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1.
J Colloid Interface Sci ; 590: 290-300, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33548612

RESUMO

The proangiogenic protein, survivin, is a client protein for heat shock protein 90 (Hsp-90), whose overexpression is induced by photodynamic therapy (PDT), leading to the inhibition of capase-9 and the blockage of apoptosis. The overexpression of Hsp-90 in cancer cells can rapidly acquire thermoresistance during photothermal therapy (PTT), leading to insufficient apoptosis, increased cell viability, and tumor recurrence. A potential approach to block the PTT-induced overexpression of Hsp-90 and the overexpression of survivin is developed by using an Hsp-90 inhibitor and anticancer agent, namely, geldanamycin (GM). These inhibitors also develop a mild-temperature PTT strategy to reach synergistic PDT and PTT efficiency. Thus, Cy7-SQ is designed by a covalent disulfide linkage between a photothermal agent (i.e., canine dye 7 [Cy7]) and a photosensitizer (i.e., squaraine dye [SQ]) for the improved photostability and thermal stability of Cy7 and SQ. The cleavage of the Cy7-SQ linkage by glutathione in a tumor microenvironment increases the efficiency of synergistic PDT and PTT. In the current study, bovine serum albumin (BSA)/Cy7-SQ/GM nanoparticles are developed through the self-assembly of BSA, Cy7-SQ, and GM to accelerate the apoptosis of cancer cells via near-infrared (NIR) laser irradiation, thus realizing Hsp-90-regulated synergistic PDT/PTT combined with chemotherapy.

2.
J Mater Chem B ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33537696

RESUMO

Effective targeting and in situ imaging-guided treatment are particularly important for accurate clinical photodynamic therapy (PDT) of malignant tumors. Herein, we propose a single molecule, named IMC-DAH-SQ, which possesses dual-targeting components, including structure-inherent targeting (SIT) and cyclooxygenase-2 (COX-2) targeting units, and controllable turn-on near infrared (NIR) fluorescence. Due to its amphiphilicity, IMC-DAH-SQ assembles into a nanoprobe with low background fluorescence. After incubation with tumor cells, the SIT and COX-2 recognition characteristics of IMC-DAH-SQ endow it with preferential tumor-targeting activity. The strong binding with overexpressed COX-2 can collapse the nanoprobe to monomers after accumulation in tumor cells, leading to turn-on NIR fluorescence that is completely different from normal cells. Additionally, benefiting from the single molecular model tactic, the nanoprobe has the advantages of simple synthesis without ever considering the loading rate and separation between the photosensitizer and targeting unit. Other favorite features, including superior biocompatibility, weak dark toxicity, and mitochondria enrichment capability, are implemented. All these traits not only afford nanoprobe precision tumor cell targeting capability but also provide promising imaging-guided antitumor therapy. We believe that the single molecular protocol will establish a novel strategy for simultaneous diagnosis and anticancer medicine treatment utilizing versatile but small compounds.

3.
Food Chem ; 346: 128895, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33421902

RESUMO

Bisphenols (BPs) are worldwide used organic compounds in plastics, belonging to the group of endocrine disrupting chemicals (EDCs) which exhibits endocrine disruption to beings. Migration of BPs from food contact materials like plastic containers, epoxy coatings in metal cans and thermal papers, would results in bioaccumulation of BPs in human beings, causing adverse health effects. Therefore, sensitive and selective determination of BPs in food is needed. Among different strategies have been explored for the detection of BPs, electrochemical sensors with relatively high sensitivity and fast response are promising. This paper is devoted to comprehensively review the developed electrochemical methods for BPs sensing in food, so that to find a direction for developing low cost, high accuracy and compatibility sensors toward the sensitive and selective detection of BPs. Different electrochemical technologies categorized by recognition agents, aptamers, enzymes, molecularly imprinted polymers and nanomaterials are discussed and summarized in their mechanisms, usages, merits and limitations. The challenges and further perspectives in the development of electrochemical sensors is also discussed.


