With regard to increasing number of antifungal-resistant dermatophytes, antifungal susceptibility testing of dermatophytes serves as a useful tool in managing clinical dermatophytosis. This study aimed to determine antifungal susceptibility profile of clinically important dermatophytes and determination of point mutations in terbinafine-resistant isolates. Based on our results, dermatophytosis was confirmed in 97 cases by direct microscopic examination, culture, and sequencing of ITS region. Antifungal susceptibility of 97 dermatophyte isolates distributed in four species including Trichophyton interdigitale (26 isolates), T. rubrum (19 isolates), T. tonsurans (29 isolates), and Epidermophyton floccosum (21 isolates) was assessed to nine antifungal agents using CLSI M38-A2 guidelines. Minimum inhibitory concentration range (MIC range) for luliconazole and terbinafine was 0.001-0.008 μg/ml and 0.003-> 32 μg/ml, compared to 0.03-64 μg/ml for griseofulvin, 0.01-16 μg/ml for itraconazole and voriconazole, 0.03-8 μg/ml for ketoconazole, 0.03-32 μg/ml for econazole, 0.03-1 μg/ml for lanoconazole, and 0.01-4 μg/ml for butenafine. Trichophyton tonsurans was the most susceptible (MIC = 0.006 μg/ml) and E. floccosum was the most resistant (MIC = 0.02 μg/ml) species to terbinafine. Terbinafine resistance was reported for two species, i.e., T. rubrum and T. tonsurans at the total rate of 2% which was due to Leu393Phe substitution in both species. Taken together, our results assist clinicians and prompt the current knowledge about the necessity of antifungal susceptibility testing to select effective strategies for management of clinical cases of dermatophytosis.

With the development of novel treatments for autoimmune disorders, it has become a popular research focus which mesenchymal stem cells (MSCs) have the capacity to counteract with autoimmune diseases progression. One of the underlying mechanisms behind their activities is the release of extracellular vesicles especially exosomes. MSC-derived exosomes are hypoimmunogenic nanocarriers which contain numerous immunoregulatory factors and similar to other exosomes, are able to pass through boundaries like the blood-brain barrier (BBB). Accumulating evidence provided by animal studies has demonstrated that MSC-derived exosomes, as a novel therapy, can re-induce self-tolerance, without subsequent complications reported for other treatments. Therefore, therapeutic applications of MSC-derived exosomes are contributing to core advances in the field of autoimmune diseases. Here, we briefly describe the biological characteristics of MSC-derived exosomes and review the experimentally verified outcomes for autoimmune disease therapy purposes.

Multiple roles have been indicated for reactive oxygen species (ROS) in the immune system in recent years. ROS have been extensively studied due to their ability to damage DNA and other subcellular structures. Noticeably, they have been identified as a pivotal second messenger for T-cell receptor signaling and T-cell activation and participate in antigen cross-presentation and chemotaxis. As an agent with direct toxic effects on cells, ROS lead to the initiation of the autoimmune response. Moreover, ROS levels are regulated by antioxidant systems, which include enzymatic and nonenzymatic antioxidants. Enzymatic antioxidants include superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase. Nonenzymatic antioxidants contain vitamins C, A, and E, glutathione, and thioredoxin. Particularly, cellular antioxidant systems have important functions in maintaining the redox system homeostasis. This review will discuss the significant roles of ROS generation and antioxidant systems under normal conditions, in the immune system, and pathogenesis of multiple sclerosis.

Background: Azole resistance in Aspergillus fumigatus is an emerging problem and reported from all continents. As triazole antifungals are the mainstay of therapy in the management of invasive aspergillosis, azole-resistant A fumigatus has become a major medical concern and with complicated clinical management. Objective: Screening of environmental presence of azole-resistant A fumigatus in Iran.Methods: Compost from Northern Iran, collected between 2017 and 2018, was screened for the presence of azole-resistant A fumigatus with azole-containing agar.Phenotypic MICs were obtained from selected, molecularly confirmed isolates.cyp51A gene sequencing and genotyping of azole-resistant isolates were done.Results: Among 300 compost samples, three A fumigatus isolates had high voriconazole MICs (≥16 mg/L) and harboured the TR 46 /Y121F/T289A mutation in the cyp51A gene. Microsatellite typing of these isolates showed that two strains had the same allele across all nine examined microsatellite loci and were genotypically related to Indian azole-resistant strains. The other isolate had a different genotype.Conclusion: This is the first report of A fumigatus with TR 46 /Y121F/T289A mutation from the region. Monitoring and surveillance of antifungal susceptibility of clinical A fumigatus is warranted in Iran and elsewhere in the region. K E Y W O R D SAspergillus fumigatus, azole resistance, compost, TR 34 /L98H, TR46/Y121F/T289A | 431 AHANGARKANI et Al.

Nod‐like receptor protein 3 (NLRP3) inflammasome is a multi‐protein complex that controls the production of pro‐inflammatory cytokines, IL‐18 and IL‐1β, through caspase‐1 activation. These inflammatory cytokines play an important role in the development of multiple sclerosis (MS). The inflammasome NLRP3 gene variations and expression level have been suggested to affect the immune system activity. This case–control study was performed to determine the association of NLRP3 genetic variants and differential expression with MS. We analysed four common single nucleotide polymorphisms (SNPs) of NLRP3 (rs‐10754558, rs‐35829419, rs‐3806265, rs‐4612666) in a group of 150 Iranian patients with relapsing–remitting MS (RRMS) in comparison with 100 healthy controls. The genotyping was performed using the TaqMan method. For the analysis of NLRP3 gene expression level, we studied a group of 37 RRMS patients (18 patients at relapse phase and 19 at remission phase, treated with IFN‐β) in comparison with 22 healthy controls using real‐time PCR. In this study, we found that NLRP3 rs3806265 C allele and CC genotype were significantly more frequent in the RRMS patients (p value = 0.03 OR = 1.66, 95% CI = 1.14–2.43) and p value = 0.04, OR = 3.26, 95% CI = 1.19–8.93, respectively), while the frequency of T allele significantly decreased in controls (p value = 0.03, OR = 0.6, 95% CI = 0.41–0.87). The frequency of CG genotype at position rs10754558 was also significantly higher in the controls compared with patients (p value = 0.03, OR = 0.5, 95% CI = 0.30–0.80). Moreover, expression level of the NLRP3 in patients at remission phase was significantly reduced in comparison with patients at relapse phase and also healthy controls (p = 0.01 and p = 0.04, respectively). The association of NLRP3 polymorphisms with the susceptibility of MS and its reduced expression after IFN‐β therapy, support the idea that NLRP3 inflammasome could have a critical role in inflammatory responses in MS.

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Efforts to investigate the progression of events that cause human cells to become neoplastic in response to ionizing radiation have been aided by the development of tissue culture systems of epithelial cells. In the present study, nontumorigenic human epidermal keratinocytes immortalized by adenovirus type 12 and simian virus 40 have been transformed by exposure to x-ray irradiation. Such transformants showed morphological alterations, formed colonies in soft agar, and induced carcinomas when transplanted into nude mice, whereas primary human epidermal keratinocytes exposed to radiation in this manner failed to show any evidence of transformation. These findings demonstrate the malignant transformation of human primary epithelial cells in culture by the combined action of a DNA tumor virus and radiation, indicating a multistep process for radiation-induced neoplastic conversion. This in vitro system may be useful as a tool for dissecting the process of radiation-induced neoplastic transformation of human epithelial cells and for detecting previously unreported human oncogenes.

Recent evidence points to a pathogenic role for CD8+ cytotoxic T (Tc) cells in Multiple sclerosis (MS). Based on cytokine profile, Tc cells can be divided into different subsets: IFN-γ (Tc1), IL-4 (Tc2), IL-10 (Tc10), IL-17 (Tc17), IL-21 (Tc21), IL-22 (Tc22) and TNF-α producing cells. In this study we evaluated the frequency of Tc cell subsets and the serum level of Tc17 differentiation cytokines in MS patients with different clinical patterns. We analyzed Tc cell subsets percentage in peripheral blood of relapsing-remitting (RRMS) (n = 28), secondary-progressive (SPMS) (n = 10) and primary-progressive (PPMS) (n = 4) MS patients in comparison to healthy controls (n = 15) using flow cytometry. Serum level of TGF-β, IL-6 and IL-23 were measured by ELISA. We showed elevated levels of Tc1 and Tc17 cells in SPMS and RRMS patients in relapse phase, respectively (P = 0.04). Interestingly, the percentage of TNF-α producing CD8+ T cells in relapse and remission phase of RRMS and SPMS patients were higher than controls (P = 0.01, P = 0.004, P = 0.01, respectively) and Tc21 increased in remission phase of RRMS compared to SPMS (P = 0.03). We also found higher frequency of CD8+ IFN-γ+ TNF-α+ IL-17+ T cells in relapse phase of RRMS compared to remission phase, SPMS patients and controls (P = 0.01, P = 0.004 and P = 0.02, respectively). TGF- β increased in sera of RRMS patients in remission phase (P = 0.03) and SPMS (P = 0.05) compared to healthy subjects. Increased level of Tc17 and CD8+ IFN-γ+ TNF-α+ IL-17+ T cells in relapse phase highlights the critical role of IL-17 in RRMS pathogenesis.