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1.
CNS Neurosci Ther ; 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34510762

RESUMO

AIMS: Human urinary kallidinogenase (HUK) has shown favorable efficacies in acute ischemic stroke (AIS) treatment. We sought confirmation of the safety and efficacy of HUK for AIS in a large population. METHODS: RESK study enrolled patients with AIS of anterior circulation to receive HUK infusion. The primary endpoint was the incidence of treatment-emergent adverse events (AEs). Secondary endpoints assessed neurological and functional improvements and stroke recurrent rate. RESULTS: Of 1206 eligible patients, 1202 patients received at least one dose of HUK infusion and 983 (81.5%) completed the study. The incidence of treatment-emergent AEs and serious AEs were 55.99% and 2.41%, respectively. Pre-specified AEs of special interest occurred in 21.71% of patients, but the majority were mild and unrelated to therapy. Hypertension, age, treatment time, and drug combination were identified to be associated with drug-related blood pressure reduction. Neurological and functional evaluations revealed favorable outcomes from baseline to post-treatment assessment. The cumulative recurrence rate of stroke was 2.50% during the 90-day assessment. CONCLUSION: HUK had an acceptable safety and tolerability profile in AIS patients. Besides, HUK demonstrated the neurological and functional improvements in AIS, further confirming its clinical efficacy in a real-world large population.

2.
Huan Jing Ke Xue ; 42(9): 4350-4357, 2021 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-34414733

RESUMO

The release of manufactured nanomaterials (MNMs) into the environment has raised concerns about combined toxicological risks, as MNMs could significantly alter the environmental behavior and fate of co-existing contaminants. Numerous studies have been published on the combined toxicity of MNMs and co-existing contaminants, but the potential mechanisms controlling the combined toxicity, especially the biological response mechanism, remain unclear. This study investigated the combined toxicity of nano-titanium dioxide (nTiO2), a typical MNM, and the heavy metal cadmium (Cd2+), using Scenedesmus obliquus as the test organism. The molecular mechanism was examined under different concentrations, using an equivalent dose (toxic ratio 1 ∶1) on S. obliquus. The results showed that the 72h-EC50 of nTiO2 and Cd2+ at the equivalent dose was significantly higher than that of single exposure, indicating an antagonistic effect. Further transcriptomics analysis revealed that the photosynthesis, chlorophyll metabolism, and starch and sucrose metabolism pathways involved in the energy metabolism of S. obliquus were significantly up-regulated in the presence of nTiO2. The arginine and proline metabolic pathways related to the anti-stress effect of algae cells also showed positive stimulation. The results of this study provide an important reference and a research basis for in-depth understanding of the environmental effects of MNMs and co-existing contaminants.


Assuntos
Clorofíceas , Nanoestruturas , Scenedesmus , Cádmio/toxicidade
3.
J Orthop Surg Res ; 16(1): 344, 2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34051808

RESUMO

BACKGROUND: In the trauma center wards, it is not unusual for patients to have sleep disorders, especially patients with an acute injury. Meanwhile, there is substantial evidence that sleep disorder is a predictor of depression and is an important feature of posttraumatic stress disorder. METHODS: All orthopedic trauma patients confined in a trauma ward in West China Hospital of Sichuan University between April 2018 and July 2019 were included in this retrospective study. Patients with mental impairment or craniocerebral injuries were excluded from the study. Basic demographic data and the Injury Severity Score (ISS) classification based on medical records were collected. The Pittsburgh sleep quality index (PSQI) was used to evaluate sleep quality, the visual analog scale (VAS) was used to evaluate physical pain, and the Barthel Index (BI) was used to evaluate activities of daily living (ADL). Univariate linear regression analysis and multivariate linear regression analysis were used to identify independently related factors. RESULTS: The average PSQI score was 6.3 (± 4.0). A total of 581 (51.4%) patients had a PSQI score > 5, indicating the presence of sleep disorders. The PSQI score was > 10 in 174 (15.4%) patients. Univariate statistical analysis showed that age, sex, education, ADL, and ISS classification were associated with increased PSQI scores. Marital status and pain were not associated with increased PSQI scores. When we used multivariate analysis to control for confounding variables, sex, ADL, and ISS classification remained independently associated with PSQI (P = 0.002, < 0.000, and 0.002, respectively). CONCLUSIONS: In our study, sleep disorders were common (51.4% with PSQI > 5) and serious (15.4% with PSQI > 10) in patients with traumatic orthopedic injury. The following factors were closely associated with sleep disorders: sex, ADL, and ISS classification. Moreover, age and educational attainment have an independent impact on sleep quality. Unexpectedly, the VAS score for pain was not independently associated with the seriousness of sleep quality, which may be related to preemptive and multimodal analgesia. Further studies are required to clarify this ambiguity.