Assuntos
Compostos Benzidrílicos/análise , Eletroquímica/métodos , Análise de Alimentos/métodos , Fenóis/análise , Disruptores Endócrinos/análise , Contaminação de Alimentos/análise , Humanos , Nanoestruturas/química
4.
J Colloid Interface Sci ; 581(Pt B): 465-474, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32805667

RESUMO

Nitric oxide (NO) is an important bio-regulatory and signaling molecule associated with various physiological and pathophysiological pathways, but its sensitive real-time detection is still very challenging due to the low concentration, large diffusivity and fast decay in biological samples. Here an antimony tetroxide (Sb2O4) nanoflowers/reduced graphene oxide (rGO) nanocomposite is synthesized via a facile and eco-friendly solvothermal method to merit-combine highly electroactive Sb2O4 nanoflowers with large surficial rGO component for a strong synergistic effect on oxidation of NO. Results demonstrate that the Sb2O4/rGO-based sensor has a low detection limit, high sensitivity, excellent selectivity and fast response for NO detection. The real-time detected NO released from living cells showed significant difference between normal and tumor cells. The Sb2O4 nanoflowers/rGO nanocomposite sensor holds a great promise for important applications in biomedical research fields and clinical diagnosis.

5.
Environ Pollut ; 265(Pt A): 114995, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32554097

RESUMO

Triclosan (TCS) and its two derivatives (2,4-dichlorophenol and 2,4,6-trichlorophenol) are priority pollutants that coexist in aquatic environments. Joint exposure of TCS, 2,4-dichlorophenol and 2,4,6-trichlorophenol, hereafter referred to as TCS-DT, contributes severe toxicity to aquatic organisms. There is currently a paucity of data regarding TCS-DT molecular toxicity, especially on cardiac diseases. We used zebrafish (Danio rerio) as a model organism, and evaluated the molecular-level cardiotoxicity induced by TCS-DT from embryonic to adult stages. TCS-DT exposure prominently led to phenotypic malformations, such as pericardial cysts, cardiac bleeding, increased SV-BA distance, decreased heart rate and reduced ejection fraction, as well as abnormal swimming behavior. Analyses of the GO and KEGG pathways revealed enrichment pathways related to cardiac development and screened for significantly down-regulated adrenaline signaling in cardiomyocytes. The cardiac marker genes (amhc, cmlc2, vmhc, and nkx2.5) were obtained through protein-protein interaction (PPI) networks, and expressed as down-regulation by WISH. After chronic exposure to TCS-DT from 30 to 90-dpf, both body mass and heart indexes prominently increased, showing myocardial hypertrophy, abnormal heart rate and histopathological injury. Heart tissue damage included disordered and ruptured myocardial fibers, broken and dissolved myofilaments, nuclear pyknosis, mitochondrial injury and inflammatory cell infiltration. Further, abnormal changes in a series of cardiac functions-related biomarkers, including superoxide dismutase, triglyceride, lactate dehydrogenase and creatinine kinase MB, provided evidence for cardiac pathological responses. These results highlight the molecular mechanisms involving TCS-DT induced cardiac toxicity, and provide theoretical data to guide prevention and treatment of pollutant-induced cardiac diseases.


Assuntos
Triclosan , Poluentes Químicos da Água , Animais , Cardiotoxicidade , Exposição Ambiental , Medição de Risco , Peixe-Zebra
6.
Front Psychol ; 11: 603, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32328013

RESUMO

Participation in private tutoring has been a global educational phenomenon and is especially prevalent in China. The present study conducted a student-report questionnaire and collected school reports of mathematical achievement to track a year of the longitudinal variation of private tutoring and obtained an analysis of the impact of metacognition on private tutoring participation and its moderating effects between environment-related and initial indicators and mathematical private tutoring participation. The empirical results of this study showed that metacognitive level for learning process monitoring, family economic condition, and mathematics achievement could impact the decision to participate in private tutoring. The results also showed that family economic condition could moderate the effect of metacognitive level for learning process monitoring on the decision to participate in private tutoring. Practical implications for educational competent department and the schoolteachers were discussed.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31963135

