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1.
World J Microbiol Biotechnol ; 36(1): 12, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31897767

RESUMO

Superoxide dismutases (SODs) have been shown to exhibit high levels of conservation and exist in almost all aerobic organisms and even many strict anaerobes. There are four SODs in Bacillus cereus 0-9, and this coexistence of multiple homologous enzymes is of great significance in the evolution of bacteria. We hypothesized that the four sod genes in B. cereus 0-9 constituted non-redundant protection against oxidative damage in vivo and played unique roles in the pathogenicity of B. cereus 0-9 during different phases or growth environments. To test this hypothesis, we constructed four single-knockout mutants (∆sodA1, ∆sodA2, ∆sodS, and ∆sodC) and a mutant lacking all four sod genes (∆sod-4) of B. cereus 0-9 and assessed their various phenotypes. Our results indicated that sodA1 plays a major role in tolerance to intracellular oxidative stress and spore formation. The ∆sodA1 and ∆sod-4 mutants were very sensitive to oxidants. The spore formation of the ∆sodA1 mutant was dramatically delayed, and the ∆sod-4 mutant did not form any spores under our experimental conditions. The sodA2 gene may play an important role in negative regulation of swarming motility, pathogenicity, and phospholipase and haemolytic activity of B. cereus but also a role in positive regulation of biofilm formation under our experimental conditions. The other two genes, sodS and sodC, were key to the pathogenicity of B. cereus. The lethal rates of Helicoverpa armigera infected by the ∆sodS and ∆sodC mutants were only 26.67%, while wild-type B. cereus 0-9 caused lethality in up to 86.67% of the insects at 24 h after injection. Moreover, the ∆sod-4 mutant caused a reduced death rate of H. armigera of 46.70%, which was slightly higher than that caused by the ∆sodS and ∆sodC strains. Thus, these four sod genes were non-redundant for oxidative stress and may play different additional roles in B. cereus 0-9. These results can help us to further understand the biocontrol characteristics of B. cereus 0-9 and lay a theoretical foundation for further research.


Assuntos
Bacillus cereus/crescimento & desenvolvimento , Lepidópteros/microbiologia , Superóxido Dismutase/genética , Animais , Bacillus cereus/enzimologia , Bacillus cereus/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Evolução Molecular , Técnicas de Inativação de Genes , Família Multigênica , Estresse Oxidativo , Fenótipo , Superóxido Dismutase/metabolismo
2.
Bioorg Med Chem ; 28(4): 115305, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31928863

RESUMO

The similarity of spatial structure between radicicol and matrine urged us to perform conformation modification of matrine, followed by L-shaped matrine derivatives, 6, 12, 21a-h and 22a-h were originally designed, synthesized and evaluated for Hsp90N inhibitors as anticancer agents. TSA (Thermal Shift Assay) results indicated that 21e, 22a-c and 22e-g exhibited strong binding force against Hsp90N with∣ΔTm∣ > 3, meanwhile, MTT assay also revealed these compounds displayed potent anticancer activity with IC50 values below 25 µM against HepG2, HeLa and MDA-MB-231 cells lines. Then, compound 22g with a high ΔTm = 10.92 was chosen as a representative to perform further mechanism study. It can induce cell apoptosis, arrest the cell cycle at the S phase and decrease the expression level of Hsp90 in Hela cell. These results originally provided targeted modification strategy for matrine derivatives to serve as Hsp90 inhibitors for cancer therapy.

3.
Ecotoxicol Environ Saf ; 190: 110094, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31869718

RESUMO

BACKGROUND: Exposure to PM2.5 can stimulate the mucus secretion of airway, affecting the development of bronchial asthma. NF-κB signal pathway plays an important role in inflammation and dysimmunity, what may contribute to the mucus secretion. The present study was undertaken to explore the effect of NF-κB signal pathway on mucus secretion induced by PM2.5 in rats with bronchial asthma. METHODS: Fifty rats (25 males and 25 females) were divided randomly into the control group, ovalbumin asthmatic model group, asthma low-, middle- and high-dose groups (n = 10, 5 males and 5 females each group). The control group, ovalbumin asthmatic model group received physiological saline; the asthma low-, middle- and high-dose groups received 1.5, 7.5 and 37.5 mg/kg PM2.5 on saline, which instilled into the trachea at 2-day intervals for two doses. Lung histopathology was observed by HE staining. The mRNA levels of NF-κB family gens were detected with real time PCR. IκB-α protein expression levels were detected with Western blot. IL-1ß, TNF-α and Muc5ac levels were detected by ELISA. RESULTS: Respiratory mucus secretion increased with increasing dose of PM2.5. Compared with healthy rats, the protein expression levels of IκB-α were significantly lower in the lung of asthmatic rats (p < 0.05), while the relative mRNA expression levels of NF-κB family genes in tracheal tissue and in lung were significantly higher in the asthmatic rats (p < 0.05). Serum IL-1ß levels were significantly higher in the high-dose group than in the control group. Muc5ac protein levels in the trachea were higher in the high-dose compared with the low-and middle-dose groups. CONCLUSION: Short-term exposure to a high concentration of PM2.5 could up-regulate the mRNA expression levels of NF-κB family genes, activate the NF-κB signal pathway, stimulate more IL-1ß and mucus secretion in rats with bronchial asthma. NF-κB signal pathway may regulate the level of IL-1ß, which could influence the mucus secretion induced by PM2.5 in asthmatic rats.


