Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 30
Filtrar
1.
Front Psychiatry ; 14: 1245563, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37680450

RESUMO

Although many studies have investigated the influencing factors of adolescents' Internet gaming addiction, few have investigated the influence factor of exposure to domestic violence, and even fewer have used the General Strain Theory to explain the influence path of exposure to domestic violence on adolescents' Internet gaming addiction. Based on the GST, this study sought to uncover further insights into the effect of exposure to family violence on adolescents' Internet gaming addiction, and the mediating role of social control-specifically, parental attachment-and self-control in the association between exposure to family violence and adolescents' Internet gaming addiction. Adopting a multi-stage cluster random sampling method, we conducted this study with 2,110 adolescents from Liangshan Yi Autonomous Prefecture in Sichuan Province, China. The results suggest that adolescents' exposure to domestic violence directly affects their addiction to Internet games and indirectly affects it by decreasing social control and self-control. The study not only supplements and improves the explanatory framework of General Strain Theory, but makes a significant contribution to research on the causes of Internet gaming addiction.

2.
ORL J Otorhinolaryngol Relat Spec ; 85(3): 128-140, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37019094

RESUMO

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.


Assuntos
Asma , Produtos Biológicos , Pólipos Nasais , Rinite , Sinusite , Humanos , Asma/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Doença Crônica , Consenso , Pólipos Nasais/complicações , Pólipos Nasais/tratamento farmacológico , Omalizumab/uso terapêutico , Qualidade de Vida , Rinite/complicações , Rinite/tratamento farmacológico , Sinusite/complicações , Sinusite/tratamento farmacológico , Esteroides/uso terapêutico
3.
BMJ Open ; 13(3): e065338, 2023 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-36882241

RESUMO

INTRODUCTION: Our previous studies have proposed the bodyweight support-t'ai chi (BWS-TC) footwork training for stroke survivors with severe motor dysfunction and fear of falling, and have proven its positive effects for motor function. Transcranial direct current stimulation (tDCS) provides a non-invasive and safe way to modulate neuronal activity and provoke neuroplastic changes and to improve the motor function of stroke survivors. However, it is unclear whether the integration of BWS-TC and tDCS has synergistic effects on improving motor function of the stroke survivors. METHODS AND ANALYSIS: This study will be an assessor-blinded randomised controlled trial involving 12-week intervention and 6-month follow-up. One hundred and thirty-five individuals with stroke will be randomly divided in a ratio of 1:1:1 into three groups. Control group A, control group B and intervention group C will receive tDCS and conventional rehabilitation programmes (CRPs), BWS-TC and CRP, tDCS-BWS-TC and CRP for 12 weeks, respectively. The primary outcome measures will include the efficacy (Fugl-Meyer Assessment), acceptability and safety of these interventions. The secondary outcome measures will include balance ability (ie, limits of stability and modified clinical test of sensory integration), walking function, brain structure and function, risk of falling, Barthel Index and 36-Item Short Form Survey. All outcomes will be assessed at baseline, 6 and 12 weeks during intervention, and 1, 3 and 6 months during the follow-up period. Two-way analysis of variance with repeated measures will be applied to examine the main effects of the group and the time factor and group-time interaction effects for all outcome measures. ETHICS AND DISSEMINATION: Ethics approval was obtained from the ethics committee of the Shanghai Seventh People's Hospital (2021-7th-HIRB-017). The results of the study will be published in a peer-reviewed journal and presented at scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR2200059329.


Assuntos
Acidente Vascular Cerebral , Tai Chi Chuan , Estimulação Transcraniana por Corrente Contínua , Humanos , Acidentes por Quedas , Medo , China , Peso Corporal , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Front Endocrinol (Lausanne) ; 13: 961803, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105392

