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1.
Brain Stimul ; 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39142380

RESUMO

BACKGROUND: Although transcranial magnetic stimulation (TMS) has become a valuable method for non-invasive brain stimulation, the cellular basis of TMS activation of neurons is still not fully understood. In vitro preparations have been used to understand the biophysical mechanisms of TMS, but in many cases these studies have encountered substantial difficulties in activating neurons. OBJECTIVE/HYPOTHESIS: The hypothesis of this work is that conductivity boundaries can have large effects on the electric field in commonly used in vitro preparations. Our goal was to analyze the resulting difficulties in in vitro TMS using a simulation study, using a charge-based boundary element model. METHODS: We decomposed the total electric field into the sum of the primary electric field, which only depends on coil geometry and current, and the secondary electric field arising from conductivity boundaries, which strongly depends on tissue and chamber geometry. We investigated the effect of the conductivity boundaries on the electric field strength for a variety of in vitro experimental settings to determine the sources of difficulty. RESULTS: We showed that conductivity boundaries can have large effects on the electric field in in vitro preparations. Depending on the geometry of the air-saline and the saline-tissue interfaces, the secondary electric field can significantly enhance, or attenuate the primary electric field, resulting in a much stronger or weaker total electric field inside the tissue; we showed this using a realistic preparation. Submerged chambers are generally much more efficient than interface chambers since the secondary field due to the thin film of saline covering the tissue in the interface chamber opposes the primary field and significantly reduces the total field in the tissue placed in the interface chamber. The relative dimensions of the chamber and the TMS coil critically determine the total field; the popular setup with a large coil and a small chamber is particularly sub-optimal because the secondary field due to the air-chamber boundary opposes the primary field, thereby attenuating the total field. The form factor (length vs width) of the tissue in the direction of the induced field can be important since a relatively narrow tissue enhances the total field at the saline-tissue boundary. CONCLUSIONS: Overall, we found that the total electric field in the tissue is higher in submerged chambers, is higher if the chamber size is larger than the coil and if the shorter tissue dimension is in the direction of the electric field. Decomposing the total field into the primary and secondary fields is useful for designing in vitro experiments and interpreting the results.

2.
J Oral Rehabil ; 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39092660

RESUMO

BACKGROUND: Individuals who suffer from simple snoring rarely go to a doctor due to a lack of medical knowledge, but simple snoring can reduce the individual's quality of life and may cause social problems to the bed partner/family members. OBJECTIVES: The aims of the present study are to explore the effects of online modified oropharyngeal exercises on the individuals with simple snoring and to provide a rehabilitation method for individuals with simple snoring. METHODS: This study is a double-blinded, two-arm, randomized controlled trial. Participants were enrolled and randomly assigned to the intervention group (n = 33) or the control group (n = 33). The participants in the control group received health education on snoring, while the participants in the intervention group received the modified oropharyngeal exercise besides health education on snoring. The intervention duration was 4 weeks. The primary outcomes included snoring index, snoring loudness, and snoring quantity. The secondary outcomes included self-reported snoring, sleep quality, daytime sleepiness, anxiety symptoms, depression symptoms, and quality of life. All outcomes were measured at baseline, 4 weeks, and 8 weeks. RESULTS: Generalized estimating equations (GEE) analyses showed significant differences between the intervention group and the control group on snoring index, loudness, and quantity (p < .001). Moreover, modified oropharyngeal exercise had effects on sleep quality, daytime sleepiness, anxiety symptoms, depression symptoms, and quality of life in individuals with simple snoring (p < .001). Self-reported snoring also improved at 8 weeks. CONCLUSION: The modified oropharyngeal exercises were effective in improving simple snoring. It could also improve sleep quality, daytime sleepiness, anxiety symptoms, depression symptoms, and quality of life.

