem to both eliminate melanoma in situ and suppress lung metastasis.


Assuntos
Antineoplásicos/uso terapêutico , Materiais Biomiméticos/química , Neoplasias Pulmonares/tratamento farmacológico , Terapia por Ultrassom/métodos , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Hipóxia Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Lipossomos/química , Neoplasias Pulmonares/secundário , Melanoma Experimental/patologia , Camundongos , Camundongos Endogâmicos C57BL , Porfirinas/química , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Tirapazamina/química , Tirapazamina/farmacologia , Tirapazamina/uso terapêutico , Distribuição Tecidual , Ensaios Antitumorais Modelo de Xenoenxerto
5.
J Control Release ; 318: 197-209, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31672622

RESUMO

With the in-depth research of organelles, the microenvironment characteristics of their own, such as the acid environment of lysosomes and the high temperature environment of mitochondria, could be used as a natural and powerful condition for tumor therapy. Based on this, we constructed a two-step precise targeting nanoplatform which can realize the drug release and drug action triggered by the microenvironment of lysosomes (endosomes) and mitochondria, respectively. To begin with, the mesoporous silica nanoparticles (MSNs) were modified with triphenylphosphonium (TPP) and loaded with 2,2'-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH). Then, folic acid (FA) targeted pH-sensitive liposomes containing docetaxel (Lipo/DTX-FA) were prepared by thin-film dispersion method, and the core-shell AIPH/MSN-TPP@Lipo/DTX-FA nanoparticles were constructed by self-assembly during the hydration of the liposomes. When this nanoplatform entered into the tumor cells through FA receptor-mediated endocytosis, the pH-sensitive liposomes were destabilized in the lysosomes, resulting in the release of DTX and AIPH/MSN-TPP nanoparticles. After that, AIPH was delivered to mitochondria by AIPH/MSN-TPP, and the alkyl radicals produced by AIPH under the high temperature environment can cause oxidative damage to mitochondria. Not only that, the DTX could enhance the anti-tumor effect of AIPH by downregulating the expression of anti-apoptotic Bcl-2 protein. The in vitro and in vivo results demonstrate that this delivery system could induce apoptosis based on organelles' s own microenvironment, which provides a new approach for tumor therapy.


Assuntos
Antineoplásicos , Nanopartículas , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Docetaxel/metabolismo , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Mitocôndrias/metabolismo , Dióxido de Silício/metabolismo
6.
ACS Nano ; 13(11): 12553-12566, 2019 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-31689085

RESUMO

Efficient cancer vaccines not only require the co-delivery of potent antigens and highly immunostimulatory adjuvants to initiate robust tumor-specific host immune response but also solve the spatiotemporal consistency of host immunity and tumor microenvironment (TME) immunomodulation. Here, we designed a biomaterials-based strategy for converting tumor-derived antigenic microparticles (T-MPs) into a cancer vaccine to meet this conundrum and demonstrated its therapeutic potential in multiple murine tumor models. The internal cavity of T-MPs was employed to store nano-Fe3O4 (Fe3O4/T-MPs), and then dense adjuvant CpG-loaded liposome arrays (CpG/Lipo) were tethered on the surface of Fe3O4/T-MP through mild surface engineering to get a vaccine (Fe3O4/T-MPs-CpG/Lipo), demonstrating that co-delivery of Fe3O4/T-MPs and CpG/Lipo to antigen presenting cells (APCs) could elicit strong tumor antigen-specific host immune response. Meanwhile, vaccines distributed in the TME could reverse infiltrated tumor-associated macrophages into a tumor-suppressive M1 phenotype by nano-Fe3O4, amazingly induce abundant infiltration of cytotoxic T lymphocytes, and transform a "cold" tumor into a "hot" tumor. Furthermore, amplified antitumor immunity was realized by the combination of an Fe3O4/T-MPs-CpG/Lipo vaccine and immune checkpoint PD-L1 blockade, specifically inhibiting ∼83% of the progression of B16F10-bearing mice and extending the median survival time to 3 months. Overall, this study synergistically modulates the tumor immunosuppressive network and host antitumor immunity in a spatiotemporal manner, which suggests a general cell-engineering strategy tailored to a personalized vaccine from autologous cancer cell materials of each individual patient.