RESUMO

Background: The association between free triiodothyronine/free thyroxine (FT3/FT4) and non-alcoholic fatty liver disease (NAFLD) in euthyroid subjects is unclear. In addition, few studies have explored whether VAI mediates the association between FT3/FT4 ratio and NAFLD in the euthyroid population. We aimed to analyze the mediating effect of VAI on the FT3/FT4 ratio and NAFLD risk in the euthyroid population. Methods: This cross-sectional study included 7 946 annual health examinees from the Health Examination Center, Hebei General Hospital, from January to December 2020. The basic information and biochemical parameters, as well as calculated FT3/FT4 ratio and VAI were collected. NAFLD was diagnosed according to abdominal ultrasonography. The fibrosis score for NAFLD positive subjects (NFS) was calculated to reflect the extent of liver fibrosis. The risk of NAFLD was analyzed by quartiles of FT3/FT4 ratio (Q1-Q4 quartiles) and VAI (V1-V4 quartiles), respectively. Pearson correlation analysis was performed to investigate the correlation between FT3/FT4 ratio and VAI. Multivariate logistic regression analysis was applied to analyze the effect of FT3/FT4 ratio and VAI on NAFLD and NFS status. Bootstrap was conducted to explore whether VAI mediated the association between FT3/FT4 ratio and NAFLD. Results: Of the 7 946 participants, 2 810 (35.36%) had NAFLD and 5 136 (64.64%) did not. Pearson correlation analysis indicated that FT3/FT4 ratio was positively associated with VAI (P<0.05). Multivariate logistic regression analysis indicated that compared to the Q1 group, the risk of NAFLD significantly increased in Q3 group [OR=1.255, 95%CI (1.011, 1.559)] and Q4 group [OR=1.553, 95%CI (1.252, 1.926)](P<0.05). Compared to the V1 group, the risk of NAFLD notably increased in V2 group [OR=1.584, 95%CI (1.205, 2.083)], V3 group [OR=2.386, 95%CI (1.778, 3.202)] and V4 group [OR=4.104, 95%CI (2.835, 5.939)] (P<0.01). There was no relevance between FT3/FT4 ratio, VAI and NFS status. Mediating effect analysis showed that FT3/FT4 ratio significantly directly influenced NAFLD prevalence [ß=3.7029, 95%CI (2.9583, 4.4474)], and VAI partly mediated the indirect effect of the FT3/FT4 ratio on NAFLD prevalence [ß=2.7649, 95%CI (2.2347, 3.3466)], and the mediating effect accounted for 42.75% of the total effects. Conclusion: Both FT3/FT4 ratio and VAI were predictors of NAFLD, and VAI partly mediated the indirect effect of the FT3/FT4 ratio on NAFLD prevalence in the euthyroid population.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Tri-Iodotironina , Adiposidade , Estudos Transversais , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Fatores de Risco , Tiroxina
5.
Environ Microbiol ; 24(10): 4755-4770, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35837862

RESUMO

Reactive oxygen species are a fatal challenge to the plant pathogenic bacterium Pseudomonas syringae. In this study, we reveal that the global regulatory protein RsmA3 from the RetS-Gac/Rsm signalling pathway modulates RpoS in the early-log growth phase in the P. syringae wild-type strain MB03, thereby regulating oxidative tolerance to H2 O2 and ultimately affecting pathogenicity to the host plant. Following increased H2 O2 by external addition or endogenous induction by menadione, the resistance of the mutant strain ΔretS to H2 O2 is significantly enhanced due to rapid increases in the transcription of Rsm-related non-coding small RNAs (nc sRNAs), a sigma factor RpoS, and H2 O2 -detoxifying enzymes. Moreover, the ΔretS mutant is significantly less pathogenic in cucumber leaves. Seven Rsm-related nc sRNAs (namely, rsmZ, rsmY and rsmX1-5 ) show functional redundancy in the RetS-Gac-Rsm signalling pathway. External addition of H2 O2 stimulates increases in the transcription of both rsmY and rsmZ. Thus, we propose a regulatory model of the RetS-Gac-Rsm signalling pathway in P. syringae MB03 for the regulation of H2 O2 tolerance and phytopathogenicity in the host plant.


Assuntos
Regulação Bacteriana da Expressão Gênica , Pseudomonas fluorescens , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Pseudomonas fluorescens/genética , Pseudomonas syringae/genética , Pseudomonas syringae/metabolismo , Espécies Reativas de Oxigênio/metabolismo , RNA não Traduzido , Fator sigma/genética , Fator sigma/metabolismo , Vitamina K 3/metabolismo , Peróxido de Hidrogênio/farmacologia
6.
BMC Med Inform Decis Mak ; 22(1): 11, 2022 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-35022039

