An in silico study to find potential effective circRNAs in the progression of Huntington's disease.

Objectives: Huntington's disease (HD) is identified as a progressive genetic disorder caused by a mutation in the Huntington gene. Although the pathogenesis of this disease has not been fully understood, investigations have demonstrated the role of various genes and non-coding RNAs in the disease progression. In this study, we aimed to discover the potential promising circRNAs which can bind to miRNAs of HD. Materials and Methods: We used several bioinformatics tools such as ENCORI, Cytoscape, circBase, Knime, and Enrichr to collect possible circRNAs and then evaluate their connections with target miRNAs to reach this goal. We also found the probable relationship between parental genes of these circRNAs and the disease progress. Results: According to the data collected, more than 370 thousand circRNA-miRNA interactions were found for 57 target miRNAs. Several of circRNAs were spliced out of parental genes involved in the etiology of HD. Some of them need to be further investigated to elucidate their role in this neurodegenerative disease. Conclusion: This in silico investigation highlights the potential role of circRNAs in the progression of HD and opens up new horizons for drug discovery as well as diagnostic approaches for the disease.

Quality of life associated with immunosuppressant treatment adherence in liver transplant recipients: A cross-sectional study.

Purpose: Transplanted organ survival after solid organ transplantation highly correlates with the adherence levels of the patients to their immunosuppressive drugs. On the other hand, one of the main goals of liver transplantation is to increase the overall quality of life (QOL) for the patient. This study is aimed to analyze the relationship between adherence and QOL in adult liver transplant recipients of the biggest liver transplant center in Asia. Methods: All of the included patients were older than 18 years and at least 6 months had passed from their liver transplantation. The adherence level was measured with BAASIS method and the QOL was assessed by SF-36 questionnaire in real-time interviews. The relationship between adherence and different aspects of QOL in addition to qualitative and quantitative influential factors on these two outcomes was calculated with statistical analysis. Results: Among the 122 included patients, 41% of the were categorized in the non-adherent group. The most important reasons for non-adherence in these patients included forgetfulness (62%), lack of medication (12%), financial problems for drug supply (9%), and side effects (2%). According to the results of the multivariate linear regression model, rejection was the only influential factor in the occurrence of non-adherence among patients (OR = 8.226 CI (1.404-48.196)). The overall mean QOL score of patients was reported 51.09 ± 21.86. The lowest is given to social functioning, while mental health has achieved the highest score. The mean QOL scores in different dimensions in patients with adherence were higher than non-adherents, which was only significant in mental health (p-value = 0.01). Additionally, in total scores related to Physical Composite Score (PSC) and Mental Composite Score (MCS), the mean MSC scores in adherent patients were significantly higher than non-adherent patients (p-value: 0.02). Although adherent patients have an overall greater QOL, the only meaningful effect on QOL total score was from income level. Conclusion: The overall QoL score has been in all parameters higher in the adherent group compared with non-adherent patients. The difference in QoL was most meaningfully significant in mental composite score among other parameters of QoL.

Drug-related Problems in Solid-Organ Transplant Recipients Hospitalized for COVID-19: An Experience of a Referral Tertiary Center in Iran.

Background: Transplanted patients receiving immunosuppressive agents are at a higher risk of Coronavirus-disease-2019 (COVID-19), and their polypharmacy state makes the choice of treatment challenging. This study aimed to assess the drug-related problems (DRP) and clinical pharmacists' interventions to manage transplanted patients and candidates for transplantation with COVID-19. Methods: This cross-sectional study was conducted in the COVID-19 intensive care unit of Shiraz Organ Transplantation Center (Iran), from March 2020 to April 2021. Patients were admitted to the COVID-19 intensive care unit based on clinical symptoms or positive polymerase chain reaction (PCR) tests. The clinical pharmacist reviewed all medications and physicians' orders on a daily basis and evaluated DRPs in accordance with the pharmaceutical care network of Europe (PCNE) classification (V 8.01). The treatment team was informed of the DRPs, and the acceptance or rejection of the intervention was also documented. Data were analyzed using SPSS (Version 25.0). In order to determine the proportion and determinants of drug-related problems, descriptive statistics and logistic regression were applied, respectively. Results: A clinical pharmacist reviewed 631 individuals with 11770 medication orders, and 639 DRPs were found in 69% of them with an average of 1.01±1 per patient. The most commonly reported DRPs were treatment efficacy issues followed by adverse drug reactions (ADRs). A total of 982 interventions were provided at prescriber, patient, and drug levels, of which 801 were accepted, and 659 (82.27%) were fully implemented. Conclusion: There have been considerable drug-related issues in managing transplanted patients with COVID-19. DRPs are more common in people with polypharmacy, more than three comorbidities, and hydroxychloroquine regimens.