4.
J Exp Clin Cancer Res ; 39(1): 256, 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33228740

RESUMO

Accumulating evidence suggests that radiation treatment causes an adaptive response of lung adenocarcinoma (LUAD), which in turn attenuates the lethal effect of the irradiation. Previous microarray assays manifested the change of gene expression profile after irradiation. Bioinformatics analysis of the significantly changed genes revealed that VANGL1 may notably influence the effect of radiation on LUAD. To determine the role of VANGL1, this study knocked down or overexpressed VANGL1 in LUAD. M6A level of VANGL1 mRNA was determined by M6A-IP-qPCR assay. Irradiation caused the up-regulation of VANGL1 with the increase of VANGL1 m6A level. Depletion of m6A readers, IGF2BP2/3, undermined VANGL1 mRNA stability and expression upon irradiation. miR-29b-3p expression was decreased by irradiation, however VANGL1 is a target of miR-29b-3p which was identified by Luciferase report assay. The reduction of miR-29b-3p inhibited the degradation of VANGL1 mRNA. Knockdown of VANGL1 enhanced the detrimental effect of irradiation on LUAD, as indicated by more severe DNA damage and increased percentage of apoptotic cells. Immunocoprecipitation revealed the interaction between VANGL1 with BRAF. VANGL1 increased BRAF probably through suppressing the protein degradation, which led to the increase of BRAF downstream effectors, TP53BP1 and RAD51. These effectors are involved in DNA repair after the damage. In summary, irradiation caused the up-regulation of VANGL1, which, in turn, mitigated the detrimental effect of irradiation on LUAD by protecting DNA from damage probably through activating BRAF/TP53BP1/RAD51 cascades. Increased m6A level of VANGL1 and reduced miR-29b-3p took the responsibility of VANGL1 overexpression upon irradiation.

5.
Ying Yong Sheng Tai Xue Bao ; 31(1): 208-218, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31957398

RESUMO

The rational delimitation of urban development boundary plays an important role in guiding the orderly growth of urban space and ensure proper environment health of urban space. In this study, we evaluated the ecological sensitivity of Nanchang City from four aspects (soil erosion, habitat, geological disaster and water resource) and simulated urban expansion in 2020 based on CA-Markov and land use data in 2000, 2010 and 2015. Spatial decision-making analysis of the two aspects was carried out in combination to the future development of the study area. We proposed a new method of delimitating urban development boundary integrating environmental protection and urban development through the dynamic coordination of both aspects. The results showed that ecological sensitivity of Nanchang City was moderate. The scale of urban construction land based on CA Markov simulation was 1239.67 km2, which slightly exceeded the planned construction land target (1201.65 km2). When the dynamic adjustment was done by superimposing the ecological sensitivity evaluation results with the expansion simulation results, the adjusted construction land scale of Nanchang City was 1193.15 km2, which met the planned requirement. Consideration of the coordination of protection and development could not only protect the ecological space, but also help to guide the orderly growth of urban space and ensure the healthy development of urban space, and thus was an important way to achieve a win-win situation between rational urban development and ecological protection.


Assuntos
Ecologia , Reforma Urbana , China , Cidades , Conservação dos Recursos Naturais , Ecossistema
6.
Probiotics Antimicrob Proteins ; 12(1): 214-223, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-30656550

RESUMO

The present study was conducted to evaluate the effects of dietary supplementation of recombinant plectasin (Ple) on the growth performance, intestinal health, and serum immune parameters in broilers. A total of 288 1-day-old male broilers (Arbor Acres) were randomly allotted to four dietary treatments including the basal diet (NC) and basal diet supplemented with 10 mg enramycin/kg (PC), 100 mg Ple/kg (LPle), and 200 mg Ple/kg (HPle) diets. The results indicated Ple increased (P < 0.01) average daily gain and decreased (P ≤ 0.02) feed to gain ratio of broilers. In addition, the supplementation of Ple in the diets increased (P ≤ 0.01) duodenal lipase (day 21) and trypsin (day 42) activities compared with the NC group. Similar as the supplementation of enramycin, Ple also increased villus height and decreased crypt depth in jejunum (day 21), and thus the villus height to crypt depth ratio (P < 0.01) was increased compared to the NC group on day 42. The serum immunoglobulin M (days 21 and 42), immunoglobulin G (day 42), complement 3 (day 21), and complement 4 (days 21 and 42) were significantly increased (P ≤ 0.02) due to the supplementation of Ple and enramycin, while the concentration of malondialdehyde in jejunum was decreased (P < 0.01) in PC, LPle, and HPle groups on day 21 compared with those in the NC group. Furthermore, Ple reduced (P < 0.01) Escherichia coli and total aerobic bacteria population in ileum and cecum of birds on days 21 and 42. These results indicate that the recombinant plectasin has beneficial effects on growth performance, intestinal health, and innate immunity in broilers.


Assuntos
Galinhas , Suplementos Nutricionais , Microbioma Gastrointestinal , Intestinos , Peptídeos/administração & dosagem , Criação de Animais Domésticos , Fenômenos Fisiológicos da Nutrição Animal , Animais , Galinhas/crescimento & desenvolvimento , Galinhas/imunologia , Galinhas/microbiologia , Intestinos/anatomia & histologia , Intestinos/microbiologia , Masculino , Proteínas Recombinantes/administração & dosagem
7.
Medicine (Baltimore) ; 98(35): e17002, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31464955

RESUMO

BACKGROUND: Chinese herbal medicine (CHM) has been shown to be effective in the treatment of stable chronic obstructive pulmonary disease (COPD) by published meta-analyses. However, disease outcomes were inconsistent and heterogeneity was observed attributed to placebo-controlled studies. We present a protocol for a systematic review aiming to evaluate the clinical efficacy and safety of CHM comparing to placebo in the treatment of stable COPD, to provide robust evidence for the use of CHM in COPD. METHODS: We will comprehensively search the following 9 databases from inception to March 2019: Web of Science, PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Chinese National Knowledge Infrastructure (CNKI), WANFANG Database, Chinese Scientific and Technological Periodical Database (VIP) and Chinese Biomedical Database (CBM), and the Cochrane Library database. All clinical randomized controlled trials comparing CHM to placebo for the treatment of stable COPD in English or Chinese will be included. The primary outcome will be quality of life, symptom score and exacerbation frequency, and the secondary outcomes include traditional Chinese medicine syndrome score and effective rate, lung function, 6-minute walk distance, and adverse events. Data extraction and quality assessment will be performed independently by 2 reviewers. Data synthesis and risk of bias will be assessed using the Review Manager software. This protocol will be conducted according to the Preferred Reporting Item for Systematic Review and Meta-analysis Protocols (PRISMA-P) guidance. RESULTS: This systematic review and meta-analysis will provide a high-quality comprehensive evaluation of the efficacy and safety based on current literature evidence of CHM intervention for stable COPD. CONCLUSION: The conclusion of this study will present the evidence of whether CHM is an effective and safe intervention for stable COPD patients.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/efeitos adversos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Testes de Função Respiratória , Teste de Caminhada
9.
ACS Appl Mater Interfaces ; 10(51): 44915-44923, 2018 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-30509069

RESUMO

Two-dimensional (2D) nanochannel arrays are constructed by bottom-up reassembly of montmorillonite monolayers that are obtained by liquid-phase exfoliation of its layered crystals, and the as-constructed interstitial space between these monolayers is uniform and provides ions with nanoscale transport channels. Surface-charge-controlled ion transport behavior is observed through these nanochannels as the electrolyte concentration reduces to 10-4 M at room temperature. Furthermore, the nanochannel structure remains even after 400 °C heat treatment, and nanofluidic devices based on the annealed nanochannel arrays still exhibit surface-charge-governed ion transport at low electrolyte concentrations. In addition, a drift-diffusion experiment is conducted to investigate the mobility ratio of cations/anions through the nanochannels with asymmetric bulk electrolyte concentrations, and the results show that the mobility of cations is about eight to nine times that of anions, which is consistent with the fact that the montmorillonite monolayers are negatively charged and the nanochannels are permselective. Last, ionic current rectification is observed in the nanofluidic system of asymmetric geometric shape, and rectification factors of ∼2.6 and ∼3.5 can be obtained in KCl and HCl electrolytes, respectively, at a bias between -1 and +1 V because of the asymmetric electrostatic potential through the nanochannels.