RESUMO

BACKGROUND: Automated ICD coding on medical texts via machine learning has been a hot topic. Related studies from medical field heavily relies on conventional bag-of-words (BoW) as the feature extraction method, and do not commonly use more complicated methods, such as word2vec (W2V) and large pretrained models like BERT. This study aimed at uncovering the most effective feature extraction methods for coding models by comparing BoW, W2V and BERT variants. METHODS: We experimented with a Chinese dataset from Fuwai Hospital, which contains 6947 records and 1532 unique ICD codes, and a public Spanish dataset, which contains 1000 records and 2557 unique ICD codes. We designed coding tasks with different code frequency thresholds (denoted as [Formula: see text]), with a lower threshold indicating a more complex task. Using traditional classifiers, we compared BoW, W2V and BERT variants on accomplishing these coding tasks. RESULTS: When [Formula: see text] was equal to or greater than 140 for Fuwai dataset, and 60 for the Spanish dataset, the BERT variants with the whole network fine-tuned was the best method, leading to a Micro-F1 of 93.9% for Fuwai data when [Formula: see text], and a Micro-F1 of 85.41% for the Spanish dataset when [Formula: see text]. When [Formula: see text] fell below 140 for Fuwai dataset, and 60 for the Spanish dataset, BoW turned out to be the best, leading to a Micro-F1 of 83% for Fuwai dataset when [Formula: see text], and a Micro-F1 of 39.1% for the Spanish dataset when [Formula: see text]. Our experiments also showed that both the BERT variants and BoW possessed good interpretability, which is important for medical applications of coding models. CONCLUSIONS: This study shed light on building promising machine learning models for automated ICD coding by revealing the most effective feature extraction methods. Concretely, our results indicated that fine-tuning the whole network of the BERT variants was the optimal method for tasks covering only frequent codes, especially codes that represented unspecified diseases, while BoW was the best for tasks involving both frequent and infrequent codes. The frequency threshold where the best-performing method varied differed between different datasets due to factors like language and codeset.


Assuntos
Aprendizado de Máquina , Processamento de Linguagem Natural , Humanos , Classificação Internacional de Doenças , Idioma
7.
Neuroimmunomodulation ; 29(3): 220-230, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34823248

RESUMO

OBJECTIVE: The immunological features between neuromyelitis optica spectrum disorder (NMOSD), multiple sclerosis (MS), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), lacked systemic comparisons. Accordingly, we aimed to investigate immunological differences between NMOSD, MS, and MOGAD. METHODS: Patients with MOGAD, MS, and NMOSD who received immunological tests including cytokine profiles and cytometry analysis of the lymphocyte subgroups were retrospectively reviewed and divided into training and validation sets. Discriminatory models based on immunological data were established to identify optimal classifiers using orthogonal partial least square discriminant analysis (OPLS-DA). Constructed models were tested in another independent cohort. RESULTS: OPLS-DA of the immunological data from 50 patients (26 NMOSD, 14 MS, and 10 MOGAD) demonstrated the discriminatory values of a relatively low level of T-lymphocyte subsets, especially the CD4+ T cells, in MOGAD; a decreased NK cell, eosinophil, and lymphocyte level; an elevated neutrophil-to-lymphocyte ratio in NMOSD; and a declined IFN-γ-producing CD4+ T cells/Th with an increased IL-8 concentration in MS. All the models (NMOSD vs. MS, NMOSD vs. MOGAD, and MS vs. MOGAD) exhibited a significant predictive value and accuracy (>85%). CONCLUSIONS: NMOSD, MS, and MOGAD may be different in pathogenesis, and several immunological biomarkers can serve as potential classifiers clinically.


Assuntos
Esclerose Múltipla , Neuromielite Óptica , Aquaporina 4 , Autoanticorpos , Sistema Nervoso Central/patologia , Humanos , Esclerose Múltipla/diagnóstico , Glicoproteína Mielina-Oligodendrócito , Estudos Retrospectivos
8.
Radiat Prot Dosimetry ; 194(4): 187-195, 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34219163

RESUMO

Magnetic confinement nuclear fusion is an important way to realize controllable nuclear fusion. Due to the large current and complicated coil arrangement, there is a complicated electromagnetic environment around the fusion device. In this paper, the B-dot sensor is used to measure the magnetic field, the D-dot sensor is used to measure the electric field, the MAXWELL electromagnetic simulation software is used to simulate the electromagnetic field strength; the simulation and measurement of the spherical Tokamak SUNIST device and the measurement of MARX generator are carried out, then we give corresponding electromagnetic protection suggestions.


