Publications by authors named "Mohammad Hedayati"

113 Publications

Investigating the challenges and factors influencing the use of the learning management system during the Covid-19 pandemic in Afghanistan.

Educ Inf Technol (Dordr) 2021 Apr 7:1-34. Epub 2021 Apr 7.

Computer Science Faculty, Kabul University, Kabul, Afghanistan.

Successful implementation and use of learning management systems (LMSs) have become a critical challenge for many higher education institutes during the Covid-19 pandemic. Although LMSs with lots of features were developed for universities, the success of those systems is highly related to a detailed understanding of challenges and factors influencing the use of the systems among their users. HELMS (Higher Education Learning Management System) is a countrywide LMS used for teaching and learning during the quarantine period caused by covid-19 in Afghanistan universities. As it was the first experience of Afghan universities in using the learning management systems during the pandemic, challenges were expected to appear. No previous research has been conducted on either studying the challenges of using the HELMS or investigating the factors influencing the use of HELMS during the Covid-19 pandemic in Afghanistan. Hence, there was no unified view of the potential challenges of using HELMS and factors influencing the use of the HELMS among the researchers. This research aims to investigate the challenges that face the use of HELMS and explore the factors influencing the use of HELMS among both lecturers and students. This study employed a qualitative research method by conducting semi-structured interviews with 100 participants including university management, lecturers, and students. Thematic analysis was used as a method for the analysis of qualitative data. The findings of this research will help policymakers, researchers, and practitioners in public and private universities to grasp knowledge on the successful implementation and use of LMSs during covid-19 and afterward.
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http://dx.doi.org/10.1007/s10639-021-10517-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8025060PMC
April 2021

Recent Advances in Genome Editing Tools in Medical Mycology Research.

J Fungi (Basel) 2021 Mar 30;7(4). Epub 2021 Mar 30.

Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari 481751665, Iran.

Manipulating fungal genomes is an important tool to understand the function of target genes, pathobiology of fungal infections, virulence potential, and pathogenicity of medically important fungi, and to develop novel diagnostics and therapeutic targets. Here, we provide an overview of recent advances in genetic manipulation techniques used in the field of medical mycology. Fungi use several strategies to cope with stress and adapt themselves against environmental effectors. For instance, mutations in the 14 alpha-demethylase gene may result in azole resistance in strains and shield them against fungicide's effects. Over the past few decades, several genome editing methods have been introduced for genetic manipulations in pathogenic fungi. Application of restriction enzymes to target and cut a double-stranded DNA in a pre-defined sequence was the first technique used for cloning in and . Genome editing technologies, including zinc-finger nucleases (ZFNs) and transcriptional activator-like effector nucleases (TALENs), have been also used to engineer a double-stranded DNA molecule. As a result, TALENs were considered more practical to identify single nucleotide polymorphisms. Recently, Class 2 type II Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 technology has emerged as a more useful tool for genome manipulation in fungal research.
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http://dx.doi.org/10.3390/jof7040257DOI Listing
March 2021

H filtering for nonlinearly coupled complex networks subjected to unknown varying delays and multiple fading measurements.

ISA Trans 2021 Mar 16. Epub 2021 Mar 16.

Department of Electrical Engineering, Imam-Khomeini International University, Qazvin, Iran. Electronic address:

In this paper, the robust filtering problem for uncertain complex networks with time-varying state delay and stochastic nonlinear coupling based on H performance criterion is studied. The random connections of coupling nodes are represented by utilizing independent random variables and the multiple fading measurements phenomenon is characterized by introducing diagonal matrices with independent stochastic elements. Moreover, the probabilistic time-varying delays in the measurement outputs are described by white sequences with the Bernoulli distributions. Furthermore, All system's matrices are supposed to have uncertainty and a quadratic bound is assumed for nonlinear part of the network. This bound can be obtained by solving a sum of squares (SOS) optimization problem. By applying the Lyapunov theory, we design a robust filter for each node of the network so that the filtering error system is asymptomatically stable and the H performances are met. Then, the parameters of the filters are achieved by solving a linear matrix inequality (LMI) feasibility problem. Finally, the applicability and performance of the proposed H filtering approach are demonstrated via a practical example.
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http://dx.doi.org/10.1016/j.isatra.2021.03.008DOI Listing
March 2021

Molecular Identification and Antifungal Susceptibility of Yeasts and Molds Isolated from Patients with Otomycosis.

Mycopathologia 2021 Mar 15. Epub 2021 Mar 15.

Invasive Fungi Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran.

Fungal otitis externa, an infection of the external auditory canal caused by molds and yeasts, accounts for approximately 10-20% of ear canal infections accompanying high recurrence. The purpose of the current study was to assess the pattern of etiological agents of otomycosis and resistance profile as well as the rate of tympanic membrane perforation. A total of 1040 patients with symptoms of fungal otitis externa, in a period of two years, were investigated. The mycological tests revealed the presence of different fungi in 237 ears (22.8%). Fungal otitis was more related to filamentous fungi of the species Aspergillus flavus (54.43%), A. tubingensis (10.97%), and A. niger (8.86%), followed by yeasts, Candida orthopsilosis (7.59%), C. albicans (6.75%), and C. parapsilosis (5.06%). Tympanic membrane perforation rate was found to be 6.75% and was more common with otomycosis caused by A. flavus, A. tubingensis and C. albicans. In antifungal susceptibility tests, all tested drugs showed generally good activity against most isolates of molds and yeasts, while tolnaftate, clotrimazole, nystatin, and terbinafine had lowest effects. We found that among Aspergillus isolates, one A. niger isolate was resistant to voriconazole, and one A. flavus isolate was resistant to amphotericin B. Furthermore, among Candida species, three isolates of C. orthopsilosis showed high MIC values to fluconazole, two C. albicans isolates were considered fluconazole resistant and one isolate of C. parapsilosis was resistant to caspofungin and 3 isolates were resistant to fluconazole. Regarding the existence of the cases with perforated tympanic membrane and emerging species causing fungal otitis in the current report, the importance of the early physical examination, precise molecular identification, and the antifungal susceptibility evaluation is highlighted.
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http://dx.doi.org/10.1007/s11046-021-00537-1DOI Listing
March 2021

The impact of COVID-19 pandemic on AIDS-related mycoses and fungal neglected tropical diseases: Why should we worry?

PLoS Negl Trop Dis 2021 02 9;15(2):e0009092. Epub 2021 Feb 9.

Invasive Fungi Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran.

The World Health Organization (WHO) considers mycetoma, chromoblastomycosis, and paracoccidioidomycosis to be fungal neglected tropical diseases (FNTDs). Depending on climatic, cultural, and economic contexts, these diseases have a similar geographical distribution as many other diseases, particularly tuberculosis (TB) and malaria, but are often less targeted by the national and many international healthcare systems. Another subgroup of fungal infections, such as candidiasis, cryptococcosis, pneumocystosis, histoplasmosis, and to a lesser extent, aspergillosis, are known as AIDS-related mycoses. Although antiretroviral therapy (ART) has been able to decrease the mortality rate of these diseases, particularly cryptococcosis, the disproportionately low distribution of funds to their diagnosis and treatment remains an obstacle in saving and improving the lives of patients affected. A new wave of viral diseases dubbed the Coronavirus Disease 2019 (COVID-19) hit the world at the end of 2019. Due to progressive symptoms and high mortality rates of COVID-19 compared to fungal infections, particularly the FNTDs, funding is currently allocated predominantly for diagnostic and therapeutic research on COVID-19. As a result, advances in FNTDs and AIDS-related mycosis care are considerably reduced. This paper explores the association between COVID-19, FNTDs, and AIDS-related mycoses with a predictive perspective.
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http://dx.doi.org/10.1371/journal.pntd.0009092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872288PMC
February 2021

Challenges and advancements in the pharmacokinetic enhancement of therapeutic proteins.

Prep Biochem Biotechnol 2021 Jan 18:1-11. Epub 2021 Jan 18.

Department of Nanobiotechnology, New Technologies Research Group, Pasteur Institute of Iran, Tehran, Iran.

Nowadays, proteins are frequently administered as therapeutic agents in human diseases. However, the main challenge regarding the clinical application of therapeutic proteins is short circulating plasma half-life that leads to more frequent injections for maintaining therapeutic plasma levels, increased therapy costs, immunogenic reactions, and low patient compliance. So, the development of novel strategies to enhance the pharmacokinetic profile of therapeutic proteins has attracted great attention in pharmaceuticals. So far, several techniques, each with their pros and cons, have been developed including chemical bonding to polymers, hyper glycosylation, Fc fusion, human serum albumin fusion, and recombinant PEG mimetics. These techniques mainly classify into three strategies; (i) the endosomal recycling of neonatal Fc receptor which is observed for immunoglobulins and albumin, (ii) decrease in receptor-mediated clearance, and (iii) increase in hydrodynamic radius through chemical and genetic modifications. Recently, novel PEG mimetic peptides like proline/alanine/serine repeat sequences are designed to overcome pitfalls associated with the previous technologies. Biodegradability, lack of or low immunogenicity, product homogeneity, and a simple production process, currently make these polypeptides as the preferred technology for plasma half-life extension of therapeutic proteins. In this review, challenges and pitfalls in the pharmacokinetic enhancement of therapeutic proteins using PEG-mimetic peptides will be discussed in detail.
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http://dx.doi.org/10.1080/10826068.2020.1839907DOI Listing
January 2021

Familial Cases of Trichophyton benhamiae Infection Transmitted from a Guinea Pig in Iran.

Mycopathologia 2021 Mar 4;186(1):119-125. Epub 2021 Jan 4.

Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Trichophyton benhamiae is a zoophilic dermatophyte mainly transmitted to humans from guinea pigs. This zoophilic species can also cause dermatophytosis as reported by human contact with other animals, such as rabbit, cat, and fox. Here, we report the tinea faciei and tinea corporis cases: a 12-year-old girl and her 53-year-old father, with no history of immunodeficiency and underlying disease, caused by T. benhamiae transmitted from a guinea pig in Iran. Dermatological examination revealed several erythematous, round, scaly, and approximately 1-4-cm-diameter lesions in both patients. The girl had seven skin lesions, and her father presented two skin lesions on the front side of his neck. The girl's lesions had started 3 weeks before and her father's lesions appeared 7 days after the first clinical appearance of the lesions in the daughter. The girl had daily close contact with a guinea pig, while her father did not have any direct exposure to the pet. Examination of the lesions scraping with 10% potassium hydroxide (KOH 10%) revealed hyaline septate hyphae and arthroconidia. The dermatophyte isolated in culture was identified as T. benhamiae using molecular analysis. The patients were successfully treated using topical sertaconazole nitrate 2% cream twice a day for 4 weeks.
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http://dx.doi.org/10.1007/s11046-020-00513-1DOI Listing
March 2021

Diagnosis of allergic bronchopulmonary aspergillosis in patients with persistent allergic asthma using three different diagnostic algorithms.

Mycoses 2021 Mar 8;64(3):272-281. Epub 2020 Dec 8.

Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Background: Allergic bronchopulmonary aspergillosis (ABPA) has been reported in various degrees among patients with persistent allergic asthma (PAA). Currently, there is no gold standard approach for diagnosis of ABPA.

Objectives: In the current study, we aimed the evaluation of three different mainly used algorithms as Rosenberg & Patterson (A), ISHAM Working Group (B) and Greenberger (C) for diagnosis of ABPA in 200 patients with underlying PAA.

Methods: All patients were evaluated using Aspergillus skin prick test (SPTAf), Aspergillus-specific IgE (sIgEAf) and IgG (sIgGAf), total IgE (tIgE), pulmonary function tests, radiological findings and peripheral blood eosinophil count. The prevalence rate of ABPA in PAA patients was estimated by three diagnostic criteria. We used Latent Class Analysis for the evaluation of different diagnostic parameters in different applied ABPA diagnostic algorithms.

Results: Aspergillus sensitisation was observed in 30 (15.0%) patients. According to algorithms A, B and C, nine (4.5%), six (3.0%) and 11 (5.5%) of patients were diagnosed with ABPA, respectively. The sensitivity and specificity of criteria B and C were (55.6% and 99.5%) and (100.0% and 98.9%) respectively. sIgEAf and sIgGAf showed the high significant sensitivity. The performance of algorithm A, in terms of sensitivity and specificity, was somewhat better than algorithm B.

Conclusion: Our study demonstrated that the sensitivity of different diagnostic algorithms could change the prevalence rate of ABPA. We also found that all of three criteria resulted an adequate specificity for ABPA diagnosis. A consensus patterns combining elements of all three criteria may warrant a better diagnostic algorithm.
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http://dx.doi.org/10.1111/myc.13217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902363PMC
March 2021

Investigation of in vitro antifungal susceptibility testing and genetic diversity of clinical isolates of Trichophyton benhamiae and Trichophyton eriotrephon in Iran.

Mycoses 2021 Mar 25;64(3):316-323. Epub 2020 Nov 25.

Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Background: Trichophyton benhamiae is a zoophilic dermatophyte, known as one of the causative agents of dermatophytosis.

Objectives: The purpose of this study was to explore the genotypes of T. benhamiae strains isolated from geographically different areas of Iran and also to evaluate in vitro antifungal susceptibility profile of these strains against seven antifungal drugs.

Methods: Twenty-two strains of T. benhamiae and two strains of T. eriotrephon were isolated from patients with distinct types of dermatophytosis. DNA extraction and amplification of rDNA regions using ITS1 and ITS4 primers were conducted on the isolates. The in vitro antifungal susceptibility of posaconazole (PSC), voriconazole (VRC), itraconazole (ITC), ketoconazole (KET), caspofungin (CAS), terbinafine (TRB) and griseofulvin (GRZ) was evaluated according to CLSI M38-A2 protocol.

Results: The multiple alignment of the ITS-rDNA sequences of T. benhamiae indicated a mean similarity of 99.5%, with 0-3 interspecies nucleotide difference. The geometric mean (GM) values of minimum inhibitory concentrations (MICs) and minimum effective concentrations (MECs) across the all isolates were respectively: TRB: 0.025 mg/L, PSC: 0.032 mg/L, ITC: 0.050 mg/L and VRC: 0.059 mg/L with lower values and CAS: 0.31 mg/L, KTZ: 0.56 mg/L and GRZ: 0.76 mg/L with higher values.

Conclusion: Diverse ITS sequence types of T. benhamiae were shown in different geographical regions of Iran. The TRB, PSC and ITC were the most effective drugs against T. benhamiae strains, respectively. Furthermore, in our study, two strains of T. eriotrephon as a scarce dermatophyte species were described.
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http://dx.doi.org/10.1111/myc.13210DOI Listing
March 2021

COVID-19-Associated Candidiasis (CAC): An Underestimated Complication in the Absence of Immunological Predispositions?

J Fungi (Basel) 2020 Oct 8;6(4). Epub 2020 Oct 8.

Clinical and Translational Fungal-Working Group, University of California San Diego, La Jolla, CA 92093, USA.

The recent global pandemic of COVID-19 has predisposed a relatively high number of patients to acute respiratory distress syndrome (ARDS), which carries a risk of developing super-infections. species are major constituents of the human mycobiome and the main cause of invasive fungal infections, with a high mortality rate. Invasive yeast infections (IYIs) are increasingly recognized as s complication of severe COVID-19. Despite the marked immune dysregulation in COVID-19, no prominent defects have been reported in immune cells that are critically required for immunity to . This suggests that relevant clinical factors, including prolonged ICU stays, central venous catheters, and broad-spectrum antibiotic use, may be key factors causing COVID-19 patients to develop IYIs. Although data on the comparative performance of diagnostic tools are often lacking in COVID-19 patients, a combination of serological and molecular techniques may present a promising option for the identification of IYIs. Clinical awareness and screening are needed, as IYIs are difficult to diagnose, particularly in the setting of severe COVID-19. Echinocandins and azoles are the primary antifungal used to treat IYIs, yet the therapeutic failures exerted by multidrug-resistant spp. such as and call for the development of new antifungal drugs with novel mechanisms of action.
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http://dx.doi.org/10.3390/jof6040211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7712987PMC
October 2020

In vitro activities of antifungal drugs against a large collection of Trichophyton tonsurans isolated from wrestlers.

Mycoses 2020 Dec 13;63(12):1321-1330. Epub 2020 Sep 13.

Invasive Fungi Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran.

Background: Trichophyton tonsurans is the most common agent causing tinea gladiatorum in wrestlers, and limited data on susceptibility profiles of Trichophyton tonsurans are available.

Objectives: We aimed to assess the in vitro activity of the common antifungal drug against a large collection of T tonsurans.

Materials/methods: The in vitro activities to eight common antifungal drugs (sertaconazole, itraconazole, clotrimazole, fluconazole, butenafine, tolnaftate, terbinafine and griseofulvin) against 128 clinical isolates of T tonsurans strains, obtained from wrestlers with dermatophytosis, were performed according to CLSI M38-A2 broth microdilution document.

Results: The geometric mean minimum inhibitory concentration was the lowest for tolnaftate (0.022 µg/mL), followed by itraconazole (0.026 µg/mL), terbinafine (0.033 µg/mL), butenafine (0.088 µg/mL), griseofulvin (0.566 µg/mL), sertaconazole (2.875 µg/mL), clotrimazole (3.419 µg/mL) and fluconazole (12.540 µg/mL).

Conclusions: Evaluation of antifungal susceptibility of dermatophytes showed that tolnaftate and itraconazole were the most effective drugs against T tonsurans and fluconazole had the least effect.
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http://dx.doi.org/10.1111/myc.13172DOI Listing
December 2020

Exposure to endotoxins and respiratory health in composting facilities.

Ecotoxicol Environ Saf 2020 Oct 2;202:110907. Epub 2020 Jul 2.

Department of Environmental Health Engineering, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; Department of Research Methodology and Data Analysis, Institute for Environmental Research (IER), Tehran University of Medical Sciences, Tehran, Iran. Electronic address: http://yunesian.tums.ac.ir.

The impact of bioaerosols in municipal solid waste management is nowadays identified as a growing health concern worldwide. In this study, exposure to endotoxin in composting facilities and its association with lung function and clinical symptoms was investigated in Tehran municipal solid waste management complex (Aradkooh) as one of the largest solid waste management facilities in the Middle East. Airborne endotoxins were collected between June and July 2019 and the concentrations were determined by Limulus Amebocyte Lysate (LAL) method. Healthy workers with no history of respiratory disease were recruited and data on clinical symptoms (cough, phlegm, wheezing, dyspnea, fatigue, headache, eye irritation, runny nose, runny eyes, and sore throat) was obtained by the modified American Thoracic Society questionnaire, and spirometric measurement was performed by an expert. The binary logistic regression test was used and adjusted for confounding variables. The results didn't show any difference in lung function parameters (FEV, FVC, FEV/FVC, PEF, FEF), and most of the respiratory symptoms despite a relatively high difference in the concentration of endotoxin observed in air samples of different locations. Only the increased risk of cough (OR 10.5, 95% CI: 2.4 to 44.8 in the moderately exposed group and 7.8, 95% CI: 1.6 to 39.1 in highly exposed ones), fatigue (OR 3.7, 95% CI: 1.2 to 11.7), and headache (OR 6.02, 95% CI: 1.4 to 24.5) were found in the exposed groups compared to controls after adjusting for age, active and passive smoking. However, findings of the study might be underestimated due to some issues including healthy worker effect, intra and intersubject variability, and self-reporting bias, thereby the results should be interpreted with caution. Although we did not find any relationship, due to the high concentrations of endotoxins observed in some sites, it is recommended to consider some possible prevention measures such as using personal protective equipment to reduce the exposure of workers at an acceptable level.
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http://dx.doi.org/10.1016/j.ecoenv.2020.110907DOI Listing
October 2020

Fatal Prosthetic Valve Endocarditis Due to in a Diabetic Patient.

Infect Drug Resist 2020 10;13:2245-2250. Epub 2020 Jul 10.

Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

endocarditis (AE) accounts for a-quarter of all fungal endocarditis, mainly in immunocompromised hosts prior to heart-valve surgery with high mortality, even with treatment. Herein, we report a rare case of AE in a diabetic 60-year-old woman with a history of redo mitral valve prosthesis suspecious of acute endocarditis. She underwent second redo surgical mitral valve replacement in combination with mechanical aortic valve replacement. Blood cultures were negative. The explanted valve and vegetation were subjected to identification. Grown colonies were identified as , based on conventional and molecular methods. Despite the administration of liposomal amphotericin B and improvement in her general condition shortly after initiation of therapy, the patient passed away. As AE is a late consequence of redo prosthetic valve replacement, extended follow-up, early diagnosis, repeating valve-replacement surgeries, and timely selective antifungal treatments are warranted.
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http://dx.doi.org/10.2147/IDR.S258637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360421PMC
July 2020

Echinocandin resistance in Candida parapsilosis sensu stricto: Role of alterations in CHS3, FKS1 and Rho gene expression.

J Glob Antimicrob Resist 2020 09 9;22:685-688. Epub 2020 Jul 9.

Invasive Fungi Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran; Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Electronic address:

Objectives: The rate of resistance of Candida parapsilosis to echinocandins remains unexplored in Iran. The main aims of this study were to investigate the susceptibility patterns and possible mechanisms of echinocandin resistance in echinocandin-resistant clinical C. parapsilosis isolates in Iran.

Methods: A total of 105 isolates of C. parapsilosis sensu stricto underwent antifungal susceptibility testing to echinocandins by the broth microdilution reference method. Sequences of the CpERG3 and CpFKS1 genes were analysed using MEGA6 software, and alterations in CHS3, FKS1 and Rho gene expression were evaluated by quantitative reverse transcription (RT-qPCR). REST® software was used to analyse the results.

Results: The rate of echinocandin cross-resistance was 2.9% (3/105). No substitutions were detected in Fks1p except for the naturally occurring P660A amino acid substitution observed in isolates both with high and low minimum inhibitory concentrations (MICs). Moreover, the G111R amino acid substitution was not found in Erg3p. Following echinocandin exposure, expression of Rho and FKS1 genes was significantly increased in resistant isolates, whilst the CHS3 gene showed no change.

Conclusion: Alterations in the expression of some key genes may be responsible for echinocandin resistance among C. parapsilosis isolates. Understanding the mechanisms responsible for drug resistance in C. parapsilosis is not only crucial for the development of new antifungals but is also important in choosing appropriate antifungals for patient treatment at the earliest stage.
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http://dx.doi.org/10.1016/j.jgar.2020.06.025DOI Listing
September 2020

The first rare and fatal case of invasive aspergillosis of spinal cord due to in an Iranian child with chronic granulomatosis disease: review of literature.

Curr Med Mycol 2020 ;6(1):55-60

Department of Infectious Diseases, Children Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Background And Purpose: Invasive aspergillosis (IA) of the central nervous system (CNS) is a devastating complication which is rarely reported in immunocompromised children. In this case presentation, we reported a rare and fatal IA with spinal cord involvement in a 10-year-old child with X-linked chronic granulomatosis disease (CGD).

Case Report: The child had a previous history of pulmonary tuberculosis. A cervical spine X-ray revealed the involvement of cervical vertebrae (T4/T5) and s causing spinal cord compression and epidural abscess The patient underwent a decompressive laminectomy and mass removal. The histopathology and culture results suggested IA. Despite the aggressive and prolonged therapy, he died within one year. was identified as the causative agent based on morphological and molecular studies.

Conclusion: This synopsis represents the aggressive behavior of infection caused by in the CGD patient.
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http://dx.doi.org/10.18502/cmm.6.1.2551DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7217256PMC
January 2020

Preparation, characterization, and anticancer efficacy of novel cobalt oxide nanoparticles conjugated with thiosemicarbazide.

3 Biotech 2020 May 5;10(5):230. Epub 2020 May 5.

1Department of Biology, Rasht Branch, Islamic Azad University, Rasht, Iran.

Gastric cancer is one of the most common cancers in modern societies. Previous studies have shown that the use of nanoparticle complexes is effective in the treatment of cancer. The aim of this study was to investigate the cytotoxicity and anticancer properties of cobalt oxide (CoO) nanoparticles (NPs) functionalized by glutamic acid (Glu) and conjugated with thiosemicarbazide (TSC) on gastric cancer (AGS) cell line. First, the CoO@Glu/TSC nanoparticles were synthesized via co-condensation reaction. Fourier-transform infrared (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) tests were performed for identifying the morphology, structure, size and functional groups of produced nanoparticles. MTT assay was also performed to evaluate cytotoxicity effect. Moreover, Annexin V/PI staining with flow cytometry analysis, caspase-3 activation assay, and Hoechst 33258 staining was carried out for evaluating apoptosis. The FTIR results showed that the components of CoO@Glu/TSC NPs complex were successfully fabricated. Crystallographic structure of CoO@Glu/TSC NPs was confirmed by XRD patterns. SEM results indicated that the size of the nanoparticles was in the range of 16-40 nm. An EDX spectrum was determined and data explained the existence of cobalt as the prominent element. MTT test results showed that AGS cell life was significantly decreased compared to the control group with increasing concentration of nanoparticles (dose-dependent) ( < 0.05), IC = 107.5 μg/mL. The results of flow cytometry assay and caspase-3 activity showed that fabricated CoO@Glu/TSC NPs induced apoptosis in the treated group. Moreover, CoO@Glu/TSC NPs treated AGS cells indicate an increase in the apoptotic characteristics including nuclear fragmentation. In the current work, the promising cytotoxicity and anti-cancer activities of CoO@Glu/TSC NPs complex toward gastric cancer (AGS) cell line were showed and it can be suggested for the drug delivery system.
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http://dx.doi.org/10.1007/s13205-020-02230-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7200957PMC
May 2020

Galactomannan detection in bronchoalveolar lavage fluids: A diagnostic approach for fungus ball in patients with pulmonary tuberculosis?

Mycoses 2020 Jul 24;63(7):755-761. Epub 2020 May 24.

Invasive Fungi Research Center/Department of Medical mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Background: Several previous studies have shown cavitary lung lesions in old pulmonary tuberculosis (PTB) increase the risk of fungus ball. Detection of galactomannan (GM) in bronchoalveolar lavage (BAL) is also proposed as a diagnostic approach for the fungus ball.

Objectives: We evaluated the diagnosis of fungus balls and GM levels in BAL samples in PTB patients.

Methods: A total of 110 PTB patients were evaluated for fungus ball during 2017-2019. The patients were evaluated for radiological, histopathological results and mycological findings of BAL including GM detection and culture. The sensitivity, specificity and positive and negative predictive value for GM test were calculated. The optimal cut-off for BAL GM testing was determined by receiver operating characteristic (ROC).

Results: Of 110 PTB patients, nine (8.18%) showed fungus ball, all with old PTB. The molecularly confirmed Aspergillus species were A. flavus, A. fumigatus and A. ochraceus. The sensitivity and specificity of BAL GM ≥ 0.5 in old PTB patients with fungus ball were 100%, 41.5%, respectively. The statistical analysis of the mean ± SEM of BAL GM levels was demonstrated a higher levels of GM in patients with fungus ball/aspergilloma compared to old PTB patients without fungus ball/aspergilloma. The optimal cut-off value for BAL GM was determined as 0.50 by ROC curve analysis.

Conclusion: According to our results, we can recommend the detection of GM in BAL samples as a diagnostic approach for fungus ball in PTB patients.
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http://dx.doi.org/10.1111/myc.13099DOI Listing
July 2020

Nanoparticle interactions with immune cells dominate tumor retention and induce T cell-mediated tumor suppression in models of breast cancer.

Sci Adv 2020 03 25;6(13):eaay1601. Epub 2020 Mar 25.

Department of Radiation Oncology and Molecular Radiation Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD 21231, USA.

The factors that influence nanoparticle fate in vivo following systemic delivery remain an area of intense interest. Of particular interest is whether labeling with a cancer-specific antibody ligand ("active targeting") is superior to its unlabeled counterpart ("passive targeting"). Using models of breast cancer in three immune variants of mice, we demonstrate that intratumor retention of antibody-labeled nanoparticles was determined by tumor-associated dendritic cells, neutrophils, monocytes, and macrophages and not by antibody-antigen interactions. Systemic exposure to either nanoparticle type induced an immune response leading to CD8 T cell infiltration and tumor growth delay that was independent of antibody therapeutic activity. These results suggest that antitumor immune responses can be induced by systemic exposure to nanoparticles without requiring a therapeutic payload. We conclude that immune status of the host and microenvironment of solid tumors are critical variables for studies in cancer nanomedicine and that nanoparticle technology may harbor potential for cancer immunotherapy.
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http://dx.doi.org/10.1126/sciadv.aay1601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096167PMC
March 2020

Relationship between spirometry results and colonisation of Aspergillus species in allergic asthma.

Clin Respir J 2020 Mar 26. Epub 2020 Mar 26.

Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Introduction And Objectives: Exposure to fungi in patients with asthma leads to the release of various fungal antigens, which can increase the severity of asthma. Regarding this, the present study was conducted to evaluate the relationship between the colonisation of Aspergillus species and spirometry results in allergic asthma.