Assuntos
Poluentes Atmosféricos/toxicidade , NF-kappa B/metabolismo , Material Particulado/toxicidade , Animais , Asma/imunologia , Feminino , Inflamação/metabolismo , Pulmão/efeitos dos fármacos , Masculino , Muco/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , Ovalbumina , Ratos , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
4.
Arch Biochem Biophys ; 663: 269-275, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30677405

RESUMO

Gastric cancer is the second most leading cause of cancer related mortality across the world over. Although the incidence of GC has declined to some extent but it is still the fourth highly diagnosed cancer across the world. GC generally remains undiagnosed till advanced stages due to unavailability of biomarkers and when diagnosed it becomes difficult to manage due to the lack of therapeutic targets and efficient chemotherapy. There are concrete evidences suggesting that miRNAs may prove important therapeutic targets for the treatment of devastating diseases such as cancer. The study was designed to investigate the tumor suppressive role of miR-31 via regulation of zeste homolog 2 (ZH2). It was found that miR-31 is significantly downregulated in GC cell lines. Overexpression of miR-31 causes significant (P < 0.05) decrease in the viability and colony formation via initiation of G2/M cell cycle arrest of the AGS cancer cells. Moreover, miR-31 overexpression also enhanced the chemosensitivity of miR-31 to the anticancer drug 5-fluorouracil. In silico analysis together with dual luciferase reporter assay indicated zeste homolog 2 (ZH2) to be the potential target of miR-31 in AGS cells. Investigation of ZH2 expression in GC cell lines showed it to be significantly (P < 0.05) upregulated. Nonetheless, overexpression of miR-31 in AGS cells resulted in the suppression of ZH2 expression. Additionally, silencing of ZH2 in the AGS cells also caused inhibition of AGS cell proliferation and colony formation via G2/M arrest. Moreover, overexpression of ZH2 could at least partially reverse the tumor suppressive effects of miR-31 indicating direct involvement of ZH2 in the miR-31 mediated inhibitory effects on AGS cell proliferation. Finally, miR-31 overexpression caused significant (P < 0.05) inhibition of the migration and invasion of the AGS gastric cancer cells. The overexpression of miR-31 also caused downregulation of mesenchymal markers (Vimentin and N-cadherin) and upregulation of epithelial marker (E-cadherin) protein expression was in AGS cells. It is therefore concluded that miR-31 acts as a tumor suppressor and may prove essential in the treatment of GC.


Assuntos
Divisão Celular/genética , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Fase G2/genética , MicroRNAs/fisiologia , Invasividade Neoplásica/genética , Metástase Neoplásica/genética , Neoplasias Gástricas/patologia , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo/genética , Humanos
5.
Phys Chem Chem Phys ; 20(45): 28886-28893, 2018 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-30420980

RESUMO

Nanopore-based DNA sequencing is considered to be a low-cost, high resolution and superfast method. Solid state nanopores, especially MoS2 nanopores, have been considered to be a promising choice for DNA sequencing. However, researchers still have a very limited understanding of the effects of multiple factors on MoS2-based DNA sequencing. In this study, the effects of the applied voltage and the diameter of the MoS2 nanopore on the resolution of DNA sequencing were investigated. Our results demonstrate that the translocation time of DNA can increase with a decrease in the applied voltage. DNA can be stretched significantly to translocate a 2 nm nanopore under a high applied voltage (>400 mV nm-1). To achieve a 1 base per µs translocation speed (1 GHz bandwidth), we suggest that three methods could be applied, including a decrease in the applied voltage, a decrease in the diameter of the MoS2 nanopore or modification of the MoS2 nanopore. In addition, the size of the nanopore can severely affect the possibility of DNA entering the nanopore, and the translocation time of DNA could be significantly increased with a smaller MoS2 nanopore. These findings may help to design MoS2 nanopores with higher resolution for use in DNA sequencing.


