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1.
J Ethnopharmacol ; 248: 112262, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31585162

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia ordosica Krasch. (AOK) has been used for rheumatic arthritis, cold headache, sore throat, etc. in traditional Chinese/Mongolian medicine and is used for nasosinusitis by local Mongolian "barefoot" doctors. Up to now, their mechanisms are still unclear. AIM: To evaluate the in vivo anti-inflammatory and allergic rhinitis (AR) alleviating effect as well as in vitro antimicrobial activities of AOK extracts to verify its ethno-medicinal claims. MATERIALS AND METHODS: Crude extracts (methanol/95%-ethanol/ethyl acetate) of AOK root/stem/leaf and fractions (petroleum ether/ethyl acetate/n-butanol/aqueous) of AOK root extract were prepared. Xylene-induced ear swelling model in mouse and ovalbumin (OVA)-induced AR model in guinea pig were established. Ear swelling degrees of mice were measured. The numbers of rubbing movement and sneezes of guinea pigs were counted to evaluate the symptoms of AR. The serum levels of histamine, INF-γ, IL-2/4/10, and VCAM-1 were measured by ELISA assay. The histological changes of nasal mucosa were investigated by light microscope after H&E staining. Antimicrobial activities of AOK extracts were also tested. LC-MS/MS analysis was performed to characterize the constituents of active extract and molecular docking was conducted to predict the biological mechanism. RESULTS: In ear-swelling model, extract (100.00 mg/kg) from the ethyl acetate layer of 95% ethanol (100.00 mg/kg) showed better swelling inhibition in mice than positive control (dexamethasone, 191.91 mg/kg). In AR model, extract from the ethyl acetate layer of 95% ethanol significantly alleviated the AR symptoms in guinea pigs, decreased the serum levels of histamine, INF-γ, IL-2/4/10, and VCAM-1, and reduced the infiltration of eosinophil in nasal mucosa. For Staphylococcus aureus, the ethyl acetate extract of AOK stem showed the highest inhibition (MIC=1.25 mg/mL), for Escherichia coli, n-butanol layer of 95% ethanol extract of AOK root showed the highest inhibition (MIC=15.00 mg/mL), for Candida glabrata, 95%-ethyl acetate extract of AOK leaf showed the best inhibition (MIC=0.064 mg/mL), while ethyl acetate and n-butanol layers showed similar inhibition on MRSA (MIC=7.50 mg/mL). LC-MS/MS characterization showed that dicaffeoylquinic acids account for more than 30% of ethyl acetate layer of AOK extract. Dicaffeoylquinic acids bind with histamine-1 receptor with high affinities and interesting modes. CONCLUSIONS: Extracts from AOK had interesting anti-inflammatory activity in mice, alleviating effect against OVA-induced AR in guinea pigs, and antimicrobial activities in vitro, which support the ethno-medicinal use of it. The main constituents in ethyl acetate layer of AOK root extract are dicaffeoylquinic acids and could bind with histamine-1 receptor well. These findings highlighted the importance of natural product chemistry study of AOK.

2.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 37(6): 608-614, 2019 Dec 01.
Artigo em Chinês | MEDLINE | ID: mdl-31875438