3.
Thromb J ; 22(1): 34, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38576023

RESUMO

As an autoimmune disease, the persistent systemic inflammatory response associated with connective tissue disease (CTD) is involved in the development of venous thromboembolism (VTE). However, clinical data showed that the risk of VTE in patients differed between subtypes of CTD, suggesting that different subtypes may have independent mechanisms to promote the development of VTE, but the specific mechanism lacks sufficient research at present. The development of pulmonary fibrosis also contributes to the development of VTE, and therefore, patients with CTD-associated interstitial lung disease (CTD-ILD) may be at higher risk of VTE than patients with CTD alone or patients with ILD alone. In addition, the activation of the coagulation cascade response will drive further progression of the patient's pre-existing pulmonary fibrosis, which will continue to increase the patient's risk of VTE and adversely affect prognosis. Currently, the treatment for CTD-ILD is mainly immunosuppressive and antirheumatic therapy, such as the use of glucocorticoids and janus kinase-inhibitors (JAKis), but, paradoxically, these drugs are also involved in the formation of patients' coagulation tendency, making the clinical treatment of CTD-ILD patients with a higher risk of developing VTE challenging. In this article, we review the potential risk factors and related mechanisms for the development of VTE in CTD-ILD patients to provide a reference for clinical treatment and prevention.

4.
World J Clin Cases ; 12(2): 354-360, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38313637

RESUMO

BACKGROUND: There are few cases of pulmonary granulomatous changes secondary to primary biliary cirrhosis (PBC). No case of granulomatous lung disease secondary to PBC misdiagnosed as lung cancer had been reported. CASE SUMMARY: A middle-aged woman presented with lung nodules and was misdiagnosed with lung cancer by positron emission tomography/computed tomography. She underwent left lobectomy, and the pathology of the nodules showed granulomatous inflammation, which was then treated with antibiotics. However, a new nodule appeared. Further investigation with lung biopsy and liver serology led to the diagnosis of PBC, and chest computed tomography indicated significant reduction in the pulmonary nodule by treatment with methylprednisolone and ursodeoxycholic acid. CONCLUSION: Diagnosis of pulmonary nodules requires integrating various clinical data to avoid unnecessary pulmonary lobectomy.

5.
Eur J Intern Med ; 124: 46-53, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38350784

RESUMO

BACKGROUND: The performance of existing prognostic scores including the simplified Pulmonary Embolism Severity Index (sPESI) for short-term mortality of non-high-risk PE in Chinese population has not been widely validated. METHODS: Non-high-risk patients were included from the prospective cohort of the China pUlmonary Thromboembolism REgistry Study (CURES). The sPESI, RIETE, Geneva, modified FAST, and Bova score were validated. The discriminatory performance was measured by the area under the curve (AUC). We also compared the sensitivity, odds ratio, specificity, positive predictive value and negative predictive value of these scores. RESULTS: A total of 6,873 non-high-risk patients with acute PE were included and 241 (3.5 %) patients died within 30 days. Compared to the Geneva, modified FAST, and Bova score, the AUCs for predicting 30-day death of sPESI and RIETE score were higher at 0.712 (95 % CI, 0.680, 0.743) and 0.723 (95 % CI, 0.691, 0.755) respectively. The sPESI demonstrated the highest sensitivity at 0.809, while the RIETE score, Geneva, Modified FAST and BOVA score showed sensitivities of 0.622, 0.568, 0.477 and 0.502 respectively. A sPESI ⩾1 point was associated with a 4.7-fold increased risk of 30-day all-cause mortality (95 % CI, 3.427, 6.563, p < 0.001), while a RIETE score of ⩾1 point was associated with a 4.5-fold increased risk (95 % CI, 3.127, 6.341, p < 0.001). The Geneva score, modified FAST and Bova score showed inferior performance. CONCLUSIONS: The implementation of the fewer-parameter, easier-to-calculate sPESI in Chinese patients with PE can help to discriminate patients with extremely low risk of short-term mortality for home treatment or early discharge.


Assuntos
Embolia Pulmonar , Sistema de Registros , Índice de Gravidade de Doença , Humanos , Embolia Pulmonar/mortalidade , Embolia Pulmonar/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , China/epidemiologia , Prognóstico , Área Sob a Curva , Medição de Risco/métodos , Valor Preditivo dos Testes , Curva ROC , Doença Aguda
6.
Cells ; 12(1)2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36611974

RESUMO

Peroxiredoxin 6 (PRDX6) is widely distributed in several organs, especially the lungs. The role of PRDX6 in oxidative stress is controversial and even contradictory, as indicated by research conducted over the past 20 years. PRDX6 has anti-oxidant or pro-oxidant effects on oxidative stress in different diseases. It can even exhibit both anti-oxidant and pro-oxidant effects in the same disease. These findings are attributed to the fact that PRDX6 is a multifunctional enzyme. The peroxidase and phospholipase A2 activity of PRDX6 is closely related to its anti-oxidant and pro-oxidant effects, which leads to the conflicting regulatory effects of PRDX6 on oxidative stress in respiratory diseases. Moreover, PRDX6 interacts with multiple redox signaling pathways to interfere with cell proliferation and apoptosis. PRDX6 has become a new target in respiratory disease research due to its important regulatory role in oxidative stress. In this paper, the role of PRDX6 in oxidative stress in respiratory diseases and the research progress in targeting PRDX6 are reviewed.


Assuntos
Antioxidantes , Doenças Respiratórias , Humanos , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/metabolismo , Peroxirredoxina VI/metabolismo , Estresse Oxidativo
7.
Int J Biol Sci ; 18(15): 5641-5652, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36263182

RESUMO

Background: Traditional Chinese Medicine (TCM) JingYinGuBiao formula (JYGB) was recommended by the Expert consensus on Traditional Chinese Medicine diagnosis and treatment of COVID-19 infection in Shanghai. We evaluated the safety and efficacy of JYGB in treating mild COVID-19 patients. Methods: A prospective, double-blind, randomized, controlled trial was conducted (ClinicalTrial.gov registration number: ChiCTR2200058695). A total of 885 patients were randomized into the treatment group (administration of JYGB,n=508) or the control group (administration of TCM placebo, n=377) with 7-day treatment. The primary outcomes were the negative conversion rate and negative conversion time of SARS-CoV2 RNA. Secondary outcomes included the hospitalized days and symptom improvement. Results: A total of 490 and 368 patients in the treatment and control groups completed the study. The cumulative negative conversion rates at 2 days, 3 days, 4 days, and 6 days post randomization in the treatment group were all markedly higher than those in the control group (13.88% vs. 9.24%, P=0.04; 32.24% vs. 16.58%, P<0.001; 51.43% vs. 36.14%, P <0.001; 77.76% vs. 69.84%, P=0.008). Compared with the control group, after JYGB treatment, the median negative conversion time (4.0 [3.0-6.0] vs. 5.0 [4.0-7.0] days, P<0.001) and hospitalized days (6.0 [4.0-8.0] vs. 7.0 [5.0-9.0] days, P<0.001) were reduced. While the symptoms were improved, there were no significant differences in symptom disappearance rates between both groups. In addition, further sub-group analysis showed that for patients with interval time ≤4 days or patients≤ 60 years, the clinical effects of JYGB were more remarkable with an increase in cumulative negative conversion rates, a decrease in negative conversion time and hospitalized days. JYGB was well tolerated without any severe side effects. Conclusion: JYGB, a TCM prescription, improves the negative conversion rate of SARS-CoV2 in mild COVID-19 patients.


Assuntos
Tratamento Farmacológico da COVID-19 , Humanos , SARS-CoV-2 , RNA Viral , Medicina Tradicional Chinesa , Estudos Prospectivos , China , Resultado do Tratamento
8.
World J Clin Cases ; 10(20): 7060-7067, 2022 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-36051128