RESUMO

The purpose of this paper is to investigate the existence of stratification heterogeneity in traffic accidents in Shenzhen, what factors influence the casualties, and the interaction of those factors. Geographical detection methods are used for the analysis of traffic accidents in Shenzhen. Results show that spatial stratification heterogeneity does exist, and the influencing factors of fatalities and injuries are different. The traffic accident causes and types of primary responsible party have a strong impact on fatalities and injuries, followed by zones and time interval. However, road factors, lighting, topography, etc., only have a certain impact on fatalities. Drunk driving, speeding over 50%, and overloading are more likely to cause more casualties than other illegal behaviors. Speeding over 50% and speeding below 50% have significant different influences on fatalities, while the influences on injuries are not obvious, and so do drunk driving (Blood Alcohol Concentration ≥ 0.08) and driving under the influence of alcohol (0.08 > Blood Alcohol Concentration ≥ 0.02). Both pedestrians and cyclists violating the traffic law are vulnerable to fatality. Heavy truck overloading is more likely to cause major traffic accidents than minibuses. More importantly, there are nonlinear enhanced interactions between the influencing factors, the combination of previous non-significant factors and other factors can have a significant impact on the traffic accident casualties. The findings could be helpful for making differentiated prevention and control measures for traffic accidents in Shenzhen and the method selection of subsequent research.


Assuntos
Acidentes de Trânsito/estatística & dados numéricos , Condução de Veículo/estatística & dados numéricos , China , Geografia , Humanos
8.
Sleep Breath ; 24(2): 471-482, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31270727

RESUMO

OBJECTIVES: To reveal the characteristics of genioglossus (GG) activation in moderate and severe obstructive sleep apnea (OSA) patients during rapid eye movement (REM) sleep compared with non-rapid eye movement (NREM) sleep and to determine whether continuous positive airway pressure (CPAP) could improve GG activation in OSA patients during sleep. METHODS: All subjects underwent polysomnography (PSG) with synchronous GG electromyography (GGEMG) recording with intra-oral surface electrodes at baseline on the first night. Only those subjects diagnosed with moderate and severe OSA were included and were manually titrated with CPAP to achieve a therapeutic pressure (Pt) with GGEMG recording on the second night. RESULTS: Nine OSA patients and six normal controls were analyzed in this study. The tonic GGEMG was higher in OSA patients during wakefulness (p = 0.003) and NREM sleep (p = 0.015), but it was not higher in REM sleep (p = 0.862). The average phasic activity of OSA patients was significantly higher in all stages, including wakefulness (p = 0.007), NREM sleep (p = 0.005), and REM sleep (p = 0.021). The peak phasic GGEMG was not different in wakefulness compared with normal controls (p = 0.240), but it was higher in OSA patients in NREM sleep (p = 0.001) and REM sleep (p = 0.021), and it was significantly reduced by using CPAP during sleep (NREM sleep: p = 0.027; REM sleep: p = 0.001). CONCLUSIONS: Our results demonstrate that GG activation during NREM and REM sleep is associated with component differences. The tonic component of GGEMG exhibited less of a compensatory increase compared with the phasic component in REM sleep, suggesting that it may be one of the pathological mechanisms of UA collapsibility in REM sleep. In addition, treatment with CPAP can normalize GGEMG activity and mostly reduced the peak phasic GGEMG during sleep.

9.
Otolaryngol Head Neck Surg ; 162(1): 148-154, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31635534

RESUMO

OBJECTIVE: To assess the long-term effects of velopharyngeal surgery on objective and subjective symptoms in patients with obstructive sleep apnea (OSA). STUDY DESIGN: Prospective cohort study. SETTING: University medical center. SUBJECTS AND METHODS: Eighty-six patients with OSA underwent velopharyngeal surgery, which consisted of revised uvulopalatopharyngoplasty with uvula preservation, with or without concomitant transpalatal advancement pharyngoplasty. The results from polysomnography and the Epworth Sleep Scale after 6 months and 5 years were compared with baseline. Baseline variables were compared between responders and nonresponders. RESULTS: Sixty-three patients were successfully followed up at the end of study. The surgical success rate after 6 months and 5 years was 66.67% (42 of 63) and 60.32% (38 of 63), respectively, with no significant difference (P = .459). The apnea-hypopnea index and Epworth Sleep Scale dramatically decreased from baseline after 6 months and 5 years in responders and nonresponders (P < .001 for all). As compared with nonresponders, the responders exhibited larger tonsil size, higher nocturnal lowest oxygen desaturation, lower CT90 (percentage of time with oxygen saturation <90%), and shorter MH (vertical distance between the lower edge of the mandible and hyoid in the midsagittal plane of computed tomography). Tonsil size and CT90 showed significant predictive value for surgery success (P < .001 for both). CONCLUSION: Velopharyngeal surgery was effective in improving nocturnal respiration and excessive daytime sleepiness in patients with OSA at 6-month and 5-year follow-up. Tonsil size and CT90 could be predictors for surgery responders.