RESUMO

OBJECTIVE: To investigate the caries status of the first permanent molars in urban and rural children aged 10-12 in Chongqing and analyze the related factors in order to provide a theoretical basis for the prevention and treatment of children's caries and targeted suggestions for oral health education. METHODS: A multi-stage, stratified, cluster, and random sampling method was used to extract 5 057 children from 18 schools in three districts and three counties in Chongqing for oral health examination and questionnaire survey from March to May 2018. RESULTS: The total caries rate of the first permanent molar was 39.2%. The decayed-missing-filled tooth was 0.84±1.20. The rate of filling teeth was 3.4%. The rate of pit and fissure sealing was 6.1%. The prevalence of the first permanent molars was significantly different between men and women, between urban and rural areas, between only children and non-only children, and between ethnic minorities and Han nationality (P<0.001). The gap between the pit and fissure sealing was significantly different between urban and rural areas (P<0.001). Multiple logistic regression analysis showed that many independent factors influence the occurrence of caries, including the frequency of brushing teeth every day, the frequency of eating desserts, the habit of eating dessert/drinking milk before going to bed, whether only-children or not, and parents' education background, among others. CONCLUSIONS: The first permanent molars of children aged 10-12 in Chongqing have a high rate of caries but low rates of pit and fissure sealing and dental caries filling. The difference between urban and rural areas is large, children's oral health knowledge is scarce, and children have bad oral hygiene behaviors and eating habits. Children's oral health education must be strengthened, oral health preaching must be implemented in schools, the oral health knowledge of children in school must be improved, and urban-rural differences must be minimized.


Assuntos
Cárie Dentária , Criança , Índice CPO , Feminino , Humanos , Masculino , Saúde Bucal , Higiene Bucal , Prevalência , Estudantes
3.
Hum Genet ; 138(11-12): 1217-1225, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31606751

RESUMO

Pluripotent stem cell (PSC) cultures form an integral part of biomedical and medical research due to their capacity to rapidly proliferate and differentiate into hundreds of highly specialized cell types. This makes them a highly useful tool in exploring human physiology and disease. Genomic editing of PSC cultures is an essential method of attaining answers to basic physiological functions, developing in vitro models of human disease, and exploring potential therapeutic strategies and the identification of drug targets. Achieving reliable and efficient genomic editing is an important aspect of using large-scale PSC cultures. The CRISPR/Cas9 genomic editing tool has facilitated highly efficient gene knockout, gene correction, or gene modifications through the design and use of single-guide RNAs which are delivered to the target DNA via Cas9. CRISPR/Cas9 modification of PSCs has furthered the understanding of basic physiology and has been utilized to develop in vitro disease models, to test therapeutic strategies, and to facilitate regenerative or tissue repair approaches. In this review, we discuss the benefits of the CRISPR/Cas9 system in large-scale PSC cultures.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Técnicas de Inativação de Genes , Genômica/métodos , Células-Tronco Pluripotentes/fisiologia , Humanos , Células-Tronco Pluripotentes/citologia
4.
Shanghai Kou Qiang Yi Xue ; 28(2): 204-206, 2019.
Artigo em Chinês | MEDLINE | ID: mdl-31384911

RESUMO

PURPOSE: To investigate the degree of satisfaction with educational environment among dental students in College of Stomatology, Chongqing Medical University. METHODS: In 2017, students' perceptions of the educational environment were evaluated using the 50-item DREEM. SPSS 24.0 software package was used for statistical analysis. RESULTS: A total of 260 valid questionnaires were recovered. The total Cronbach's α coefficient of DREEM was 0.915, and the total score of the DREEM was 164.99±19.53. CONCLUSIONS: The DREEM showed excellent internal consistency for the overall scores, and the education environment of dental education in our college is at a very good level.


Assuntos
Educação em Odontologia , Educação de Graduação em Medicina , Medicina Bucal , Estudantes de Medicina , China , Humanos , Meio Social , Estudantes de Odontologia , Inquéritos e Questionários , Universidades
5.
Clin Oral Investig ; 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31435823

