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Human islet amyloid polypeptide (amylin or hIAPP) is a 37 residue hormone co-secreted with insulin from ß cells of the pancreas. In patients suffering from type-2 diabetes, amylin self-assembles into amyloid fibrils, ultimately leading to the death of the pancreatic cells. However, a research gap exists in preventing and treating such amyloidosis. Plumbagin, a natural compound, has previously been demonstrated to have inhibitory potential against insulin amyloidosis. Our investigation unveils collapsible regions within hIAPP that, upon collapse, facilitates hydrophobic and pi-pi interactions, ultimately leading to aggregation. Intriguingly plumbagin exhibits the ability to bind these specific collapsible regions, thereby impeding the aforementioned interactions that would otherwise drive hIAPP aggregation. We have used atomistic molecular dynamics approach to determine secondary structural changes. MSM shows metastable states forming native like hIAPP structure in presence of PGN. Our in silico results concur with in vitro results. The ThT assay revealed a striking 50% decrease in fluorescence intensity at a 1:1 ratio of hIAPP to Plumbagin. This finding suggests a significant inhibition of amyloid fibril formation by plumbagin, as ThT fluorescence directly correlates with the presence of these fibrils. Further TEM images revealed disappearance of hIAPP fibrils in plumbagin pre-treated hIAPP samples. Also, we have shown that plumbagin disrupts the intermolecular hydrogen bonding in hIAPP fibrils leading to an increase in the average beta strand spacing, thereby causing disaggregation of pre-formed fibrils demonstrating overall disruption of the aggregation machinery of hIAPP. Our work is the first to report a detailed atomistic simulation of 22 µs for hIAPP. Overall, our studies put plumbagin as a potential candidate for both preventive and therapeutic candidate for hIAPP amyloidosis.
RESUMO
Background Coronavirus disease 2019 (COVID-19) is a major public health problem worldwide, and vaccination is currently the most effective way to control its spread and reduce its severity. Diabetes mellitus (DM) is a prevalent chronic disease that poses a significant health risk and is a frequent comorbidity in COVID-19 patients. Therefore, this study aimed to assess the frequency of local and systemic side effects of the AstraZeneca vaccine among diabetic and non-diabetic participants. Methodology This multicenter study was designed as a cross-sectional prospective study and was conducted in Pakistan using a non-probability consecutive sampling method. The study duration was eight months from August 1, 2022, to March 31, 2023. A total of 700 participants who received both (first and second) doses of the AstraZeneca immunization were included in the study. An independent t-test was applied to determine the association between the means and standard deviations of age, height, weight, and duration of DM and hypertension. The chi-square test was used to evaluate the association between local and systemic side effects. Results Among the 700 participants, 173 (49.4%) males and 177 (50.6%) females had diabetes, whereas 183 (52.3%) males and 167 (47.7%) females did not have DM; their mean ages were 46.95 ± 12.73 years (diabetics) and 38.10 ± 14.14 years (non-diabetics). The most frequent adverse effects of the AstraZeneca vaccine after the first dose were pain at the injection site, reported by 259 (74.0%) diabetics and 226 (64.6%) non-diabetic participants; however, after the second dose, injection site swelling in 170 (48.6%) diabetic and 163 (46.6%) non-diabetic recipients was the most commonly reported local side effects. Conclusions This study concluded that concurrent medical conditions such as DM had substantially more local and systemic side effects than those without the disease. After receiving both doses of the AstraZeneca vaccine, the most frequently reported local side effects in both diabetic and non-diabetic participants were pain, swelling, and burning at the injection site, followed by systemic side effects such as fever.
RESUMO
Introduction The most efficient method of combating the coronavirus disease 2019 (COVID-19) pandemic would be to use effective, safe, and proven vaccines; however, their widespread use has been hampered partly by concerns over possible adverse effects. Therefore, this study aimed to assess the prevalence of Oxford/AstraZeneca vaccine side effects among participants. Methods This was a multicenter, cross-sectional study conducted using a non-probability sampling technique. The duration of the study was nine months, from February 1, 2022, to October 31, 2022. The study included 900 participants who provided informed consent and had received two doses of the AstraZeneca vaccine. Demographic characteristics of participants, such as gender, age, comorbidities, AstraZeneca vaccine with both doses along with booster dose, previous exposure to COVID-19 infection, and the prevalence of any local and systemic side effects following the first and second doses of vaccine, were documented. Results The study findings showed that of the 900 participants, 414 (46.0%) were males and 486 (54.0%) were females; their mean age was 40.72 ± 13.47 years. Among them, 198 (22.0%) had hypertension and 144 (16.0%) had diabetes mellitus. Following the first dose of the AstraZeneca vaccine, pain at the injection site was the most commonly reported side effect in 594 (66.0%) participants. Moreover, swelling at the injection site was the most commonly reported side effect in 522 (58.0%) participants after receiving the second dose of the vaccine. The level of satisfaction showed that the majority of the 648 participants (72.0%) were satisfied with their vaccination. Conclusion This study concluded that pain at the injection site was the most commonly reported side effect, followed by swelling and fever after the first dose of the vaccine. Following the second dose of the vaccine, adverse effects included headache, swelling, and burning at the injection site.
