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1.
IEEE Trans Cybern ; PP2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33001814

RESUMO

In this article, direct adaptive actuator failure compensation control is investigated for a class of noncanonical neural-network nonlinear systems whose relative degrees are implicit and parameters are unknown. Both the state tracking and output tracking control problems are considered, and their adaptive solutions are developed which have specific mechanisms to accommodate both actuator failures and parameter uncertainties to ensure the closed-loop system stability and asymptotic state or output tracking. The adaptive actuator failure compensation control schemes are derived for noncanonical nonlinear systems with neural-network approximation, and are also applicable to general parametrizable noncanonical nonlinear systems with both unknown actuator failures and unknown parameters, solving some key technical issues, in particular, dealing with the system zero dynamics under uncertain actuator failures. The effectiveness of the developed adaptive control schemes is confirmed by simulation results from an application example of speed control of dc motors.

2.
Cell Death Dis ; 11(10): 868, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067425

RESUMO

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

3.
Medicine (Baltimore) ; 99(41): e22516, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031291

RESUMO

BACKGROUND: Xihuang pill, a famous traditional Chinese medicine formulation, is a broad-spectrum anti-tumor drug and has been widely used for the treatment of lung cancer in China. The aim of this study is to systematically investigate the efficacy and safety of Xihuang pill for the treatment of lung cancer. METHODS: We will perform the comprehensive literature search in the following databases from their inceptions to August 2020 for data extraction: PubMed, the Cochrane Library, Embase, the China National Knowledge Infrastructure, Wanfang Database, Chinese Science and Technology Periodical Database, and Chinese Biomedical Literature Database. Cochrane Risk of Bias tool will be used to assess the risk of bias of included studies. The RevMan 5.4 and Stata 16.0 software will be applied for statistical analyses. Statistical heterogeneity will be computed by I tests. Sensitivity analysis will be conducted to evaluate the stability of the results. The publication bias will be evaluated by funnel plots and Egger test. The quality of evidence will be assessed by the Grading of Recommendations Assessment, Development and Evaluate system (GRADE) system. RESULTS: The results of our research will be published in a peer-reviewed journal. CONCLUSION: The conclusion of this study will provide evidence to show whether Xihuang pill is an effective intervention for patient with lung cancer. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/W2GHN.


Assuntos
Antineoplásicos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Administração Oral , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Metanálise como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Comprimidos
4.
Epidemiol Infect ; 148: e211, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32900409

RESUMO

The Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a public health emergency of international concern. The current study aims to explore whether the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are associated with the development of death in patients with COVID-19. A total of 131 patients diagnosed with COVID-19 from 13 February 2020 to 14 March 2020 in a hospital in Wuhan designated for treating COVID-19 were enrolled in the current study. These 131 patients had a median age of 64 years old (interquartile range: 56-71 years old). Furthermore, among these patients, 111 (91.8%) patients were discharged and 12 (9.2%) patients died in the hospital. The pooled analysis revealed that the NLR at admission was significantly elevated for non-survivors, when compared to survivors (P < 0.001). The NLR of 3.338 was associated with all-cause mortality, with a sensitivity of 100.0% and a specificity of 84.0% (area under the curve (AUC): 0.963, 95% confidence interval (CI) 0.911-1.000; P < 0.001). In view of the small number of deaths (n = 12) in the current study, NLR of 2.306 might have potential value for helping clinicians to identify patients with severe COVID-19, with a sensitivity of 100.0% and a specificity of 56.7% (AUC: 0.729, 95% CI 0.563-0.892; P = 0.063). The NLR was significantly associated with the development of death in patients with COVID-19. Hence, NLR is a useful biomarker to predict the all-cause mortality of COVID-19.