10.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 49(5): 749-753, 2018 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-30378338

RESUMO

OBJECTIVE: To determine consistencies between MR perfusion weighted imaging (PW-MRI) and CT perfusion imaging (CTP) in assessing hemodynamics of patients with moyamoya disease (MMD). METHODS: Images of PWI and CTP scan [including the map of cerebral blood flow (CBF), cerebral blood volume (CBV), time to peak (TTP), and mean transmit time (MTT)] of 24 MMD patients diagnosed by digital subtraction angiography(DSA) or time of flight-MR angiography (TOF-MRA) were obtained in the week before vascular reconstruction operations. Relative perfusion parameters (rCBF, rCBV, rMTT, rTTP) at the operative side within the middle cerebral artery territory and cerebellar hemisphere were compared with those of 17 patients without hypoperfusion and cerebrovascular disease using independent sample t test. Paired t test and Pearson correlation analyses were performed between the results of PWI-MRI and CTP. RESULTS: Different parameters were found in the MMD patients compared with the controls (P<0.05). The parameter results of PWI-MRI differed from those of CTP, but they were strongly correlated. CONCLUSION: Both PWI-MRI and CTP can detect the area and degree of hypoperfusion of MMD patients.


Assuntos
Hemodinâmica , Doença de Moyamoya/diagnóstico por imagem , Imagem de Perfusão , Estudos de Casos e Controles , Cérebro/irrigação sanguínea , Humanos , Angiografia por Ressonância Magnética , Imageamento por Ressonância Magnética , Fluxo Sanguíneo Regional , Tomografia Computadorizada por Raios X
12.
Cell Physiol Biochem ; 43(5): 2037-2046, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29059670

RESUMO

BACKGROUND/AIMS: CRIP1 (cysteine-rich intestinal protein 1) has been found in several tumor types; however, its prognostic impact and role in cellular processes, particularly in thyroid carcinoma, are still unclear. METHODS: To elucidate the prognostic impact of CRIP1, we analyzed tissues from 58 primary invasive thyroid carcinomas using immunohistochemistry. Western blotting was performed to investigate CRIP1 protein expression in the thyrocyte cell line Nthy-ori 3-1 and four different thyroid carcinoma cell lines, K1, TPC-1, TT, and SW579. Endogenous expression of CRIP1 was suppressed using a siRNA (si-CRIP1). The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to investigate cell viability. Flow cytometric analysis was used to detect cell cycle progression and cell apoptosis. The effects of silencing CRIP1 on cell migration and invasion were detected using the transwell assay. RESULTS: The immunohistochemistry results showed that CRIP1 was overexpressed in thyroid carcinoma. CRIP1 expression was associated with tumor size, TNM stage, and lymphatic metastasis, but not with age, gender, and tumor location. In addition, the expression of CRIP1 in K1, TPC-1, TT, and SW529 cells was higher than that in the Nthy-ori 3-1 cells. The highest expression was observed in the SW579 and TT cells. Furthermore, silencing CRIP1 inhibited the proliferation, migration, and invasion of thyroid carcinoma cell lines SW579 and TT. We also found that silencing CRIP1 induced G1 arrest and apoptosis of thyroid carcinoma cell lines SW579 and TT. CONCLUSION: In conclusion, CRIP1 acts as an oncogene in the cell proliferation, migration, and invasion processes of thyroid carcinoma. CRIP1 may serve well as an independent prognostic marker with significant predictive power for use in thyroid carcinoma therapy.


