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Monkeypox virus (MPXV) outbreaks have been reported in various countries worldwide; however, there is no specific vaccine against MPXV. In this study, therefore, we employed computational approaches to design a multi-epitope vaccine against MPXV. Initially, cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), linear B lymphocytes (LBL) epitopes were predicted from the cell surface-binding protein and envelope protein A28 homolog, both of which play essential roles in MPXV pathogenesis. All of the predicted epitopes were evaluated using key parameters. A total of 7 CTL, 4 HTL, and 5 LBL epitopes were chosen and combined with appropriate linkers and adjuvant to construct a multi-epitope vaccine. The CTL and HTL epitopes of the vaccine construct cover 95.57% of the worldwide population. The designed vaccine construct was found to be highly antigenic, non-allergenic, soluble, and to have acceptable physicochemical properties. The 3D structure of the vaccine and its potential interaction with Toll-Like receptor-4 (TLR4) were predicted. Molecular dynamics (MD) simulation confirmed the vaccine’s high stability in complex with TLR4. Finally, codon adaptation and in silico cloning confirmed the high expression rate of the vaccine constructs in strain K12 of Escherichia coli ( E . coli ). These findings are very encouraging; however, in vitro and animal studies are needed to ensure the potency and safety of this vaccine candidate.

Emergence of vancomycin-intermediate Staphylococcus aureus (VISA) and vancomycin-resistant S. aureus (VRSA) strains has led to great concern in global public health in both developing and developed countries. This study investigated distribution and molecular characterization of VRSA strains in Tehran's hospitals using a combination of molecular typing methods. A total of 1789 S. aureus isolates obtained between 2014 and 2017 and were characterized using antibiogram, SCCmec typing, spa typing, and multilocus-sequence typing. Resistance to vancomycin was determined by E-test method. After confirmation of the isolated VRSA strain, genetic analysis was performed by evaluating vanA and vanB genes presence.The presence of resistance (ermA, ermB, ermC, mupA, msrA, msrB, tetM, ant (4΄)-Ia, aac (6΄)-Ie/aph (2˝), aph (3΄)-IIIa) and toxin (etb, eta, pvl, tst) encoding genes was investigated by the polymerase chain reaction (PCR) technique. Of all S. aureus tested isolates, four isolates were confirmed as VRSA isolates and two isolates confirmed as VISA isolates. ST5- SCCmec II/t002 and ST239-SCCmec III/t037 strains had MIC values of 512μg/ml, ST239-SCCmec III/t037 and ST8-SCCmecIV/t008 strains had MIC values of 64μg/ml and ST22-SCCmec IV/t790 and ST239-SCCmec III/t030 strains had MIC values ≥ 8 μg/ml. pvl-encoding gene was confirmed in ST8-SCCmecIV/t008 and ST22-SCCmec IV/t790 strains. The isolates differed in the carriage of resistance and toxin encoding genes. The study revealed the existence of VRSA strains in capital of Iran, Tehran. To our knowledge, this is the first report of ST239-SCCmec III/t037 as VRSA strain. These findings support the need for future surveillance studies on VRSA strains to keep the emergence and transmission of these isolates to a minimum.

The emergence of methicillin-resistant Staphylococcus aureus (MRSA) in different patient populations is a major public health concern. This study determined the prevalence and distribution of circulating molecular types of MRSA in hospitalized patients in ICU of hospitals in Tehran. A total of 70 MRSA isolates were collected from patients in eight hospitals. Antimicrobial resistance patterns were determined using the disk diffusion method. The presence of toxin encoding genes and the vancomycin resistance gene were determined by PCR. The MRSA isolates were further analyzed using multi-locus sequence, spa, SCCmec, and agr typing. The MRSA prevalence was 93.3%. Antimicrobial susceptibility testing revealed a high resistance rate (97.1%) to ampicillin and penicillin. The rate of resistance to the majority of antibiotics tested was 30% to 71.4%. Two isolates belonging to the ST22-SCCmec IV/t790 clone (MIC ≥ 8 μg/ml) had intermediate resistance to vancomycin. The majority of MRSA isolates (24.3%) were associated with the ST22-SCCmec IV/t790 clone; the other MRSA clones were ST859-SCCmec IV/t969 (18.6%), ST239-SCCmec III/t037 (17.1%), and ST291-SCCmec IV/t030 (8.6%). The circulating MRSA strains in Iranian hospitals were genetically diverse with a relatively high prevalence of the ST22-SCCmec IV/t790 clone. These findings support the need for future surveillance studies on MRSA to better elucidate the distribution of existing MRSA clones and detect emergence of new MRSA clones.