Assuntos
Campos Eletromagnéticos , Campos Magnéticos , Simulação por Computador , Magnetismo , Software
9.
Hum Genomics ; 15(1): 30, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34034810

RESUMO

UDP-glucuronosyltransferases (UGTs) are the main phase II drug-metabolizing enzymes mediating the most extensive glucuronidation-binding reaction in the human body. The UGT1A family is involved in more than half of glucuronidation reactions. However, significant differences exist in the distribution of UGT1As in vivo and the expression of UGT1As among individuals, and these differences are related to the occurrence of disease and differences in metabolism. In addition to genetic polymorphisms, there is now interest in the contribution of epigenetics and noncoding RNAs (especially miRNAs) to this differential change. Epigenetics regulates UGT1As pretranscriptionally through DNA methylation and histone modification, and miRNAs are considered the key mechanism of posttranscriptional regulation of UGT1As. Both epigenetic inheritance and miRNAs are involved in the differences in sex expression and in vivo distribution of UGT1As. Moreover, epigenetic changes early in life have been shown to affect gene expression throughout life. Here, we review and summarize the current regulatory role of epigenetics in the UGT1A family and discuss the relationship among epigenetics and UGT1A-related diseases and treatment, with references for future research.


Assuntos
Epigênese Genética/genética , Glucuronosiltransferase/genética , Inativação Metabólica/genética , Glucuronosiltransferase/metabolismo , Humanos , MicroRNAs/genética , Família Multigênica/genética
10.
Infect Dis Model ; 5: 282-292, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32292868

RESUMO

Based on the official data modeling, this paper studies the transmission process of the Corona Virus Disease 2019 (COVID-19). The error between the model and the official data curve is quite small. At the same time, it realized forward prediction and backward inference of the epidemic situation, and the relevant analysis help relevant countries to make decisions.

11.
Int J Mol Sci ; 21(6)2020 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-32235814

RESUMO

The pathogenicity of the common phytopathogenic bacterium Pseudomonas syringae toward Caenorhabditis elegans has been recently demonstrated. However, the major virulence factors involved in this interaction remain unknown. In this study, we investigated the nematocidal activity of P. syringae against C. elegans under iron-sufficient/limited conditions, primarily focusing on the role of the ferric chelator pyoverdine in a P. syringae-C. elegans liquid-based pathogenicity model. Prediction-based analysis of pyoverdine-encoding genes in the genome of the wild-type P. syringae strain MB03 revealed that the genes are located in one large cluster. Two non-ribosomal peptide synthetase genes (pvdD and pvdJ) were disrupted via a Rec/TE recombination system, resulting in mutant strains with abrogated pyoverdine production and attenuated virulence against C. elegans. When used alone, pure pyoverdine also showed nematocidal activity. The role of iron used alone or with pyoverdine was further investigated in mutant and MB03-based bioassays. The results indicated that pyoverdine in P. syringae MB03 is a robust virulence factor that promotes the killing of C. elegans. We speculate that pyoverdine functions as a virulence determinant by capturing environmentally available iron for host bacterial cells, by limiting its availability for C. elegans worms, and by regulating and/or activating other intracellular virulence factors that ultimately kills C. elegans worms.


Assuntos
Proteínas de Bactérias/metabolismo , Caenorhabditis elegans/microbiologia , Ferro/metabolismo , Oligopeptídeos/metabolismo , Pseudomonas syringae/patogenicidade , Animais , Proteínas de Bactérias/genética , Caenorhabditis elegans/fisiologia , Genoma Bacteriano , Interações Hospedeiro-Patógeno , Oligopeptídeos/genética , Pseudomonas syringae/genética , Pseudomonas syringae/fisiologia , Sideróforos/genética , Sideróforos/metabolismo , Fatores de Virulência/genética , Fatores de Virulência/metabolismo
12.
Radiat Prot Dosimetry ; 188(2): 205-212, 2020 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-31822916

RESUMO

The safety zone of a large flat-plate bounded-wave electromagnetic pulse simulator was analyzed using the 3D electromagnetic simulation software Computer Simulation Technology. First, the double-limit requirement cited from the GB 8702 for an instantaneous pulse was clarified compared with the International Commission on Non-Ionizing Radiation Protection guidelines. This means that both the amplitude of the time-domain waveforms and all frequency components should be satisfied with the respective exposure limits. Then, the leakage field of a large flat-plate bounded-wave simulator was simulated. After analyzing the peak amplitude of an instantaneous electric field in a certain area, the observation points along six directions were specified, and the corresponding amplitudes were given. Furthermore, it was verified that the time-domain electric field of the critical points was satisfied with the frequency-domain exposure limits. Finally, the safety distances lower than the reference levels were given, and the safety zones corresponding to the three common exposure limits were obtained.