RESUMO

OBJECTIVE: To assess dental treatment under dental general anesthesia (DGA) among Chinese preschool children by investigating changes in their oral health-related quality of life (OHRQoL), the incidence of postoperative complications, and parental satisfaction. METHOD: A single-center prospective cohort study was conducted. A total of 190 children who received treatment for early childhood caries (ECC) under DGA were included. The primary outcome was a change in the children's OHRQoL at 1 month after the operation compared to that at baseline, which was measured by the Early Childhood Oral Health Impact Scale (ECOHIS). The secondary outcomes were the incidence of complications within 1 day after treatment and parental satisfaction with the DGA treatment. RESULTS: In total, 180 participants were successfully reevaluated after the operation, yielding a 94.7% follow-up response rate. The total ECOHIS score decreased by 76.3% (P < 0.01) after treatment, demonstrating a large effect. Approximately 74.4% of the children complained of at least one complication, including sleepiness (43.3%), emergence agitation (38.9%), nausea/vomiting (13.9%), dizziness (10.6%), and fever (3.3%), on the first day. Approximately 85.5% of the parents were satisfied with the DGA treatment. CONCLUSION: DGA treatment has a positive effect on Chinese preschool children's OHRQoL and is evaluated highly by their parents. CLINICAL RELEVANCE: Dental treatment under general anesthesia improved the OHRQoL of Chinese preschool children.

6.
World J Pediatr ; 15(3): 246-254, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30796731

RESUMO

BACKGROUND: Preoperative planning for children with congenital heart diseases remains crucial and challenging. This study aimed to investigate the roles of three-dimensional printed patient-specific heart models in the presurgical planning for complex congenital heart disease. METHODS: From May 2017 to January 2018, 15 children diagnosed with complex congenital heart disease were included in this study. Heart models were printed based on computed tomography (CT) imaging reconstruction by a 3D printer with photosensitive resin using the stereolithography apparatus technology. Surgery options were first evaluated by a sophisticated cardiac surgery group using CT images only, and then surgical plans were also set up based on heart models. RESULTS: Fifteen 3D printed heart models were successfully generated. According to the decisions based on CT, 13 cases were consistent with real options, while the other 2 were not. According to 3D printed heart models, all the 15 cases were consistent with real options. Unfortunately, one child diagnosed with complete transposition of great arteries combined with interruption of aortic arch (type A) died 5 days after operation due to postoperative low cardiac output syndrome. The cardiologists, especially the younger ones, considered that these 3D printed heart models with tangible, physical and comprehensive illustrations were beneficial for preoperative planning of complex congenital heart diseases. CONCLUSION: 3D printed heart models are beneficial and promising in preoperative planning for complex congenital heart diseases, and are able to help conform or even improve the surgery options.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Cardiopatias Congênitas/cirurgia , Coração/diagnóstico por imagem , Modelos Anatômicos , Impressão Tridimensional , Cirurgia Assistida por Computador/métodos , Feminino , Cardiopatias Congênitas/diagnóstico por imagem , Humanos , Lactente , Recém-Nascido , Masculino , Tomografia Computadorizada por Raios X
7.
Angew Chem Int Ed Engl ; 58(13): 4339-4344, 2019 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-30672103

RESUMO

We report three self-assembled iron complexes that comprised an anti-parallel open form (o-Lanti ), a parallel open form (o-Lsyn ), and a closed form (c-L) of diarylethene conformers. Under kinetic control, FeII 2 (o-Lanti )3 was isolated, which exhibited a dinuclear structure with diamagnetic properties. Under light-irradiation control, FeII 2 (c-L)3 was prepared and exhibited paramagnetism and spin-crossover behaviour. Under thermodynamic control and in the presence of indispensable [FeIII (Tp*)(CN)3 ]- , FeII 2 (o-Lanti )3 and FeII 2 (c-L)3 transformed into tetranuclear FeIII 2 FeII 2 (o-Lsyn )2 , which exhibited complete spin-crossover behaviour at T1/2 =353 K.

8.
Chem Asian J ; 14(6): 760-764, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30556960

RESUMO

A tetraphenylethylene (TPE) derivative bearing two dimethylformamidine units was synthesized. The dihydrogen chloride salt of this TPE derivative was soluble in water and showed almost no emission. By addition of phosphate anions, the dihydrogen chloride salt could be transformed into the monohydrogen chloride salt, which was barely soluble and emitted strong fluorescence through aggregation-induced emission (AIE), while many other anions could not bring about a fluorescence enhancement. Meanwhile, the dihydrogen chloride salt and monohydrogen chloride salt could be reversible transformed by addition of acid and base alternately in the presence of phosphate anion, which led to fluorescence turn-on and turn-off. Therefore, the TPE dimethylformamidine holds potential for selectively sensing phosphate anions in water and use as fluorescence pH switch. This study provided a new approach to AIEgen sensors by using formamidine groups.