Assuntos
Betacoronavirus , Plaquetas , Infecções por Coronavirus/mortalidade , Linfócitos , Neutrófilos , Pneumonia Viral/mortalidade , Adolescente , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Criança , Pré-Escolar , Infecções por Coronavirus/sangue , Infecções por Coronavirus/etiologia , Humanos , Lactente , Recém-Nascido , Pacientes Internados , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/etiologia , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
5.
Artigo em Inglês | MEDLINE | ID: mdl-32954584

RESUMO

Narrow-bandgap polymer semiconductors are essential for advancing the development of organic solar cells. Here, a new narrow-bandgap polymer acceptor L14, featuring an acceptor-acceptor (A-A) type backbone, is synthesized by copolymerizing a dibrominated fused-ring electron acceptor (FREA) with distannylated bithiophene imide. Combining the advantages of both the FREA and the A-A polymer, L14 not only shows a narrow bandgap and high absorption coefficient, but also low-lying frontier molecular orbital (FMO) levels. Such FMO levels yield improved electron transfer character, but unexpectedly, without sacrificing open-circuit voltage (Voc ), which is attributed to a small nonradiative recombination loss (Eloss,nr ) of 0.22 eV. Benefiting from the improved photocurrent along with the high fill factor and Voc , an excellent efficiency of 14.3% is achieved, which is among the highest values for all-polymer solar cells (all-PSCs). The results demonstrate the superiority of narrow-bandgap A-A type polymers for improving all-PSC performance and pave a way toward developing high-performance polymer acceptors for all-PSCs.

6.
Cell Rep ; 32(10): 108120, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32905781

RESUMO

N6-methyladenosine (m6A), the most abundant reversible modification on eukaryote messenger RNA, is recognized by a series of readers, including the YT521-B homology domain family (YTHDF) proteins, which are coupled to perform physiological functions. Here, we report that YTHDF2 and YTHDF3, but not YTHDF1, are required for reprogramming of somatic cells into induced pluripotent stem cells (iPSCs). Mechanistically, we found that YTHDF3 recruits the PAN2-PAN3 deadenylase complex and conduces to reprogramming by promoting mRNA clearance of somatic genes, including Tead2 and Tgfb1, which parallels the activity of the YTHDF2-CCR4-NOT deadenylase complex. Ythdf2/3 deficiency represses mesenchymal-to-epithelial transition (MET) and chromatin silencing at loci containing the TEAD motif, contributing to decreased reprogramming efficiency. Moreover, RNA interference of Tgfb1 or the Hippo signaling effectors Yap1, Taz, and Tead2 rescues Ythdf2/3-defective reprogramming. Overall, YTHDF2/3 couples RNA deadenylation and regulation with the clearance of somatic genes and provides insights into iPSC reprogramming at the posttranscriptional level.

7.
ISA Trans ; 2020 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-32873373

RESUMO

Aiming at the problem that the navigation performances of unmanned underwater vehicle (UUV) may be affected by inaccurate prior navigation information and external environmental interference, which may make the accuracy and reliability of strapdown inertial navigation system (SINS) and global position system (GPS) integrated navigation results worse, positioning divergent and system even invalid, an adaptive H-infinite kalman filtering algorithm based on multiple fading factors (MAHKF) is proposed in this paper. Firstly, the time-varying adaptive fading factor is used to modify the filter parameters on-line to make the initial error of navigation filter converge quickly. Secondly, the H-infinite kalman filter of the SINS/GPS system is built on combining the advantages of robust control, which improved the system robustness under extreme external environment. Further, the adaptive thresholdγ of the H-infinite kalman filter is introduced to make the filter adaptive to the environment change. Results of the simulation and experiment demonstrate that the initial error is converged at the beginning stage of navigation process, and the interference from external uncertainty inputs to the integrated navigation system are suppressed effectively with the proposed algorithm. Compared with the conventional kalman filter algorithm (KF), the position errors in three directions of the UUV are reduced by 66.57%,67.98% and 64.51% respectively with the proposed MAHKF.