Assuntos
Laringoplastia/métodos , Faringe/cirurgia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/cirurgia , Úvula/cirurgia , Adulto , Idoso , Distribuição de Qui-Quadrado , Estudos de Coortes , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Polissonografia/métodos , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
10.
Am J Otolaryngol ; 41(2): 102373, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31879164

RESUMO

PURPOSE: To evaluate the effects of short-term postoperative continuous positive airway pressure (CPAP) on the outcomes of velopharyngeal surgery for obstructive sleep apnea (OSA). MATERIALS AND METHODS: This study included 119 OSA patients who underwent velopharyngeal surgery. Based on the results of postoperative pulse oximetry, the patients were divided into 3 groups: intervention, control, and observation. Patients with oxygen desaturation index (ODI) > 10 and lowest SpO2 < 90% were randomly assigned to the CPAP intervention group and non-CPAP control. Patients with ODI ≤10 or lowest SpO2 ≥ 90% were assigned to the non-CPAP observation group. Patients in the intervention group completed at least 3 months of CPAP treatment. Postoperative polysomnography data were compared to assess the difference of prognosis between the three groups. RESULTS: Baseline data showed no significant differences between the three groups except the observational group showed a significantly larger tonsil size relative to the intervention and control groups. However, there was no significant difference in terms of tonsil size between the control and intervention groups. The surgical success rate of the intervention group was 80.65%, whereas it was 55.17% in the control group, with significant difference. The success rate of the observation group was 85.71% which was significantly different from that of the control group, but not the intervention group. CONCLUSION: Short-term postoperative CPAP treatment may improve the outcomes of velopharyngeal surgery for OSA in patients who have respiratory events related hypoxia after surgery. Further studies are necessary for the underlying mechanisms.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Procedimentos Cirúrgicos Otorrinolaringológicos/métodos , Faringe/cirurgia , Apneia Obstrutiva do Sono/cirurgia , Apneia Obstrutiva do Sono/terapia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Fatores de Tempo , Resultado do Tratamento
11.
Appl Environ Microbiol ; 85(21)2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31444209

RESUMO

Cyclic diguanosine monophosphate (c-di-GMP) is an important second messenger involved in bacterial switching from motile to sessile lifestyles. In the opportunistic pathogen Pseudomonas aeruginosa, at least 40 genes are predicted to encode proteins for the making and breaking of this signal molecule. However, there is still paucity of information concerning the systemic expression pattern of these genes and the functions of uncharacterized genes. In this study, we analyzed the phylogenetic distribution of genes from P. aeruginosa that were predicted to have a GGDEF domain and found five genes (PA5487, PA0285, PA0290, PA4367, and PA5017) with highly conserved distribution across 52 public complete pseudomonad genomes. PA5487 was further characterized as a typical diguanylate cyclase (DGC) and was named dgcH A systemic analysis of the gene expression data revealed that the expression of dgcH is highly invariable and that dgcH probably functions as a conserved gene to maintain the basal level of c-di-GMP, as reinforced by gene expression analyses. The other four conserved genes also had an expression pattern similar to that of dgcH The functional analysis suggested that PA0290 encoded a DGC, while the others functioned as phosphodiesterases (PDEs). Our data revealed that there are five DGC and PDE genes that maintain the basal level of c-di-GMP in P. aeruginosa IMPORTANCE Pseudomonas aeruginosa is an opportunistic pathogen that can cause infections in animals, humans, and plants. The formation of biofilms by P. aeruginosa is the central mode of action to persist in hosts and evade immune and antibiotic attacks. Cyclic-di-GMP (c-di-GMP) is an important second messenger involved in the regulation of biofilm formation. In P. aeruginosa PAO1 strain, there are around 40 genes that encode enzymes for making and breaking this dinucleotide. A major missing piece of information in this field is the phylogeny and expression profile of those genes. Here, we took a systemic approach to investigate this mystery. We found that among 40 c-di-GMP metabolizing genes, 5 have well-conserved phylogenetic distribution and invariable expression profiles, suggesting that there are enzymes required for the basal level of c-di-GMP in P. aeruginosa This study thus provides putative therapeutic targets against P. aeruginosa infections.