9.
Huan Jing Ke Xue ; 39(10): 4825-4833, 2018 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-30229633

RESUMO

Diethyl phthalate (DEP) is a plastic additive that entered the soil environment due to the extensive use of plastic products. However, its toxicity to soil animals and the associated toxicity mechanism were not completely understood. Eisenia foetida was selected as the research object and exposed to simulated contaminated soil with different concentrations of DEP. Antioxidant enzyme activity, reactive oxygen species (ROS) content, Glutathione-S-Transferase (GST) activity, Malondialdehyde (MDA) content and amount of DNA damage in the earthworms were used as evaluation parameters for the study. The results showed that under DEP stress, the activities of antioxidant enzymes, GST and ROS in earthworms changed and resulted in gene damage. Under the stress of 0.1-50 mg·kg-1 DEP exposure during the 28 d experiment, the level of ROS increased and there was a "dose-effect" relationship. Excessive ROS gave rise to an increase of MDA content in the body from lipid peroxidation. Under the combined action of ROS and MDA, DNA in the body cavity of earthworm was damaged and there was also a "dose-effect" relationship between the degree of damage and the concentration of DEP. In summary, DEP may cause a certain degree of damage to organisms, with damage to the DNA of earthworms representing fairly strong eco-toxicological effects. Therefore, adequate attention should be paid to DEP disposal.


Assuntos
Dano ao DNA , Oligoquetos/efeitos dos fármacos , Estresse Oxidativo , Ácidos Ftálicos/toxicidade , Poluentes do Solo/toxicidade , Animais , Catalase/metabolismo , Glutationa Transferase/metabolismo , Malondialdeído/metabolismo , Oligoquetos/enzimologia , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo
10.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 36(3): 267-270, 2018 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-29984926

RESUMO

OBJECTIVE: This review aims to identify the dimensional structure of the shortened dentine hypersensitivity experience questionnaire (DHEQ-15) using confirmatory factor analysis (CFA). METHODS: The Chinese language version of DHEQ-15 was applied to 210 patients with dentine hypersensitivity aged 18-70 years old. The three-dimensional construct was confirmed by CFA. RESULTS: All the questionnaires were fully completed. The item "Because of the sensations, I take longer to finish a meal than others" was the most frequently reported by the parents. The modified three-factor model is suitable for the data. The chi-square fit statistics/degree of freedom was 2.213, the goodness-of-fit index was 0.905, the adjusted goodness-of-fit index was 0.872, the normed fit index was 0.845, the incremental fit index was 0.962, the Tucker-Lewis index was 0.969, the comparative fit index was 0.977, and the root mean square error of approximation was 0.068. CONCLUSIONS: Our findings generally support the three-dimensional construct of the DHEQ-15. Thus, DHEQ-15 can be used as a valid instrument in patients with dentine hypersensitivity in China.


Assuntos
Sensibilidade da Dentina , Adolescente , Adulto , Idoso , China , Sensibilidade da Dentina/complicações , Sensibilidade da Dentina/diagnóstico , Análise Fatorial , Humanos , Pessoa de Meia-Idade , Psicometria , Qualidade de Vida , Reprodutibilidade dos Testes , Inquéritos e Questionários , Adulto Jovem
11.
Huan Jing Ke Xue ; 39(7): 3118-3125, 2018 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-29962134