Assuntos
Apoptose/fisiologia , Proteínas de Transporte/metabolismo , Ciclo Celular/fisiologia , Proteínas com Domínio LIM/metabolismo , Neoplasias da Glândula Tireoide/metabolismo , Apoptose/genética , Western Blotting , Proteínas de Transporte/genética , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Proliferação de Células/fisiologia , Sobrevivência Celular/genética , Sobrevivência Celular/fisiologia , Feminino , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Proteínas com Domínio LIM/genética , Masculino , Pessoa de Meia-Idade , Interferência de RNA , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias da Glândula Tireoide/genética
13.
BMJ Open ; 7(9): e015895, 2017 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-28871018

RESUMO

INTRODUCTION: The association between early exposure to ambient air pollution and adverse pregnancy outcomes in China is unclear. This study will assess the risk of early-life exposure to air pollutants in Beijing and explore the viability of 8-hydroxydeoxyguanosine (8-OHdG) as a biological indicator to assess oxidative stress induced by early-life exposure to air pollution. METHODS AND ANALYSIS: Here, 2500 women with singleton pregnancies and their infants will be recruited from the Beijing Obstetrics and Gynecology Hospital. We will collect nine types of biological samples, including maternal serum, urine, placental tissue, umbilical cord tissue and umbilical cord blood during all three trimesters. The air pollution data (particulate matter (PM)2.5, PM10 and similar factors) will be recorded at official fixed-site monitoring stations closest to where the pregnant women live. We plan to assess the effect of air pollutants on adverse pregnancy outcomes and infant respiratory and circulatory disease using Cox regression and competitive risk analysis and explore possible critical windows of exposure during pregnancy using daily pollutant concentrations averaged over various periods of pregnancy combined with individual activity and physiological parameters. Maternal and umbilical cord blood samples (1000 samples) will be randomly selected for 8-OHdG assays to assess the correlation between exposures to air pollutants and oxidative stress. We will determine whether air pollutant exposure or 8-OHdG levels are associated with adverse pregnancy outcomes. SPSS and SAS statistical software will be used for data analysis. Cox regression and competing risk analysis will be used to compute the HR and population attributable risk. ETHICS AND DISSEMINATION: This research protocol has already been approved by the Medical Ethics Committee of Beijing Obstetrics and Gynecology Hospital. Written informed consent will be obtained from all study participants prior to enrolment. The results will be published in peer-reviewed journals or disseminated through conference presentations. TRIAL REGISTRATION NUMBER: This study has been registered in WHO International Clinical Trial Register-Chinese Clinical Trial Registry under registrationnumber ChiCTR-ROC-16010181 (http :// www.chictr.org.cn / showproj.aspx ?proj=17328).


Assuntos
Poluentes Atmosféricos/efeitos adversos , Poluição do Ar/efeitos adversos , Desoxiguanosina/análogos & derivados , Exposição Materna/efeitos adversos , Resultado da Gravidez , 8-Hidroxi-2'-Desoxiguanosina , Pequim , Doenças Cardiovasculares/induzido quimicamente , Desoxiguanosina/sangue , Monitoramento Ambiental , Feminino , Humanos , Lactente , Recém-Nascido , Material Particulado/análise , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Modelos de Riscos Proporcionais , Estudos Prospectivos , Projetos de Pesquisa , Doenças Respiratórias/induzido quimicamente
14.
Materials (Basel) ; 10(3)2017 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-28772664

RESUMO

Among the natural macromolecules potentially used as the scaffold material in hydrogels, xylan has aroused great interest in many fields because of its biocompatibility, low toxicity, and biodegradability. In this work, new pH and thermoresponsive hydrogels were prepared by the cross-linking polymerization of maleic anhydride-modified xylan (MAHX) with N-isopropylacrylamide (NIPAm) and acrylic acid (AA) under UV irradiation to form MAHX-g-P(NIPAm-co-AA) hydrogels. The pore volume, the mechanical properties, and the release rate for drugs of hydrogels could be controlled by the degree of substitution of MAHX. These hydrogels were characterized by swelling ability, lower critical solution temperature (LCST), Fourier-transform infrared (FTIR), and SEM. Furthermore, the cumulative release rate was investigated for acetylsalicylic acid and theophylline, as well as the cytocompatibility MAHX-based hydrogels. Results showed that MAHX-based hydrogels exhibited excellent swelling-deswelling properties, uniform porous structure, and the temperature/pH dual sensitivity. In vitro, the cumulative release rate of acetylsalicylic acid for MAHX-based hydrogels was higher than that for theophylline, and in the gastrointestinal sustained drug release study, the acetylsalicylic acid release rate was extremely slow during the initial 3 h in the gastric fluid (24.26%), and then the cumulative release rate reached to 90.5% after sustained release for 5 h in simulated intestinal fluid. The cytotoxicity experiment demonstrated that MAHX-based hydrogels could promote cell proliferation and had satisfactory biocompatibility with NIH3T3 cells. These results indicated that MAHX-based hydrogels, as new drug carriers, had favorable behavior for intestinal-targeted drug delivery.