RESUMO

BACKGROUND: Myotonic dystrophy type 1 (DM1) is a genetic neuromuscular disease involving multiple systems, especially the cardiopulmonary system. The clinical phenotype of DM1 patients is highly variable, which limits early diagnosis and treatment. In the present study, we reported a 35-year-old female DM1 patient with dyspnea as the primary onset clinical manifestation, analyzed her family's medical history, and reviewed related literature. CASE SUMMARY: A 35-year-old woman was admitted to the hospital with dyspnea of 1 mo duration, and sleep apnea for 3 d. Her respiratory pattern and effort were normal, but limb muscle tension was low. Investigation into the patient's medical history revealed that she might have hereditary neuromuscular disease. Electromyography showed that her myotonia potentials were visible in the resting state of the examined muscles, with decreased motor unit potential time limit and amplitude. Genetic testing for DM1 revealed that the cytosine-thymine-guanine (CTG) repeat number of the DMPK gene exceeded 50, while cytosine-CTG expansion in intron 1 of ZNF9 gene was < 30 repeats. The patient was diagnosed with DM1. CONCLUSION: DM1 is a genetic neuromuscular disease involving multiple systems, and the clinical phenotype in DM1 is extremely variable. Some patients with DM1 may be presented at the respiratory department because of dyspnea, which should be cautioned by the pulmonologists. There may be no obvious or specific symptoms in the early stage of disease, and clinicians should improve their understanding of DM1 and make an early diagnosis, which will improve patients' quality of life.

9.
J Environ Manage ; 324: 116246, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36162320

RESUMO

Hazardous waste incineration fly ash (HFA) is considered a hazardous waste owing to the high associated concentrations of heavy metals and soluble salts. Hence, cost effective methods are urgently needed to properly dispose HFA. In this study, geopolymers were prepared by alkali-activation technology to stabilize and solidify heavy metals in HFA. In addition, the effects of three different aluminosilicates (metakaolin, fly ash, and glass powder) on the heavy metal immobilization efficiency were investigated. Because the soluble salt content of HFA is too high for their direct placement in flexible landfill sites and water washing can lead to heavy metal leaching, water-washing experiments were conducted after alkali-activation treatment to remove soluble salts. The results suggest that the concentrations of heavy metals leached from geopolymers can satisfy the Chinese Standard limits (GB18598-2019) when the addition of aluminosilicates exceeds 20 wt%. More than 77% of Cl- and >64% of SO42- in geopolymers could be removed via water-washing treatment. The Zn leaching concentration was maintained below approximately 0.52 ppm. After alkali-activation treatment, the water-washing process could efficiently remove soluble salts while inhibiting heavy metal leaching. Sodium-aluminosilicate-hydrate (N-A-S-H) gel, a product of the geopolymerization process in this study, was demonstrated to act as a protective shell that inhibited heavy metal leaching. Hence, HFA-based geopolymers are considered suitable for disposal in flexible landfills.


Assuntos
Metais Pesados , Eliminação de Resíduos , Incineração/métodos , Cinza de Carvão , Resíduos Perigosos , Sais , Metais Pesados/análise , Álcalis , Água , Eliminação de Resíduos/métodos , Resíduos Sólidos/análise , Carbono , Material Particulado
10.
J Hazard Mater ; 437: 129405, 2022 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-35753298

RESUMO

In contaminated soil, pristine biochar has poor applicability for immobilizing vanadium (V), which mainly exists as oxyanions in soil. To elucidate the immobilization potential and biotic/abiotic stabilizing mechanisms of a ferrous sulfate (FS)-modified sludge biochar in a V-contaminated soil from a mining area, we investigated the effects of biochar addition on the soil characteristics, growth of alfalfa, leachability, bioavailability, speciation, and fractionation of V, and changes in the microbial community structure and metabolic response. The results showed that the water extractable, acid-soluble (F1), and pentavalent fractions of V in soil decreased by up to 99 %, 95 %, and 55 %, respectively, whereas the reducible and (F2) oxidizable (F3) fractions increased by up to 45 % and 76 %, respectively. After the soil was treated with the FS-modified biochar for 90 d, the V concentration in the roots and shoots of alfalfa (Medicago sativa L.) decreased by up to 81.5 % and 96 %, respectively. The changes in the speciation, fractionation, and efficient immobilization of V in the studied soil were due to the combined effects of the biochar-induced decrease in soil pH, adsorption and precipitation by elevated iron concentrations, reduction and complexation due to an increase in the organic matter content, and microbial reduction by Proteobacteria.


