38 research outputs found

    Anaphylaxis as a Rare Side Effect of Pantoprazole; a Case Report

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    Anaphylaxis is a serious life-threatening allergic reaction. Any medication may potentially trigger anaphylaxis, but reaction to pantoprazole is rare. Our case is a 21 year-old girl with anaphylactic reaction to pantoprazole a short time after prescription

    Comparative modeling of CCRL1, a key protein in masked immune diseases and virtual screening for finding inhibitor of this protein

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    Human CCRL1 belongs to the family of silent chemokine receptors. This transmembrane protein plays a role in blunting function of chemokines through binding to them. This will attenuate immune responses. Interaction between CCRL1 and CCL21 determines this immune extinction. Thus inhibiting the action of this atypical chemokine seems to stimulate immune responses especially in the case of suppressed and immune deficient conditions. In this study we predicted 3D structure of CCRL1 using comparative modeling and Hiddebn Markov Model algorithm. Final predicted model optimized by Modeller v9.8 and minimized regarding energy level using UCSF chimera candidate version1.5.3. ClasPro webserver was used to find interacting residues between CCRL1 and CCL21. Interacting residues were used as target for chemical inhibitors by simulated docking study. For finding potential inhibitors, library of KEGG compounds screened and 97 obtained chemicals docked against interacting residues between CCRL1- CCL21 and MolDock was used as docking scoring function. Results indicated that Hexadecanal is a potential inhibitor of CCRL1- CCL21 interaction. Inhibition of this interaction will increase intercellular level of CCl21 and interaction between CCL21 and CCR7 causes immune potentiaiton

    Comparison of the extracellular full-length and truncated recombinant protein A production in Escherichia coli BL21 (DE3)

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         Protein A is a commercially important protein in biotechnological and medicinal applications. The great value of this protein and its applications in genetic and protein engineering and microbial researches as well as the growing use in biochemical industries, biotechnology, medicine and pharmacology, highlight the importance of the present study. In this survey the encoding genes of full-length and truncated forms of protein A were expressed in E. coli under an optimized expression condition. Optimization of the culture conditions resulted in an increase in expression and secretion of both forms of the protein, the pattern of expression and secretion levels for two forms was completely different. A minimum of 10-fold higher expression was observed for the truncated protein in comparison to that of the full-length recombinant form. Hydropathy plot of both forms of proteins showed that the missing domains in the truncated form contain groups of amino acids with high hydrophobicity score. Deletion of the terminal region could led to a higher expression level of the recombinant protein in E. coli. The function of these two proteins was studied using ELISA, which showed a higher activity for the truncated form for binding to IgG, compared to the full-length protein.

    Robust Adaptive Control of a Micro Telemanipulation System Using Sliding Mode-Based Force Estimation

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    Abstract-Piezoelectric actuators are widely used in micro manipulation applications. However, hysteresis nonlinearity limits the accuracy of these actuators. This paper presents a novel approach for utilizing a piezoelectric nano-stage as the slave manipulator of a teleoperation system based on a sliding mode controller. The Prandtl-Ishlinskii (PI) model is used to model actuator hysteresis in feedforward scheme to cancel out this nonlinearity. The presented approach requires full state and force measurements at both the master and slave sides. Such a system is costly and also difficult to implement. Therefore, sliding mode unknown input observer (UIO) is proposed for full state and force estimations. Furthermore, the effects of uncertainties in the constant parameters on the estimated external forces should be eliminated. So, a robust adaptive controller is proposed and its stability is guaranteed through the Lyapunov criterion. Performance of the proposed control architecture is verified through experiments

    A Comparative Study on Anticancer Effects of the Alhagi maurorum and Amygdalus haussknechtii Extracts Alone and in Combination with Docetaxel on 4T1 Breast Cancer Cells

