Effect of iguratimod on diclofenac metabolism by CYP2C9 in rats and human recombinant CYP2C9 yeast cells

Iguratimod (IGU, also known as T-614), a novel disease modifying antirheumatic drug intended to cure patients with rheumatoid arthritis (RA). The purpose of this study is to evaluate the effect of IGU on the pharmacokinetics of CYP2C9 probe drug diclofenac and its metabolite 4′-hydroxy diclofenac in vivo and in vitro. In in vivo experiments, 24 rats were randomly assigned to three groups consisting of the control group (Normal saline), low dose IGU group (10 mg/kg) and high dose IGU group (30 mg/ kg). Blood samples were collected from orbital sinuses vein before 1 hour and serial times of giving diclofenac (15 mg/kg) to all the rats. Plasma concentration of diclofenac and its metabolite 4´-hydroxy diclofenac were assayed by high performance liquid chromatography. Pharmacokinetic parameters were assessed by Winnonlin 6.4 pharmacokinetic software. Moreover, in vitro studies were performed in recombinant human CYP2C9 yeast cell system. IGU at low dose showed no significant differences in the pharmacokinetic parameters of diclofenac and 4-hydroxy diclofenac in vivo when compared with control group (p>0.005). However, at the high dose of IGU, the pharmacokinetic parameters of 4´-hydroxy metabolite of diclofenac increase in half-life (T1/2) and mean area under the curve (AUC0→24), while a decrease in mean clearance (CL, mL/h/kg) and volume of distribution Vz (mL/kg). In addition, in in vitro study, high doses of IGU reduces the metabolism rate of diclofenac. IGU at high dose significantly increase the pharmacokinetics parameters of 4´-hydroxy diclofenac in rats. Additionally, it also showed the potent inhibitory effect on diclofenac metabolism in recombinant human CYP2C9 yeast cells

The Research Progress on China Major Minority Detoxification Methods

Based on the research and material—sorting in recent decades involving Tibetan medicine Mongolia medicine Dai medicine Zhuang medicine Yao medicine, Yi medicine, Miao medicine, Jinuo medicine. Tibetan medicine has a unique system of medical theory, which posits that poisoning incidents have close relation with rLung, nKhris-pa, Badkan three factors (namely three due to), which by adjusting three due to is balance and achieve detoxification. Mongolian medicine believes that there are five-element doctrine, cold and heat, the strength and size of detoxifying respectively. "Disease first solution, the solution after the first treatment," Dai medicine "Yajie" theory and the series of Yajie (antidote)", which play a role in detoxification lies. Zhuang medicine theory includes "virtual drug-induced diseases," the etiology and pathogenesis. By correcting the bias by that bias, in order to achieve the purpose of detoxification. Yao medical theory: the Profit and Loss Balance Theory, the Cause Theory, which are related to detoxification. According to the theory of three gas, toxin factor theory as the core contents of Yi medical theory, which the application of detoxification method is associated with. Miao medicine thinks Poison for all ills, highlight the dispel toxin factor to the poison thery of nine. Jinuo medicine is fully application of national folk-detoxification plant and animal medicines, achieve the purposes of detoxification. In this review, we summarized the major approaches applied for detoxification methods by different ethnic groups in order to provide better guide for clinical practice of food, drugs, poisons and other toxics. This work provides also potential clinical application to open up a new way of thinking and new perspective for detoxification therapy based on the accumulated knowledge in traditional Chinese medicine

Oscillatory tunnel magnetoresistance in double barrier magnetic tunnel junctions

We report an unconventional oscillatory tunnel magnetoresistance as a function of the applied bias in double barrier magnetic tunnel junctions that were made of two Al2O3 barriers sandwiched by three ferromagnetic layers. When the center ferromagnetic layer is aligned antiparallel to the top and bottom magnetic layers, a distinct magnetoresistance oscillation appears with respect to the increase of the bias voltage at 4.2 K and at room temperature. The period of the oscillation is about 1.6 mV

Anxiety and depression mediate the relationship between digestive tract conditions and oral health-related quality of life in orthodontic patients

BackgroundAnxiety and depression are common psychological problems in orthodontic patients whose diet habits and oral health status change frequently during treatment. However, relationships between anxiety and depression, digestive tract condition, and impaired oral health-related quality of life remain unknown.Materials and methodsIn this study, clinical assessments, including anxiety, depression, digestive tract condition, and oral health-related quality of life, were collected from 769 outpatients in the orthodontic department using three self-reported questionnaires. Correlation analysis was used to investigate the relationships among different clinical assessments. A chained mediation analysis model was further conducted to explore the direct and indirect effects of these various clinical factors.ResultsChanges in digestive tract conditions were positively correlated with the psychological status and oral health-related quality of life. Anxiety and depression partially mediated the relationship between them, and the indirect effect was 0.68 (30%), of which the mediation effect of anxiety accounted for 56%.ConclusionAnxiety and depression mediate the relationship between gastrointestinal conditions and oral health. In particular, anxiety seems to play a significant mediating role. Our findings indicate that psychological status must be paid more attention to in future clinical practices and supervision for digestive tract symptoms of orthodontic patients

Electrospun PEDOT:PSS/PVP Nanofibers for CO Gas Sensing with Quartz Crystal Microbalance Technique

Poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate)/polyvinylpyrrolidone (PEDOT:PSS/PVP) composite nanofibers were successfully fabricated via electrospinning and used as a quartz crystal microbalance (QCM) sensor for detecting CO gas. The electrical property of individual PEDOT:PSS/PVP nanofibers was characterized and the room temperature resistivity was at the magnitude of 105 Ω·m. The QCM sensor based on PEDOT:PSS/PVP nanofibers was sensitive to low concentration (5–50 ppm) CO. In the range of 5–50 ppm CO, the relationship between the response of PEDOT:PSS nanofibers and the CO concentration was linear. Nevertheless, when the concentration exceeded 50 ppm, the adsorption of the nanofiber membrane for CO gas reached saturation and the resonant frequency range had no change. Therefore, the results open an approach to create electrospun PEDOT:PSS/PVP for gas sensing applications

Electrical transport properties of an isolated CdS microrope composed of twisted nanowires

CdS is one of the important II-VI group semiconductors. In this paper, the electrical transport behavior of an individual CdS microrope composed of twisted nanowires is studied. It is found that the current–voltage (I-V) characteristics show two distinct power law regions from 360 down to 60 K. Space-charge-limited current (SCLC) theory is used to explain these temperature- and electric-field-dependent I-V curves. The I-V data can be well fitted by this theory above 100 K, and the corresponding carrier mobility, trap energy, and trap concentration are also obtained. However, the I-V data exhibit some features of the Coulomb blockade effect below 80 K

Pituitary tissue-specific miR-7a-5p regulates FSH expression in rat anterior adenohypophyseal cells

The follicle-stimulating hormone (FSH), which is synthesized and secreted by the anterior pituitary gland, plays an important role in regulating reproductive processes. In this study, using the TargetScan program, we predicted that microRNAs (miRNAs) regulate FSH secretion. Dual-luciferase reporter assays were performed and identified miR-7a-5p. MiR-7a-5p has been reported to regulate diverse cellular functions. However, it is unclear whether miR-7a-5p binds to mRNAs and regulates reproductive functions. Therefore, we constructed a suspension of rat anterior pituitary cells and cultured them under adaptive conditions, transfected miR-7a-5p mimics or inhibitor into the cell suspension and detected expression of the FSHb gene. The results demonstrated that miR-7a-5p downregulated FSHb expression levels, while treatment with miR-7a-5p inhibitors upregulated FSHb expression levels relative to those of negative control groups, as shown by quantitative PCR analysis. The results were confirmed with a subsequent experiment showing that FSH secretion was reduced after treatment with mimics and increased in the inhibitor groups, as shown by enzyme-linked immunosorbent assay. Our results indicated that miR-7a-5p downregulates FSHb expression levels, resulting in decreased FSH synthesis and secretion, which demonstrates the important role of miRNAs in the regulation of FSH and animal reproduction

Epidemiology of autism spectrum disorders: Global burden of disease 2019 and bibliometric analysis of risk factors

BackgroundTo explore the geographical pattern and temporal trend of autism spectrum disorders (ASD) epidemiology from 1990 to 2019, and perform a bibliometric analysis of risk factors for ASD.MethodsIn this study, ASD epidemiology was estimated with prevalence, incidence, and disability-adjusted life-years (DALYs) of 204 countries and territories by sex, location, and sociodemographic index (SDI). Age-standardized rate (ASR) and estimated annual percentage change (EAPC) were used to quantify ASD temporal trends. Besides, the study performed a bibliometric analysis of ASD risk factors since 1990. Publications published were downloaded from the Web of Science Core Collection database, and were analyzed using CiteSpace.ResultsGlobally, there were estimated 28.3 million ASD prevalent cases (ASR, 369.4 per 100,000 populations), 603,790 incident cases (ASR, 9.3 per 100,000 populations) and 4.3 million DALYs (ASR, 56.3 per 100,000 populations) in 2019. Increases of autism spectrum disorders were noted in prevalent cases (39.3%), incidence (0.1%), and DALYs (38.7%) from 1990 to 2019. Age-standardized rates and EAPC showed stable trend worldwide over time. A total of 3,991 articles were retrieved from Web of Science, of which 3,590 were obtained for analysis after removing duplicate literatures. “Rehabilitation”, “Genetics & Heredity”, “Nanoscience & Nanotechnology”, “Biochemistry & Molecular biology”, “Psychology”, “Neurosciences”, and “Environmental Sciences” were the hotspots and frontier disciplines of ASD risk factors.ConclusionsDisease burden and risk factors of autism spectrum disorders remain global public health challenge since 1990 according to the GBD epidemiological estimates and bibliometric analysis. The findings help policy makers formulate public health policies concerning prevention targeted for risk factors, early diagnosis and life-long healthcare service of ASD. Increasing knowledge concerning the public awareness of risk factors is also warranted to address global ASD problem

Genomic and oncogenic preference of HBV integration in hepatocellular carcinoma

Hepatitis B virus (HBV) can integrate into the human genome, contributing to genomic instability and hepatocarcinogenesis. Here by conducting high-throughput viral integration detection and RNA sequencing, we identify 4,225 HBV integration events in tumour and adjacent non-tumour samples from 426 patients with HCC. We show that HBV is prone to integrate into rare fragile sites and functional genomic regions including CpG islands. We observe a distinct pattern in the preferential sites of HBV integration between tumour and non-tumour tissues. HBV insertional sites are significantly enriched in the proximity of telomeres in tumours. Recurrent HBV target genes are identified with few that overlap. The overall HBV integration frequency is much higher in tumour genomes of males than in females, with a significant enrichment of integration into chromosome 17. Furthermore, a cirrhosis-dependent HBV integration pattern is observed, affecting distinct targeted genes. Our data suggest that HBV integration has a high potential to drive oncogenic transformation