Assuntos
Esgotos , Poluentes do Solo , Bioacumulação , Cádmio/análise , Carvão Vegetal/química , Compostos Ferrosos , Medicago sativa , Solo/química , Poluentes do Solo/análise , Vanádio
11.
Medicine (Baltimore) ; 101(3): e28617, 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35060536

RESUMO

BACKGROUND: The relationship between neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) and the dire prognosis of non-small cell lung carcinoma patients who received immune checkpoint inhibitors (ICIs) are not known yet. METHODS: We screened the articles that meet the criteria from the database. The relationship between NLR/PLR/LMR levels and the survival and prognosis of non-small cell lung cancer patients treated with ICIs was analyzed. Summarize hazard ratio (HR) with 95% confidence interval (CI) to study progression-free survival (PFS) and overall survival (OS). RESULTS: Thirty-four studies involving 3124 patients were enrolled in the final analysis. In short, high pre-treatment NLR was related to poor OS (HR = 2.13, 95% CI:1.74-2.61, P < .001, I2 = 83.3%, P < .001) and PFS (HR = 1.77, 95% CI:1.44-2.17, P < .001, I2 = 79.5%, P < .001). Simultaneously, high pre-treatment PLR was related to poor OS (HR = 1.49, 95% CI:1.17-1.91, P < .001, I2 = 57.6%, P = .003) and PFS (HR = 1.62, 95% CI:1.38-1.89, P < .001, I2 = 47.1%, P = .036). In all subgroup analysis, most subgroups showed that low LMR was related to poor OS (HR = 0.45, 95% CI: 0.34-0.59, P < .001) and PFS (HR = 0.60, 95% CI: 0.47-0.77, P < 0.001, I2 = 0.0%, P < .001). CONCLUSION: High pre-treatment NLR and pre-treatment PLR in non-small cell lung carcinoma patients treated with ICIs are associated with low survival rates. Low pre-treatment and post-treatment LMR are also related to unsatisfactory survival outcomes. However, the significance of post-treatment NLR and post-treatment PLR deserve further prospective research to prove.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/sangue , Neoplasias Pulmonares/sangue , Linfócitos/patologia , Monócitos/patologia , Neutrófilos/patologia , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores/sangue , Contagem de Células Sanguíneas , Plaquetas , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Humanos , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Prognóstico , Taxa de Sobrevida
12.
Comput Math Methods Med ; 2020: 1541989, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32411277

RESUMO

The accurate differentiation of the subtypes of benign paroxysmal positional vertigo (BPPV) can significantly improve the efficacy of repositioning maneuver in its treatment and thus reduce unnecessary clinical tests and inappropriate medications. In this study, attempts have been made towards developing approaches of causality modeling and diagnostic reasoning about the uncertainties that can arise from medical information. A dynamic uncertain causality graph-based differential diagnosis model for BPPV including 354 variables and 885 causality arcs is constructed. New algorithms are also proposed for differential diagnosis through logical and probabilistic inference, with an emphasis on solving the problems of intricate and confounding disease factors, incomplete clinical observations, and insufficient sample data. This study further uses vertigo cases to test the performance of the proposed method in clinical practice. The results point to high accuracy, a satisfactory discriminatory ability for BPPV, and favorable robustness regarding incomplete medical information. The underlying pathological mechanisms and causality semantics are verified using compact graphical representation and reasoning process, which enhance the interpretability of the diagnosis conclusions.


Assuntos
Algoritmos , Vertigem Posicional Paroxística Benigna/diagnóstico , Diagnóstico por Computador/métodos , Vertigem Posicional Paroxística Benigna/classificação , Vertigem Posicional Paroxística Benigna/terapia , Causalidade , Biologia Computacional , Gráficos por Computador , Diagnóstico por Computador/estatística & dados numéricos , Diagnóstico Diferencial , Humanos , Modelos Biológicos , Membrana dos Otólitos/fisiopatologia , Posicionamento do Paciente , Canais Semicirculares/fisiopatologia , Incerteza
13.
IEEE Trans Neural Netw Learn Syst ; 31(10): 4239-4253, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-31905150