15.
Plant Sci ; 259: 12-23, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28483050

RESUMO

Chitinases function in the digestion of chitin molecules, which are present principally in insects and fungi. In plants, chitinase genes play important roles in defense, and their expression can be triggered in response to both biotic and abiotic stresses. In this study, we cloned and characterized an endochitinase (VDECH) from Verticillium dahliae, strain Vd080. The VDECH coding region consists of 1845bp with two exons and one 54bp intron, encoding a 615 amino acid protein with the predicted molecular weight (MW) of 63.9kDa. The VDECH cDNA without signal peptide-encoding region was introduced into pCold-TF vector and the recombinant protein HIS-VDECH with a predicted MW of ∼114kDa was expressed. HIS-VDECH showed high tolerance to extreme temperature, exhibiting efficient chitinolytic activity at 50°C. In addition, VDECH triggered typical plant defense responses, including a hypersensitive response, oxidative burst, and elicited increased expression of defense-related genes in both Arabidopsis and cotton. VDECH-treatment of the conidial spores of V. dahliae and Fusarium oxysporum resulted in marked reductions in the germination of these spores in both fungi. After 36h of incubation with VDECH, the inhibition rate of germination was recorded at 99.57% for V. dahliae, and 96.89% for F. oxysporum. These results provide evidence that VDECH is recognized by the plant to elicit defense responses, and also that VDECH is an effective inhibitor of conidia germination, both of which may be exploited for disease control.


Assuntos
Quitinases/metabolismo , Esporos Fúngicos/enzimologia , Esporos Fúngicos/imunologia , Verticillium/enzimologia , Verticillium/imunologia , Quitinases/genética , Regulação da Expressão Gênica de Plantas/genética , Regulação da Expressão Gênica de Plantas/imunologia , Doenças das Plantas/imunologia , Doenças das Plantas/microbiologia , Imunidade Vegetal/imunologia , Esporos Fúngicos/patogenicidade , Verticillium/patogenicidade
16.
J Neurosurg Anesthesiol ; 29(2): 132-139, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26641648

RESUMO

BACKGROUND: We conducted a randomized trial to evaluate the efficacy and safety of dexmedetomidine for prophylactic analgesia and sedation in patients with delayed extubation after craniotomy. METHODS: From June 2012 to July 2014, 150 patients with delayed extubation after craniotomy were randomized 1:1 and were assigned to the dexmedetomidine group that received a continuous infusion of 0.6 µg/kg/h (10 µg/mL) or the control group that received a maintenance infusion of 0.9% sodium chloride for injection. The mean percentage of time under optimal sedation (SAS3-4), the percentage of patients who required rescue with propofol/fentanyl, and the total dose of propofol/fentanyl required throughout the course of drug infusion, as well as VAS, HR, MAP, and SpO2 were recorded. RESULTS: The percentage of time under optimal sedation was significantly higher in the dexmedetomidine group than in the control group (98.4%±6.7% vs. 93.0%±16.2%, P=0.008). The VAS was significantly lower in the dexmedetomidine group than in the control group (1.0 vs. 4.0, P=0.000). The HR and mean BP were significantly lower in the dexmedetomidine group than in the control group at all 3 time points (before endotracheal suctioning, immediately after extubation, and 30 min after extubation). No significant difference in SpO2 was observed between the 2 groups. For hemodynamic adverse events, patients in the dexmedetomidine group were more likely to develop bradycardia (5.3% vs. 0%, P=0.043) but had a lower likelihood of tachycardia (2.7% vs. 18.7%, P=0.002). CONCLUSIONS: Dexmedetomidine may be an effective prophylactic agent to induce sedation and analgesia in patients with delayed extubation after craniotomy. The use of dexmedetomidine (0.6 µg/kg/h) infusion does not produce respiratory depression, but may increase the incidence of bradycardia.


