32 research outputs found

    Identification of NLRP3 PYD Homo-Oligomerization Inhibitors with Anti-Inflammatory Activity

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    [EN] Inflammasomes are multiprotein complexes that represent critical elements of the inflammatory response. The dysregulation of the best-characterized complex, the NLRP3 inflammasome, has been linked to the pathogenesis of diseases such as multiple sclerosis, type 2 diabetes mellitus, Alzheimer's disease, and cancer. While there exist molecular inhibitors specific for the various components of inflammasome complexes, no currently reported inhibitors specifically target NLRP3(PYD) homo-oligomerization. In the present study, we describe the identification of QM380 and QM381 as NLRP3(PYD) homo-oligomerization inhibitors after screening small molecules from the MyriaScreen library using a split-luciferase complementation assay. Our results demonstrate that these NLRP3(PYD) inhibitors interfere with ASC speck formation, inhibit pro-inflammatory cytokine IL1-beta release, and decrease pyroptotic cell death. We employed spectroscopic techniques and computational docking analyses with QM380 and QM381 and the PYD domain to confirm the experimental results and predict possible mechanisms underlying the inhibition of NLRP3(PYD) homo-interactions.This research was funded by EC-funded RISE (EPIC 690939), Spanish Ministry of Economy and Competitiveness, FEDER (SAF2017-84689-R), Generalitat Valenciana (PROMETEO/2019/065), research council of Tarbiat Modares University (#IG/39803).Moasses Ghafary, S.; Soriano-Teruel, P.; Lotfollahzadeh, S.; Sancho, M.; Serrano-Candelas, E.; Karami, F.; Barigye, SJ.... (2022). Identification of NLRP3 PYD Homo-Oligomerization Inhibitors with Anti-Inflammatory Activity. International Journal of Molecular Sciences. 23(3):1-15. https://doi.org/10.3390/ijms2303165111523

    Label-Free and Bioluminescence-Based Nano-Biosensor for ATP Detection

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    A bioluminescence-based assay for ATP can measure cell viability. Higher ATP concentration indicates a higher number of living cells. Thus, it is necessary to design an ATP sensor that is low-cost and easy to use. Gold nanoparticles provide excellent biocompatibility for enzyme immobilization. We investigated the effect of luciferase proximity with citrate-coated gold, silver, and gold–silver core–shell nanoparticles, gold nanorods, and BSA–Au nanoclusters. The effect of metal nanoparticles on the activity of luciferases was recorded by the luminescence assay, which was 3–5 times higher than free enzyme. The results showed that the signal stability in presence of nanoparticles improved and was reliable up to 6 h for analytes measurements. It has been suggested that energy is mutually transferred from luciferase bioluminescence spectra to metal nanoparticle surface plasmons. In addition, we herein report the 27-base DNA aptamer for adenosine-5′-triphosphate (ATP) as a suitable probe for the ATP biosensor based on firefly luciferase activity and AuNPs. Due to ATP application in the firefly luciferase reaction, the increase in luciferase activity and improved detection limits may indicate more stability or accessibility of ATP in the presence of nanoparticles. The bioluminescence intensity increased with the ATP concentration up to 600 µM with a detection limit of 5 µM for ATP

    Students' Attitude Towards Marriage and Factors Affecting It

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    Introduction The aim of this research is to study female students' attitude towards marriage and factors affecting it in Ferdowsi University of Mashhad. Marriage is a basic institution in all societies and, which prepares the conditions for forming families and reproduction as one of most basic functions of society (Larson and Holman 1994; Higgins et al 2002). Not only does marriage have positive influences on physical and mental health of individuals, but it also plays a great role in transmitting to adulthood. As marriage is not isolated from specific conditions of time and location, it has its own characteristics in any given society (Shoa Kazemi and Harandi 2010:112). The Iranian society in recent years, along with changes in technology and relationships with other nations, has undergone many changes. Values and attitudes to the family and marriage are a part of these changes. When it come to women's role in different aspects of society, studying their values and attitudes become important. Changes in the structure of education, women's employment, improvements in their professional skills and diffusion of feminist ideas, all have led women to reflect on their traditional roles and identities. For example, they ask for equal rights in all aspects and want more freedom in mating. Materials and Methods This study is a cross-sectional survey with descriptive goals. The data was gathered by a researcher-made questionnaire from a population of 13181 female students in 2014 in Ferdowsi University of Mashhad. The sample includes 374 students who were selected using stratified random sampling method. Discussion of Results and Conclusions   The results of the study show that our main hypothesis, which says “there is a significant relationship between perceptions of gender role clichés and attitudes towards marriage” is confirmed. This means that people who easily internalize and accept gender role clichés have more traditional attitudes toward marriage and vice versa. Likewise, the results also show that there is a significant relationship between respondents' religious background with their attitude towards marriage. This means that those with more religiosity, hold more traditional attitudes toward marriage, and those who have lower levels of religiosity, are more likely to have a modern attitude towards marriage.   The findings also show that there is significant relationship between attitude towards marriage and the variable of cost-benefit opportunity, namely, the respondents who believe marriage is a cost-benefit exchange, have a more modern attitude towards marriage. On the contrary, those respondents who believed marriage cannot be looked at as a cost-benefit transaction, have a more traditional attitude towards marriage.   The result of multiple regression analysis show that the amount of F is equal to 357/05 and the level o the significance is 0/000. Therefore, the model in its entirety is significant. By comparing the standardized regression coefficients (Beta) outputs of the multiple regression model for, we realized that religiosity has the most powerful effect on the dependent variable. The second most powerful independent variable is the variable of cost-benefit opportunity. Both of these variables had the highest effect on attitude towards marriage in a path analysis model as well. In sum this research show that student's attitude toward marriage is more traditional, when religiosity is the strongest predictor of attitude towards marriage

    Design and bioinformatics analysis of novel biomimetic peptides as nanocarriers for gene transfer

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    Objective(s): The introduction of nucleic acids into cells for therapeutic objectives is significantly hindered by the size and charge of these molecules and therefore requires efficient vectors that assist cellular uptake. For several years great efforts have been devoted to the study of development of recombinant vectors based on biological domains with potential applications in gene therapy. Such vectors have been synthesized in genetically engineered approach, resulting in biomacromolecules with new properties that are not present in nature. Materials and Methods: In this study, we have designed new peptides using homology modeling with the purpose of overcoming the cell barriers for successful gene delivery through Bioinformatics tools. Three different carriers were designed and one of those with better score through Bioinformatics tools was cloned, expressed and its affinity for pDNA was monitored. Results: The resultszz demonstrated that the vector can effectively condense pDNAinto nanoparticles with the average sizes about 100 nm. Conclusion: We hope these peptides can overcome the biological barriers associated with gene transfer, and mediate efficient gene delivery

    Investigation on the mechanical and decay resistance properties of wood modified with maleic anhydride and methyl metacrylate

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    This research was conducted to investigate the effect of modification with maleic anhydride and methyl methacrylate on mechanical properties and decay resistance of poplar wood. Samples of mechanical and biological resistance tests were prepared according to ASTM D143-94 and EN113 standards. Treatment levels were divided into 4 groups; control, methyl methacrylate, maleic anhydride and combined of maleic anhydride/ methyl methacrylate. Samples were impregnated with maleic anhydride and monomer using vacuum- pressure method with experimental cylinder. Maleic anhydride treated samples were heated in oven for 4 and 24 hours at 150 and 103ÂşC. For polymerization, methyl methacrylate monomer treated samples were heated in oven at 90ÂşC for 24 hours, consequently at 103ÂşC for the same time. Methyl methacrylate polymer coating formed on the cell wall, causing 22.57% improvement in the lateral stability under pressure parallel to grain. Highest value in modules of rupture, elasticity and hardness were measured in combined level with 24.13, 47.13 and 45.53% improvement compared with the control, respectively. Maleic anhydride in the presence of methyl methacrylate, with decreasing polarity of the wood and create a good distribution of the particle and the polymer, resulting in the cross linking formation and transmission of uniform tension that would lead to improved mechanical properties. Also, decay resistance was improved in all levels of modification, so that weight loss declined from 80.4% in control to 4.29% in combined level. Modified with maleic anhydride because of the wood composition change, reduction in moisture absorption ability of cell wall and bulking effect, and the presence of methyl methacrylate in the cell cavities as a physical barrier to the movement of fungi mycelium and moisture, were leading to improved decay resistance
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