Research in Molecular Medicine
Year:2020 | Volume:8 | Issue:2|Papers Count:6

On March 11, 2020, the World Health Organization (WHO) announced the pandemic outbreak of coronavirus disease 2019 (COVID-19), due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which began in December 2019 in Wuhan, China [1]. . .

Asthma is one of the most common chronic inflammatory respiratory disorders with many different presentations. It has different endotypes and genotypes and causes significant morbidity and mortality in both children and adults. Asthma is the most common cause of emergency department visits, absence from school, and hospitalization in children. . .

Background: One of the main causes of male infertility is the negative effects of oxidative stress. Follicle-Stimulating Hormone (FSH) plays an essential role in spermatogenesis, as well as in the maintenance of sperm DNA integrity. This study aimed to determine whether the recombinant human Follicle-Stimulating Hormone (rhFSH) treatment of sperm parameters could positively affect sperm DNA and oxidative DNA fragmentation in oligozoospermic infertile men. Materials and Methods: This interventional study was carried out on a sample of 50 oligozoospermic infertile men. To this end, sperm DNA fragmentation and ROS, as an oxidative stress marker, were measured before and after treatment with rhFSH sperm parameters. Results: The sperm parameters (concentration, mobility, and morphology) were significantly different in the oligozoospermic infertile patients before and after the rhFSH treatment (P<0. 05). Moreover, sperm DNA fragmentation had a significant decrease in patients after the FSH treatment (P<0. 05). Besides, the ROS level in sperm and the malondialdehyde level of seminal plasma significantly decreased after the treatment (P<0. 05). Conclusion: Treatment with rhFSH significantly improved sperm parameters. Furthermore, the treatment led to a significant reduction of sperm DNA fragmentation and oxidative stress in the oligozoospermic infertile patients. Similarly, the malondialdehyde concentration markedly decreased in correlation with DNA fragmentation after the rhFSH treatment.

Background: Multi-drug resistant (MDR) Citrobacter freundii (C. freundii) as a causative agent of nosocomial infections is a health threat, especially in hospitals. This study was conducted to determine the prevalence of MDR C. freundii, considering isolation sites and a variety of utilized antibiotics. Materials and Methods: In this cross-sectional study, the clinical samples of C. freundii strains were collected and screened using traditional bacteriological tests in Zareh Hospital, Sari City, Iran, during 2016-2017. We used disk diffusion methods to assess the susceptibility patterns of isolates according to the Clinical Laboratory Standard Institute (CLSI) guidelines. Results: Out of 3248 clinical samples, C. freundii strains were detected in 109 samples (32. 1% females and 67. 9% males). Susceptibility tests indicated that 89 isolates (81. 65%) were MDR strains. Frequencies of MDR C. freundii strains were higher in the Behavioral Intensive Care Unit (BICU) (37. 61%) and restoration ward (29. 35%) compared with other hospital wards. Conclusion: Considering the MDR C. freundii strains detected from burn hospital wards, it is necessary to implement prevention criteria for their eradication from burn hospitals. The results indicate the urgent need to design more practical methods for controlling infection in hospital wards.

Background: Contraceptive Vaccines (CVs) can be used as a valuable and alternative method for the prevention of gestation in humans and animals. These vaccines can have several targets, such as superficial sperm proteins. Vaccines based on sperm antigens are quite efficacious to create a contraceptive effect. However, multi-epitope vaccines are more effective in stimulating the immune system and producing more antibodies to reduce the infertility rate. Materials and Methods: This study aimed to design and evaluate a chimeric fusion protein containing IZUMO, SACA3, and PH-20 epitopes. IZUMO1, SACA3, and PH-20 were assessed, and appropriate regions were selected using various bioinformatics tools, including IEDB, I-TASSER, ProtParam, Asa-View, and Chimera software. Protein epitopes were selected based on various characters, including specificity, solvent accessibility, their weight and length, antigenic intensity, and topology. Epitopes with high antigenic potential were selected and joined together by linkers. The designed fusion protein was simulated using Molecular Dynamic, GROMACS 5, and Chimera 1. 14 software. Results: The results demonstrated that all antigenic plots and availability of epitopes in the new construct remained constant. The spermatic antigens were combined using rigid linkers as a new construct and showed a stable formation with proper solvent accessibility validated by ProSA-web and PROCHECK. Also, comparing the new structure with its original one did not show any structural change. Conclusion: Based on bioinformatics results, the fusion protein that consists of three spermatic antigens has productive potential to stimulate the immune system and capable of producing more antibodies in circulation and reliable infertility.

Background: Denileukin diftitox (trade name, Ontak) is the first recombinant Immunotoxin (IM), in which the binding domain of diphtheria toxin has been replaced by the amino acid sequence of human interleukin-2 (DT389IL-2) using genetic engineering. Purity, stability, and structural property of the protein are critical factors for the scale-up production of this fusion protein. In this IM, location 519 has free cysteine residue that leads to cross S-S bound formation in the refolding process and, as a result, misfolding/aggregation of the protein may occur. Materials and Methods: To inhibit misfolding/aggregation, we substituted cysteine 519 by a serine residue with site-directed mutagenesis, and then the ability of the mutated protein for binding to the IL-2 receptor was predicted and determined by bioinformatics tools. For this purpose, the sequence of the denileukin diftitox was adopted from Drugbank, and the mentioned substitution applied. Two methods determined the folding of the fusion protein: de novo modeling method (by utilizing the I-TASSER database) and homology modeling method (by using some databases and tools, including Swiss-Model, PHYRE2, M4T, ModWeb, RaptorX, and EasyModeller). Finally, the ability of the proteins for binding to the IL-2 receptor was investigated by pyDock and Zdock docking servers, as well as Hex software. Results: The result showed that the mutated form (C519S) of this protein folds appropriately, and the Δ G of the models, measured by STRUM, showed no significant variation. Also, docking analysis has shown that the protein can efficiently bind to the IL-2 receptor without any substantial changes in the binding energy. Conclusion: The present study shows that the suggested mutation of this protein can be an acceptable replacement for denileukin diftitox with a similar affinity and a more proper refolding process.