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    Medicinal plants have long been studied due to their anticancer effects and use of them is commonly increased as a complementary and alternative medicine (CAM therapies) among patients with cancer. In this study, Alhagi maurorum (A.m) and Amygdalus haussknechtii (A.h) extracts were evaluated for their effects on inhibiting the growth of 4T1 breast cancer cells. Based on MTT assay results, the IC50s of A.m and A.h extracts were 57 mu g/ml and 85 mu g/ml, respectively. Then the cell migration, gene expression, and degree of apoptosis after 48 hours in each treated group with A.m and A.h extracts alone or in combination with docetaxel (DTX) on 4T1 cells were evaluated. A.m had a synergistic behavior with DTX (CI 1. Cell migration assay showed that each extract alone or in combination with DTX prevented the migration of 4T1 cells. The Ao/EB staining and flowcytometry results confirmed that, in combination therapy, A.m + DTX and A.h + DTX induced apoptosis close to the level of DTX. Real-time PCR analysis showed that A.m + DTX (IC50 + IC25) downregulated the mRNA expression of HIF-1 alpha and FZD7. A.m + DTX (IC50 + IC10) group decreased the expression of HIF-1 alpha. Moreover, in A.h + DTX (IC50 + IC25) group, beta-Catenin and FZD7 were downregulated and upregulated, respectively. Generally, our findings suggest that the combination of A.m and DTX possesses synergistic antitumor effects on 4T1 cells, which may be a valuable choice for CAM therapies. A.h has an acceptable antitumor activity but not in combination with DTX

    New mechanistic insights into hepatoprotective activity of milk thistle and chicory quantified extract: The role of hepatic Farnesoid-X activated receptors

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    Objective: Farnesoid-X-activated receptors (FXR) are key modulators of liver regeneration. Milk thistle and Chicory are known as potent protective remedies in several liver disorders. The objective of this work was to examine the role of FXR in the hepato-healing properties of milk thistle (MTE) and chicory extracts (CE) in a rat model of acetaminophen-induced hepatotoxicity. Materials and Methods: Male Wistar rats were randomly divided into seven groups including control, vehicle, acetaminophen (500 mg/kg/day, oral), acetaminophen plus oral MTE 200 and 400 mg/kg/day, and acetaminophen plus oral CE 500 and 1000 /kg/day for 28 days. Liver function and histology as well as the pattern of hepatic FXR expression were assessed after 4 weeks. Results: Administration of acetaminophen was associated with a significant elevation of liver transaminase along with the architectural injuries. In contrast, chronic concomitant administration of both MTE and CE significantly restored the liver function and structural abnormality. The main molecular findings of the study revealed that the lower doses of both MTE and CE led to a marked upregulation of hepatic FXR expression. Conclusion: Discovery of the involvement of the nuclear modulating pathways in hepatoprotective activity of the extracts, providesa new mechanistic insight which needs further investigations

    Activation of PI3-Kinase Is Required for AMPA Receptor Insertion during LTP of mEPSCs in Cultured Hippocampal Neurons

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    AbstractHippocampal CA1 homosynaptic long-term potentiation (LTP) is expressed specifically at activated synapses. Increased insertion of postsynaptic α-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptors (AMPARs) appears to be crucial for CA1 LTP. However, the mechanism underlying AMPAR insertion during LTP remains largely unknown. We now report that phosphatidylinositol 3-kinase (PI3K) is complexed with AMPARs at synapses and activated by selective stimulation of synaptic N-methyl-D-aspartate (NMDA) receptors. Activation of the AMPAR-associated PI3K is required for the increased cell surface expression of AMPARs and LTP. Thus, our results strongly suggest that the AMPAR-PI3K complex may constitute a critical molecular signal responsible for AMPAR insertion at activated CA1 synapses during LTP, and consequently, this lipid kinase may serve to determine the polarity of NMDA receptor-dependent synaptic plasticity

    The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017 : a systematic analysis for the Global Burden of Disease Study 2017