Assuntos
DNA/química , Dissulfetos/química , Molibdênio/química , Nanoporos , Sequência de Bases , Técnicas Eletroquímicas/métodos , Simulação de Dinâmica Molecular , Análise de Sequência de DNA/métodos
6.
Eur J Med Chem ; 156: 479-492, 2018 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-30025344

RESUMO

Based on the mechanism of action, novel scaffolds as Topo I inhibitors bearing indole and sophoridinine were designed. Preliminary docking study revealed that some molecules among the designed series possessed promising Topo I inhibitor properties. Subsequently, thirty new compounds were synthesized and characterized by 1H NMR, 13C NMR, and Mass spectral analyses. The compounds were then screened for their antiproliferative and enzymatic inhibitory activities. The results affirmed the consistency between docking and activities and the rationality of the design strategy. Furthermore, compound 10b was chosen as a representative compound to test its anticancer effects in vitro and in vivo. The results showed that 10b caused prominent S phase cell cycle arrest and significantly suppressed tumor growth in HepG2 cell derived mouse model. These findings present a promising series of lead molecules which can serve as potential Topo I inhibitors for the treatment of cancer and a theoretical basis for structural modifications.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Indóis/química , Indóis/farmacologia , Inibidores da Topoisomerase I/química , Inibidores da Topoisomerase I/farmacologia , Animais , Antineoplásicos/uso terapêutico , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Desenho de Drogas , Feminino , Células Hep G2 , Humanos , Indóis/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Camundongos , Camundongos Endogâmicos BALB C , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Inibidores da Topoisomerase I/uso terapêutico
7.
Chin Med J (Engl) ; 131(9): 1030-1033, 2018 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-29692372

RESUMO

Background: Asthma is a common chronic respiratory disease and is related to air pollution exposure. However, only a few studies have concentrated on the association between air pollution and adult asthma. Moreover, the results of these studies are controversial. Therefore, the present study aimed to analyze the influence of various pollutants on hospitalization due to asthma in adults. Methods: A total of 1019 unrelated hospitalized adult asthma patients from Northeast China were recruited from 2014 to 2016. Daily average concentrations of air pollutants (particulate matter <2.5 µm [PM2.5], particulate matter <10 µm [PM10], sulfur dioxide [SO2], nitrogen dioxide [NO2], and carbon monoxide [CO]) were obtained from the China National Environmental Monitoring Centre website from 2014 to 2016. Cox logistic regression analysis was used to analyze the relationship between air pollutants and hospital admissions in adult asthma. Results: The maximum odds ratio (OR) value for most air pollutants occurred on lag day 1. Lag day 1 was chosen as the exposure period, and 8 days before onset was chosen as the control period. Three pollutants (PM2.5, CO, and SO2) were entered into the regression equation, and the corresponding OR (95% confidence interval) was 0.995 (0.991-0.999), 3.107 (1.607-6.010), and 0.979 (0.968-0.990), respectively. Conclusions: A positive association between hospital admissions and the daily average concentration of CO was observed. CO is likely to be a risk factor for hospital admissions in adults with asthma.


Assuntos
Poluição do Ar/efeitos adversos , Asma/epidemiologia , Hospitalização/estatística & dados numéricos , Poluentes Atmosféricos/toxicidade , Monóxido de Carbono/toxicidade , China , Monitoramento Ambiental/estatística & dados numéricos , Feminino , Humanos , Masculino , Razão de Chances , Material Particulado/toxicidade , Fatores de Risco , Dióxido de Enxofre/toxicidade
8.
Molecules ; 22(11)2017 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-29135958

RESUMO

Using sophoridine 1 and chalcone 3 as the lead compounds, a series of novel α, ß-unsaturated sophoridinic derivatives were designed, synthesized, and evaluated for their in vitro cytotoxicity. Structure-activity relationship (SAR) analysis indicated that introduction of α, ß-unsaturated ketone moiety and heterocyclic group might significantly enhance anticancer activity. Among the compounds, 2f and 2m exhibited potential effects against HepG-2 and CNE-2 human cancer cell lines. Furthermore, molecular docking studies were performed to understand possible docking sites of the molecules on the target proteins and the mode of binding. This work provides a theoretical basis for structural optimizations and exploring anticancer pathways of this kind of compound.