8.
Work ; 66(4): 861-869, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32925143

RESUMO

BACKGROUND: A high prevalence of work-related musculoskeletal disorders (WMSDs) has been reported among flight attendants. Identifying the root causes of these disorders may improve the health conditions of flight attendants and further improve flight safety and service quality. OBJECTIVE: In this study, we aimed to identify WMSD risk factors for a specific population, namely Chinese female flight attendants. METHODS: A two-stage survey including an online questionnaire (46 flight attendants) and a semi-structured interview (16 flight attendants) was used to assess the WMSDs of Chinese female flight attendants. Text analysis tools in NVivo 11 were used to identify the main concerns and risk factors for WMSDs of Chinese flight attendants. RESULTS: In the online questionnaire, more than 86% of the participants reported discomfort in at least one body part. Biomechanical factors, work organizational factors, and psychosocial factors were reported by participants in this study. Chinese passengers were found to have an effect on WMSD development in Chinese flight attendants. CONCLUSIONS: The results of this study suggested that WMSDs are severe problems among Chinese flight attendants. General factors as well as the passenger-relevant factor were identified as the most influential causes of WMSDs.

9.
Antimicrob Resist Infect Control ; 9(1): 153, 2020 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-32962731

RESUMO

BACKGROUND: A considerable proportion of patients hospitalized with coronavirus disease 2019 (COVID-19) acquired secondary bacterial infections (SBIs). The etiology and antimicrobial resistance of bacteria were reported and used to provide a theoretical basis for appropriate infection therapy. METHODS: This retrospective study reviewed electronic medical records of all the patients hospitalized with COVID-19 in the Wuhan Union Hospital between January 27 and March 17, 2020. According to the inclusion and exclusion criteria, patients who acquired SBIs were enrolled. Demographic, clinical course, etiology, and antimicrobial resistance data of the SBIs were collected. Outcomes were also compared between patients who were classified as severe and critical on admission. RESULTS: Among 1495 patients hospitalized with COVID-19, 102 (6.8%) patients had acquired SBIs, and almost half of them (49.0%, 50/102) died during hospitalization. Compared with severe patients, critical patients had a higher chance of SBIs. Among the 159 strains of bacteria isolated from the SBIs, 136 strains (85.5%) were Gram-negative bacteria. The top three bacteria of SBIs were A. baumannii (35.8%, 57/159), K. pneumoniae (30.8%, 49/159), and S. maltophilia (6.3%, 10/159). The isolation rates of carbapenem-resistant A. baumannii and K. pneumoniae were 91.2 and 75.5%, respectively. Meticillin resistance was present in 100% of Staphylococcus aureus and Coagulase negative staphylococci, and vancomycin resistance was not found. CONCLUSIONS: SBIs may occur in patients hospitalized with COVID-19 and lead to high mortality. The incidence of SBIs was associated with the severity of illness on admission. Gram-negative bacteria, especially A. baumannii and K. pneumoniae, were the main bacteria, and the resistance rates of the major isolated bacteria were generally high. This was a single-center study; thus, our results should be externally examined when applied in other institutions.


Assuntos
Coinfecção/tratamento farmacológico , Coinfecção/epidemiologia , Farmacorresistência Bacteriana/fisiologia , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções Estafilocócicas/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Betacoronavirus , China/epidemiologia , Coinfecção/mortalidade , Infecções por Coronavirus/patologia , Feminino , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/patologia , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico
10.
Nanomaterials (Basel) ; 10(10)2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32977574

RESUMO

V2O5-WO3/TiO2 as a commercial selective catalytic reduction (SCR) catalyst usually used at middle-high temperatures was modified by loading of MnOx for the purpose of enhancing its performance at lower temperatures. Manganese oxides were loaded onto V-W/Ti monolith by the methods of impregnation (I), precipitation (P), and in-situ growth (S), respectively. SCR activity of each modified catalyst was investigated at temperatures in the range of 100-340 °C. Catalysts were characterized by specific surface area and pore size determination (BET), X-ray diffraction (XRD), temperature programmed reduction (TPR), etc. Results show that the loading of MnOx remarkably enhanced the SCR activity at a temperature lower than 280 °C. The catalyst prepared by the in-situ growth method was found to be most active for SCR.

11.
Int J Pharm ; 590: 119877, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32927003

RESUMO

The limited therapeutic option for respiratory infections caused by multi-drug resistant microbial pathogens is a major global health threat. Topical delivery of antibacterial combinations to the lung could dramatically enhance antibacterial activities and provide a means to overcome bacterial resistance development. The aim of the study was to investigate the potential of new inhalable dry powder combinations consisting of a fixed dose of aztreonam (Azt) and tobramycin (Tob) using a spray drying process, against antibiotic resistant Gram-negative respiratory pathogens. The interactions of Azt with Tob on resistant Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii were determined by calculating factional inhibitory concentration indices (FICI). A fixed concentration ratio of Azt and Tob that exhibited a synergistic antimicrobial effect was selected and formulated into inhalable dry powders by co-spray drying with and without L-leucine. The obtained dry powders were characterized with respect to the morphology, particle size distribution, solid state, moisture sorption behaviour, and in vitro dissolution. Storage stability, aerosol performance, and in vitro antibacterial activity were also evaluated. Inhalable dry powders consisting of Azt, Tob and L-leucine could be readily obtained via the spray drying process with a fine particle fraction of above 40% as determined using a next generation impactor. The co-spray drying process resulted in amorphous Azt/Tob dry powders with or without the addition of L-leucine as indicated by X-ray powder diffraction. The dissolution rates of the co-spray dried Azt/Tob dry powders were decreased, and the storage stability was improved with an increase in the proportion of L-leucine in the formulations. The inclusion of L-leucine did not affect the minimum inhibitory concentration and the co-spray dried powders reserved the synergistic antibacterial effects and exhibited enhanced antibacterial activities as compared to the individual antibiotic used alone on multidrug-resistant (Azt and Tob resistant) P. aeruginosa 25756 and A. baumannii K31. This study demonstrates that inhalable Azt/Tob dry powders using L-leucine as a moisture protector as well as a dispersing agent can be readily prepared by the spray drying process. This new inhalable fixed dose combinational dry powders may represent an alternative treatment against multidrug-resistant Gram-negative respiratory pathogens.

12.
Phytochemistry ; 179: 112499, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32980712

RESUMO

The effects of S (as sulphate) and Se (as selenite) treatment (S mM/Se µM: 1/0, 1/50, 1/100, 1/150, 4/0, 4/50, 4/100, and 4/150) on the production of sulforaphane (an anticancer compound), the accumulation of its precursor substance, and the expression of genes related to glucoraphanin biosynthesis in broccoli were examined. Sulforaphane yield and myrosinase activity increased significantly with the combined application of 4 mM S and 100 µM Se on broccoli. Furthermore, the concentrations of glucoraphanin (a sulforaphane precursor) and methionine (a glucoraphanin substrate) slightly changed after Se application. And the strong anticancer activity of compound Se-SMC was further improved. Analysis of related gene expression showed that MY, which encodes myrosinase, was strongly induced by Se treatment. Thus, the myrosinase activity induced by Se treatment is the dominant factor affecting sulforaphane yield from glucoraphanin hydrolyzation. Selenium-sulfur biofortification provides a technical support for the cultivation of broccoli with high sulforaphane and high anti-cancer selenium compounds.

13.
World J Surg Oncol ; 18(1): 196, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32767974

RESUMO

BACKGROUND: Patients with stage II deficient mismatch repair (dMMR) show a better prognosis than patients with colorectal cancer (CRC) with proficient mismatch repair (pMMR). However, this beneficial effect is decreased in advanced stages of the disease. This study was conducted to investigate the prognostic value of dMMR in different stage and alterations in the tumor microenvironment. METHODS: This was a matched retrospective cohort study. Thirty-two patients with stage III&IV dMMR matched with 32 patients with stage I&II dMMR and 64 patients with pMMR were evaluated. Immunohistochemistry analysis was performed for the 64 patients with dMMR to explore the expression and prognostic effect of CD3, CD4, CD8, and PD-L1. RESULTS: Patients with stage III-IV dMMR showed no advantage in overall survival (OS) and disease-free survival (DFS) compared to patients with pMMR (P = 0.244, P = 0.667). No expression differences in CD3, CD4, CD8, and PD-L1 at the center of the tumor (CT) or invasive margin (IM) were found between patients with stage I&II and stage III&IV dMMR. High CD3 expression at the CT and high CD3 an CD4 expression at the IM improved both OS and DFS. High CD8 expression showed opposite prognostic value in patients with stage I&II and III&IV dMMR. A similar tendency was observed for PD-L1 expression. CONCLUSION: Patients with stage III-IV dMMR showed no prognostic advantage over patients with pMMR. Expression of CD3, CD4, CD8, and PD-L1 was similar between stage I&II and III&IV dMMR CRC. High CD3 expression at the CT and high CD3 and CD4 expression at the IM can significantly improve patient prognosis. The opposite prognostic tendency of CD8 and PD-L1 for patients with stage I&II and III&IV dMMR may be relevant to CD8+T cell exhaustion and functional changes at inhibitory immune checkpoints.