Evaluation of the therapeutic regimen in COVID-19 in transplant patients: where do immunomodulatory and antivirals stand?

BACKGROUND: The management of COVID-19 in organ transplant recipients is among the most imperative, yet less discussed, issues based on their immunocompromised status along with their vast post-transplant medication regimens. No conclusive study has been published to evaluate proper anti-viral and immunomodulator medications effect in treating COVID-19 patients to this date. METHOD: This retrospective study was conducted in Shiraz Transplant Hospital, Iran from March 2020 to May 2021 and included COVID-19 diagnosed patients based on SARS-CoV-2 RT-PCR positive test who had been hospitalized for at least 48 h before enrolling in the study. Clinical and demographic information of patients, along with their treatment course and the medication used were evaluated and analyzed using multiple regression analysis. RESULTS: A total of 245 patients with a mean age of 49.59 years were included with a mortality rate of 8.16%. The administration of Remdesivir as an anti-viral drug (P value < 0.001) and Tocilizumab as an immunomodulator drug (P value < 0.001) could reduce the hospitalization period in the hospital and the intensive care unit, as well as the mortality rates significantly. Meanwhile, the patients treated with Lopinavir/Ritonavir experienced a lower chance of survival (OR < 1, P value = 0.04). No significant difference was observed between various therapeutic regimens in clinical complications such as bacterial coinfections, cardiovascular and gastrointestinal adverse reactions, and liver or kidney dysfunctions. CONCLUSION: The administration of Remdesivir as an anti-viral and Tocilizumab as an immunomodulatory drug in solid-organ transplant recipients could be promising treatments of choice to manage COVID-19.

A systems pharmacology approach to identify the autophagy-inducing effects of Traditional Persian medicinal plants.

Aging is correlated with several complex diseases, including type 2 diabetes, neurodegeneration diseases, and cancer. Identifying the nature of this correlation and treatment of age-related diseases has been a major subject of both modern and traditional medicine. Traditional Persian Medicine (TPM) embodies many prescriptions for the treatment of ARDs. Given that autophagy plays a critical role in antiaging processes, the present study aimed to examine whether the documented effect of plants used in TPM might be relevant to the induction of autophagy? To this end, the TPM-based medicinal herbs used in the treatment of the ARDs were identified from modern and traditional references. The known phytochemicals of these plants were then examined against literature for evidence of having autophagy inducing effects. As a result, several plants were identified to have multiple active ingredients, which indeed regulate the autophagy or its upstream pathways. In addition, gene set enrichment analysis of the identified targets confirmed the collective contribution of the identified targets in autophagy regulating processes. Also, the protein-protein interaction (PPI) network of the targets was reconstructed. Network centrality analysis of the PPI network identified mTOR as the key network hub. Given the well-documented role of mTOR in inhibiting autophagy, our results hence support the hypothesis that the antiaging mechanism of TPM-based medicines might involve autophagy induction. Chemoinformatics study of the phytochemicals using docking and molecular dynamics simulation identified, among other compounds, the cyclo-trijuglone of Juglans regia L. as a potential ATP-competitive inhibitor of mTOR. Our results hence, provide a basis for the study of TPM-based prescriptions using modern tools in the quest for developing synergistic therapies for ARDs.

Harnessing the non-specific immunogenic effects of available vaccines to combat COVID-19.

No proven remedy is identified for COVID-19 yet. SARS-CoV-2, the viral agent, is recognized by some endosomal and cytosolic receptors following cell entry, entailing innate and adaptive immunity stimulation, notably through interferon induction. Impairment in immunity activation in some patients, mostly elderlies, leads to high mortalities; thus, promoting immune responses may help. BCG vaccine is under investigation to prevent COVID-19 due to its non-specific effects on the immune system. However, other complementary immune-induction methods at early stages of the disease may be needed. Here, the potentially preventive immunologic effects of BCG and influenza vaccination are compared with the immune response defects caused by aging and COVID-19. BCG co-administration with interferon-α/-ß, or influenza vaccine is suggested to overcome its shortcomings in interferon signaling against COVID-19. However, further studies are highly recommended to assess the outcomes of such interventions considering their probable adverse effects especially augmented innate immune responses and overproduction of proinflammatory mediators.