Assuntos
GMP Cíclico/análogos & derivados , GMP Cíclico/classificação , GMP Cíclico/genética , Diester Fosfórico Hidrolases/metabolismo , Fósforo-Oxigênio Liases/metabolismo , Filogenia , Pseudomonas aeruginosa/metabolismo , Transcriptoma , Proteínas de Bactérias/classificação , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biofilmes/crescimento & desenvolvimento , GMP Cíclico/metabolismo , Proteínas de Escherichia coli , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica , Genes Bacterianos/genética , Genoma Bacteriano , Metanálise como Assunto , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/genética , Virulência
12.
Nanoscale ; 11(10): 4471-4477, 2019 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-30801590

RESUMO

Electrochemical sensors actually involve an electrocatalytic process in efficient and selective energy conversion. In this work, we use different components to innovatively produce a core@cage material, in which the outer cage, iron phosphate, offers a high electrocatalytic ability to electrochemically oxidize NO, while the inner material, cuprous oxide, could absorb the intermediary HO- ions to kinetically promote NO oxidation for fast electron transfer, resulting in a strong synergistic effect. The unique core@cage structure also increases the active surface area and provides plenty of channels via the porous cage for significantly enhanced mass transport. The as-prepared core@cage NO sensor shows a high sensitivity of 326.09 µA cm-2 µM-1, which is the highest among the reported non-noble metal-based NO biosensors based on the electrooxidation scheme. A free-standing flexible NO sensor was further fabricated with the material for the in situ detection of NO released from cancer cells, demonstrating a low detection limit (0.45 nM) and a fast response time (0.8 s). This work holds great promise for its practical applications in the diagnosis or research of complicated biological processes, especially in real-time in situ detection approaches.


Assuntos
Cobre/química , Técnicas Eletroquímicas/métodos , Compostos de Ferro/química , Óxido Nítrico/análise , Fosfatos/química , Transporte de Elétrons , Humanos , Células MCF-7 , Porosidade
13.
IEEE Trans Neural Syst Rehabil Eng ; 27(2): 118-128, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30605104

RESUMO

Deep brain stimulation (DBS) is an established treatment for patients with Parkinson's disease (PD). Sleep disorders are common complications of PD and affected by subthalamic DBS treatment. To achieve more precise neuromodulation, chronicsleepmonitoringand closed-loop DBS toward sleep-wake cycles could potentially be utilized. Local field potential (LFP) signals that are sensed by the DBS electrode could be processed as primary feedback signals. This is the first study to systematically investigate the sleep-stage classification based on LFPs in subthalamic nucleus (STN). With our newly developed recording and transmission system, STN-LFPs were collected from 12 PD patients during wakefulness and nocturnal polysomnography sleep monitoring at one month after DBS implantation. Automatic sleep-stage classificationmodels were built with robust and interpretable machine learning methods (support vector machine and decision tree). The accuracy, sensitivity, selectivity, and specificity of the classification reached high values (above90% at most measures) at group and individual levels. Features extracted in alpha (8-13 Hz), beta (13-35 Hz), and gamma (35-50 Hz) bandswere found to contribute the most to the classification. These results will directly guide the engineering development of implantable sleepmonitoring and closed-loopDBS and pave the way for a better understanding of the STN-LFP sleep patterns.


Assuntos
Estimulação Encefálica Profunda , Eletroencefalografia/classificação , Fases do Sono/fisiologia , Núcleo Subtalâmico/fisiologia , Adulto , Idoso , Algoritmos , Árvores de Decisões , Eletrodos Implantados , Feminino , Humanos , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/terapia , Polissonografia , Máquina de Vetores de Suporte , Vigília/fisiologia
14.
Chemosphere ; 214: 228-238, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30265930