RESUMO

In order to evaluate the pollution levels of and risk from heavy metals in the atmospheric deposition of different functional urban districts, dust samples were collected from 20 sampling sites in typical industrial, traffic, residential, and educational districts of Nanjing. The concentrations of As, Ba, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Sr, Ti, V, and Zn were analyzed. The potential ecological risk and health risk were evaluated using the potential ecological risk index and U.S. EPA's health risk assessment models. Enrichment factors, correlation analysis, and principal component analysis were used to analyze the sources of heavy metals. Results showed that the concentrations of As, Cd, Co, Cr, Cu, Fe, Mn, Pb, and Zn were the highest in the industrial district and the concentrations of Ba, Ni, Ti, and V were the highest in the traffic district. The value of the potential ecological risk index was the highest in the industrial district and lowest in the educational district. Meanwhile, the ecological risk of Cr was the highest, achieving a moderate ecological hazard level. None of the studied heavy metals had noncarcinogenic risk or carcinogenic risk, according to the results of health risk assessment. Source analysis indicated that heavy metals in the atmospheric deposition from the study areas were mainly from traffic and industrial activities, coal combustion, natural process and life sources.


Assuntos
Monitoramento Ambiental , Poluição Ambiental/análise , Metais Pesados/análise , China , Poeira , Poluição Ambiental/efeitos adversos , Humanos , Metais Pesados/efeitos adversos , Medição de Risco
12.
Ecotoxicol Environ Saf ; 153: 68-77, 2018 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-29407740

RESUMO

Laboratory analysis of trace metals using inductively coupled plasma (ICP) spectroscopy is not cost effective, and the complex spatial distribution of soil trace metals makes their spatial analysis and prediction problematic. Thus, for the health risk assessment of exposure to trace metals in soils, portable X-ray fluorescence (PXRF) spectroscopy was used to replace ICP spectroscopy for metal analysis, and robust geostatistical methods were used to identify spatial outliers in trace metal concentrations and to map trace metal distributions. A case study was carried out around an industrial area in Nanjing, China. The results showed that PXRF spectroscopy provided results for trace metal (Cu, Ni, Pb and Zn) levels comparable to ICP spectroscopy. The results of the health risk assessment showed that Ni posed a higher non-carcinogenic risk than Cu, Pb and Zn, indicating a higher priority of concern than the other elements. Sampling locations associated with adverse health effects were identified as 'hotspots', and high-risk areas were delineated from risk maps. These 'hotspots' and high-risk areas were in close proximity to and downwind from petrochemical plants, indicating the dominant role of industrial activities as the major sources of trace metals in soils. The approach used in this study could be adopted as a cost-effective methodology for screening 'hotspots' and priority areas of concern for cost-efficient health risk management.


Assuntos
Monitoramento Ambiental/métodos , Metais Pesados/análise , Poluentes do Solo/análise , Solo/química , Oligoelementos/análise , China , Análise Custo-Benefício , Monitoramento Ambiental/estatística & dados numéricos , Humanos , Indústrias , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Análise Espacial , Espectrometria por Raios X
13.
Org Lett ; 20(2): 321-324, 2018 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-29313689

RESUMO

A new [3 + 3] trimeric macrocycle, based on tetraphenylethylene having an aggregation-induced emission effect, could form a interdigitation molecular cage with a big void by host-guest interactions. The cage could accommodate two TNT molecules and detect TNT at the 1.7 fg level per mL of air. Moreover, the cage could give permanent pores that had a BET surface area of 347 m2/g and could adsorb 7.8 wt % CO2 with high CO2/N2 selectivity up to 32 (273 K, 1 bar).