RESUMO

To meet the demand for dynamic and highly reliable real-time fault diagnosis for complex systems, we extend the dynamic uncertain causality graph (DUCG) by proposing novel temporal causality modeling and reasoning methods. A new methodology, the Cubic DUCG, is therefore developed. It exploits an efficient scheme for compactly representing and accurately reasoning about the dynamic causalities in the system fault-spreading process. The Cubic DUCG is characterized by: 1) continuous generation of a causality graph that allows for causal connections penetrating among any number of time slices and discards the restrictive assumptions (about the underlying graph structure) upon which the existing research commonly relies; 2) a modeling scheme of complex causalities that includes dynamic negative feedback loops in a natural and intuitive manner; 3) a rigorous and reliable inference algorithm based on complete causalities that reflect real-time fault situations rather than on the cumulative aggregation of static time slices; and 4) some solutions to causality simplification and reduction, graphical transformation, and logical reasoning, for the sake of reducing the reasoning complexity. A series of fault diagnosis experiments on a nuclear power plant simulator verifies the accuracy, robustness, and efficiency of the proposed methodology.

14.
Genet Test Mol Biomarkers ; 21(8): 491-496, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28753063

RESUMO

OBJECTIVE: This study was designed to investigate the association between single nucleotide polymorphisms (SNPs) of the ß2-adrenergic receptor (ADRB2) gene and the risk of chronic obstructive pulmonary disease (COPD) in a Chinese population. METHODS: From January 2010 to October 2014, 261 COPD patients were selected as the case group and 239 healthy subjects were selected as the control group. Pulmonary function tests were performed to detect forced vital capacity (FVC), 1-s forced expiratory volume (FEV1), and FEV1/FVC (%). rs1042711, rs1042714, and rs1042718 were selected as tagSNPs of the ADRB2 gene from the HapMap database in accordance with previous studies. The ADRB2 genotypes were established by real-time polymerase chain reaction assays using TaqMan-labeled probes. The relationships between the ADRB2 polymorphisms and COPD risk were estimated using logistic regression analyses. RESULTS: The frequency of the genotypes and alleles of rs1042711 in ADRB2 showed a significant difference between the COPD and control groups (p < 0.05); compared with the CC genotype, the non-CC genotypes showed an increased COPD risk (p = 0.002). Compared with the CC haplotype, the TG haplotype increased COPD risk, while the CG haplotype reduced COPD risk for normal individuals. Compared with the CC genotype, the TT genotype showed significantly lower FEV1 and FEV1/FVC (p = 0.022, p = 0.0191, respectively). Both the TC and TG haplotypes showed lower FEV1 and FEV1/FVC in comparison with the CC haplotype (both p < 0.05). The results of logistic regression analysis showed that rs1042711 of ADRB2 and smoking history were associated with COPD risk (both p < 0.05). CONCLUSION: It is indicated that the TT genotype of rs1042711 and smoking pack years are both risk factors for COPD.


Assuntos
Doença Pulmonar Obstrutiva Crônica/genética , Receptores Adrenérgicos beta 2/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , China , Feminino , Volume Expiratório Forçado , Frequência do Gene/genética , Estudos de Associação Genética/métodos , Predisposição Genética para Doença/genética , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Reação em Cadeia da Polimerase em Tempo Real , Testes de Função Respiratória , Fatores de Risco , Fumar
15.
Bioorg Chem ; 70: 12-16, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27881238

RESUMO

The oncogenic transcription factor forkhead box M (Foxm) is overexpressed in human colorectal cancer (CRC). Targeting the protein interaction with its cognate DNA has been established as an attractive approach to anti-CRC chemotherapy. State-of-the-art molecular dynamics (MD) simulations revealed that the Foxm adopts considerably different conformations to interact with and without its DNA partner; the holo conformation is tightly packed as a typical globulin configuration, whereas the apo form is locally unstructured that exhibits intrinsic disorder in DNA recognition helix, indicating that DNA binding can help the Foxm refolding. With this finding, the MD equilibrium structure of DNA-free Foxm was utilized to perform molecular docking virtual screening against a natural organic compound library. Consequently, six hit compounds were identified as potential small-molecule mediators of Foxm-DNA interaction; their binding affinities (KD) to Foxm DNA-binding domain were then determined to range between 3.8 and 230µM by using isothermal titration calorimetry. These compounds were suggested to recognize and stabilize the apo conformation of Foxm, thus shifting the binding reaction equilibrium of Foxm from DNA-bound to DNA-free states to disrupt the formation of Foxm-DNA adduct.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Neoplasias Colorretais/tratamento farmacológico , DNA/metabolismo , Descoberta de Drogas , Proteína Forkhead Box M1/metabolismo , Sítios de Ligação/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , DNA/química , Proteína Forkhead Box M1/química , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Conformação de Ácido Nucleico/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos
16.
Oncotarget ; 7(31): 49699-49709, 2016 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-27391073