Assuntos
Antígenos de Neoplasias , Vacinas Anticâncer , Imunomodulação/imunologia , Imunoterapia/métodos , Microambiente Tumoral/imunologia , Animais , Antígenos de Neoplasias/química , Antígenos de Neoplasias/imunologia , Vacinas Anticâncer/química , Vacinas Anticâncer/imunologia , Engenharia Celular , Sistemas de Liberação de Medicamentos , Feminino , Óxido Ferroso-Férrico/química , Camundongos , Camundongos Endogâmicos C57BL
7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 27(3): 850-854, 2019 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-31204943

RESUMO

OBJECTIVE: To investigate the efficacy of disease control, survival time and safely in treatment of newly diagnosed multiple mycloma patients with different dose of tenalidomide regimens. METHODS: The clinical data of 116 patients with multiple myeloma from June 2011 to June 2015 were collected and analyzed retrospectively. According to doses of used lenalidomide based on dexamethasone plus lenalidomide regimen 116 patients were divided into 2 groups: conventional dose group (58 cases) and low dose group (58 cases). The ORR, PFS rate and OS rate during followed-up for 3 years, KPS score, RNS score and immunophenotypic index before and after treatment and drug toxicity incidence were compared between 2 groups. RESULTS: The ORR for 2 treatment courses of low dose group was significantly lower than that in conventienal dose group (P<0.05). The ORR for 4 and 6 treatment courses was not significantly different between 2 groups (P>0.05). The PFS rate and OS rate during followed-up for 3 years was no significantly different between 2 groups (P>0.05). The KPS score and RNS score after treatment of low dose group were significantly better than those in conventional dose group and before treatment (P<0.05). The levels of immunophenotypic index after treatment of both groups were significantly better than those before treatment (P<0.05). The incidence of III-IV grade hematological toxicity, pulmonary infection and herpes were not significantly different between 2 groups (P>0.05). The incidence of peripheral neuropathy and gastrointestinal reactions in the low dose group were significantly lower than that in conventional dose group (P<0.05). CONCLUSION: Conventional and low doses of lenalidomide possess the same control effects and survival time for treatment of newly dingnosed patients with multiple myeloma; Despite, the initiation of effects from the low dose lenalidomide is relatively slower, it contributes to raise the overall quality of life and reduce the risk of drug toxicity.


Assuntos
Mieloma Múltiplo , Púrpura de Schoenlein-Henoch , Tromboelastografia , Protocolos de Quimioterapia Combinada Antineoplásica , Coagulação Sanguínea , Criança , Dexametasona , Humanos , Qualidade de Vida , Estudos Retrospectivos , Talidomida , Resultado do Tratamento
8.
Ultrasonics ; 91: 103-113, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30081330

RESUMO

The accuracy of measuring inclusion size in direct C-scan image of immersion ultrasonic testing is restricted by the lateral resolution of the focused transducer, even if a high frequency is used, and the blurred edge due to scattering of sound waves at inclusions. In this work, an improved image restoration method that is based on the Richardson-Lucy (RL) iterative algorithm is proposed, which is used to restore the C-scan image and improve the accuracy of inclusion size measurement in immersion ultrasonic testing. For the improved RL iterative algorithm, the point spread function (PSF) is derived based on the multi-Gaussian beam model and Kirchhoff approximation, which considers the propagation properties of sound waves at water-steel interface and the spectral characteristics of the transducer with high frequency. In order to determine the final iteration number, the relationship between final iteration number and size of the inclusion in the image is established by restoring the simulated C-scan image and further calibrated with size correction factor. The size correction factor considers the effect of sound attenuation and electro-mechanical transformation encountered in practical testing equipment. Experimental results show that the inclusion sizes measured in restored C-scan images agree well with the optical micrograph results, which prove the effectiveness of the proposed method.

9.
ACS Appl Mater Interfaces ; 10(37): 31124-31135, 2018 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-30141614

RESUMO

Poor tumor accumulation, rapid clearance from blood circulation, and high risk of invasive and metastasis are the major barriers that encumber the conventional nanodrug-based tumor therapy. In this work, macrophage membrane (M)-camouflaged quercetin (QE)-loaded hollow bismuth selenide nanoparticles (abbreviated as M@BS-QE NPs) are fabricated for combination therapy of breast cancer. The resulting M@BS-QE NPs are comprehensively characterized, possessing prolonged circulation life, as well as accelerated and enhanced tumoritropic accumulation, compared with those of bare BS NPs because of the immune evading capacity, C-C chemokine ligand 2 (CCL2)-mediated recruitment properties, and active targeting ability. The subsequent QE release under near-infrared (NIR) laser irradiation can selectively sensitize cancer cells to photothermal therapy (PTT) by depleting heat shock protein 70 (HSP70, one malignancy-specific-overexpressed thermoresistance-related chaperone) to realize such a cascaded synergistic effect. At the same time, M@BS-QE NPs down-regulated p-Akt and matrix metalloproteinase-9 (MMP-9, which degrades the extracellular matrix to promote invasion and metastasis of tumors) signal axis to suppress breast cancer lung metastasis. Thus, our results provide a biomimetic strategy, using the characteristics of breast cancer and biological properties of macrophages, that hold great promise to enhance the therapeutic efficacy and improve the accuracy of treatment with minimal side effects on both primary and lung metastasis of breast cancer.


Assuntos
Neoplasias da Mama/terapia , Quimiocina CCL2/metabolismo , Nanopartículas/química , Metástase Neoplásica , Compostos Organosselênicos , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Feminino , Temperatura Alta , Macrófagos/química , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica/terapia , Compostos Organosselênicos/administração & dosagem , Compostos Organosselênicos/química , Compostos Organosselênicos/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Quercetina/química , Células RAW 264.7
10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 25(5): 1397-1405, 2017 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-29070114

RESUMO

OBJECTIVE: To explore the effects of mTOR inhibitor rapamycin on proliferation, cell cycle and apoptosis of Burkitt's lymphoma cell line Raji and CA46 cells and its mechanism, so as to provide the experimental evidence for a therapeutic target of Burkitt's lymphoma. METHODS: 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide(MTT) assay was performed to assess the inhibitory effect of rapamycin on proliferation of Burkitt's lymphoma cell line Raji and CA46 cells. The cell cycle distribution of Raji and CA46 cells was analyzed by flow cytometry with propidium iodide(PI) single staining. The cell apoptosis of Raji and CA46 cells was analyzed by flow cytometry with FITC Annexin V+PI double staining. The expressions of RPS6, p-RPS6, survivin and caspase-3 proteins were detected by Western blot after treating with rapamycin. RESULTS: Rapamycin markedly inhibited the proliferation of both Raji and CA46 cells in a time- and concentration-dependent manners, showing good biological activity, the cell proliferation inhibition rate reached about 20% after treatment with 1 nmol/L rapamycin. After treatment with different concentrations of rapamycin for 24 and 48 hours, the proportion of both cells in G1/G0 phase in the treated groups was significantly increased in a time- and concentration-dependent manners in comparison with the solvent control group. With regard to the cells in S and G2/M phase, the decreased population was accompanied by the increase of G1/G0 phase cells. After treatment with 100 nmol/L rapamycin for 48 hours, both Raji and CA46 cells demonstrated an apparent apoptosis,especially late apoptosis by flow cytometry with Annexin V+PI staining. After treatment with rapamycin, the expression of p-RPS6 and survivin of Raji and CA46 cells was obviously down-regulated, the expression of caspase-3 was obviously up-regulated in a time- and dose-dependent manners. However, rapamycin did not obviously affect the expression of RPS6. CONCLUSION: The rapamycin can effectively inhibit cell proliferation, arrest Raji and CA46 cells in G1/G0 phase, and this effect associates with inhibiting the activation of mTOR/RPS6 signal pathway through down-regulating the expression of phosphorylated RPS6, i.e. mTOR downstream signal pathway. It also can induce apoptosis by down-regulating the expression of anti-apoptotic protein survivin and activating the intrinsic pro-apoptotic protein caspase-3.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linfoma de Burkitt/tratamento farmacológico , Sirolimo/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Serina-Treonina Quinases TOR
11.
Drug Des Devel Ther ; 11: 1115-1126, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28435223