14.
J Asian Nat Prod Res ; 20(3): 277-291, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29090602

RESUMO

A series of new sinomenine derivatives were designed, synthesized, and evaluated in tumor inhibitory activity, such as human triple negative breast cancer cell line (MDA-MB-231), glioma cell line (A172), human lung cancer cell line (A549), human colon cancer cell line (HCT-8). The modifications were carried out on rings A and C of the sinomenine by esterificating on phenolic hydroxyl with good yields. The highlight of this work was that the synthetic procedures were concise and sinomenine derivatives demonstrated promising antitumor activities.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Morfinanos/síntese química , Morfinanos/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Desenho de Drogas , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Morfinanos/química , Ressonância Magnética Nuclear Biomolecular , Relação Estrutura-Atividade
15.
Chemistry ; 24(8): 2004-2012, 2018 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-29205563

RESUMO

Tetraphenylethylene (TPE) foldamers with double hairpin-turn linkers showing an aggregation-induced emission (AIE) effect have been synthesized for the first time. A crystal structure of a foldamer-TNT complex has been obtained, enabling unprecedented direct observation of the interactions between TNT molecules and the chromophores of the foldamer. Instead of π-π stacking interactions, which have often been considered to be the key mechanism in the binding of TNT by chromophoric receptors, strong n-π interactions between the nitro groups of TNT and the aromatic rings of the foldamer have been found. Exceptionally, by addition of 1 % NaF to a suspension of the foldamer in H2 O/THF (95:5), the fluorescence quenching efficiency by TNT vapor significantly increased from about 20 % to more than 90 %. Even after diluting TNT-saturated air at 25 °C by a factor of 2×104 , an obvious quenching response was observed, indicating that ultratrace TNT vapor (down to 3.4 fg per mL of air) could be detected.

16.
Oncotarget ; 8(25): 41189-41201, 2017 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-28476025

RESUMO

BACKGROUND: Wiskott-Aldrich syndrome verprolin-homologous (WAVE) 3, a member of the WASP/WAVE family of proteins, plays a critical role in cell motility and acts as an oncogene in some human cancers, but no sufficient information available to illustrate its involvement in ovarian cancer tumorigenesis and progression. METHODS: The expression of WAVE3 in human ovarian cancer and normal tissue was analyzed by immunohistochemistry. WAVE3 gene and protein expression in different human ovarian cancer cell lines was tested by RT-PCR and western blotting. Stable cells of WAVE3-knockdown in SKOV3 cells or transfected high expression in A2780 cells were constructed. The WAVE3 expression and its correlation with MMPs, p38 MAPK and other factors were studied. The relationship between WAVE3 and oncogenicity in vivo was also evaluated by nude mice xenograft model. RESULTS: Immunohistochemistry staining showed the highest WAVE3 expression in ovarian cancer metastases, high in ovarian cancer and weak in normal. In different cell lines, SKOV3 cells showed the highest WAVE3 expression, A2780 cells expressed the lowest. Elevated WAVE3 expression in A2780 cells promoted proliferation and decreased apoptosis, increased the cell number in G2/M phase and promoted migration significantly. Correspondingly, knockdown of WAVE3 in SKOV3 cells showed opposite effects. The WAVE3 expression showed positive correlation with MMPs, NF-κB, COX-2, VEGF and phospho-p38 MAPK, but not p38. The high expression of WAVE3 promoted tumorigenesis in vivo. CONCLUSIONS: Our results suggested that WAVE3 may be pivotal in ovarian cancer cell motility, invasion and oncogenesis, which might be related with MMPs production and p38 MAPK pathway.


Assuntos
Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Ovarianas/genética , Família de Proteínas da Síndrome de Wiskott-Aldrich/genética , Adulto , Idoso , Animais , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Sistema de Sinalização das MAP Quinases , Metaloproteinases da Matriz/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Transplante Heterólogo , Família de Proteínas da Síndrome de Wiskott-Aldrich/metabolismo
17.
J Asian Nat Prod Res ; 19(6): 630-643, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28440085

