Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 490
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
J Periodontol ; 2020 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-32149391

RESUMO

BACKGROUND: To investigate soft- and hard-tissue changes after augmented corticotomy in Chinese adult patients with skeletal Angle class III malocclusion. METHODS: This non-randomized controlled trial included 357 anterior teeth from 30 Chinese adult patients with skeletal Angle class III malocclusion for whom the proposed treatment was augmented corticotomy. Jaws receiving surgery were allocated to a test group (S group, n = 47) and jaws not receiving surgery were allocated to into a control group (NS group, n = 13). Changes in the periodontal biotype, width of the keratinized gingiva (WKG), and labial and lingual horizontal bone thicknesses (BTs) were compared 6 months after surgery by univariate and multivariate analyses. RESULTS: After adjustment for confounding variables, average gains of 0.473 mm in the WKG and 0.649 mm in the labial BT were found in the S group relative to the NS group (p < 0.05). The odds of transition from a thin periodontal biotype to a thick biotype in the S group were about 230 times those in the NS group, and the odds of the reverse biotype transition in the NS group were about 83 times those in the S group (p < 0.05). CONCLUSION: Within the limitations of the present study, augmented corticotomy is a promising approach to improve insufficient periodontal soft and hard tissues in Chinese adult patients with skeletal Angle class III malocclusion. This article is protected by copyright. All rights reserved.

4.
Artigo em Inglês | MEDLINE | ID: mdl-32153115

RESUMO

The purpose of this study was to assess the association of blood pressure (BP) measurements with the risk of cardiovascular disease (CVD) and examine whether central systolic BP (CSBP) predicts CVD better than brachial BP measurements (SBP and pulse pressure [PP]). Based on a cross-sectional study conducted in 2009-2010 with follow-up in 2016-2017 among 35- to 64-year-old subjects in China, we evaluated the performance of non-invasively predicted CSBP over brachial BP measurements on the first CVD events. Each BP measurement, individually and jointly with another BP measurement, was entered into the multivariate Cox proportional-hazards models, to examine the predictability of central and brachial BP measurements. Mean age of participants (n = 8710) was 50.1 years at baseline. After a median follow-up of 6.36 years, 187 CVD events occurred. CSBP was a stronger predictor for CVD than brachial BP measurements (CSBP, 1-standard deviation increment HR = 1.49, 95%CI: 1.31-1.70). With CSBP and SBP entering into models jointly, the HR for CSBP and SBP was 1.28 (1.04-1.58) and 1.22 (0.98-1.50), respectively. With CSBP and PP entering into models jointly, the HR for CSBP and PP was 1.51 (1.28-1.78) and 0.98 (0.83-1.15), respectively. For subgroup analysis, the association of CSBP with CVD was stronger than brachial BP measurements in women, those with hypertension and obesity. In the middle-aged Chinese population, noninvasively estimated CSBP may offer advantages over brachial BP measurements to predict CVD events, especially for participants with higher risk. These findings suggest prospective assessment of CSBP as a prevention and treatment target in further trials.

5.
BMC Infect Dis ; 20(1): 167, 2020 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-32087689

RESUMO

BACKGROUND: Even though enterococci can cause serious infections in multiple sites, they are a rare cause of pneumonia. We reported a uremic patient with vancomycin-resistant E. faecium (VRE-fm) pneumonia, possibly related to epileptic seizures. CASE PRESENTATION: A 57-year old man with uremia on hemodialysis was admitted to the hospital with complaint of recurrent epileptic seizures, followed by a two-week history of recurrent fever and cough with purulent sputum. Chest CT demonstrated multiple exudation of both lungs. He was diagnosed as community acquired pneumonia. Despite antibiotic combination therapy, abnormal chest shadows aggravated. Sputum and blood cultures were initially negative, but later blood culture grew VRE-fm. We suspected aspiration of gastrointestinal content induced by epilepsy as the most likely mechanism. The patient was successfully treated with a four-week course of linezolid according to the antibiotic susceptibility testing. CONCLUSIONS: Physicians should consider multi-drug resistant organisms such as VRE in uremic patients with pneumonia that fails to resolve with broad-spectrum antibiotics, especially in the cases with aspiration induced by epilepsy, immunocompromised conditions, and repeated or prolonged hospitalizations.

6.
Chemistry ; 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31943405

RESUMO

With the assistance of hydrogen bonds of the o-amino group, we have successfully tuned a coordination structure from a metal-organic polyhedron (MOP) to a two-dimensional (2D) metal-organic framework (MOF). The amino group forms hydrogen bonds with the two vicinal carboxylic groups, and induces the ligand to coordinate with copper ions to form the 2D structure. The obtained 2D Cu-based MOF (Cu-AIA) has been applied as an efficient heterogeneous catalyst in the aerobic epoxidation of olefins by using air as oxygen source. Without the aggregation problem of active sites in MOPs, Cu-AIA possesses much higher reactivity than MOP-1. Furthermore, the amino group of the framework has been used as a modifiable site through post-synthetic metalation (PSMet) to prepare a 2D MOF-supported Pd single-site heterogeneous catalyst, which shows excellent catalytic performance for the Suzuki reaction. It indicates that Cu-AIA can also work as a good 2D MOF carrier for the derivation of other heterogeneous catalysts.

7.
Environ Toxicol ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31916403

RESUMO

Bisphenol A (BPA) and 4-cumylphenol (4-CP), as estrogen-like chemicals, are ubiquitous in the environment media and associated with the occurrence and development of hormone-dependent tumors. However, the combinatorial effects of these two structurally similar alkylphenols are not well informed. In the present study, the classic breast cancer cell line MCF-7 was used as in vitro model to estimate the estrogenic proliferative effects of BPA and 4-CP. MTT assay, reactive oxygen species, cell apoptosis, cell cycle, and real-time fluorescent quantitative Step One Plus Real-time PCR System (Applied Biosystems, CA, USA) were applied to explore their proliferative mechanisms. MTT results showed that both BPA and 4-CP ranging from 10-9 to 10-5 M stimulated cell proliferation in a nonmonotonic dose-response manner. Along with the proliferative effects, cell cycle was progressed from G0/G1 to S and G2/M phase. Meanwhile, the expression levels of ERα, pS2, and Bcl-2 mRNA were also upregulated. In contrast, 4-CP and BPA at high dose (10-4 M) obviously displayed antiproliferative effects in MCF-7 cells via inducing cell apoptosis and blocking cell cycle in G0/G1 phase. As expected, the relative expression levels of ERα, pS2, and Bcl-2 mRNA were decreased, whereas Bax mRNA was increased. Interestingly, the proliferative or antiproliferative effects of 4-CP were higher than that of BPA. Moreover, coexposure of lower concentrations BPA and 4-CP significantly induced cell proliferation in a synergistic manner. These findings indicated that the potential environmental risks of coexposure of BPA and 4-CP were greater than either of them.

8.
Org Lett ; 22(2): 395-399, 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31891270

RESUMO

A highly enantioselective formal [4 + 2] annulation involving electron-deficient allenes as C2-synthons has been developed under bifunctional phosphonium salt catalysis. With this catalytic protocol, a wide range of synthetically interesting and highly functionalized chiral 4H-pyran derivatives were readily prepared in good yields (up to 99%) with outstanding diastereo- and enantioselectivities (up to >20:1 dr, up to >99.9% ee). The utility and the practicality of this method were demonstrated by the gram-scale reaction and facile elaboration. Of note, this is the first example of an asymmetric annulation reaction involving allenic reactants under a phase-transfer catalysis system.

9.
BMC Surg ; 20(1): 4, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31907042

RESUMO

BACKGROUND: To evaluate the efficacy of a sensitive, real-time tool for identification and protection for parathyroid glands during thyroidectomy. METHODS: Near-infrared (NIR) auto-fluorescence was measured intraoperatively from 20 patients undergoing thyroidectomy. Spectra were measured from suspicious parathyroid glands and surrounding neck tissues during the operation with a NIR fluorescence system. Fast frozen sections were performed on the suspicious parathyroid glands. Accuracy was evaluated by comparison with histology and NIR identification. Data were attracted for Fisher's linear discriminant analysis. RESULTS: The auto-fluorescence intensity of parathyroid was significantly higher than that of thyroid, fat and lymph node. The peak intensity of auto-fluorescence from parathyroid was 5.55 times of that from thyroid at the corresponding wave number. Of the 20 patients, the parathyroid was accurately detected and identified in 19 patients by NIR system, compared with their histologic results. One suspicious parathyroid did not exhibit typical spectra, and was proved to be fat tissue by histology. The NIR auto-fluorescence method had a 100% sensitivity of parathyroid glands identification and a high accuracy of 95%. The positive predictive value was 95%. The parathyroid gland have specific auto-fluorescence spectrum and can be separated from the other three samples through the Fisher's linear discriminant analysis. CONCLUSIONS: NIR auto-fluorescence spectroscopy can accurately identify normal parathyroid gland during thyroidectomy. The Fisher's linear discriminant analysis demonstrated the specificity of the NIR auto-fluorescence of parathyroid tissue and its efficacy in parathyroid discrimination.


Assuntos
Glândulas Paratireoides/diagnóstico por imagem , Espectrometria de Fluorescência/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Cirurgia Assistida por Computador/métodos , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Adulto , Idoso , Análise Discriminante , Feminino , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Curva ROC , Neoplasias da Glândula Tireoide/diagnóstico
10.
Int J Syst Evol Microbiol ; 70(1): 611-617, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31661042

RESUMO

Strains HY041T and HY039 were oxidase- and Gram-stain-negative, catalase-positive, rod-shaped, non-motile, and facultatively anaerobic bacteria. They were isolated from the feces of bats of the Hipposideros and Taphozous spp. collected from Chongqing City and Guangxi province (PR China), respectively. Phylogenetic analysis based on the 16S rRNA gene and 463 core genes indicated that HY041T and HY039 represent members of the genus Apibacter, forming a clade with Apibacter adventoris wkB301T (95.2 % 16S rRNA gene sequence similarity) and Apibacter mensalis R-53146T (94.0 %). In silico DNA-DNA hybridization (isDDH) and average nucleotide identity (ANI) values of our isolates with the most closely related species were lower than the 70 % and 95-96 % threshold, respectively, in contrast to values above these two thresholds (isDDH value: 89.1 %; ANI value: 98.5 %) between strains HY041T and HY039. The novel isolates could grow on nutrient and MacConkey agar. HY041T and HY039 could produce ß-galactosidase and N-acetyl-ß-glucosaminidase, and utilize d-adonitol, d-mannose, gentiobiose, glucose and salicin. The major fatty acids (>10.0 %) of HY041T were iso-C17 : 0 3OH, iso-C15 : 0, C16 : 0, summed feature 9 (C16 : 0 10-methyl and/or iso-C17 : 1ω9c) and C16 : 0 3OH. Polar lipids included phosphatidylethanolamine, glycolipid, two unidentified aminolipids and four unidentified lipids. Menaquinone 6 (MK-6) was the sole respiratory quinone. On the basis of all analyses so far, strains HY041T and HY039 represent a novel species of the genus Apibacter, for which the name Apibacter raozihei sp. nov. is proposed. The type strain is HY041T (=CGMCC 1.16567T=JCM 33423T) with a genomic DNA G+C content of 32.2 mol%.


Assuntos
Quirópteros/microbiologia , Fezes/microbiologia , Flavobacteriaceae/classificação , Filogenia , Animais , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Flavobacteriaceae/isolamento & purificação , Hibridização de Ácido Nucleico , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
11.
Org Biomol Chem ; 18(2): 191-204, 2020 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-31793614

RESUMO

The ring-opening of cyclopropanols is one of the most active areas of research and it has been well documented in recent years owing to subsequent coupling with various partners, thus providing the facile syntheses of a large number of multifunctional compounds that may otherwise be difficult to access. Evidently, the useful cascade reaction requires easy access to diversely functionalized cyclopropanol substrates. However, developments in the construction of cyclopropanols have not received adequate attention. Herein, recent reports on the formation of cyclopropanols are summarized, and the highly stereoselective production of new promising substrates for the cyclopropanol ring-opening/cross-coupling reactions are introduced and improved syntheses of known cyclopropanols are depicted. This review may facilitate more interesting applications of the cyclopropanol ring-opening/coupling reaction in the synthesis of pharmaceutical compounds, natural products, and structurally more diversified organic synthetic intermediates.

12.
J Oral Pathol Med ; 49(2): 137-144, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31651066

RESUMO

OBJECTIVE: To investigate possible associations between disease-specific survival (DSS) of oral cancer and single nucleotide polymorphisms (SNPs) in transforming growth factor beta receptor 1 (TGFBR1). METHODS: Using iPLEX Sequenom MassARRAY platform, three SNPs in TGFBR1 gene were genotyped in 356 newly diagnosed patients with histologically confirmed primary oral cancer. Demographic and clinical information of all cases were obtained from face-to-face interviews and electronic medical records, and telephone interviews were carried out every 6 months to timely gain follow-up data. Univariate and multivariate Cox proportional hazards model were used to assess the association between the polymorphisms of tagging loci and DSS of oral cancer. RESULTS: TGFBR1 rs33438 polymorphism was protective against death of oral cancer in codominant (AG vs AA: HR = 0.55, 95% CI = 0.35-0.88) and dominant (GG + AG vs AA: HR = 0.57, 95% CI = 0.38-0.87) models. Moreover, better DSS was particularly significant in radiotherapy patients who carrying GG + AG genotype. There also existed a positive multiplicative interaction on DSS between the polymorphism of TGFBR1 rs334348 and radiotherapy (P = .001). Not any associations between TGFBR1 rs334354 or rs3739798 polymorphism and DSS were observed. CONCLUSIONS: This preliminary prospective study suggests that polymorphism of TGFBR1 rs334348 may act as a potentially independent factor and novel genetic biomarker to predict oral cancer DSS especially for patients with radiotherapy. A much more extensive investigation will need to confirm our findings.


Assuntos
Neoplasias Bucais , Receptor do Fator de Crescimento Transformador beta Tipo I/genética , Predisposição Genética para Doença , Genótipo , Humanos , Neoplasias Bucais/genética , Polimorfismo de Nucleotídeo Único , Prognóstico , Estudos Prospectivos
13.
Int J Syst Evol Microbiol ; 70(1): 58-64, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31613742

RESUMO

Two previously undescribed, Gram-stain-positive, rod-shaped strains, 410T and 553, were isolated from faeces of the Tibetan antelope (Pantholops hodgsonii) from the Tibet-Qinghai Plateau, PR China. The optimum growth conditions of the two novel strains were 1 % (w/v) NaCl, 37 °C and pH 7. The end products from glucose fermentation included ethanol and lactic acid. Based on results of 16S rRNA gene sequence comparison and phylogenetic and phylogenomic analyses, strains 410T and 553 were classified into the genus Actinomyces, and were closely related to Actinomyces ruminicola (97.6 %), Actinomyces oricola (93.5 %) and Actinomyces dentalis (90.8 %). The genomic G+C content of strain 410T was 67.4 mol%. Digital DNA-DNA hybridization values between strain 410T and each of the closely related species were under 70 %. The respiratory quinones were MK-10 (68 %) and MK-9 (32 %). The main cellular fatty acids of the isolates were C16 : 0, followed by C18 : 1 ω9c. The major polar lipids were diphosphatidylglycerol and phosphatidylinositol-mannoside. The whole-cell sugars contained rhamnose, ribose and glucose. The diagnostic amino acids of cell-wall peptidoglycan included alanine, glutamic acid, lysine and ornithine. The results of biochemical, chemotaxonomic and genotypic analyses revealed that the two novel strains represent a novel species of genus Actinomyces, for which the name Actinomyces qiguomingii sp. nov. is proposed. The type strain is 410T (=CGMCC 1.16361T= DSM 106201T).


Assuntos
Actinomyces/classificação , Antílopes/microbiologia , Filogenia , Actinomyces/isolamento & purificação , Animais , Técnicas de Tipagem Bacteriana , Composição de Bases , Parede Celular/química , China , DNA Bacteriano/genética , Ácidos Graxos/química , Fezes/microbiologia , Hibridização de Ácido Nucleico , Peptidoglicano/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Tibet , Vitamina K 2/química
14.
J Chromatogr A ; 1610: 460540, 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31543337

RESUMO

Silver magnetic amino silicone adhesive (Fe3O4@SiO2@NH2@Ag) particles were prepared for the purification of α-linolenic acid from tree peony seed oil under applied magnetic field. First, Fe3O4@SiO2@NH2@Ag particles were prepared and physicochemically characterized, including XRD, TG, FTIR, SEM, magnetic hysteresis curves and elemental analysis. The static process for the purification of α-linolenic acid using Fe3O4@SiO2@NH2@Ag particles was investigated, including adsorption curve, desorption curve, elution solvent composition and adsorption isotherm. The result indicated that 0-1-4% acetone-n-hexane elution solvent was selected for the gradient elution process, 2 h and 60 min were the time required to reach adsorption and desorption equilibrium, 20 °C was selected as the adsorption temperature, Langmuir model was suitable to fit and explain the equilibrium data, and the adsorption process was spontaneous and exothermic. Under applied magnetic field, the dynamic process for the purification of α-linolenic acid using Fe3O4@SiO2@NH2@Ag particles was investigated, and the optimum conditions were 20:1 µL/g loading amount, 0.5 mL/min flow rate and 51.73 Oe magnetic field intensity. After purification, the purity and recovery ratio of α-linolenic acid were calculated to be 94% and 74%, respectively. Furthermore, the recycled Fe3O4@SiO2@NH2@Ag particles still achieved better purification result. Therefore, the developed method shows a good application prospect in the field of separation and purification of α-linolenic acid.

15.
Int Immunopharmacol ; 78: 106015, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31780369

RESUMO

Lymphocyte antigen 6Chigh (Ly-6Chigh) inflammatory monocytes, as novel mononuclear cells in the innate immune system, participate in infectious diseases. In this study, we investigated the potential role of these monocytes in ventilator-induced lung injury (VILI) and the possible mechanism involved in their migration to lung tissue. Our results showed that mechanical ventilation with high tidal volume (HTV) increased the accumulation of Ly-6Chigh inflammatory monocytes in lung tissues and that blocking C­C chemokine receptor 2 (CCR2) could significantly reduce Ly-6Chigh inflammatory-monocyte migration and attenuate the degree of inflammation of lung tissues. In addition, inhibition of p38 mitogen-activated protein kinase (p38 MAPK) activity could decrease the secretion of monocyte chemoattractant protein 1 (MCP-1), which in turn decreased the migration of Ly-6Chigh inflammatory monocytes into lung tissue. We also demonstrated that high ventilation caused Ly-6Chigh inflammatory monocytes in the bone marrow to migrate into and aggregate in the lungs, creating inflammation, and that the mechanism was quite different from that of infectious diseases. Ly-6Chigh inflammatory monocytes might play a pro-inflammatory role in VILI, and blocking their infiltration into lung tissue might become a new target for the treatment of this injury.

16.
Environ Res ; 180: 108867, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31708170

RESUMO

The increased nitrogen (N) fertilizer usage caused substantial nitrate (NO3-) leaching into groundwater and eutrophication in downstream aquatic systems. Riparian zones positioned as the link interfaces of terrestrial and aquatic environments are effective in NO3- removal. However, the microbial mechanisms regulating NO3- reduction in riparian zones are still unclear. In this study, four microbial NO3- reduction processes were explored in fine-scale riparian soil horizons by isotopic tracing technique, qPCR of functional gene, high-throughput amplicon sequencing, and phylogenetic molecular ecological network analysis. Interestingly, anaerobic ammonium oxidation (anammox) contributed to NO3- removal of up to 48.2% only in waterward sediments but not in landward soil. Denitrification was still the most significant contributor to NO3- reduction (32.0-91.8%) and N-losses (51.7-100%). Additionally, dissimilatory nitrate reduction to ammonium (DNRA) played a key role in NO3- reduction (4.4-67.5%) and was even comparable to denitrification. Community structure analysis of denitrifying, anammox, and DNRA bacterial communities targeting the related functional gene showed that spatial heterogeneity played a greater role than both temporal and soil type (rhizosphere and non-rhizosphere soil) variability in microbial community structuring. Denitrification and DNRA communities were diverse, and their activities did not depend on gene abundance but were significantly related to organic matter, suggesting that gene abundance alone was insufficient in assessing their activity in riparian zones. Based on networks, DNRA plays a keystone role among the microbial NO3- reducers. As the last line of defense in the interception of terrestrial NO3-, these findings contribute to our understanding of NO3- removal mechanisms in riparian zones, and could potentially be exploited to reduce the diffusion of NO3- pollution.

17.
ACS Appl Mater Interfaces ; 12(2): 2884-2891, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31872755

RESUMO

Low-dimensional organic-inorganic hybrid perovskites have demonstrated to be promising semiconductor materials due to their unique optoelectronic properties, however, the controllable growth of high-quality ultrathin 2D perovskites with large lateral dimension still faces great challenges. Herein, we report the controllable growth of large-scale ultrathin 2D (C6H5(CH2)3NH3)3Pb2I7 ((PPA)3Pb2I7) perovskite nanosheets (NSs) using a facile antisolvent-assisted crystallization approach under mild condition. As a result, the well-defined regular-shaped (PPA)3Pb2I7 NSs, with the largest lateral size over 100 µm, have been successfully synthesized, which is more than several ten times larger than that of other 2D perovskite NSs previously reported. Moreover, the thickness of the achieved 2D perovskite NSs can be well-tuned by altering the concentration of the precursor solution, with the smallest thickness down to ∼4.7 nm. More importantly, the photodetectors based on the high-quality (PPA)3Pb2I7 perovskites exhibit fascinating performance, including an extremely low dark current (∼1.5 pA), fast response/recovery rate (∼850/780 µs), and high detectivity (∼1.2 × 1010 Jones). This work provides a simple and promising strategy to controllably grow large-scale and ultrathin 2D perovskite NSs for low-cost and high-performance optoelectronic devices.

18.
Free Radic Biol Med ; 147: 159-166, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31874250

RESUMO

OBJECTIVE: To investigate the role of geranylgeranyl diphosphate synthase 1 (GGPPS1) in ventilator-induced lung injury along with the underlying mechanism. METHODS: A murine VILI model was induced by high-tidal volume ventilation in both wild-type and GGPPS1 knockout mice. GGPPS1 expression was detected in the bronchoalveolar lavage fluid (BALF) supernatants of acute respiratory distress syndrome (ARDS) patients and healthy volunteers, as well as in lung tissues and BALF supernatants of the VILI mice using enzyme-linked immunosorbent assay (ELISA), quantitative reverse transcription polymerase chain reaction (qRT-PCR), western bolt and immunohistochemical (IHC). The wet/dry ratio, total BALF proteins, and lung injury score were analyzed. The percentage of neutrophils was detected by flow cytometry and IHC. Inflammatory cytokine levels were measured by ELISA and qRT-PCR. The related expression of Toll-like receptor (TLR)2/4 and its downstream proteins was evaluated by western blot. RESULTS: GGPPS1 in BALF supernatants was upregulated in ARDS patients and the VILI mice. Depletion of GGPPS1 significantly alleviated the severity of ventilator induced lung injury in mice. Total cell count, neutrophils and inflammatory cytokines (interleukin [IL]-6, IL-1ß, IL-18 and tumor necrosis factor-α) levels in BALF were reduced after GGPPS1 depletion. Moreover, addition of exogenous GGPP in GGPPS-deficient mice significantly exacerbated the severity of ventilator induced lung injury as compared to the PBS treated controls. Mechanistically, the expression of TLR2/4, as well as downstream proteins including activator protein-1 (AP-1) was suppressed in lung tissues of GGPPS1-deficient mice. CONCLUSION: GGPPS1 promoted the pathogenesis of VILI by modulating the TLR2/4-AP-1 signaling pathway, and GGPPS1 knockout significantly alleviated the lung injury and inflammation in the VILI mice.

19.
Int Immunopharmacol ; 78: 106069, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31841755

RESUMO

Inflammation plays a criticalrole in the development of ventilator-induced lung injury (VILI). Endoplasmic reticulum (ER) stress is associated with a variety of diseases through the modulation of inflammatory responses. However, little is known about how ER stress is implicated in VILI. In this study, murine mechanical ventilation models were constructed. Total protein and inflammatory cytokines were measured in bronchoalveolar lavage fluid (BALF),and lung tissue injurywasassessedby histology. Our data revealed that mice subjected to high tidal ventilation (TV) for 4 h showed more severe pulmonary edema and inflammation than those of mice with spontaneous breathing and low TV-treatment. In addition, the high TV-treated animals upregulated the ER stress markers GRP78, CHOP, p-IRE1α, TRAF2, and p-NF-κB expression at both the mRNA and protein levels in lung tissue. Administration of thapsigargin exacerbated the histological changes, inflammation and expression of GRP78 and CHOP after high TV, but treatment with ER stress and IRE1α kinase inhibitors attenuated the pathological damage and downregulated the high expression of GRP78, CHOP, p-IRE1α, TRAF2, and p-NF-κB, suggesting that ER stress is involved in VILI though the IRE1α/TRAF2/NF-κB signaling pathway in mice.

20.
Exp Ther Med ; 18(6): 4790-4798, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31798704

RESUMO

Pioglitazone, a type of insulin sensitizer, serves as an effective anti-hyperglycemic drug. The mechanism of action of pioglitazone is through the activation of the peroxisome proliferator-activated receptor (PPAR), which results in enhanced insulin sensitivity of peripheral tissues and the liver, causing a reduction in the production and output of liver sugar. It has been reported that pioglitazone increases the risk of bladder cancer, but the underlying mechanisms have remained elusive. It was hypothesized that modulation of pioglitazone activity may be predicted by systematically analyzing data published on drugs. This hypothesis was tested by querying the Drug-Target Interactome (DTome), a web-based tool that provides open-source data from three databases (DrugBank, PharmGSK and Protein Interaction Network analysis). A total of 4 direct target proteins (DTPs) and further DTP-associated genes were identified for pioglitazone. Subsequently, an enrichment analysis was performed for all DTP-associated genes using Cytoscape software. A total of 12 Kyoto Encyclopedia of Genes and Genomes pathways were identified, including the 'PPAR signaling pathway' as well as 'pathways in cancer' as relevant pathways. Functional network analysis was able to identify direct and indirect target genes of pioglitazone, resulting in a list of possible biological functions based on published databases. Furthermore, Kaplan-Meier analysis indicated that pioglitazone may affect the survival rate of patients with bladder cancer through genetic alterations (missense mutation, truncating mutation, amplification, deep deletion and fusion) of target genes. Therefore, it should be used with caution.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA