22 research outputs found

    Comprehensive analysis of epigenetic clocks reveals associations between disproportionate biological ageing and hippocampal volume

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    The concept of age acceleration, the difference between biological age and chronological age, is of growing interest, particularly with respect to age-related disorders, such as Alzheimer’s Disease (AD). Whilst studies have reported associations with AD risk and related phenotypes, there remains a lack of consensus on these associations. Here we aimed to comprehensively investigate the relationship between five recognised measures of age acceleration, based on DNA methylation patterns (DNAm age), and cross-sectional and longitudinal cognition and AD-related neuroimaging phenotypes (volumetric MRI and Amyloid-β PET) in the Australian Imaging, Biomarkers and Lifestyle (AIBL) and the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Significant associations were observed between age acceleration using the Hannum epigenetic clock and cross-sectional hippocampal volume in AIBL and replicated in ADNI. In AIBL, several other findings were observed cross-sectionally, including a significant association between hippocampal volume and the Hannum and Phenoage epigenetic clocks. Further, significant associations were also observed between hippocampal volume and the Zhang and Phenoage epigenetic clocks within Amyloid-β positive individuals. However, these were not validated within the ADNI cohort. No associations between age acceleration and other Alzheimer’s disease-related phenotypes, including measures of cognition or brain Amyloid-β burden, were observed, and there was no association with longitudinal change in any phenotype. This study presents a link between age acceleration, as determined using DNA methylation, and hippocampal volume that was statistically significant across two highly characterised cohorts. The results presented in this study contribute to a growing literature that supports the role of epigenetic modifications in ageing and AD-related phenotypes

    Construction of a recombinant B-cell epitope vaccine based on a der p1-derived hypoallergen: A bioinformatics approach

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    Aim: House dust mite (HDM) allergens are important elicitors of IgE-mediated allergies. This study was aimed at constructing and characterizing a recombinant fusion protein, DpTTDp, which was based on carrier-bound Der p 1-derived peptides for HDM allergen immunotherapy. Methods: Using the Immune Epitope Database (IEDB), we identified from Der p 1, a 34-mer hypoallergenic peptide. Two copies of the hypoallergen were then fused to a partial fragment of a tetanus toxoid molecule's N-and C terminus and expressed in Escherichia coli. After purification to homogeneity, the protein was evaluated for allergenicity and its ability to induce blocking antibodies upon immunization. Results: Upon immunization of mice, DpTTDp induced high levels of protective IgG-antibodies that blocked allergic patients' IgE reactivity to HDM. In addition, DpTTDp lacked relevant IgE-reactivity, induced low T-cell proliferation and IFN-γ in peripheral blood mononuclear cells of HDM-allergic patients' sera. Conclusion: The protein represents a promising HDM-allergy immunotherapy candidate vaccine. © 2018 Future Medicine Ltd

    Iranian Society of Asthma and Allergy Codes of Professional Ethics

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    The advances in science and technology in recent decades, especially in medical sciences, have raised new ethical challenges. Hence, professional organizations in the field of medical science are trying to develop regulations in the field of medical ethics to help medical science professionals in making the best decisions in different circumstances and moral dilemmas. The organizations also try to monitor their performance using those regulations. On the other hand, due to the specialization of medical science as well as the complexity of communication between these disciplines, there is a growing need for regulations to answer questions and resolve the challenges of each discipline. Certainly, scientific societies, due to benefit from relevant specialists, are the best reference for the development of specialized guidelines, one of which is the Iranian Society of Asthma and Allergy (ISAA). The aim of the current study was to develop codes of ethics for ISAA members, using a qualitative study. Generally, the ISAA codes of professional ethics consists of general and specific sections. In order to compile the general section, the upstream medical documents, including the patients' rights charter in Iran, the research ethics guidelines approved by the Ministry of Health and Medical Education (MOHME), ethical codes from the international societies of asthma and allergy, the general codes of professional ethics of the Iran Medical Council and the Islamic jurisprudential rules and the statute law of the country were used. To develop specific sections, we interviewed the experts in the field of Asthma and Allergy about the ethical challenges they had ever faced with. The ISAA codes of professional ethics developed in five chapters, entitled "Ethical Guidelines for the Mangers and Director of the Society, General Guidelines, Specific Guidelines, Ethical Guidelines for Research and Education, and Procedure for Supervision on the Professional Behavior of the ISAA Members", and approved by the board of directors of ISAA

    Construction of a recombinant B-cell epitope vaccine based on a der p1-derived hypoallergen: A bioinformatics approach

    No full text
    Aim: House dust mite (HDM) allergens are important elicitors of IgE-mediated allergies. This study was aimed at constructing and characterizing a recombinant fusion protein, DpTTDp, which was based on carrier-bound Der p 1-derived peptides for HDM allergen immunotherapy. Methods: Using the Immune Epitope Database (IEDB), we identified from Der p 1, a 34-mer hypoallergenic peptide. Two copies of the hypoallergen were then fused to a partial fragment of a tetanus toxoid molecule's N-and C terminus and expressed in Escherichia coli. After purification to homogeneity, the protein was evaluated for allergenicity and its ability to induce blocking antibodies upon immunization. Results: Upon immunization of mice, DpTTDp induced high levels of protective IgG-antibodies that blocked allergic patients' IgE reactivity to HDM. In addition, DpTTDp lacked relevant IgE-reactivity, induced low T-cell proliferation and IFN-γ in peripheral blood mononuclear cells of HDM-allergic patients' sera. Conclusion: The protein represents a promising HDM-allergy immunotherapy candidate vaccine. © 2018 Future Medicine Ltd

    Exposure to ambient air pollution and prevalence of asthma in adults

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    Air pollution is defined as the risk factors for asthma. This study aimed to investigate the effect of exposure to ambient air pollution and prevalence of asthma in adults. This cross-sectional study was done between November 2015 and February 2016. The asthma prevalence was surveyed in 3172 adults between 20 and 44 years old in Tehran, Iran. Face to face interview and standardized questionnaire (European Community Respiratory Health Survey (ECRHS)) were used for data gathering. Concentrations of air pollutants in the whole city of Tehran were obtained from Tehran Air Quality Control Company (AQCC). Air pollution exposure assessed by the spatial analysis based on GIS method. The effect of ambient air pollution on the asthma symptoms was assessed with the crude and adjusted logistic regression. Results were reported as odds ratios (OR) with 95 confidence interval (CI). Results showed that the asthma prevalence in adults in Tehran was 11.73, higher than the average prevalence of asthma in the whole country equal to the 8.9. The prevalence of asthma in males (6.43, n=204) was significantly higher than females (5.26, n=167), but this difference was not significant (P = 0.29). A significant positive association was observed between the asthma prevalence and the concentration of CO (OR 1.64; 1.26 to 1.85) and PM10 (1.04; 1.01 to 1.08) (P <0.05). Finally, we concluded that exposure to some air pollutants can affect the asthma prevalence in adults. Therefore, control of air pollution is recommended to reduce the asthma in Tehran metropolis. © 2021, The Author(s), under exclusive licence to Springer Nature B.V

    Identification of differentially expressed micrornas in primary esophageal achalasia next-generation sequencing

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    Molecular knowledge regarding the primary esophageal achalasia is essential for the early diagnosis and treatment of this neurodegenerative motility disorder. Therefore, there is a need to find the main microRNAs (miRNAs) contributing to the mechanisms of achalasia. This study was conducted to determine some patterns of deregulated miRNAs in achalasia. This case-control study was performed on 52 patients with achalasia and 50 nonachalasia controls. The miRNA expression profiling was conducted on the esophageal tissue samples using the next-generation sequencing (NGS). Differential expression of miRNAs was analyzed by the edgeR software. The selected dysregulated miRNAs were additionally confirmed using the quantitative reverse transcription polymerase chain reaction (qRT-PCR). Fifteen miRNAs were identified that were significantly altered in the tissues of the patients with achalasia. Among them, three miRNAs including miR-133a-5p, miR-143-3p, and miR-6507-5p were upregulated. Also, six miRNAs including miR-215-5p, miR-216a-5p, miR-216b-5p, miR-217, miR-7641 and miR-194-5p were downregulated significantly. The predicted targets for the dysregulated miRNAs showed significant disease-associated pathways like neuronal cell apoptosis, neuromuscular balance, nerve growth factor signaling, and immune response regulation. Further analysis using qRT-PCR showed significant down-regulation of hsa-miR-217 (p-value = 0.004) in achalasia tissue. Our results may serve as a basis for more future functional studies to investigate the role of candidate miRNAs in the etiology of achalasia and their application in the diagnosis and probably treatment of the disease. © T�BİTAK
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