RESUMO

The aim of this study is to investigate the synergism of low dose of actinomycin D (LDActD) to the cytotoxicity of cisplatin (CDDP) on KB cells. The role of P53 reactivation by LDActD in the synergism and its mechanism were further studied. Cell viability was determined by MTT assay. Apoptosis was determined by AnnexinV-FITC/PI staining. Mitochondrial membrane potential (MMP) was detected by JC-1 staining. Expression of proteins was detected by Western blotting (WB) and/or immunofluorescence (IF). Molecular docking of actinomycin D (ACTD) to Mouse double minute 2 homolog (MDM2) and Mouse double minute 2 homolog X (MDMX). MDMX was analyzed by Discovery Studio. The content of P53-MDM2 complex was detected by ELISA assay. The cytotoxicity of CDDP was increased by the combination of LDActD in kinds of cancer cells. Molecular docking showed strong interaction between ACTD and MDM2/MDMX. Meanwhile, LDActD significantly decreased P53-MDM2 complex. Significant increase of the apoptotic activity by the combination therapy in KB cells is P53 upregulated modulator of apoptosis (PUMA) dependent. In addition to the decrease in MMP, LDActD increased P53 regulated protein and decreased BCL-XL in KB cells. LDActD efficiently enhanced the cytotoxicity of CDDP in cancer cells and induced P53-PUMA-dependent and mitochondria-mediated apoptosis in KB cells. The reactivation of P53 was probably achieved by disturbing the interaction of P53 and MDM2/MDMX.


Assuntos
Cisplatino/farmacologia , Dactinomicina/farmacologia , Proteína Supressora de Tumor p53/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Benzimidazóis/química , Carbocianinas/química , Sobrevivência Celular/efeitos dos fármacos , Dactinomicina/química , Humanos , Imidazóis/farmacologia , Células KB , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Simulação de Acoplamento Molecular , Estrutura Molecular , Transdução de Sinais/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo
18.
Cell Physiol Biochem ; 41(5): 1766-1776, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28365686

RESUMO

BACKGROUND/AIMS: Stress response is determined by the brain, and the brain is a sensitive target for stress. Our previous experiments have confirmed that once the stress response is beyond the tolerable limit of the brain, particularly that of the hippocampus, it will have deleterious effects on hippocampal structure and function; however, the metabolic mechanisms for this are not well understood. METHODS: Here, we used morris water maze, elisa and gas chromatography-time of flight/mass spectrometry to observe the changes in cognition, neuropathology and metabolomics in the hippocampus of APP/PS1 mice and wild-type (C57) mice caused by chronic unpredictable mild stress (CUMS), we also further explored the correlation between cognition and metabolomics. RESULTS: We found that 4 weeks of CUMS aggravated cognitive impairment and increased amyloid-ß deposition in APP/PS1 mice, but did not affect C57 mice. Under non-stress conditions, compared with C57 mice, there were 8 different metabolites in APP/PS1 mice. However, following CUMS, 3 different metabolites were changed compared with untreated C57 mice. Compared to APP/PS1 mice, there were 7 different metabolites in APP/PS1+CUMS mice. Among these alterations, 3-hydroxybutyric acid, valine, serine, beta-alanine and o-phosphorylethanolamine, which are involved in sphingolipid metabolism, synthesis and degradation of ketone bodies, and amino acid metabolism. CONCLUSION: The results indicate that APP/PS1 mice are more vulnerable to stress than C57 mice, and the metabolic mechanisms of stress-related cognitive impairment in APP/PS1 mice are related to multiple pathways and networks, including sphingolipid metabolism, synthesis and degradation of ketone bodies, and amino acid metabolism.


Assuntos
Precursor de Proteína beta-Amiloide , Disfunção Cognitiva , Hipocampo , Metaboloma , Estresse Psicológico , Aminoácidos/genética , Aminoácidos/metabolismo , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Doença Crônica , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/genética , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Hipocampo/metabolismo , Hipocampo/patologia , Corpos Cetônicos/genética , Corpos Cetônicos/metabolismo , Camundongos , Camundongos Transgênicos , Esfingolipídeos/genética , Esfingolipídeos/metabolismo , Estresse Psicológico/complicações , Estresse Psicológico/genética , Estresse Psicológico/metabolismo , Estresse Psicológico/patologia
19.
Huan Jing Ke Xue ; 38(12): 5282-5291, 2017 Dec 08.
Artigo em Chinês | MEDLINE | ID: mdl-29964592

RESUMO

The use of mineral magnetic measurements as a potential pollution proxy is explored as an alternative means of monitoring heavy metal pollution in playground dust in industrial areas. Dust samples were collected from playgrounds in an industrial area in Nanjing. The magnetic properties of the samples were analyzed, and the total and acid-extractable concentrations of heavy metals were measured.Mineral magnetic concentration parameters[mean magnetic susceptibility (χlf) 939.31×10-8 m3·kg-1 and saturation isothermal remanent magnetization (SIRM) 16618.74×10-5 A·m2·kg-1] indicate that the dust samples contain high concentrations of magnetic minerals when compared to the non-industrial zone of the city. High and stable S-ratio values (mean 0.97, standard deviation 0.01) indicate the prominence of ferromagnetic minerals. Low values of anhysteretic remanent magnetization (χARM)/χlf(2.35) and χARM/SIRM (0.12×10-3 m·A-1) indicate predominantly coarse pseudo single domain (PSD) and multi-domain (MD) magnetic grain size assemblages. The playground dust is considered moderately to highly polluted, and the enrichment factor values for Cd, Zn, Cu, and Pb indicate extremely high contamination levels in the playground dust. Mineral magnetic parameters[χlf, SIRM, hard isothermal remanent magnetization (HIRM), χARM, and χARM/SIRM] reveal significant correlations with total and acid-extractable concentrations of the trace metals, and the correlations with total concentrations are stronger. The most significant correlations were found with mineral magnetic concentrations (χARM and SIRM) and total concentrations of the elements Mn, Ni, and Cr and the Tomlinson pollution load index (PLI) (0.69 ≤ r ≤ 0.86, P<0.01). Consistent spatial characteristics between them were also found, showing that the total concentrations of heavy metals and magnetic parameter values are higher in the playgrounds near and downwind of the power plant. Results of a principal component analysis indicate that anthropogenic activities (mainly from coal consumption by power plants) are the main sources for both heavy metals and magnetic minerals. In summary, significant correlations and consistent spatial characteristics between heavy metal contents and magnetic parameters and the same anthropogenic source for heavy metals and magnetic minerals confirm that magnetic parameters could be considered as efficient indicators for heavy metal contamination in the playground dust in industrial areas.

20.
Cell Physiol Biochem ; 40(3-4): 549-557, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27889749

RESUMO

BACKGROUND/AIMS: An enriched environment (EE) ameliorates learning and memory impairments induced by chronic cerebral hypoperfusion, and the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway exerts both beneficial and deleterious effects on the nervous system during the progression of ischemia. METHODS: The present study investigated whether p38 MAPK participates in the process by which EE exposure ameliorates the cognitive deficits induced by chronic cerebral hypoperfusion. RESULTS: EE exposure significantly enhanced the cognitive performance of vascular dementia (VD) model rats, and p38 MAPK protein decreased in parallel with cognitive improvements. Inhibition of p38 MAPK function by its selective inhibitor SB203580 improved the cognition index of VD rats and upregulated p38 MAPK expression with p38 MAPK antisense oligodeoxynucleotides. This impaired cognition in VD rats could not be rescued by EE exposure. CONCLUSION: p38 MAPK participates in the process by which EE exposure ameliorates cognitive deficits induced by chronic cerebral hypoperfusion.


Assuntos
Encéfalo/irrigação sanguínea , Encéfalo/patologia , Transtornos Cognitivos/enzimologia , Perfusão , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Western Blotting , Região CA1 Hipocampal/enzimologia , Doença Crônica , Transtornos Cognitivos/patologia , Imuno-Histoquímica , Masculino , Aprendizagem em Labirinto , Fosforilação , Ratos Wistar
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