Network coding and relay selection have attracted significant attention due to their performance improvement and spectral efficiency in wireless networks. In this work, we study joint relay selection and network coding cooperation schemes for M source-destination pairs assisted with N relays. We propose a new smart decode-and-forward max-min relay selection scheme based on the source-destination links’ outage status and L selected relays to enhance the communication system diversity. Our objective is realize joint network coding and relay selection strategies for maximizing the expected number of recovered packets by the intended destinations in various situations. We analyze the performance of the proposed scheme and prove that the maximum diversity order of N + 1 is achieved when the number of active relays is at least ⌈ N + 1 3 ⌉ . Also, we show that the scheme can achieve a diversity order of 3 L when L < ⌈ N + 1 3 ⌉ . Our analytical and simulation results indicate that the proposed scheme provides higher performance than the existing network coded cooperation schemes.

The endoplasmic reticulum (ER) response mechanism to cellular stress is mediated by the unfolded protein response/ER-associated degradation (UPR/ERAD) pathway. A viral infection can trigger ER stress and engage some transcription factors, depending on the host cell and virus type, activating or inhibiting autophagy. The relationship between ER response and autophagy in rabies has not been investigated yet. In the present study, the mouse brain was infected with street rabies virus (SRABV). Total RNA was extracted from the brains of animals, and cDNA was synthesized. Next, real-time PCR assay was performed using specific primers. The expression of hypoxanthine–guanine phosphoribosyltransferase (Hprt), CCAAT/enhancer binding protein homologous protein (CHOP), apoptosis signal-regulating kinase 1 (ASK1), activating transcription factor 6 (ATF6), and caspase 3 (CASP3) genes was also investigated. Based on the results, SRABV caused significant changes in the mRNA expression of ATF6, CHOP, and ASK1 genes in the brains of infected mice in the control group (group V). Treatment of infected cells with the pIRES-EGFP-Beclin-1 vector and rapamycin caused changes in nearly most of the parameters. However, alterations in CASP3 gene expression were only observed when the vector and the virus were simultaneously injected into the cells. Overall, protection and autophagy against cell death induced by SRABV infection can be achieved by activating the ER stress pathway, followed by a marked increase in the expression of ATF6, CHOP, ASK1, and CASP3 genes.

Objective(s): Difficult-to-treat Streptococcus agalactiae infections are increasingly described in patients with urinary tract infections (UTIs). This occurrence could be due to the production of virulence determinants. This study aimed to characterize the molecular features of S. agalactiae responsible for UTIs. Materials and Methods:In this cross-sectional study, 70 S. agalactiae isolated from UTIs were examined. Antibiotic susceptibility testing was performed using the disk diffusion method. All S. agalactiae isolates were confirmed by atr and dltS PCR assays. Virulence, alpha protein-like, and pilus island genes were detected by PCR. Isolates were characterized using the multilocus sequence typing method. Results: Multidrug resistance was observed in 80% of isolates. Five virulence profiles were detected, wherein cylE, lmb, bca, rib (35.7%), cylE, lmb, alp3 (27.1%), and cylE, lmb, bac, rib, alp2 (21.4%) were the most frequent detected profiles. S. agalactiae was isolated and categorized within three clonal complexes (CCs) including CC22 (40%), CC17 (25.7%), and CC23 (20%). The main sequence types (STs) found were ST22 (27.1%), ST23 (17.1%), ST17 (12.9%), ST31 (8.7%), ST40 (8.7%), ST74 (7.1%), ST48 (4.3%), ST890 (4.3%), ST189 (2.8%), ST38 (2.8%), ST52 (2.8%), and ST155 (1.4%). ST74 and ST38 were reported for the first time in Tehran-Iran. Conclusion: This study highlights the predominance of the CC22 lineage among S. agalactiae strains isolated from UTIs in Tehran, Iran, and highlights the significant penetration of this lineage into hospitals. MDR patterns among these strains appear to be becoming a major concern in the management of infections.

The present study aimed to evaluate the effects of Nutrition Bio-shield Superfood (NBS) powder on the immune system function and clinical manifestations in patients with COVID-19. We compare the effects of NBS powder on the immune system function and clinical manifestations among two different groups: 1) intervention group receiving standard treatment scheduled according to treatment guidelines plus NBS powder, and 2) control group receiving only the same standard treatment. The serum levels of IL-2, IL-6, IL-17, IFNγ, and TNFα were determined after four weeks of treatment by specific ELISA kits according to the manufacturer’s instructions. Finally, the level of immune system stimulation and inflammatory markers were compared at baseline and after intervention in both groups. Data were analyzed using SPSS (version 22). A p-value of ≤ 0.05 was set as significant. A total of 47 patients with COVID-19 (24 patients in the intervention group and 23 patients in the control group) were included in this study. Results showed that the differences in the mean decrease of IL-2, IL-6, and TNF-α in the intervention group in comparison to the control group were 0.93, 10.28, and 8.11 pg/ml, respectively (P<0.001). On the other hand, there was no difference in IL-17, IFNγ, monocytes, eosinophil, and other inflammatory indices between the intervention and control groups. Although NBS powder was able to significantly decrease the levels of some proinflammatory cytokines in patients with COVID-19, however, it is noteworthy that the course of the disease was to large part unaffected by NBS power and there was a reduction independent of treatment. The present study indicates that NBS powder could provide a beneficial anti-inflammatory effect in patients with COVID-19. Hence, NBS in treating patients with COVID-19 shows promise as an adjuvant to the current standard antiviral treatment of such patients.

Rabies is the most critical zoonotic disease in Iran, which imposes many extra costs on health care system in each country. The present study aimed to determine the molecular characteristics of the wild circulating strains of the rabies virus (RABV) collected in Iran during 2015–2017. Rabies-suspected samples were collected from different regions of Iran and identified for RABV antigen confirmation using fluorescent antibody tests. Polymerase chain reaction (PCR) was performed on positive samples and gene sequencing was done on rabies nucleoprotein and glycoprotein genes to determine the rabies molecular characteristics. Accordingly, nine street RABVes were isolated. Then, N (802 bp) and G (735 bp) genes were amplified with specific primers using PCR. The sequence of nine strains was determined and compared with another 50 close to them, and the phylogenetic tree was plotted using neighbor-joining method by Mega 7 software. The molecular characteristic results indicated that all new strains belong to RABV wild species. As a result, the most prevalent strains of RABV in northwest, west, center, and south of Iran were identified. The present study may provide a better insight into the identification of all RABV strains, and understanding the evolutionary nature of RABV and how its hosts change in the world over the centuries.

Introduction: Over the past decades, prevalence of biofilm-forming Staphylococcus aureus strains has significantly increased in urinary tract infections. The aim of this study was to investigate prevalence of biofilm forming and adhesion encoding genes and to analyze distribution of different agr and spa types in S. aureus isolates. Methodology: In the present study, 75 S. aureus isolates obtained from patients with urinary tract infections were examined for susceptibility to antimicrobial agents. Adhesion, biofilm, and spa encoding genes were detected by PCR screening; agr types were determined using multiplex PCR. Results: Among the 75 isolates, 72% were biofilm producers and 28% were non-biofilm producers. Notably, the ability to produce biofilm was higher among MRSA strains ompared to MSSA strains. The most prevalent biofilm forming gene was icaD (77.3%), followed by icaA (76%), icaB (57.3%) and icaC (50.7%). Adhesion genes clfA, clfB, fnbB, can, fnbA, ebp and bap were detected in 94.7%, 92%, 68%, 64%, 64%, 60% and 5.3% of the isolates, respectively. The spa types t426 and t7789 were found among the non-MDR isolates. It was found that t790, t084, t7789 and t325 spa types were biofilm producers, while t426 and t1339 spa types were non-biofilm producers. Conclusion: Biofilm encoding genes icaD and spa type t790 and agr type III were the most prevalent factors among MDR biofilm producer isolates. The study emphasized that identification of genes and characterization of molecular types involved in biofilm formation should be considered.