Assuntos
Eletricidade , Software , Simulação por Computador , Campos Eletromagnéticos
13.
Int J Nanomedicine ; 14: 7447-7460, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31686816

RESUMO

OBJECTIVE: This study aimed to investigate the interaction between the ion-complementary self-assembling peptide RADA16-I and the hydrophobic drug mangiferin (MA), and the potential of the self-assembling peptide to be exploited as a drug carrier of MA. METHODS: The RADA16-I-MA suspension was prepared by magnetic stirring, followed by fluorescence spectrophotometry, particle size determination, rheological properties analysis, and in vitro release assay to characterize the interaction between RADA16-I and MA. Then, the effects of in situ MA-loaded hydrogel on the proliferation of KYSE 30 and DLD-1 tumor cells and the toxic effect of the hydrogel on 293T renal epithelial cells were studied by the Cell Counting Kit 8 method. RESULTS: The RADA16-I-MA suspension was formed in water under magnetic stirring; the in situ hydrogel was formed when the suspension was added to PBS. The particle size in the RADA16-I-MA suspension was around 300-600 nm with an average size of 492 nm. Within 24 h, the cumulative release of MA from the RADA16-I-MA hydrogel was about 80%. The release rate of MA from the hydrogel was dependent on the concentration of RADA16-I and the release can be fitted with a first-order kinetic equation. The results suggested that the self-assembling peptide can stabilize MA in water to form a relatively stable suspension; the results also indicated that controlled release of MA from the RADA16-I-MA in situ hydrogel formed from the RADA16-I-MA suspension can be achieved by adjusting the concentration of the peptide in suspension. The cell viability studies showed that the RADA16-I-MA in situ hydrogel not only can maintain or enhance the intrinsic proliferation inhibition effects of MA on tumor cells, but also can reduce the toxicity of MA to normal cells. CONCLUSION: The self-assembling peptide RADA16-I can be a potential candidate for constructing a delivery system of the hydrophobic drug MA.


Assuntos
Liberação Controlada de Fármacos , Hidrogéis/química , Peptídeos/química , Xantonas/química , Morte Celular , Linhagem Celular , Proliferação de Células , Sobrevivência Celular/efeitos dos fármacos , Coloides/química , Elasticidade , Humanos , Tamanho da Partícula , Reologia , Espectrometria de Fluorescência , Suspensões , Viscosidade
14.
Artif Cells Nanomed Biotechnol ; 47(1): 3961-3975, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31588802

RESUMO

Ion-complementary self-assembling peptides have potential in delivering hydrophobic drugs. This study involved two self-assembling peptides, RADA16-I and RVDV16-I, of which RVDV16-I was a novel self-assembling peptide with different hydrophobic side chains designed from RADA16-I. The purpose of this study was to observe the interaction between different self-assembling peptides and emodin through fluorescence spectrophotometry, CD, SEM and AFM; to construct a preliminary suspension in-situ hydrogel delivery system for emodin with the self-assembling peptides; and to investigate the drug-loading and drug-releasing properties of the self-assembling peptides on emodin. The results showed that both peptides can interact with emodin and the interaction was dominated by hydrophobic interaction. The aqueous solutions of both self-assembling peptides can form relatively stable suspensions with emodin under mechanical stirring, and the suspension can form in-situ hydrogel under physiological condition. In vitro release of emodin from the hydrogels showed a manner of sustained release to some extent. Cell viability studies showed inherent proliferation inhibiting effects of emodin on tumor cells was maintained or enhanced through the in-situ hydrogels. The self-assembling peptides RADA16-I and RVDV16-I had showed promising drug-loading and drug-releasing performance for hydrophobic drugs. It is reasonable to exploit self-assembling peptides as drug carriers for their great potential to improve delivery of hydrophobic drugs.


