Investigating possible effects of aryl hydrocarbon receptor G1661A polymorphism on asthma severity in adults

311-319Aryl hydrocarbon Receptor (AhR) is a ligand-activated transcription factor with an important role in lung health. The association of AhR polymorphisms with asthma severity has not been yet investigated. We analyzed the association of G1661A, the most prevalent polymorphism of AhR, with the asthma stages in a population-based study including 555 asthmatics (Intermittent: 93, Mild: 240, Moderate: 158, and Severe: 64). The SNP was genotyped using allele-specific PCR. Obtained data were analyzed using the Generalized-Ordered Logit Estimates. Genotypes GA (OR: 0.53, CI: 0.32-0.90, P=0.019) and AA (OR: 0.22, CI: 0.06-0.76, P=0.017) were associated with decreased risk of Severe, Moderate, Mild vs. Intermittent stage; and Severe, Moderate, vs. Mild, Intermittent stages respectively. However, Genotype GA (OR: 1.90, CI: 1.05-3.44, P=0.033), dominant model GA+AA (OR: 2.04, CI: 1.17-3.57, P=0.012), and allele A (OR: 1.68, CI: 1.06-2.66, P=0.027) were associated with increased risk of Severe stage vs. Moderate, Mild, Intermittent stages. Also, male sex and higher age were associated with an increased odds ratio for severe asthma. Furthermore, significant associations with asthma stages were found for the interactions of the SNP and sex, smoking, and alcohol consumption. In conclusion, we revealed that the mutant allele of AhR-G1661A may interact with independent variables and act as a protective factor against lower stages of asthma but it may increase the risk of severe asthma

Computational-based strategies to deal with liver injuries induced by the repurposed drugs against SARS-CoV-2

SARS-CoV-2 has impacted human health with varying degrees of illness, including liver injuries resulting from the repurposed drugs against it. It means that even after recovering the patients, they may encounter the side effects of the exploited medicines. This review categorizes the liver-related anomalies caused by repurposed drugs against COVID-19 and discusses the potential of computational biology-based drug repurposing approaches to address these anomalies. The present review introduces various data resources and software packages that aid in designing drug repurposing methods for treating liver injuries induced not only by SARS-CoV-2 but also by other emerging infectious viruses. To achieve this, a possible efficient solution may involve three main steps. Firstly, virtual screening approaches are used for identifying candidate drugs from large databases. Secondly, molecular docking methods are applied for assessing ligand-protein interactions. Finally, the molecular dynamic simulation techniques are performed to model dynamic interactions of atoms associated with proteins and ligands. Additionally, this review suggests a candidate list of paired drugs for treating liver injuries. The findings of this review offer insights into drug repurposing strategies and their potential impact on liver injury treatment

Development of a novel multi‑epitope vaccine against the pathogenic human polyomavirus V6/7 using reverse vaccinology

Abstract Background Human polyomaviruses contribute to human oncogenesis through persistent infections, but currently there is no effective preventive measure against the malignancies caused by this virus. Therefore, the development of a safe and effective vaccine against HPyV is of high priority. Methods First, the proteomes of 2 polyomavirus species (HPyV6 and HPyV7) were downloaded from the NCBI database for the selection of the target proteins. The epitope identification process focused on selecting proteins that were crucial, associated with virulence, present on the surface, antigenic, non-toxic, and non-homologous with the human proteome. Then, the immunoinformatic methods were used to identify cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and B-cell epitopes from the target antigens, which could be used to create epitope-based vaccine. The physicochemical features of the designed vaccine were predicted through various online servers. The binding pattern and stability between the vaccine candidate and Toll-like receptors were analyzed through molecular docking and molecular dynamics (MD) simulation, while the immunogenicity of the designed vaccines was assessed using immune simulation. Results Online tools were utilized to forecast the most optimal epitope from the immunogenic targets, including LTAg, VP1, and VP1 antigens of HPyV6 and HPyV7. A multi-epitope vaccine was developed by combining 10 CTL, 7 HTL, and 6 LBL epitopes with suitable linkers and adjuvant. The vaccine displayed 98.35% of the world's population coverage. The 3D model of the vaccine structure revealed that the majority of residues (87.7%) were located in favored regions of the Ramachandran plot. The evaluation of molecular docking and MD simulation revealed that the constructed vaccine exhibits a strong binding (-1414.0 kcal/mol) towards the host's TLR4. Moreover, the vaccine-TLR complexes remained stable throughout the dynamic conditions present in the natural environment. The immune simulation results demonstrated that the vaccine design had the capacity to elicit robust immune responses in the host. Conclusion The multi-parametric analysis revealed that the designed vaccine is capable of inducing sustained immunity against the selected polyomaviruses, although further in-vivo investigations are needed to verify its effectiveness

A novel radiofrequency modulation therapy versus routine physiotherapy modalities in treatment of myofascial pelvic pain syndrome: a pilot randomized trial

Objective The current study aimed to compare the effectiveness of novel radiofrequency modulation (RM) therapy with a tailored physiotherapy course for patients with chronic pelvic pain (CPP) of myofascial origin, also known as myofascial pelvic pain syndrome (MPPS). Methods We enrolled 46 patients with myofascial CPP to compare the effectiveness of a 10-session routine physiotherapy course versus a 6-session RM with an integrated device (HIGGS) in alleviating MPPS morbidity and pelvic floor muscle (PFM) rehabilitation. The primary outcome was reduction in pelvic pain after the final session and in the follow-up period 3 months after the final intervention session. Results The 6-session therapy in the RM group and the manual, biofeedback, and transcutaneous electrical nerve stimulation therapies in the physiotherapy group were similarly effective in reducing pain and improving PFM endurance after the final intervention session in each group, whereas perineometer readings and PFM strength were associated with greater improvements in the physiotherapy group. Conclusion The results of this study demonstrated comparable effectiveness of RM in the management of MPPS and improvement of PFM function compared to routine physiotherapy programs with fewer sessions of therapy

Investigating possible effects of aryl hydrocarbon receptor G1661A polymorphism on asthma severity in adults

Aryl hydrocarbon Receptor (AhR) is a ligand-activated transcription factor with an important role in lung health. The association of AhR polymorphisms with asthma severity has not been yet investigated. We analyzed the association of G1661A, the most prevalent polymorphism of AhR, with the asthma stages in a population-based study including 555 asthmatics (Intermittent: 93, Mild: 240, Moderate: 158, and Severe: 64). The SNP was genotyped using allele-specific PCR. Obtained data were analyzed using the Generalized-Ordered Logit Estimates. Genotypes GA (OR: 0.53, CI: 0.32-0.90, P=0.019) and AA (OR: 0.22, CI: 0.06-0.76, P=0.017) were associated with decreased risk of Severe, Moderate, Mild vs. Intermittent stage; and Severe, Moderate, vs. Mild, Intermittent stages respectively. However, Genotype GA (OR: 1.90, CI: 1.05-3.44, P=0.033), dominant model GA+AA (OR: 2.04, CI: 1.17-3.57, P=0.012), and allele A (OR: 1.68, CI: 1.06-2.66, P=0.027) were associated with increased risk of Severe stage vs. Moderate, Mild, Intermittent stages. Also, male sex and higher age were associated with an increased odds ratio for severe asthma. Furthermore, significant associations with asthma stages were found for the interactions of the SNP and sex, smoking, and alcohol consumption. In conclusion, we revealed that the mutant allele of AhR-G1661A may interact with independent variables and act as a protective factor against lower stages of asthma but it may increase the risk of severe asthma