Objective To evaluate the possible similarity between the AA sequences of human insulin and human glutamic acid decarboxylase-65 (GAD65) with the SARS-CoV-2/COVID proteins to explain the possible trigger of DM1. Methods AA sequences of human insulin, GAD65 and SARS-CoV-2 were obtained from the Protein Data Bank archive information database (RCSB PDB). NetMHCpan v4.1 was used for epitope prediction. Sequences were compared using BLAST for epitope comparison and Pairwise Structure Alignment to assess protein similarity. The AA sequences of human insulin (4F0N) and GAD65 (2OKK) were compared with the sequences of the following SARS-CoV-2 proteins: SARS-Cov2 S protein at open state (7DDN), SARS-Cov2 S protein at close state (7DDD), SARS CoV-2 Spike protein (6ZB5), Crystal structure of SARS-CoV-2 nucleocapsid protein N-terminal RNA binding domain (6M3M), Crystal structure of SARS-CoV-2 nucleocapsid protein C-terminal RNA binding domain (7DE1), Crystal structure of NSP1 from SARS-CoV-2 (7K3N), and SARS-CoV-2 S trimer (7DK3)). Results The percent similarity between epitopes ranged from 45 to 60% (P 0.048) between both human insulin and SARS-CoV2 and for GAD 65 and SARS-CoV2, while the AA similarity of the evaluated samples ranged from 5.00–45.45% between human insulin and SARS-CoV2 and from 10.45–22.22% between GAD65 and SARS-CoV2. Conclusion Immunoinformatics data suggest a potential pathogenic link between SARS-CoV-2/COVID and DM1. Thus, by molecular mimicry, we found that sequence similarity between epitopes and AA sequence between SARS-CoV-2 / COVID and human insulin and GAD65 could lead to the production of an immune cross-response to self-antigens, with self-tolerance breakdown, which could thus trigger DM1.
Objective Employ fuzzy logic to auxiliary in diagnosis and malignancy grade of thyroid nodules by ultrasound. Methods A cross-sectional study evaluating 75 exams results from patients with a thyroid nodule. The following ultrasound findings were evaluated employing a quantitative score: not suspicious, not very suspicious, moderately suspicious, and highly suspicious. The echographic features evaluated for suspicion of malignancy were based on the following nodule components: composition, echogenicity, shape, margin, and echogenic foci, graded using the Thyroid Imaging Data and Reporting System by the American College of Radiology. By combining ultrasound scoring and the Bethesda System for Reporting Thyroid Cytopathology using fuzzy logic, a classification for thyroid nodules was constructed. Results Hypoechogenicity and microcalcifications were the findings that showed the best interaction with malignancy on ultrasound, while shape and margin showed the smallest estimation errors when compared with composition. A classification for thyroid nodules was suggested based on the 95% confidence interval of hypoechogenicity and microcalcifications: not suspicious (< 24.6); not very suspicious (24.6–48.0); moderate (48.1–64.5); moderately suspicious (64.6–77.0); highly suspicious (77.1–92.7); and malignant (> 92.7). Conclusion By fuzzy logic, a classification for thyroid nodules diagnosed by ultrasound supported by echogenicity and nodular microcalcifications was constructed with a simple practical application.
Introduction The halogens are the non-metallic chemical elements belonging to group 17 of the Periodic Table, namely: fluorine, chlorine, bromine, iodine, astate, and teness. Halogens are biologically atypical components, however are frequent as replacement in the binders of the thyroid hormones and inhibitors, binding precisely to nucleic acids and proteins. Objective Simulate in sílico and through a mathematical model the interactions between the ionic changes in the thyroxine (T4) molecule in the process of autoimmunity induction. Methods We used an online application to simulate the docking of fluorine, chlorine, and bromine in the T4 molecule in place of iodine. A hypothetical-deductive mathematical model was assembled to evaluate halogen substitution in the T4 molecule and immune system and its correlation with the development of autoimmune thyroiditis. Results Simulation of the coupling of fluorine, chlorine and bromine, instead of iodine, to T4 were successful using the induced fit docking program. Positioning of each halogen ion in replacing the iodine at position 5 of T4 was achieved. The mathematical model used demonstrated that the change of the halogen ion in the T4 molecule has been shown to be the trigger for the autoimmune trigger of thyroiditis. Conclusion The findings from this study suggest that halogens of lower atomic weight than iodine may act as a trigger for the onset of autoimmune thyroiditis.
Introduction: Type 1 diabetes mellitus (T1DM) is an autoimmune disease that develops due to the destruction of insulin-producing beta cells in the pancreas by the immune system. Cow milk is one of the dietary factors associated with the development of T1DM, as it contains proteins that may trigger the autoimmune response. Studies in silico have investigated the molecular mimicry mechanisms between cow milk proteins and human beta-cell antigens which may contribute to the development of T1DM in susceptible individuals. Objective: To analyze in silico the evidence of molecular mimicry between GAD65/ Human insulin and bovine serum albumin (BSA) and beta-lactoglobulin (BLG) as a potential trigger for T1DM. Method: The in silico analysis was performed using bioinformatics tools to compare the amino acid sequences of cow milk proteins (BSA and BLG) and human beta-cell autoantigens (GAD65 and Human Insulin). The structural and functional characteristics of the proteins were analyzed to identify potential molecular mimicry mechanisms. Results: The results of the in silico analysis showed significant sequence similarity between BSA and BLG, and GAD65 and Human insulin. The cow's milk proteins evaluated shared structural features with the beta cell antigens selected for comparison, indicating the potential for molecular mimicry between these proteins. Conclusion: The findings of this study provide further evidence for the potential role of cow milk proteins in the triggering of T1DM. The in silico analysis suggests that molecular mimicry mechanisms between cow milk proteins and human beta-cell antigens may contribute to the autoimmune response that leads to T1DM. This study highlights the importance of dietary factors in the development of T1DM and the need for further research to understand the mechanisms involved.
Introduction: there are reports of autoimmune disease related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) such neurological syndromes and hematological syndromes, and more recently autoimmune thyroid dysfunctions have been described. These reports suggest that SARS-CoV-2 acts as a probable trigger for triggering the autoimmunity process. Aim: to evaluate structural similarity between thyroid peroxidase [Homo sapiens] (TPO) and SARS-CoV-2 spike glycoprotein (COVID-19), and to propose this similarity as a likely trigger for autoimmune thyroiditis. Methodology: using bioinformatics tools, we compare the amino acids (AA) sequences between protein structure of TPO and chain A COVID-19, chain B COVID-19, and chain C COVID-19, accessible in the National Center for Biotechnology Information database, by Basic Local Alignment Search Tool in order to locate the homologous regions between the sequences of AA. Results: the homology sequence between the TPO and COVID-19 ranged from 27.0 % (10 identical residues out of 37 AA in the sequence) to 56.0% (5 identical residues out of 9 AA in the sequence). The similar alignments demonstrated relatively high E values in function of short alignment. Conclusion: data suggest a possible pathological link between TPO and COVID-19. The structural similarity of AA sequences between TPO and COVID-19 may present a molecular mimicry suggesting the possibility of antigen crossover between TPO and COVID-19 that might represent an immunological basis for autoimmune thyroiditis associated with COVID-19.
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