14.
Org Lett ; 22(15): 5833-5838, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32790422

RESUMO

A palladium-catalyzed asymmetric [3+2] cycloaddition reaction of methyleneindolinones with vinylethylene carbonates has been successfully developed, which provides a highly efficient method for the synthesis of structurally diverse 3,3'-tetrahydrofuryl spirooxindoles in high yields (≤99%) with excellent stereoselectivities (>20:1 dr, ≤99% ee). Furthermore, this methodology shows a wide substrate scope and high utility in diversity-oriented synthesis.

15.
J Org Chem ; 85(17): 11240-11249, 2020 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-32786616

RESUMO

An organocatalytic domino aza/oxa-Michael/1,6-addition reaction of ortho-tosylaminophenyl or ortho-hydroxyphenyl-substituted para-quinone methides and ynals has been developed. In the presence of 20 mol % of morpholine, this unprecedented cascade reaction occurs readily in good yield (up to 99%), providing a highly efficient synthetic approach to synthetically valuable 1,4-dihydroquinolines and 4H-chromenes.

16.
World J Gastroenterol ; 26(24): 3401-3412, 2020 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-32655264

RESUMO

Long noncoding RNAs (lncRNAs) are important regulators of cell processes that are usually dysregulated in gastric cancer (GC). Based on their high specificity and ease of detection in tissues and body fluids, increasing attention has spurred the study of the roles of lncRNAs in GC patients. Thus, it is necessary to elucidate the molecular mechanisms and further explore the clinical applications of lncRNAs in GC. In this review, we summarize current knowledge to examine dysregulated lncRNAs in GC and their underlying molecular mechanisms and activities in GC, which involve microRNA sponging, mRNA stability, genetic variants, alternative splicing, transcription factor binding, and epigenetic modification. More significantly, the potential of lncRNAs as prognostic, circulating, and drug-resistant biomarkers for GC is also described. This review highlights the method of dissecting molecular mechanisms to explore the clinical application of lncRNAs in GC. Overall, this review offers assistance in using lncRNAs as novel candidates for molecular mechanisms and for the identification of revolutionary biomarkers for GC.

17.
Microb Pathog ; 147: 104385, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32659314

RESUMO

In order to investigate enterobacteria presence involved in the secondary infections in Porcine Reproductive and Respiratory Syndrome (PRRS) pigs with different viral co-infections, we identified enterobacteria for guiding clinical treatment. Twenty-one diseased pigs were diagnosed with the PRRS virus (PRRSV) and other 7 virus primers by PCR/RT-PCR in the lung and spleen samples. Enterobacteria were isolated using MacConkey agar from 5 visceral samples of PRRS pigs, and identified by 16S rDNA sequencing. PRRSV was positive in 100% of the lung samples and 81.0% of the spleen samples. Seven diseased pigs were diagnosed with only PRRSV infection (33.3%), 7 pigs with PRRSV and 1 or 2 other viruses (33.3%) and 7 pigs with PRRSV and more than 2 types of other viruses (33.3%). PRRSV was more inclined to co-infect pigs with porcine group A rotavirus (PARV) with the co-infection rate of 52.4% (11/21). Approximately 13 types of bacteria were successfully isolated from lung, spleen, liver, kidney and lymph node samples of different PRRS pigs. Enterobacteria were isolated in 100% of lung, liver and lymph samples from pigs infected with PRRSV alone. However, the isolation rates were significantly decreased in the more than 3 viruses co-infection group. Escherichia coli was the most prevalent bacterium, followed by Morganella, Proteus, Shigella, Salmonella, Klebsiella and Aeromonas. Most of the isolated enterobacteria were opportunistic pathogens. Therefore, timely combination with antimicrobial agents is necessary for effective treatment of PRRS-infected pigs.

18.
Steroids ; 161: 108691, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32603755

RESUMO

A novel method for determining the testosterone/epitestosterone concentration ratio in human urine was established by capillary electrophoresis with diode-array detector. The urine samples were firstly purified by the solid extraction. The optimal experimental conditions were: running buffer pH = 4.74, 15.0 mmol L-1 HAc-NaAc, separation voltage 25 kV, temperature 25 °C, sample injection pressure 3.43 × 103 Pa, and duration 10 s. The testosterone and epitestosterone linear range were determined as 8.0-960.0 ng mL-1, respectively. The testosterone and epitestosterone detection limits were determined as 4.6 and 4.5 ng mL-1, respectively. The relative standard deviation was less than 0.36%.

19.
Biotechnol Lett ; 2020 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-32567013

RESUMO

OBJECTIVE: Immune response initiation and regulation require activation of dendritic cells (DCs). However, the mechanism by which ferritin, a carrier for immunogen, induces DCs maturation remains unclear. RESULTS: Recombinant ferritin nanoparticle (RFNp), were prepared through the baculovirus expression vector system, formed spherical and hollow cage-liked proteins with a diameter of approximately 12.17 ± 0.87 nm. They induced bone marrow-derived DC (BMDC) maturation via surface molecules up-regulation of (MHC II, CD80, CD86 and CD40), increased pro-inflammatory cytokines production (IL-6, IL-12, TNF-α, and IFN-γ), and decreased antigen capturing capacity. They positively regulated IκBα and NF-κB (p65) phosphorylation, and facilitate NF-κB (p65) translocation into mature BMDCs nuclei. Following pre-treatment of RFNp-treated BMDCs with TLR4 and NF-κB (p65) inhibitors, respectively, surface molecule expression, pro-inflammatory cytokines production, and IκBα and NF-κB (p65) activities were suppressed. RFNp-treated BMDCs can also facilitate T-cell proliferation and differentiation into Th1 and Th2. CONCLUSION: RFNps induced DCs maturation lends the potential application of RFNps as carrier platforms in DC-based vaccine.

20.
Eur J Pharm Sci ; 152: 105435, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32590123

RESUMO

Thiamphenicol (TAP) is reported to be effective against many respiratory pathogens including methicillin-resistant Staphylococcus aureus (MRSA). However, its poor solubility in water remains as one of the obstacles hindering the preparation of inhalable TAP formulations. The aim of this study was to improve the dissolution rate of TAP by micronization, and investigate whether variations in the dissolution rates of TAP would affect its in vitro antibacterial activity. Inhalable dry powders composed of TAP microcrystals (MDP) or nanocrystals (NDP) were prepared by using a wet ball milling method followed by spray drying. The morphology, solid state and in vitro dissolution of these dry powders were characterized. In vitro antibacterial activities of the inhalable TAP dry powders against a MRSA strain were evaluated. A dissolution-efficacy model relating antibacterial activity with time and dissolution rate was established via modified time-kill assays. Upon being spray dried, the volumetric mean diameters of MDP and NDP were found to be around 5 µm. Solid state analyses showed that MDP and NDP possess the same crystalline form as the raw materials. NDP exhibited faster in vitro dissolution rate as compared to MDP. The in vitro antibacterial efficiency of NDP and MDP were superior to raw TAP when the test was performed at a TAP concentration of 32 mg/L. Simulated colony forming units predictions were consistent with the result measured in the time-kill experiments with Raw TAP, MDP and NDP. This study characterized the effect of the dissolution rate of TAP dry powders on in vitro antibacterial activity against MRSA, and an enhanced antibacterial activity of TAP was observed with an increase in the dissolution rate of TAP from the dry powders at certain concentration ranges.

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