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    Background Cirrhosis and other chronic liver diseases (collectively referred to as cirrhosis in this paper) are a major cause of morbidity and mortality globally, although the burden and underlying causes differ across locations and demographic groups. We report on results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 on the burden of cirrhosis and its trends since 1990, by cause, sex, and age, for 195 countries and territories. Methods We used data from vital registrations, vital registration samples, and verbal autopsies to estimate mortality. We modelled prevalence of total, compensated, and decompensated cirrhosis on the basis of hospital and claims data. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost due to premature death and years lived with disability. Estimates are presented as numbers and age-standardised or age-specific rates per 100 000 population, with 95% uncertainty intervals (UIs). All estimates are presented for five causes of cirrhosis: hepatitis B, hepatitis C, alcohol-related liver disease, non-alcoholic steatohepatitis (NASH), and other causes. We compared mortality, prevalence, and DALY estimates with those expected according to the Socio-demographic Index (SDI) as a proxy for the development status of regions and countries. Findings In 2017, cirrhosis caused more than 1.32 million (95% UI 1.27-1.45) deaths (440000 [416 000-518 000; 33.3%] in females and 883 000 [838 000-967 000; 66.7%] in males) globally, compared with less than 899 000 (829 000-948 000) deaths in 1990. Deaths due to cirrhosis constituted 2.4% (2.3-2.6) of total deaths globally in 2017 compared with 1.9% (1.8-2.0) in 1990. Despite an increase in the number of deaths, the age-standardised death rate decreased from 21.0 (19.2-22.3) per 100 000 population in 1990 to 16.5 (15.8-18-1) per 100 000 population in 2017. Sub-Saharan Africa had the highest age-standardised death rate among GBD super-regions for all years of the study period (32.2 [25.8-38.6] deaths per 100 000 population in 2017), and the high-income super-region had the lowest (10.1 [9.8-10-5] deaths per 100 000 population in 2017). The age-standardised death rate decreased or remained constant from 1990 to 2017 in all GBD regions except eastern Europe and central Asia, where the age-standardised death rate increased, primarily due to increases in alcohol-related liver disease prevalence. At the national level, the age-standardised death rate of cirrhosis was lowest in Singapore in 2017 (3.7 [3.3-4.0] per 100 000 in 2017) and highest in Egypt in all years since 1990 (103.3 [64.4-133.4] per 100 000 in 2017). There were 10.6 million (10.3-10.9) prevalent cases of decompensated cirrhosis and 112 million (107-119) prevalent cases of compensated cirrhosis globally in 2017. There was a significant increase in age-standardised prevalence rate of decompensated cirrhosis between 1990 and 2017. Cirrhosis caused by NASH had a steady age-standardised death rate throughout the study period, whereas the other four causes showed declines in age-standardised death rate. The age-standardised prevalence of compensated and decompensated cirrhosis due to NASH increased more than for any other cause of cirrhosis (by 33.2% for compensated cirrhosis and 54.8% for decompensated cirrhosis) over the study period. From 1990 to 2017, the number of prevalent cases snore than doubled for compensated cirrhosis due to NASH and more than tripled for decompensated cirrhosis due to NASH. In 2017, age-standardised death and DALY rates were lower among countries and territories with higher SDI. Interpretation Cirrhosis imposes a substantial health burden on many countries and this burden has increased at the global level since 1990, partly due to population growth and ageing. Although the age-standardised death and DALY rates of cirrhosis decreased from 1990 to 2017, numbers of deaths and DALYs and the proportion of all global deaths due to cirrhosis increased. Despite the availability of effective interventions for the prevention and treatment of hepatitis B and C, they were still the main causes of cirrhosis burden worldwide, particularly in low-income countries. The impact of hepatitis B and C is expected to be attenuated and overtaken by that of NASH in the near future. Cost-effective interventions are required to continue the prevention and treatment of viral hepatitis, and to achieve early diagnosis and prevention of cirrhosis due to alcohol-related liver disease and NASH. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.Peer reviewe
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