RESUMO

Dasatinib (DAS), a second-generation tyrosine kinase inhibitor, is highly effective in treating chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. However, its clinical use is limited due to serious adverse effects. DAS can disrupt endothelial barrier integrity and increase endothelial permeability which may cause peripheral edema and pleural effusion. Albumin nanoparticles (NPs) as a drug carrier may serve as a useful tool for cell-selective drug delivery to reduce DAS-induced endothelial hyperpermeability and maintain endothelial barrier integrity. In this study, we reported that DAS-loaded NPs exhibited potent anti-leukemia efficacy as DAS alone. Importantly, albumin NPs as a drug carrier markedly reduced DAS-induced endothelial hyperpermeability by restraining the inhibition of Lyn kinase signaling pathway in endothelial cells. Therefore, albumin NPs could be a potential tool to improve anti-leukemia efficacy of DAS through its cell-selective effects.


Assuntos
Albuminas/química , Antineoplásicos/administração & dosagem , Dasatinibe/administração & dosagem , Portadores de Fármacos/química , Leucemia/tratamento farmacológico , Linhagem Celular , Sobrevivência Celular , Impedância Elétrica , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Quinase 1 de Adesão Focal/metabolismo , Humanos , Células K562 , Leucemia/metabolismo , Luz , Nanopartículas/química , Permeabilidade , Artéria Pulmonar/citologia , Espalhamento de Radiação , Quinases da Família src/metabolismo
17.
IEEE Trans Neural Netw Learn Syst ; 27(8): 1615-30, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27101619

RESUMO

Identifying the pivotal causes and highly influential spreaders in fault propagation processes is crucial for improving the maintenance decision making for complex systems under abnormal and emergency situations. A dynamic uncertain causality graph-based method is introduced in this paper to explicitly model the uncertain causalities among system components, identify fault conditions, locate the fault origins, and predict the spreading tendency by means of probabilistic reasoning. A new algorithm is proposed to assess the impacts of an individual event by investigating the corresponding node's time-variant betweenness centrality and the strength of global causal influence in the fault propagation network. The algorithm does not depend on the whole original and static network but on the real-time spreading behaviors and dynamics, which makes the algorithm to be specifically targeted and more efficient. Experiments on both simulated networks and real-world systems demonstrate the accuracy, effectiveness, and comprehensibility of the proposed method for the fault management of power grids and other complex networked systems.

18.
PLoS One ; 11(2): e0149280, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26910324

RESUMO

Iron is essential for the growth and survival of many organisms. Intracellular iron homeostasis must be maintained for cell survival and protection against iron toxicity. The ferric uptake regulator protein (Fur) regulates the high-affinity ferric uptake system in many bacteria. To investigate the function of the fur gene in Xanthomonas vesicatoria (Xv), we generated a fur mutant strain, fur-m, by site-directed mutagenesis. Whereas siderophore production increased in the Xv fur mutant, extracellular polysaccharide production, biofilm formation, swimming ability and quorum sensing signals were all significantly decreased. The fur mutant also had significantly reduced virulence in tomato leaves. The above-mentioned phenotypes significantly recovered when the Xv fur mutation allele was complemented with a wild-type fur gene. Thus, Fur either negatively or positively regulates multiple important physiological functions in Xv.


Assuntos
Proteínas de Bactérias/metabolismo , Ferro/metabolismo , Doenças das Plantas/microbiologia , Folhas de Planta/microbiologia , Proteínas Repressoras/metabolismo , Solanum lycopersicum/microbiologia , Xanthomonas vesicatoria/metabolismo , Xanthomonas vesicatoria/patogenicidade , Alelos , Proteínas de Bactérias/genética , Mutagênese Sítio-Dirigida , Proteínas Repressoras/genética , Xanthomonas vesicatoria/genética
19.
Springerplus ; 5(1): 2107, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28066696

RESUMO

This study intends to investigate the correlations of miR-124a and miR-30d with clinicopathological features of breast cancer (BC) patients with type 2 diabetes mellitus (T2DM). A total of 72 BC patients with T2DM (diabetic group) and 144 BC patients without T2DM (non-diabetic group) were enrolled in this study. Blood glucose was detected by glucose oxidase methods. Glycosylated hemoglobin (HbA1c) was measured by high performance liquid chromatography. Fasting insulin (FIns) was measured by chemiluminescent microparticle immunoassay. Automatic biochemical analyzer was used to detect triglyceride, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C). Estradiol (E2) was detected by radioimmunoassay. Homeostasis model assessment was applied to assess the insulin resistance (HOMA-IR) and ß-cell insulin secretion (HOMA-IS). The expressions of miR124a and miR-30d were measured by quantitative real-time polymerase chain reaction (qRT-PCR). There were significant differences in age, the ratio of menopause, body mass index (BMI), HDL-C, TC, 2-h plasma glucose (2hPG), FIns, HbA1c, HOMA-IS and HOMA-IR between the diabetic and non-diabetic groups. The diabetic group had higher incidence of lymph node metastasis than non-diabetic group. The miR-124a expression was down-regulated while the miR-30d expression was up-regulated in BC patients with T2DM. The correlation analysis showed that miR-124a expression was positively correlated with HDL-C, while it was negatively correlated with age, HbA1c, LDL-C and E2. However, the miR-30d expression was negatively correlated with HDL-C but positively correlated with age, HbA1c, LDL-C and E2. In conclusion, miR-124a and miR-30d may be correlated with clinicopathological features of BC patients with T2DM. The miR-124a and miR-30d could serve as novel biomarkers for early diagnosis of BC in patients with T2DM.

20.
J Cell Biochem ; 116(12): 2970-9, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26212040

RESUMO

This study investigated the influence of miR-150 expression on osteoblast matrix mineralization and its mechanisms. The mouse osteoblast cell line MC3T3-E1 was used as an in vitro model of bone formation. On the fifth day of mineralization, transfection experiments using agomiR-150, agomiR-NC, antagomiR-150 antagomiR-NC, and mock groups were set up to test the effects of miR-150 in MC3T3-E1 model. The mRNA and protein levels of OC, ALP, type I collagen, and OPN were measured by qRT-PCR and ELISA. Matrix mineralization was detected by alizarin red S (ARS) staining and flow cytometry was employed to quantify apoptosis in each group. RT-PCR and Western blot were applied to detect the expression of target gene MMP14. Our results demonstrated that the endogenous expression levels of miR-150, OC, ALP, type I collagen, and OPN in MC3T3-E1 cells increased steadily. Exogenous expressions of agomiR-150 and antagomiR-150 can significantly up-/down-regulate, respectively, the expression level of miR-150 in MC3T3-E1 cells. Compared with the mock group, higher expression levels of OC, ALP, type I collagen, and OPN mRNA were observed in the agomiR-150 group, while lower mRNA expression levels of OC, ALP, type I collagen, and OPN were found in the antagomiR-150 group. Based on these results, potential miR-150 targeted genes are discussed. Our results showed that miR-150 supports the osteoblastic phenotype related to osteoblast function and bone mineralization. Thus, miR-150 may have potential therapeutic applications in promoting bone formation in certain disease settings, such as in osteoporosis and in elderly patients.


Assuntos
Calcificação Fisiológica/efeitos dos fármacos , MicroRNAs/biossíntese , Osteoblastos/metabolismo , RNA Mensageiro/biossíntese , Animais , Calcificação Fisiológica/genética , Diferenciação Celular/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Humanos , Camundongos , MicroRNAs/antagonistas & inibidores , MicroRNAs/metabolismo , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteogênese/genética
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