Assuntos
Antineoplásicos/química , Preparações de Ação Retardada/química , Emodina/química , Hidrogéis/química , Peptídeos/química , Células A549 , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/farmacologia , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Emodina/administração & dosagem , Emodina/farmacologia , Células Hep G2 , Humanos , Hidrogéis/farmacologia , Interações Hidrofóbicas e Hidrofílicas , Estrutura Molecular , Suspensões
17.
J Huazhong Univ Sci Technolog Med Sci ; 34(2): 157-160, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24710924

RESUMO

Autophagy dysregulation, mitochondrial dynamic abnormality and cell cycle re-entry are implicated in the vulnerable neurons of patients with Alzheimer's disease. This study was designed to testify the association among autophagy, mitochondrial dynamics and cell cycle in dividing neuroblastoma (N2a) cells. The N2a cells were cultured in vitro and treated with different concentrations of 3-methyladenine (3-MA). The cell viability was detected by methyl thiazolyl tetrazolium (MTT) assay. They were randomly divided into control group (cells cultured in normal culture medium) and 3-MA group (cells treated with 10 mmol/L 3-MA). The cell cycle was analyzed in the two groups 3, 6, 12, and 24 h after treatment by flow cytometry. Western blotting was used to evaluate the expression levels of mitofission 1 (Fis1), mitofusin 2 (Mfn2), microtubule-associated protein 1 light chain 3 (LC3), cell cycle-dependent kinase 4 (CDK4) and cdc2. The flow cytometry revealed that the proportion of cells in G(2)/M was significantly increased, and that in G0/G1 was significantly reduced in the 3-MA group as compared with the control group. Western blotting showed that the expression levels of Fis1, LC3, and CDK4 were significantly up-regulated in the 3-MA group at the four indicated time points as compared with the control group. Mfn2 was initially decreased in the 3-MA group, and then significantly increased at 6 h or 12 h. Cdc2 was significantly increased in the 3-MA group at 3 h and 6 h, and then dropped significantly at 12 h and 24 h. Our data indicated that 3-MA-induced suppressed autophagy may interfere with the cell cycle progression and mitochondrial dynamics, and cause cell death. There are interactions among cell cycle, mitochondrial dynamics and autophagy in neurons.


Assuntos
Autofagia/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Adenina/administração & dosagem , Adenina/análogos & derivados , Apoptose/efeitos dos fármacos , Autofagia/genética , Proteína Quinase CDC2 , Ciclo Celular/genética , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ciclina B/biossíntese , Quinases Ciclina-Dependentes , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas de Membrana/biossíntese , Proteínas Associadas aos Microtúbulos/biossíntese , Dinâmica Mitocondrial/efeitos dos fármacos , Dinâmica Mitocondrial/genética , Proteínas Mitocondriais/biossíntese , Neuroblastoma , Transdução de Sinais/efeitos dos fármacos
18.
Immunogenetics ; 65(11): 829-34, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23974322

RESUMO

Toll-like receptors (TLRs) play a crucial role in innate immunity, serving as pattern-recognition receptors and the first barrier in host defense against microbial infections. Genetic variations of TLR2 and TLR4 are closely associated with a variety of infectious diseases, particularly lung diseases. In this study, we detected six and four single nucleotide polymorphisms (SNPs) in the coding sequences of porcine TLR2 and TLR4 genes, respectively. Only SNP 1027C>A of TLR4 was shown to be markedly biased in Western and Oriental pig populations. Hence, the susceptibility of pigs with different genotype at position 1027C>A to Mycoplasma hyopneumoniae (Mhp) infection was investigated, and changes to the expression of TLR2, TLR4, TNF-α and IL-1ß were monitored. The results showed that there was no significant difference in susceptibility to Mhp infection between AA and CC individuals despite expression levels for all detected genes of the challenge groups being significantly higher than the corresponding control groups. Furthermore, porcine alveolar macrophages of different genotype were collected and stimulated by lipopolysaccharide. We found that the expression of TLR2, TLR4, TNF-α and IL-1ß genes were enhanced to different levels by lipopolysaccharide stimulation. TLR2 and TLR4 gene expressions and their rates of increase of 1027CC pigs were significantly higher than for 1027AC pigs (P < 0.01), while TNF-α and IL-1ß expressions were significantly lower than for 1027AC pigs (P < 0.01). We predict that allele C at position 1027 of the TLR4 gene contributes to the pig's immune response to gram-negative bacterial infections.


Assuntos
Cruzamento , Lipopolissacarídeos/farmacologia , Mycoplasma pneumoniae/patogenicidade , Pneumonia por Mycoplasma/prevenção & controle , Polimorfismo de Nucleotídeo Único/genética , Receptor 2 Toll-Like/genética , Receptor 4 Toll-Like/genética , Animais , Células Cultivadas , Feminino , Imunidade Inata/efeitos dos fármacos , Macrófagos Alveolares/citologia , Macrófagos Alveolares/efeitos dos fármacos , Macrófagos Alveolares/imunologia , Mycoplasma pneumoniae/genética , Mycoplasma pneumoniae/imunologia , Pneumonia por Mycoplasma/genética , Pneumonia por Mycoplasma/imunologia , Suínos , Receptor 2 Toll-Like/imunologia , Receptor 4 Toll-Like/imunologia
19.
Chin Med J (Engl) ; 125(9): 1603-7, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22800829

RESUMO

BACKGROUND: Interleukin-l7 (IL-17), which exerts strong pro-inflammatory effects, has emerged as an important mediator in inflammation-associated cancer. The aim of this study was to clarify the relationship between IL-17 and tumor associated macrophages (TAMs), and the correlation of the microvessel density in the development of laryngeal squamous cell carcinoma (LSCC). METHODS: Histopathological observations and immunohistochemistry staining for IL-17, CD68, and CD34 were performed on 72 specimens (32 cases of LSCC, 20 cases of adjacent tissues of carcinoma as controls, and 20 cases of chronic hypertrophic laryngitis). Double immunohistochemical staining was done to determine which cells expressed IL-17. Real-time quantitative PCR determined the mRNA expression of IL-17. ELISA was used to detect the expression of the serum level of IL-17 in the three groups. RESULTS: The inflammation response had increased in LSCC. Overexpression of IL-17 and CD68 protein were seen in LSCC (P < 0.01). The expression of IL-17 was different between well and poorly differentiated LSCC (P < 0.01). The IL-17 expressing cells were mainly located in macrophages (CD68(+)/IL17(+)) as demonstrated by double immunohistochemical staining. IL-17 expression significantly correlated with high microvessel density (CD34(+)) in LSCC (P < 0.05). Relatively higher mRNA expression levels of IL-17 were seen in LSCC compared to the controls (P < 0.05). The serum expression of IL-17 was similar among the three groups (P > 0.05). CONCLUSION: IL-17 was expressed by TAMs, and IL-17 may significantly correlate to the differentiation and angiogenesis in the development of LSCC.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Interleucina-17/metabolismo , Neoplasias Laríngeas/metabolismo , Macrófagos/metabolismo , Adulto , Idoso , Carcinoma de Células Escamosas/genética , Feminino , Humanos , Imuno-Histoquímica , Interleucina-17/genética , Neoplasias Laríngeas/genética , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/genética , Neovascularização Patológica/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem
20.
Huan Jing Ke Xue ; 33(2): 481-7, 2012 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-22509585

RESUMO

The aqueous photolysis of beta-blocker atenolol (ATL) using Xe lamp as simulated solar irradiation source was investigated in the presence of nitrate ions. The effects of nitrate ion concentration, solution pH value, and concentration of bicarbonate and humic substance on the photodegradation of ATL were studied. The results showed that photodegradation of ATL in nitrate solution followed pseudo-first-order kinetics. The increasing concentration of nitrate ion promoted the photodegradation rate of ATL. The first-order rate constant increased from 0.002 26 min(-1) to 0.009 4 min(-1) with nitrate concentration increasing from 0 to 5 mmol x L(-1). Acidic or alkaline condition of the solution favored the photodegradation of ATL. Different concentration of bicarbonate showed insignificant effect of the degradation while the increasing concentration of fulvic acid showed inhibiting effect. Hydroxyl radical was determined to be formed during the photolysis process of ATL using isopropanol as molecular probe. The main photoproducts of ATL were identified by using SPE-LC-MS techniques and possible photoinduced degradation pathways in nitrate solution were proposed.


Assuntos
Atenolol/química , Atenolol/isolamento & purificação , Nitratos/química , Fotólise , Poluentes Químicos da Água/isolamento & purificação , Antagonistas de Receptores Adrenérgicos beta 1/química , Antagonistas de Receptores Adrenérgicos beta 1/isolamento & purificação , Soluções , Poluentes Químicos da Água/química
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA