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Per Med ; 17(1): 15-22, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31797717


Aim: This study investigated the association between voriconazole-induced liver injury and gene polymorphisms of CYP2C19 and UGT1A4. Materials & methods: Thirty-eight adult patients who received voriconazole therapy were included in the study. Genotype of CYP2C19 was detected using gene chip hybrid analysis. The UGT1A4 142T>G was genotyped using PCR-RFLP analysis. Results: Ten patients (26.3%) had voriconazole-induced liver injury and were considered as the case group There was no significant difference between the two groups in genotype and allele frequencies of CYP2C19*2 and UGT1A4 142T>G (p > 0.05), however, the GA frequency of CYP2C19 *3 in the drug-induced liver injury case group was higher than that in the control group (p < 0.05). Compared with patients carrying *1/*1 or *1/*2, there was no significant difference in voriconazole trough concentration of the patients with *1/*3 (p > 0.05). Conclusion: There was no significant correlation between voriconazole-induced liver injury and gene polymorphisms of CYP2C19 and UGT1A4.

Int Immunopharmacol ; 78: 106043, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31837574


Protectin DX (PDX) has been reported to have extensive anti-inflammatory effects. However, it is unknown whether PDX acts as an anti-inflammatory agent in the context of osteoarthritis (OA). This study aimed to evaluate the anti-inflammatory activity of PDX in vitro and in vivo in a model of OA. Primary rat chondrocytes were preincubated with PDX 1 h prior to IL-1ß treatment for 24 h. We found that PDX was nontoxic, and pretreatment with PDX increased cell viability in IL-1ß-induced chondrocytes. Preincubation with PDX also efficiently inhibited the degradation of type II collagen dose-dependently. Additionally, the expression of MMP-3, MMP-13, ADAMTS4, iNOS, COX-2, NO, and PGE2 decreased after IL-1ß stimulation when cells were preincubated with PDX. Moreover, PDX inhibited the increase in phosphorylated NF-κB p65 and IκBα upon IL-1ß stimulation, and the negative effects of IL-1ß on chondrocytes were partially blocked by treatment with pyrrolidine dithiocarbamate (PDTC), a selective NF-κB inhibitor. In addition, we found that PDX increased AMPK phosphorylation in IL-1ß-mediated chondrocytes. The phosphorylation of AMPK could be inhibited by compound C, a classic AMPK inhibitor. Compound C also remarkably reversed the decrease in p65 phosphorylation and MMP-13 expression caused by PDX. Furthermore, nuclear translocation of NF-κB was visible by immunofluorescence after PDX-induced AMPK activation. Additionally, we verified that PDX ameliorated cartilage degradation in monosodium iodoacetate (MIA)-induced OA rats through histological evaluation and ELISA of TNF-α in the serum and intra-articular lavage fluid. In conclusion, we have shown that PDX suppresses inflammation in chondrocytes in vitro and in vivo, likely through the AMPK/NF-κB signaling pathway. Our results suggest that PDX could be a useful novel therapeutic agent for OA treatment.

Sci Prog ; : 36850419877762, 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31829874


Electric vehicles can convert the kinetic energy of the vehicle into electric energy for recycling. A reasonable braking force distribution strategy is the key to ensure braking stability and the energy recovery rate. For an electric vehicle, based on the ECE regulation curve and ideal braking force distribution (I curve), the braking force distribution strategy of the front and rear axles is designed to study the braking energy recovery control strategy. The fuzzy control method is adopted while the charging power limit of the battery is considered to correct the regenerative braking torque of the motor, the ratio of the regenerative braking force of the motor to the front axle braking force is designed according to different braking strengths, then the braking force distribution and braking energy recovery control strategies for regenerative braking and friction braking are developed. The simulation model of combined vehicle and energy recovery control strategy is established by Simulink and Cruise software. The braking energy recovery control strategy of this article is verified under different braking conditions and New European Driving Cycle conditions. The results show that the control strategy proposed in this article meets the requirements of braking stability. Under the condition of initial state of charge of 75%, the variation of state of charge of braking control strategy in this article is reduced by 8.22%, and the state of charge of braking strategy based on I curve reduces by 9.12%. The braking force distribution curves of the front and rear axle are in line with the braking characteristics, can effectively recover the braking energy, and improve the battery state of charge. Taking the using range of 95%-5% of battery state of charge as calculation target, the cruising range of vehicle with braking control strategy of this article increases to 136.64 km, which showed that the braking control strategy in this article could increase the cruising range of the electric vehicle.

Microb Pathog ; 137: 103765, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31586475


OBJECTIVE: To explore the effect of sub-minimal inhibitory concentration (sub-MIC) and concentrations within resistant mutation window (MSW) of ciprofloxacin (CIP) on minimal inhibitory concentration (MIC), swimming motility and biofilm formation of Pseudomonas aeruginosa, and also to investigate the correlation between swimming motility and genes expression of lasI, lasR, rhlI, rhlR and pqsR. METHODS: The collected strains were incubated under four different concentrations for 5 days. The MIC and mutant prevention concentration (MPC) were measured by the agar dilution method. The diameter of turbid cycle was used to signify the swimming motility. The biofilm formation was measured by the crystal violet stain method. The genes expression of lasI, lasR, rhlI, rhlR and pqsR were measured by RT-PCR. RESULTS: A total of 11 P. aeruginosa which sensitive to CIP were collected. The incubation within concentrations of MSW made MICs to CIP increased more obviously than under sub-MIC (P < 0.05). The swimming motility showed a trend of being inhibited first and then promoted over time under sub-MIC (P < 0.05), whereas, it was promoted under concentrations within MSW. The biofilm formation was significantly promoted under the concentration of 4×MIC (P < 0.05). Under sub-MIC, the genes expression of rhlR and pqsR had a middle level positive correlation with the promotion of the swimming motility (P < 0.05, r = 0.788 and P < 0.05, r = 0.652, respectively). CONCLUSIONS: Under the concentration of sub-MIC (0.5×MIC) and the concentrations within MSW (1×MIC, 2×MIC and 4×MIC), the effect of CIP on MICs, swimming motility and biofilm formation of P.aeruginosa was quite different. The genes expression of rhlR and pqsR had a middle level positive correlation with the promotion of the swimming motility.

Infect Drug Resist ; 12: 261-272, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30804676


Purpose: To investigate the main molecular resistance mechanisms to fluoroquinolones (FQs) in Pseudomonas aeruginosa and also to investigate the effect of time and concentration on mutations in resistance genes. Materials and methods: The clinical isolates of P. aeruginosa which are sensitive to ciprofloxacin (CIP) or levofloxacin (LEV) were collected. The isolates were incubated with different concentrations of CIP or LEV for 5 days and the minimal inhibitory concentrations (MICs) of CIP, LEV and ofloxacin (OFX) were measured. The MIC of FQs to P. aeruginosa was measured by the agar dilution method. FQ resistance determining regions of gyrA, gyrB, parC and parE were amplified by PCR, and mutations in four genes were explored using sequence analysis with the Snapgene software. The relative expression levels of two efflux pumps genes (mexA and mexE) were measured by quantitative reverse transcription PCR. Results: A total of eleven isolates were collected from the Second Hospital of Shanxi Medical University. Amino acid alterations in gyrA and gyrB were mainly detected in resistant mutants, and the percentage of strains with amino acid alterations in gyrB was significantly higher than that in gyrA (P<0.001). MICs of strains with mutations both in gyrA and gyrB were not significantly higher than those of strains with mutations only in gyrB (P>0.05). No amino acid alterations were detected in genes of parC and parE. In both gyrA and gyrB, the number of amino acid alterations increased with incubation time prolonged and increased with increasing incubation concentration. Conclusion: CIP was more competent than LEV in making P. aeruginosa resistant to in vitro selection. Mutations occurring in gyrB played an important role in FQ resistance of P. aeruginosa in vitro selection.

J Environ Sci (China) ; 24(4): 665-74, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22894101


The formation and development of weather events has a great impact on the diffusion, accumulation and transport of air pollutants, and causes great changes in the particulate pollution level. It is very important to study their influence on particulate pollution. Lanzhou is one of the most particulate-polluted cities in China and even in the world. Particulate matter (PM) including TSP, PM >10, PM2.5-10, PM2.5 and PM1.0 concentrations were simultaneously measured during 2005-2007 in Lanzhou to evaluate the influence of three kinds of weather events--dust, precipitation and cold front--on the concentrations of PM with different sizes and detect the temporal evolution. The main results are as follows: (1) the PM pollution in Lanzhou during dust events was very heavy and the rate of increase in the concentration of PM2.5-10 was the highest of the five kinds of particles. During dust-storm events, the highest peaks of the concentrations of fine particles (PM2.5 and PM1.0) occurred 3 hr later than those of coarse particles (PM>10 and PM2.5-10). (2) The major effect of precipitation events on PM is wet scavenging. The scavenging rates of particles were closely associated with the kinds of precipitation events. The scavenging rates of TSP, PM>10 and PM2.5-10 by convective precipitation were several times as high as those caused by frontal precipitation for the same precipitation amount, the reason being the different formation mechanism and precipitation characteristics of the two kinds of precipitation. Moreover, there exists a limiting value for the scavenging rates of particles by precipitation. (3) The major effect of cold-front events on particles is clearance. However, during cold-front passages, the PM concentrations could sometimes rise first and decrease afterwards, which is the critical difference in the influence of cold fronts on the concentrations of particulate pollutants vs. gaseous pollutants.

Cidades , Tamanho da Partícula , Material Particulado/análise , Material Particulado/química , Tempo (Meteorologia) , China , Temperatura Baixa , Poeira/análise , Chuva , Estações do Ano , Neve , Fatores de Tempo