Assessment of Mouse Ileal loop Protection against Clinically Isolated Vibrio cholerae Outer Membrane Vesicles as a Vaccine Candidate.

Cholera, a life-threatening disease caused by the Gram-negative bacterium Vibrio cholera, remains a concern in developing countries. The present study investigated the immunogenicity and protective immunity of outer membrane vesicles (OMVs) and combination of OMV and killed whole cells (WC) of a local strain isolated from the last outbreak in Iran in addition to reference and local strains of V. cholerae El Tor O1 in comparison to Dukoral vaccine in mice model. The protein content, morphology, and size of extracted OMVs were evaluated by electrophoresis and microscopic analyses, respectively. The serum titers of total immunoglobulin G (IgG), IgG1, IgG2a, and immunoglobulin A (IgA) in addition to secretory IgA and total IgG in different mice groups were determined by enzyme-linked immunosorbent assay (ELISA). In addition, fluid accumulation (FA) assay regarding the resistance to live strain of V. cholerae in ligated ileal loops was carried out to determine immunogenicity by OMV or combination of OMV and WC in comparison to that reported for Dukoral vaccine. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of purified OMVs indicated protein profiles within the range of 34-52 kDa. Furthermore, transmission electron microscopy demonstrated the spherical shaped vesicles of 50-200 nm. The results of ELISA showed significant titers of systemic and mucosal immune anti-OMV IgGs in immunized BALB/c mice with different vaccine regimens. Additionally, a notable increase in the FA ratio was demonstrated in this study. The obtained results of the present study revealed that the WC-OMV combination of local strain can induce a high level of antibody response indicating more protection than OMV or WC separately. Moreover, it can be considered an effective immunogen against V. cholerae.

A systems medicine approach reveals disordered immune system and lipid metabolism in multiple sclerosis patients.

Identification of autoimmune processes and introduction of new autoantigens involved in the pathogenesis of multiple sclerosis (MS) can be helpful in the design of new drugs to prevent unresponsiveness and side effects in patients. To find significant changes, we evaluated the autoantibody repertoires in newly diagnosed relapsing-remitting MS patients (NDP) and those receiving disease-modifying therapy (RP). Through a random peptide phage library, a panel of NDP- and RP-specific peptides was identified, producing two protein data sets visualized using Gephi, based on protein--protein interactions in the STRING database. The top modules of NDP and RP networks were assessed using Enrichr. Based on the findings, a set of proteins, including ATP binding cassette subfamily C member 1 (ABCC1), neurogenic locus notch homologue protein 1 (NOTCH1), hepatocyte growth factor receptor (MET), RAF proto-oncogene serine/threonine-protein kinase (RAF1) and proto-oncogene vav (VAV1) was found in NDP and was involved in over-represented terms correlated with cell-mediated immunity and cancer. In contrast, transcription factor RelB (RELB), histone acetyltransferase p300 (EP300), acetyl-CoA carboxylase 2 (ACACB), adiponectin (ADIPOQ) and phosphoenolpyruvate carboxykinase 2 mitochondrial (PCK2) had major contributions to viral infections and lipid metabolism as significant events in RP. According to these findings, further research is required to demonstrate the pathogenic roles of such proteins and autoantibodies targeting them in MS and to develop therapeutic agents which can ameliorate disease severity.

EGFR rs11506105 and IFNL3 SNPs but not rs8099917 are strongly associated with treatment responses in Iranian patients with chronic hepatitis C.

Interferon lambda 3 (IFNL3) and epidermal growth factor receptor (EGFR) single nucleotide polymorphisms (SNPs) may play a key role in the spontaneous clearance of hepatitis C virus (HCV) and treatment responses. The aim of this study was to evaluate the effect of IFNL3 SNPs and EGFR rs11506105 on treatment outcomes in patients with chronic HCV (CHC). IFNL3 SNPs and EGFR rs11506105 were genotyped by PCR-restriction fragment length polymorphism and PCR-sequencing, respectively, in 235 naïve patients with CHC infection. The frequency of rapid virologic response (RVR), complete early virologic response (cEVR) and sustained virologic response (SVR) were 52.3%, 76.2% and 64.7% respectively. The results of this study showed that RVR was associated with ALT (P=0.015), AST (P=0.020), IFNL3 rs12979860 (CC) (P=0.043), rs12980275 (AA) (P=1 × 10-4), and EGFR rs11506105 (AA) (P=0.010), and IFNL3 rs12979860 (CC) (P=0.048), rs12980275 (AA) (P=0.022), and EGFR rs11506105 (AA) (P=0.006) were correlated with cEVR. HCV genotype (P=0.007), IFNL3 rs12979860 (CC) (P=0.023), IFNL3 rs12980275 (AA) (P=1 × 10-4), EGFR rs11506105 (AA) (P=0.005), RVR (P=1 × 10-4), and cEVR (P=0.003) were significant predictors for SVR. These results, for the first time, revealed that beside IFNL3 SNPs, EGFR rs11506105 is strongly associated with RVR, cEVR and SVR. EGFR rs11506105 besides IFNL3 SNPs could predict treatment responses in CHC patients.

Molecular characterization of intestinal carriage of carbapenem-resistant Enterobacteriaceae among inpatients at two Iranian university hospitals: first report of co-production of bla NDM-7 and bla OXA-48.

Gastrointestinal colonization of carbapenem-resistant Enterobacteriaceae (CRE) could serve as a reservoir for the transmission of these pathogens in the clinical setting. The aim of this study was to investigate the intestinal carriage of CRE and to analyze risk factors for CRE carriage. Rectal swabs were collected from 95 patients at two Iranian university hospitals. CRE screening was performed using selective media (CHROMagar and MacConkey agar). Polymerase chain reaction (PCR) was used to detect carbapenemase-encoding genes. Clonal relatedness was investigated by pulsed-field gel electrophoresis (PFGE). The rate of carriage of CRE in hospitalized patients was 37.9%. Overall, 54 CRE isolates were identified, of which 47 were carbapenemase-producers. All of the 54 CRE were detected using CHROMagar compared with 52 CRE detected using MacConkey agar. Fifteen patients were colonized by multiple CRE isolates. Three significant risk factors for CRE carriage were detected: intensive care unit (ICU) hospitalization, antibiotic exposure, and mechanical ventilation. bla OXA-48 was the most frequent carbapenemase detected, followed by bla NDM-1 and bla NDM-7. Eleven carbapenemase-producing Enterobacteriaceae (CPE) isolates co-harbored bla NDM-1 and bla OXA-48. Also, six CPE isolates co-harbored bla NDM-7 and bla OXA-48. We did not detect bla KPC, bla GES, bla IMP, or bla VIM. PFGE analysis showed that Escherichia coli clones were diverse, while Klebsiella pneumoniae isolates were divided into four clusters. Cluster I was the major clone carrying bla OXA-48 and bla CTX-M-15 genes. In our study, the carriage rate of CRE was high and the emergence of CPE isolates among patients is alarming. The implementation of adequate preventive measures such as active surveillance is urgently needed to control the spread of CPE in the healthcare setting.

Drug resistance pattern of Mycobacterium tuberculosis in the province with highest incidence of tuberculosis in Iran.

OBJECTIVE/BACKGROUND: Incidence of tuberculosis (TB) in Golestan Province is consistently higher than other provinces of Iran. This study aimed to determine the rate of drug resistance to first-line antibiotics in Mycobacterium tuberculosis (MTB) isolates recovered from new cases in this province. METHODS: The sputum and broncho-alveolar lavage samples from 3828 patients who were suspected for active TB were collected from March 2015 to July 2015. All specimens were subjected to smear microscopy and culture. Drug susceptibility testing to rifampicin, isoniazid, ethambutol, and streptomycin was performed on Löwenstein-Jensen medium using proportion method. RESULTS: Of 3828 clinical specimens, 40 were culture-positive for MTB. The mean age of patients was 48.6±17.5years and 23 (57%) patients were male. Thirty-eight patients were native Iranians while two (5%) were immigrant patients from Turkmenistan and Afghanistan. A set of 34 (85%) isolates were pan-susceptible, six (15%) were resistant to at least one drug, and one isolate (2.5%) was multidrug resistant. CONCLUSIONS: The rate of drug resistance in this study area point to the necessity for further enforcement of TB treatment and disease control management. Future studies are recommended for assessments of drug resistance pattern of MTB isolates in Golestan Province.

[Coexistence of late spondyloepiphyseal dysplasia and congenital megaloblastic anemia with proteinuria in the same family]. / Coexistence d'une dysplasie spondylo-épiphysaire tardive et d'une anémie mégaloblastique congénitale avec protéinurie dans la même famille.

A case of spondyloepiphyseal dysplasia tarda was noted in a dwarf (130 cm tall) 18 years old boy associated with congenital megaloblastic anemia and proteinuria. His two sisters and a cousin are also suffering from similar hematologic disorder. One of his brothers, 145 cm tall, is also involved by spondyloepiphyseal dysplasia, but there is no known hematologic abnormalities. Review of family history revealed that two aunts from mother's side were deceased in adulthood following a chronic anemic disease. The findings in this anemia are compatible with Imerslund-Grâsbech syndrome and coexistence of these two rare genetic disorders in a single family has not been reported previously.