Assuntos
Alcaloides/química , Alcaloides/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Técnicas de Química Sintética , Desenho de Drogas , Modelos Moleculares , Quinolizinas/química , Quinolizinas/farmacologia , Alcaloides/síntese química , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , DNA/química , Relação Dose-Resposta a Droga , Humanos , Conformação Molecular , Simulação de Acoplamento Molecular , Estrutura Molecular , Quinolizinas/síntese química , Relação Estrutura-Atividade
9.
J Craniofac Surg ; 28(6): 1586-1588, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28863110

RESUMO

Facial neural edema is the pathophysiological base of Bell's palsy. The middle cranial fossa approach is used to relieve the oppression of facial nerve at its most narrow course in the facial canal. In this research, the authors mainly discussed the internal auditory canal segment of facial nerve, completely in the shadow of the bony structure, which is inconvenient for transmastoid decompression. Therefore, the objective was to explore the definite position of the fundus meatus acustici interni from internal acoustic pore. Two hundred persons (age 22-60, 100 men and 100 women), presenting with healthy facial nerve, ear, and internal auditory canal, were investigated by computed tomography 3-dimensional reconstruction. Using statistical method to analyze, the authors obtained the definite position of the fundus meatus acustici interni, regarding the internal acoustic pore as the origin of coordinates. Our data provided more significant information for medical workers to improve the efficiency of operation and to prevent complications of surgery.


Assuntos
Orelha Interna , Nervo Facial , Osso Petroso , Tomografia Computadorizada por Raios X , Adulto , Paralisia de Bell , Descompressão Cirúrgica , Orelha Interna/anatomia & histologia , Orelha Interna/diagnóstico por imagem , Nervo Facial/anatomia & histologia , Nervo Facial/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Osso Petroso/anatomia & histologia , Osso Petroso/diagnóstico por imagem , Adulto Jovem
10.
ACS Appl Mater Interfaces ; 9(11): 9437-9448, 2017 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-28244328

RESUMO

Recently magnesium and its alloys have been proposed as a promising next generation orthopedic implant material, whereas the poor corrosion behavior, potential cytotoxicity, and the lack of efficient drug delivery system have limited its further clinical application, especially for the local treatment of infections or musculoskeletal disorders and diseases. In this study, we designed and developed a multifunctional bilayer composite coating of poly(lactic acid)/brushite with high interfacial bonding strength on a Mg-Nd-Zn-Zr alloy, aiming to improve the biocorrosion resistance and biocompatibility of the magnesium-based substrate, as well as to further incorporate the biofunctionality of localized drug delivery. The composite coating consisted of an inner layer of poly(lactic acid) serving as a drug carrier and an outer layer composed of brushite generated through chemical solution deposition, where a facile pretreatment of UV irradiation was applied to the poly(lactic acid) coating to facilitate the heterogeneous nucleation of brushite. The in vitro degradation results of electrochemical measurements and immersion tests indicated a considerable reduction of magnesium degradation provided the composite coating. A systematic investigation of cellular response with cell viability, adhesion, and ALP assays confirmed the coated Mg alloy induced no toxicity to MC3T3-E1 osteoblastic cells but rather fostered cell attachment and proliferation and promoted osteogenic differentiation, revealing excellent biosafety and biocompatibility and enhanced osteoinductive potential. An in vitro drug release profile of paclitaxel from the composite coating was monitored with UV-vis spectroscopy, showing an alleviated initial burst release and a sustained and controlled release feature of the drug-loaded composite coating. These findings suggested that the bilayer poly(lactic acid)/brushite coating provided effective protection for Mg alloy, greatly enhanced cytocompatibility and bioactivity, and, moreover, possessed local drug delivery capability; hence magnesium alloy with poly(lactic acid)/brushite coating presents great potential in orthopedic clinical applications, especially for localized bone therapy.


Assuntos
Ligas/química , Animais , Fosfatos de Cálcio , Linhagem Celular , Materiais Revestidos Biocompatíveis , Corrosão , Magnésio , Camundongos , Osteogênese , Poliésteres
11.
IEEE Trans Inf Technol Biomed ; 13(6): 926-32, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19789117

RESUMO

A body sensor network (BSN) is a network of sensors deployed on a person's body for health care monitoring. Since the sensors collect personal medical data, security and privacy are important components in a BSN. In this paper, we developed IBE-Lite, a lightweight identity-based encryption suitable for sensors in a BSN. We present protocols based on IBE-Lite that balance security and privacy with accessibility and perform evaluation using experiments conducted on commercially available sensors.


Assuntos
Confidencialidade , Armazenamento e Recuperação da Informação/métodos , Sistemas Computadorizados de Registros Médicos , Monitorização Fisiológica/métodos , Algoritmos , Identificação Biométrica , Humanos
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