Assuntos
Extubação , Analgesia/métodos , Craniotomia , Dexmedetomidina/uso terapêutico , Hipnóticos e Sedativos/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Adulto , Período de Recuperação da Anestesia , Método Duplo-Cego , Feminino , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Tempo , Resultado do Tratamento
17.
J Neurosurg Anesthesiol ; 29(3): 281-290, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27152427

RESUMO

BACKGROUND: Endotracheal extubation is a painful and stressful procedure. The authors hypothesized that the prophylactic use of remifentanil would attenuate the pain intensity and stress responses resulting from extubation in neurosurgical patients. MATERIALS AND METHODS: In this prospective, randomized, double-blinded, controlled trial, 160 patients with planned delay extubation after elective intracranial operation were randomized 1:1 to receive either remifentanil or normal saline (control) before their extubation. The dose regime of remifentanil was a bolus of 0.5 µg/kg over 1 minute, followed by a continuous infusion of 0.05 µg/kg/min for 20 minutes. The primary outcome was the incidence of severe pain during the periextubation period. Secondary outcomes included changes in the pain intensity and vital signs, failing to pass an extubation evaluation after the study drug infusion, severe adverse events, postextubation complications, and clinical outcomes. RESULTS: Two patients in the remifentanil group did not pass the extubation evaluation. The incidence of severe pain during the periextubation period was significantly lower in the remifentanil group compared with the control group (25.0% vs. 41.3%, P=0.029). Compared with the control group, the visual analog scale in the remifentanil group was significantly lower after the bolus of remifentanil (12±18 vs. 25±27, P=0.001) and immediately after extubation (19±25 vs. 34±30, P=0.001). There were no significant differences in the vital signs immediately after extubation between the 2 groups (P>0.05). CONCLUSIONS: The prophylactic use of remifentanil decreases the incidence of severe pain. Our preliminary findings merit a larger trial to clarify the effect of the prophylactic use of remifentanil on clinical outcomes and adverse events.


Assuntos
Extubação/efeitos adversos , Analgésicos Opioides/uso terapêutico , Craniotomia/efeitos adversos , Dor Pós-Operatória/prevenção & controle , Piperidinas/uso terapêutico , Adulto , Idoso , Extubação/métodos , Analgésicos Opioides/administração & dosagem , Analgésicos Opioides/efeitos adversos , Encéfalo/cirurgia , Craniotomia/métodos , Método Duplo-Cego , Feminino , Humanos , Incidência , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Medição da Dor/efeitos dos fármacos , Piperidinas/administração & dosagem , Piperidinas/efeitos adversos , Estudos Prospectivos , Remifentanil , Resultado do Tratamento
18.
PLoS One ; 11(11): e0166000, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27846253

RESUMO

Verticillium dahliae Kleb., the causal agent of vascular wilt, can seriously diminish the yield and quality of many crops, including cotton. The pathogenic mechanism to cotton is complicated and unclear now. To screen pathogencity related genes and identify their function is the reliable way to explain the mechanism. In this study, we obtained a low-pathogenicity mutant vdpr1 from a T-DNA insertional library of the highly virulent isolate of V. dahliae Vd080, isolated from cotton. The tagged gene was named pathogenicity-related gene (VdPR1). The deletion mutant ΔVdPR1 did not form microsclerotia and showed a drastic reduction in spore yield and mycelial growth, compared to wild type. Also, ΔVdPR1 showed significantly lower protease and cellulase activities than those of wild type. Complementation of the mutant strain with VdPR1 (strain ΔVdPR1-C) almost completely rescued the attributes described above to wild-type levels. The knockout mutant ΔVdPR1 showed delayed infection, caused mild disease symptoms, formed a smaller biomass in roots of the host, and showed compromised systemic invasive growth in the xylem. These results suggest that VdPR1 is a multifaceted gene involved in regulating the growth development, early infection and pathogenicity of V. dahliae.