RESUMO

BACKGROUND: Phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway is a therapy target of cancer. We aimed to confirm the effect of dual PI3K/mTOR inhibitor NVP-BEZ235 on proliferation, apoptosis, and autophagy of chronic myelogenous leukemia (CML) cells and sensitivity of tyrosine kinase inhibitor in vitro. METHODS: Two human CML cell lines, K562 and KBM7R (T315I mutant strain), were used. The proliferation of CML cells was detected by MTS (Owen's reagent) assay. Cell cycle and apoptosis assay were examined by flow cytometric analysis. The phosphorylation levels and the expression levels were both evaluated by Western blot analysis. NVP-BEZ235 in combination with imatinib was also used to reveal the effect on proliferation and apoptosis. RESULTS: NVP-BEZ235 significantly inhibited the proliferation in a time- and dose-dependent manner, and the half-maximal inhibitory concentration values of NVP-BEZ235 inhibiting the proliferation of K562 and KBM7R were 0.37±0.21 and 0.43±0.27 µmol/L, respectively, after 48 h. Cell apoptosis assay showed that NVP-BEZ235 significantly increased the late apoptotic cells. Cell cycle analysis indicated that the cells were mostly arrested in G1/G0 phase after treatment by NVP-BEZ235. In addition, results also found that, after treatment by NVP-BEZ235, phosphorylation levels of Akt kinase and S6K kinase significantly reduced, and the expression levels of cleaved caspase-3 significantly increased; meanwhile, the expression levels of caspase-3, B-cell lymphoma-2, cyclin D1, and cyclin D2 significantly decreased, and the ratio of LC3II/LC3I was significantly increased with increased LC3II expression level. Moreover, imatinib in combination with NVP-BEZ235 induced a more pronounced colony growth inhibition than imatinib alone. CONCLUSION: NVP-BEZ235 effectively inhibited cell proliferation by G0/G1 cell cycle arrest and induced apoptosis through deregulating PI3K/Akt/mTOR pathway in CML cells; in addition, NVP-BEZ235 can enhance cell autophagy, and is conducive to raising CML cell sensitivity to imatinib to inhibit the growth of imatinib-resistant cells.


Assuntos
Antineoplásicos/farmacologia , Mesilato de Imatinib/farmacologia , Imidazóis/farmacologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/farmacologia , Quinolinas/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Mesilato de Imatinib/química , Imidazóis/química , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Proteínas Quinases/química , Quinolinas/química , Relação Estrutura-Atividade , Serina-Treonina Quinases TOR/metabolismo , Células Tumorais Cultivadas
12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 25(1): 157-163, 2017 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-28245394

RESUMO

OBJECTIVE: To investigate the significance of serum interleukin-35 level and the new regulatory T cells -iTR35 cells in patients with myelodysplastic syndrome (MDS). METHODS: Twenty three cases of newly diagnosed MDS were enrolled in this study from January 2014 to January 2016 in Department of Hematology of The First Hospital of Quanzhou in Fujian Province. According to MDS International Prognostic Scoring System (IPSS), the 23 patients were divided into 4 groups: high-risk (n=4), intermediate risk-2 (n=10), intermediate risk-1 (n=5) and low-risk group(n=4). Twenty healthy people of routine physical examination were used as control during the same period. Enzyme Linked Immunosorbent assay(ELISA) and flow cytometry(FCM) were used to detect the expression level of serum IL-35, the proportion of iTR35 cells, and the expression levels of associated molecules such as IL-12p35,IL-27EBl3 respectively. RESULTS: The proportion of CD4+ CD25+ Foxp3+ Treg cells in peripheral blood of MDS patients was significantly higher than that in controls (P<0.01). The proportion of iTR35 cells was also higher than that in controls(P<0.01). However, the proportion of CD4+ CD25- Foxp3+ T cells was not significantly different between 2 groups (P>0.05). The level of serum IL-35 in MDS patients was significantly higher than that in control group (P<0.05). The expression levels of IL-12p35 and IL-27EBl3 in the Treg cells were also significantly upregulated than those in control group(P<0.05), the expression levels of IL-35, IL-12p35 and IL-27EBl3 in MDS group positively correlated with the proportion of iTR35 cells(r=0.92, 0.99 and 0.52, P<0.05, respectively). IL-35 level and the proportion of iTR35 cells in 4 groups of MDS showed significantly difference in general term, no significant difference was found in IL-35 level between the high-risk group and intermediate risk-2 group (P>0.05), but the IL-35 levels in both groups were significantly higher than those in intermediate risk-1 group and the low-risk group (P<0.05), and the level in the intermediate risk-2 group was significantly higher than that in the intermediate risk-1 group and the low-risk group (P<0.05), while there was not different between the intermediate risk-1group and the low risk group (P>0.05). The proportion of iTR35 cells was not significantly different between the high-risk group and the intermediate risk-2 group. The proportions of iTR35 cells in the high-risk group and the intermediate risk-2 group were higher than those in the intermediate risk-1 group and the low-risk group respectively (P<0.05), but there was no differentce in population of iTR35 between the intermediate risk-1 group and the low-risk group (P>0.05). CONCLUSION: The imbalance between IL-35 level and iTR35 cells propertion may play an important role in the development of MDS, which possibly to provides a new theoretical basis for the study of MDS immune targeting therapy.


Assuntos
Interleucinas/sangue , Síndromes Mielodisplásicas/sangue , Linfócitos T Reguladores , Citometria de Fluxo , Fatores de Transcrição Forkhead , Humanos , Interleucina-17 , Síndromes Mielodisplásicas/imunologia
13.
Sci Rep ; 6: 21396, 2016 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-26891761

RESUMO

The widespread occurrence of the beta-blocker labetalol causes environmental health concern. Enzymatic reactions are highly efficient and specific offering biochemical transformation of trace contaminants with short reaction time and little to none energy consumption. Our experiments indicate that labetalol can be effectively transformed by laccase-catalyzed reaction using 2, 2-Azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) as a mediator, while no significant removal of labetalol can be achieved in the absence of ABTS. A total of three products were identified. It is interesting that the presence of graphene greatly increased the reaction rate while not changed the products. In the presence of 100 µg/L graphene, the pseudo-first-order reaction rate constant was increased ~50 times. We found that the enhancement of graphene is probably attributed to the formation and releasing of ABTS(2+) which has a much greater reactivity towards labetalol when graphene is present. This study provides fundamental information for laccase-ABTS mediated labetalol reactions and the effect of graphene, which could eventually lead to development of novel methods to control beta-blocker contamination.


Assuntos
Benzotiazóis/química , Grafite/química , Labetalol/química , Lacase/química , Ácidos Sulfônicos/química , Biotransformação , Catálise , Redes e Vias Metabólicas , Especificidade por Substrato , Fatores de Tempo
14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 23(6): 1535-41, 2015 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-26708866

RESUMO

OBJECTIVE: To study the expression and its mechamisms of microRNA let-7b in adult acute lymphoblastic leukemia (ALL), so as to provide the basis for searching a new targeted therapy. METHODS: Firstly, methylation-specific polymerase chain reaction (MSP) was used to analyze the methylation status of CpG islands in microRNA let-7b promoter of bone marrow mononuclear cells in the patients with ALL and patients with non-hematologic malignancies as control, the real-time fluorescence quantitative polymerase chain reaction (qPCR) was used to detect the expression levels of microRNA let-7b in this 2 groups; and then 5-aza-2'-deoxycytidine (5-Aza-dC, DAC) was used to treat ALL cell line MOLT-4; after drug treatment, MSP was used to analyze the methylation status of the CpG islands in microRNA let-7b promoter; the qPCR was used to detect the expression levels of microRNA let-7b, and further explore the regulatory mechanism of microRNA let-7b expression. RESULTS: Hypermethylation of CpG islands in microRNA let-7b promoter in ALL patients was significantly higher than that in patients with non-hematologic malignancies, and the relative expression level of microRNA let-7b was significantly reduced in ALL patients; 5-aza-dC could significantly inhibit the growth of MOLT-4 cells and arrest the cells in G1 phase, thus biosynthesis of RNA and protein was suppressed, and the apoptosis was promoted, meanwhile, 5-Aza-dC could increase the expression of microRNA let-7b. CONCLUSION: In the patients with ALL, the expression of microRNA let-7b is regulated by methylation of CpG islands in the region of genomic promoter. The microRNA let-7b may act as a tumor suppressor, whose low expression is involved in ALL development, indicating the microRNA let-7b may become a new therapeutic target for ALL.


Assuntos
Epigênese Genética , Leucemia-Linfoma Linfoblástico de Células Precursoras , Apoptose , Azacitidina/análogos & derivados , Ilhas de CpG , Metilação de DNA , Decitabina , Humanos , MicroRNAs , Regiões Promotoras Genéticas , Reação em Cadeia da Polimerase em Tempo Real
15.
Cancer Cell Int ; 15: 65, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26130968

RESUMO

BACKGROUND: Phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway is a therapy target of cancer. We aimed to confirm the effect of dual PI3K/mTOR inhibitor NVP-BEZ235 on cell proliferation and apoptosis in Burkitt lymphoma (BL) cells. METHODS: Two human BL cell lines, CA46 and RAJI were used in this study. The proliferation of BL cells was detected by manganese tricarbonyl transfer (MTT) assay. Cell cycle and apoptosis assay were examined by flow cytometric analysis. The phosphorylation levels of AKT (Thr308), AKT (Ser473), and RPS6 were evaluated by western blot analysis. RESULTS: NVP-BEZ235 significantly inhibited the proliferation of BL cells (CA46 and RAJI) and the inhibition effect was time and dose-dependent. Cell cycle analysis indicated that the cells (CA46 and RAJI) were mostly arrested in G1/G0 phase. Cell apoptosis assay showed that the late apoptotic cells were significantly increased after 72 h treatment by 100 nmol/L of NVP-BEZ235. In addition, results also found that NVP-BEZ235 reduced the phosphorylation levels of AKT (Thr308), AKT (Ser473), and PRS6 in BL cells (CA46 and RAJI). Moreover, this inhibition effect on phosphorylation was dose-dependent. CONCLUSIONS: NVP-BEZ235 effectively inhibited cell proliferation by G0/G1 cell-cycle arrest and induced apoptosis through deregulating PI3K/Akt/mTOR pathway in BL cells.

16.
J Bacteriol ; 194(14): 3579-88, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22563053

RESUMO

Legionella pneumophila, the causative agent of Legionnaires' disease, is a ubiquitous freshwater bacterium whose virulence phenotypes require a type IV secretion system (T4SS). L. pneumophila strain JR32 contains two virulence-associated T4SSs, the Dot/Icm and Lvh T4SSs. Defective entry and phagosome acidification phenotypes of dot/icm mutants are conditional and reversed by incubating broth-grown stationary-phase cultures in water (WS treatment) prior to infection, as a mimic of the aquatic environment of Legionella. Reversal of dot/icm virulence defects requires the Lvh T4SS and is associated with a >10-fold induction of LpnE, a tetratricopeptide repeat (TPR)-containing protein. In the current study, we demonstrated that defective entry and phagosome acidification phenotypes of mutants with changes in LpnE and EnhC, another TPR-containing protein, were similarly reversed by WS treatment. In contrast to dot/icm mutants for which the Lvh T4SS was required, reversal for the ΔlpnE or the ΔenhC mutant required that the other TPR-containing protein be present. The single and double ΔlpnE and ΔenhC mutants showed a hypersensitivity to sodium ion, a phenotype associated with dysfunction of the Dot/Icm T4SS. The ΔlpnE single and the ΔlpnE ΔenhC double mutant showed 3- to 9-fold increases in translocation of Dot/Icm T4SS substrates, LegS2/SplY and LepB. Taken together, these data identify TPR-containing proteins in a second mechanism by which the WS mimic of a Legionella environmental niche can reverse virulence defects of broth-grown cultures and implicate LpnE and EnhC directly or indirectly in translocation of Dot/Icm T4SS protein substrates.


Assuntos
Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica/fisiologia , Legionella pneumophila/metabolismo , Legionella pneumophila/patogenicidade , Acanthamoeba castellanii/microbiologia , Animais , Proteínas de Bactérias/genética , Linhagem Celular , Legionella pneumophila/genética , Macrófagos Peritoneais/microbiologia , Camundongos , Mutação , Plasmídeos , Estrutura Terciária de Proteína , Vacúolos , Virulência
17.
FEMS Microbiol Lett ; 303(1): 48-54, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20002190

RESUMO

A Caulobacter crescentus rho::Tn5 mutant strain presenting a partially functional transcription termination factor Rho is highly sensitive to hydrogen peroxide in both exponential and stationary phases. The mutant was shown to be permanently under oxidative stress, based on fluorophore oxidation, and also to be sensitive to tert-butyl hydroperoxide and paraquat. However, the results showed that the activities of superoxide dismutases CuZnSOD and FeSOD and the alkylhydroperoxide reductase ahpC mRNA levels in the rho mutant were comparable to the wild-type control in the exponential and stationary phases. In contrast, the KatG catalase activity of the rho mutant strain was drastically decreased and did not show the expected increase in the stationary phase compared with the exponential phase. Transcription of the katG gene was increased in the rho mutant and the levels of the immunoreactive KatG protein do not differ considerably compared with the wild type in the stationary phase, suggesting that KatG activity is affected in a translational or a post-translational step.


Assuntos
Proteínas de Bactérias/biossíntese , Caulobacter crescentus/enzimologia , Caulobacter crescentus/genética , Peroxidases/biossíntese , Fator Rho/deficiência , Caulobacter crescentus/efeitos dos fármacos , Elementos de DNA Transponíveis , Perfilação da Expressão Gênica , Peróxido de Hidrogênio/toxicidade , Viabilidade Microbiana/efeitos dos fármacos , Mutagênese Insercional , Oxidantes/toxicidade , Estresse Oxidativo , Paraquat/toxicidade , Peroxirredoxinas/biossíntese , Superóxido Dismutase/biossíntese , terc-Butil Hidroperóxido/toxicidade
18.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 17(4): 929-32, 2009 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-19698231

RESUMO

The purpose of this study was to investigate the lethal effect of cytotoxic lymphocytes against U266 cells induced by DCs pulsed with multiple myeloma (MM) U266 lysate and transfected with GM-CSF recombinant adenovirus. The cytotoxic lymphocytes against U266 cells were induced by culturing with DCs, which pulsed with MM U266 antigens and transfected with GM-CSF recombinant adenovirus. The effect of cytotoxic lymphocytes against U266 cells were measured by LDH release detection. Experiments were divided into 3 groups: N-DC group as control in which DCs were normal; U-DC group in which DCs were pulsed by U266 soluble antigen, and G-U-DC group in which DCs were stimulated by U266 soluble antigen and GM-CSF transfected with Ad-CMV. The results showed that there was significant difference on killing rate against U266 cells between 3 groups (F = 10.939, p < 0.05). The killing rate of G-U-DC group was the highest (p < 0.001), and killing rate of U-DC group was higher than that of N-DC group (p < 0.001). It is concluded that the cytotoxic lymphocytes against U266 cells can be induced by DCs pulsed with U266 lysate, and the lethal effect of CTLs can be enhanced when DCs transfected by recombinant adenovirus with exogenous gene GM-CSF.


Assuntos
Antígenos de Neoplasias/imunologia , Vacinas Anticâncer/imunologia , Células Dendríticas/imunologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/imunologia , Linfócitos T Citotóxicos/imunologia , Adenoviridae/genética , Antígenos de Neoplasias/genética , Linhagem Celular Tumoral , Citotoxicidade Imunológica , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Humanos , Mieloma Múltiplo , Proteínas Recombinantes , Transfecção
19.
Infect Immun ; 72(8): 4541-51, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15271914

RESUMO

Legionella pneumophila, the causative agent of Legionnaires' disease, expresses a type IVB secretion apparatus that translocates bacterial proteins into amoeba and macrophage hosts. When stationary-phase cultures are used to infect hosts, the type IVB apparatus encoded by the icm/dot genes is required for entry, delay of phagosome-lysosome fusion, and intracellular multiplication within host cells. Null mutants with mutations in icm/dot genes are defective in these phenotypes. Here a new model is described in which hosts are infected with stationary-phase cultures that have been incubated overnight in pH 6.5 buffer. This model is called Ers treatment because it enhances the resistance to acid, hydrogen peroxide, and antibiotic stress beyond that of stationary-phase cultures. Following Ers treatment entry into amoeba and macrophage hosts does not require dotA, which is essential for Legionella virulence phenotypes when hosts are infected with stationary-phase cultures, dotB, icmF, icmV, or icmX. Defective host entry is also suppressed for null mutants with mutations in the KatA and KatB catalase-peroxidase enzymes, which are required for proper intracellular growth in amoeba and macrophage hosts. Ers treatment-induced suppression of defective entry is not associated with increased bacterial adhesion to host cells or with morphological changes in the bacterial envelope but is dependent on protein expression during Ers treatment. By using proteomic analysis, Ers treatment was shown to induce a protein predicted to contain eight tetratricopeptide repeats, a motif previously implicated in enhanced entry of L. pneumophila. Characterization of Ers treatment-dependent changes in expression is proposed as an avenue for identifying icm/dot-independent factors that function in the entry of Legionella into amoeba and macrophage hosts.


Assuntos
Acanthamoeba/microbiologia , Proteínas de Bactérias/metabolismo , Resposta ao Choque Térmico , Legionella pneumophila/patogenicidade , Macrófagos/microbiologia , Animais , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Cloranfenicol/farmacologia , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica , Células HL-60 , Humanos , Peróxido de Hidrogênio/farmacologia , Concentração de Íons de Hidrogênio , Legionella pneumophila/genética , Legionella pneumophila/crescimento & desenvolvimento , Proteoma , Virulência
20.
Cell Microbiol ; 5(7): 445-53, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12814435

RESUMO

We have assessed the kinetics of host gene expression in granulomas of mice infected with virulent Mycobacterium tuberculosis, using an approach that incorporates the laser capture microdissection (LCM) and real-time PCR technology in conjunction with a newly derived mathematical equation. The results have provided evidence indicating that conventional use of whole infected lungs to study granuloma-specific gene expression can yield data that may not genuinely reflect intralesional events. Significantly, the expression of nine host genes known to regulate the inflammatory response to M. tuberculosis, as determined by real-time PCR analysis of microdissected granuloma-derived cDNAs, was downregulated (up to 27-fold) at around the time when the rapid growth phase of the bacilli in the lungs of infected mice ends. This downregulation was masked when whole infected lungs were used for the studies. The data suggest that the host immune system can adjust and respond to, or can be modulated by specific physiological states of the tubercle bacillus in vivo. The LCM/real-time PCR-based system described in this study can be applied to safely and accurately evaluate gene expression in any lesions that can be microscopically visualized, including those contained in biohazardous tissues.


Assuntos
Expressão Gênica , Tuberculoma/genética , Tuberculoma/imunologia , Tuberculose Pulmonar/genética , Tuberculose Pulmonar/imunologia , Animais , Regulação para Baixo , Feminino , Perfilação da Expressão Gênica , Lasers , Pulmão/imunologia , Pulmão/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Micromanipulação , Mycobacterium tuberculosis/patogenicidade , Reação em Cadeia da Polimerase , Proteínas/genética , Proteínas/metabolismo , Tuberculoma/microbiologia , Tuberculose Pulmonar/microbiologia , Virulência
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