RESUMO

Chronic ototoxicity of ß-diketone antibiotics (DKAs) to zebrafish (Danio rerio) was explored in detail by following abnormal expressions of two hearing-related miRNAs. Dose-dependent down-regulation of miR-96 and miR-184 was observed in otoliths during embryonic-larval development. Continuous DKA exposure to 120-hpf larva decreased sensitivity to acoustic stimulation. Development of otolith was delayed in treatment groups, showing unclear boundaries and vacuolization at 72-hpf, and utricular enlargement as well as decreased saccular volume in 96-hpf or latter larval otoliths. If one miRNA was knocked-down and another over-expressed, only a slight influence on morphological development of the otic vesicle occurred, but knocked-down or over-expressed miRNA both significantly affected zebrafish normal development. Injection of miR-96, miR-184 or both micRNA mimics to yolk sac resulted in marked improvement of otic vesicle phenotype. However, hair cell staining showed that only the injected miR-96 mimic restored hair cell numbers after DKA exposure, demonstrating that miR-96 played an important role in otic vesicle development and formation of hearing, while miR-184 was only involved in otic vesicle construction during embryonic development. These observations advance our understanding of hearing loss owing to acute antibiotic exposure and provide theoretical guidance for early intervention and gene therapy for drug-induced diseases.


Assuntos
Antibacterianos/toxicidade , Perda Auditiva/induzido quimicamente , MicroRNAs/fisiologia , Animais , Desenvolvimento Embrionário , Células Ciliadas Auditivas/efeitos dos fármacos , Perda Auditiva/genética , Cetonas/toxicidade , Larva/efeitos dos fármacos , MicroRNAs/genética , MicroRNAs/metabolismo , Membrana dos Otólitos/efeitos dos fármacos , Membrana dos Otólitos/crescimento & desenvolvimento , Peixe-Zebra/embriologia , Peixe-Zebra/crescimento & desenvolvimento
15.
Chem Commun (Camb) ; 54(87): 12408-12411, 2018 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-30328856

RESUMO

Rationally tuning the atomic ratio of electrodeposited NixPy for an optimal composition (Ni90P10) greatly enhances hydrogen evolution. Density functional theory calculations shed light on the enhancement mechanism, that in comparison to other examined atomic ratios Ni90P10 has a more moderate free energy of H adsorption and easier adsorption of water molecules toward greatly improved hydrogen production.

16.
Environ Microbiol Rep ; 10(5): 583-593, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30047246

RESUMO

Biofilm bacteria are embedded within a self-secreted extracellular matrix that contains a considerable amount of proteins including many extracellular enzymes. However, little is known about the roles of such enzymes in biofilm development. Here, we studied Pseudomonas aeruginosa aminopeptidase (PaAP, encoded by PA2939 that we named the gene as paaP in this study), a quorum-sensing-regulated enzyme and one of the most abundant extracellular proteins in the biofilm matrix of this opportunistic pathogen and environmental bacterium. We found that deletion of paaP in P. aeruginosa increased initial attachment and biofilm formation at early stages of biofilm development. After 24 h growth, loss of PaAP resulted in substantial cell death and biofilm disruption. Bacterial cell death was independent of biofilm matrix polysaccharide Psl, while biofilm disruption was due to the degradation of Psl matrix by dead-bacteria-released glycosyl hydrolase PslG, thereby leading to biofilm dispersion. PaAP functioned extracellularly and aminopeptidase catalytic activity was essential for its effect on biofilm development. Our data reveal an important role of extracellular aminopeptidase in biofilm development, suggesting PaAP as a therapeutic target for preventing P. aeruginosa infection and combating biofilm-related complications.


Assuntos
Aminopeptidases/metabolismo , Proteínas de Bactérias/metabolismo , Biofilmes/crescimento & desenvolvimento , Matriz Extracelular de Substâncias Poliméricas/enzimologia , Pseudomonas aeruginosa/fisiologia , Aminopeptidases/genética , Aderência Bacteriana , Proteínas de Bactérias/genética , Matriz Extracelular de Substâncias Poliméricas/metabolismo , Deleção de Genes , Viabilidade Microbiana , Polissacarídeos Bacterianos/genética , Polissacarídeos Bacterianos/metabolismo , Pseudomonas aeruginosa/enzimologia , Pseudomonas aeruginosa/metabolismo
17.
Laryngoscope ; 128(12): 2902-2909, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29658112

RESUMO

OBJECTIVE: This study aimed to evaluate the influential factors on the morphological changes of upper airway caused by mouth opening (MO). METHODS: One hundred and thirty-eight obstructive sleep apnea-hypopnea syndrome (OSAHS) patients were enrolled. Anthropometric and demographic data, Friedman tongue position (FTP), and tonsil scores were recorded. Overnight polysomnography and upper airway computed tomography scans under two conditions (mouth closed [MC] and MO) were acquired. Morphological parameters of upper airway were compared between MC and MO. Stepwise multiple linear regression analyses were performed with the variation ratio of upper airway parameters (Para-VRs) from MC to MO as the dependent variable, with age, gender, body mass index, neck circumference, waist circumference, four mandibular indexes, net angle or amount of MO, FTP, and tonsil scores as the independent variables. RESULTS: Overall analysis and subgroup analyses based on OSAHS severity revealed that the minimal cross-sectional area of oropharyngeal lumen (OXmin) significantly decreased (P < 0.05) with MO, whereas the minimal cross-sectional area of velopharyngeal lumen (VXmin) did not significantly change with MO (P > 0.05). The net angle of MO or amount of MO combined with tonsil scores were identified to have significant positive correlation with EXP (OXmin-VR), [OXmin-VR was logarithmically transformed with an exponential function, EXP(n) = en ]; FTP appeared to be more related to EXP (VXmin-VR). Mouth opening induced a significant increase VXmin for patient subgroup with FTP grading I and a significant decrease VXmin for patient subgroup with FTP grading IV (P < 0.05). CONCLUSION: Wider MO combined with larger tonsils lead to narrower oropharyngeal airway. The relative position of tongue to soft palate is the main factor influencing the changes of velopharyngeal lumen with MO. LEVEL OF EVIDENCE: 4 Laryngoscope, 128:2902-2909, 2018.


Assuntos
Orofaringe/diagnóstico por imagem , Palato Mole/diagnóstico por imagem , Apneia Obstrutiva do Sono/diagnóstico , Língua/diagnóstico por imagem , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Orofaringe/fisiopatologia , Palato Mole/fisiopatologia , Polissonografia , Estudos Retrospectivos , Apneia Obstrutiva do Sono/fisiopatologia , Tomografia Computadorizada por Raios X , Língua/fisiopatologia , Adulto Jovem
18.
Food Chem ; 258: 35-42, 2018 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-29655744

RESUMO

Chinese jujube is commonly used in folklore medicine. This study aimed to examine the in vivo immunomodulatory activity of two acidic polysaccharides, HP1 and HP2, extracted and purified from Zizyphus jujuba cv. Huizao (which remains extensively unexplored). HP1 and HP2 had the same monosaccharide species and manganese contents, but differed in their molar rhamnose, arabinose, mannose, glucose, galactose and uronic acid contents (7.32 and 35.9%, as galacturonic acid), Mw (68.7 and 111 kDa, respectively), and contents of K, Cr, Cu, Zn, Pb and Ca. Both HP1 and HP2 could significantly (P < 0.05) increase spleen and thymus indices, promote serum hemolysin formation, enhance the phagocytic activity of macrophages and inhibit footpad edema of mice, with HP2 likely being a more consistent and potent immunomodulator. This study clearly demonstrates the potential of Z. jujuba cv. Huizao polysaccharides as immunomodulators and their associated chemical characteristics and working mechanisms.


Assuntos
Fatores Imunológicos/química , Polissacarídeos/química , Ziziphus/metabolismo , Animais , Edema/patologia , Edema/prevenção & controle , Eritrócitos/citologia , Eritrócitos/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Fatores Imunológicos/uso terapêutico , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Masculino , Manganês/análise , Camundongos , Peso Molecular , Monossacarídeos/análise , Monossacarídeos/metabolismo , Fagocitose/efeitos dos fármacos , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Ovinos , Espectroscopia de Infravermelho com Transformada de Fourier , Ziziphus/química
19.
Environ Toxicol Pharmacol ; 57: 9-18, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29169085