Assuntos
Proteínas Fúngicas/genética , Gossypium/microbiologia , Doenças das Plantas/genética , Verticillium/genética , Clonagem Molecular , DNA Bacteriano/genética , Regulação Fúngica da Expressão Gênica , Gossypium/genética , Gossypium/crescimento & desenvolvimento , Mutagênese Insercional , Doenças das Plantas/microbiologia , Raízes de Plantas/microbiologia , Esporos Fúngicos/genética , Esporos Fúngicos/patogenicidade , Verticillium/patogenicidade
19.
Cell Cycle ; 15(20): 2819-26, 2016 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-27579513

RESUMO

Asthma is a chronic respiratory disease characterized by reversible airway obstruction with persistent airway inflammation and airway remodeling. Features of airway remodeling include increased airway smooth muscle (ASM) mass. A disintegrin and metalloproteinase (ADAM)-33 has been identified as playing a role in the pathophysiology of asthma. ADAM-33 is expressed in ASM cells and is suggested to play a role in the function of these cells. However, the regulation of ADAM-33 is not fully understood. Vascular endothelial growth factor (VEGF) has been implicated in inflammatory and airway blood vessel remodeling in asthmatics. Although VEGF was initially thought of as an endothelial-specific growth factor, recent reports have found that VEGF can promote proliferation of other cell types, including ASM cells. To investigate the precise mechanism of VEGF's effect on ASM cell proliferation, we tested the expression of ADAM-33, phospho-extracellularsignal-regulated kinase 1/2 (ERK1/2), and phospho-Akt in VEGF-stimulated ASM cells. We found that VEGF up-regulates ADAM-33 mRNA and protein levels in a dose- and time-dependent manner as well as phosphorylation of ERK1/2 and Akt. We also found that VEGF-induced ASM cell proliferation is inhibited by both ADAM-33 knockdown and a selective VEGF receptor 2 (VEGFR2) inhibitor (SU1498). Furthermore, VEGF-induced ADAM-33 expression and ASM cell proliferation were suppressed by inhibiting ERK1/2 activity, but not by inhibiting Akt activity. Collectively, our findings suggest that VEGF enhances ADAM-33 expression and ASM cell proliferation by activating the VEGFR2/ERK1/2 signaling pathway, which might be involved in the pathogenesis of airway remodeling. Further elucidation of the mechanisms underlying these observations might help develop therapeutic strategies for airway diseases associated with smooth muscle hyperplasia such as asthma.


Assuntos
Proteínas ADAM/genética , Asma/genética , Pulmão/patologia , Miócitos de Músculo Liso/metabolismo , Regulação para Cima/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/farmacologia , Proteínas ADAM/metabolismo , Asma/patologia , Butadienos/farmacologia , Proliferação de Células , Cinamatos/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Humanos , Miócitos de Músculo Liso/efeitos dos fármacos , Nitrilas/farmacologia , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Transfecção , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo
20.
DNA Cell Biol ; 35(10): 622-627, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27383136

RESUMO

Drug resistance is an obstacle in the chemotherapeutic treatment of lung cancers. In the present study, the effects of high-mobility group box 1 (HMGB1) protein in chemotherapeutic resistance and the relationships between HMGB1 and chemotherapy drug-induced cell apoptosis or necrosis were clarified. We used cisplatin-sensitive A549 cells and cisplatin-resistant A549/DDP cells as cell models with IC50 of 11.58 and 46.95 µM, respectively. A549/DDP had higher level of HMGB1 compared with A549 cells. Interestingly, with the increasing concentration of DDP, HMGB1 was gradually located into cytoplasm in cisplatin-sensitive A549 cells. Moreover, interference with endogenous HMGB1 sensitized the effects of chemotherapeutic drugs, including 5-Fu, DDP, and OXA. Furthermore, results from an in vivo tumorigenesis experiment demonstrated that serum concentration of HMGB1 was much lower in the group inoculated with HMGB1 shRNA-transfected A549 cells than in the N.C. shRNA-transfected A549 inoculated group, as well as the tumor volume, suggesting that serum HMGB1 contributed to tumor growth in a mouse model. In conclusion, higher levels of HMGB1 probably contributed to chemotherapy drug resistance, and higher serum concentration of HMGB1 promoted in vivo tumor growth. The study would provide new clues to overcome drug resistance in chemotherapy of human lung cancers.


Assuntos
Antineoplásicos/administração & dosagem , Cisplatino/administração & dosagem , Resistencia a Medicamentos Antineoplásicos , Proteína HMGB1/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Células A549 , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Cisplatino/farmacologia , Técnicas de Silenciamento de Genes , Proteína HMGB1/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus
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