RESUMO

Triclosan (TCS), 2,4,6-trichlorophenol (2,4,6-TCP) and 2,4-dichlorophenol (2,4-DCP) are the most prevalent chlorinated phenolic pollutants in aquatic environments. Our results showed LC50 and EC50 values of 0.51, 1.11, 2.45mg/L, and 0.36, 0.74, 1.53mg/L for TCS, 2,4,6-TCP and 2,4-DCP, respectively, to 120hpf zebrafish. The highest TCSD (the mixture of TCS, 2,4,6-TCP and 2,4-DCP) toxicity was observed at a TCS:2,4,6-TCP:2,4-DCP concentration ratio of 1:2:4. LC50 and EC50 values of TCSD mixtures for 120-hpf zebrafish were 2.28 and 1.16mg/L, respectively. Two toxicity assessment methods (Toxic Unit and Mixture Toxicity Index) indicated that TCSD interactions produced partly additive toxicity. TCSD exposure decreased zebrafish hatching rate and led to a series of malformations. Following alkaline phosphatase staining, a large area of vascular ablation was observed with almost complete disappearance of vascular branches and a smaller coverage range. Prominent reddening of the yolk sac and visceral mass after oil red O staining implied that TCSD exposure severely affected fat metabolism. Following acridine orange staining, cell death occurred in eyes while high TCSD concentrations (0.84mg/L) induced cardiovascular circulation dysfunction. Alcian blue staining increased the α angle between Meckel's cartilages and ß angle between two ceratobranchial. Basihyal and palatoquadrate became shorter and developmental abnormality or defects occurred in the fifth ceratobranchial. Overall, these results provide a theoretical basis for systematically evaluating the combined toxicity of the prevalent chlorinated phenolic pollutants in real-world aquatic environments.


Assuntos
Clorofenóis/toxicidade , Mutagênicos/toxicidade , Triclosan/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Animais Geneticamente Modificados , Anti-Helmínticos/toxicidade , Anti-Infecciosos Locais/toxicidade , Sinergismo Farmacológico , Embrião não Mamífero/anormalidades , Embrião não Mamífero/efeitos dos fármacos , Peixe-Zebra/anormalidades , Peixe-Zebra/embriologia , Peixe-Zebra/genética
20.
J Clin Sleep Med ; 13(9): 1029-1037, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28818154

RESUMO

STUDY OBJECTIVES: To test whether the integration of both anatomical and nonanatomical parameters (ventilatory control, arousal threshold, muscle responsiveness) in a physiology-based model will improve the ability to predict outcomes after upper airway surgery for obstructive sleep apnea (OSA). METHODS: In 31 patients who underwent upper airway surgery for OSA, loop gain and arousal threshold were calculated from preoperative polysomnography (PSG). Three models were compared: (1) a multiple regression based on an extensive list of PSG parameters alone; (2) a multivariate regression using PSG parameters plus PSG-derived estimates of loop gain, arousal threshold, and other trait surrogates; (3) a physiological model incorporating selected variables as surrogates of anatomical and nonanatomical traits important for OSA pathogenesis. RESULTS: Although preoperative loop gain was positively correlated with postoperative apnea-hypopnea index (AHI) (P = .008) and arousal threshold was negatively correlated (P = .011), in both model 1 and 2, the only significant variable was preoperative AHI, which explained 42% of the variance in postoperative AHI. In contrast, the physiological model (model 3), which included AHIREM (anatomy term), fraction of events that were hypopnea (arousal term), the ratio of AHIREM and AHINREM (muscle responsiveness term), loop gain, and central/mixed apnea index (control of breathing terms), was able to explain 61% of the variance in postoperative AHI. CONCLUSIONS: Although loop gain and arousal threshold are associated with residual AHI after surgery, only preoperative AHI was predictive using multivariate regression modeling. Instead, incorporating selected surrogates of physiological traits on the basis of OSA pathophysiology created a model that has more association with actual residual AHI. COMMENTARY: A commentary on this article appears in this issue on page 1023. CLINICAL TRIAL REGISTRATION: ClinicalTrials.Gov; Title: The Impact of Sleep Apnea Treatment on Physiology Traits in Chinese Patients With Obstructive Sleep Apnea; Identifier: NCT02696629; URL: https://clinicaltrials.gov/show/NCT02696629.


Assuntos
Sistema Respiratório/fisiopatologia , Sistema Respiratório/cirurgia , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/cirurgia , Adulto , China , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Polissonografia/estatística & dados numéricos , Estudos Retrospectivos , Resultado do Tratamento
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