Materials And Methods: Two hundred sixteen patients with mild to severe asthma and 30 healthy controls were included. All participants underwent pulmonary function tests. Furthermore, sputum samples were collected from each subject. Each sputum sample was subjected to direct microscopic examination and fungal culture. All cultured Aspergillus colonies were identified at species level by molecular methods. Finally, all available data from sputum culture and spirometry test were analysed.

Results: Out of 216 sputum samples, 145 (67.1%) were positive for fungal growth. Furthermore, out of 264 grown fungal colonies, 137 (51.9%) were Aspergillus species. Among the Aspergillus isolates, A. flavus (29.2%) was the most prevalent species, followed by A. fumigatus (27.7%). The mean forced expiratory volume in one second (FEV1) in the mild, moderate and severe asthmatic patients with a positive sputum culture for fungi were obtained as 90.0 ± 11.1, 71.1 ± 15.9 and 54.9 ± 16.4, respectively. In general, Aspergillus species colonisation had no statistically significant effect on spirometry results of study patients.

Conclusion: Our results showed that there is no difference in the FEV1 and forced vital capacity between Aspergillus positive and negative patients in any asthma severity group.
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http://dx.doi.org/10.1111/crj.13192DOI Listing
March 2020

Molecular epidemiology of Tinea gladiatorum in contact sports in northern Iran.

Mycoses 2020 May 13;63(5):509-516. Epub 2020 Mar 13.

Invasive Fungi Research Center, Mazandaran University of Medical Sciences, Sari, Iran.

Background: Tinea gladiatorum as the major health concern among combat athletes and the most common cause of a decrease in the quality of their sports activities.

Objectives: This study aimed to determine the molecular epidemiology of tinea gladiatorum in contact sports in Mazandaran Province, Northern Iran.

Materials/methods: In total, 631 suspected athletes out of 4240 ones were screened for tinea gladiatorum in this cross-sectional study from May 2018 to February 2019. The infection was confirmed by direct microscopy and culture tests. The causative agents were identified by polymerase chain reaction-restriction fragment length polymorphism method on ITS rDNA region. The indoor environmental factors were evaluated in 81 sports halls in terms of temperature (°C), humidity (%), density (m /athletes) and the number of ventilators.

Results: Tinea gladiatorum was confirmed in 6.5% (278/4240) of the athletes. Tinea corporis was the most common type of tinea (192/278; 69.0%), and 175 cases (27.7%) had more than one type of tinea. Moreover, Trichophyton tonsurans (192/203; 94.5%) was the most aetiological agent in all athletes followed by Microsporum canis (6/203; 2.9%), Trichophyton rubrum (2/203; 0.9%) and Trichophyton interdigitale (1/203; 0.4%). There was no significant association between the prevalence of tinea gladiatorum and the indoor environmental factors.

Conclusion: T. tonsurans is the most common agent of tinea gladiatorum in Northern Iran. Since no positive culture of dermatophyte was obtained from mats, it seems that skin-to-skin contact would be the most probable mode of transmission among wrestlers. Accordingly, periodical checkups should be considered by health care providers.
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http://dx.doi.org/10.1111/myc.13069DOI Listing
May 2020

Safety and efficacy of stem cell therapy for treatment of neural damage in patients with multiple sclerosis.

Stem Cell Investig 2019 27;6:44. Epub 2019 Dec 27.

Marine Medicine Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.

Multiple sclerosis (MS) is a multifocal inflammatory disease that involves the central nervous system and associated with limbs paralysis and serious problems in sensation, limbs, visual and sphincter. This disease is a result of autoimmune mechanism in which autoantibodies target the self-myelin antigens and cause demyelination. Because of the myelin dysfunction, MS is clinically identified with neurological disabilities. Furthermore, it can be entered into the progressive phase because of irreversible neurodegeneration and axons damage. Unfortunately, there is no effective therapeutic method for this disease and current medications have been focused on amelioration of symptoms and chronic inflammation. Although current immunotherapies ameliorate the reactivity of autoimmune anti-myelin and MS relapse rate, there is no approved method for improvement of the disease progression and repairing of the damaged myelin. Therefore, finding an appropriate clinical treatment for improvement of neurological damages in MS patients is essential. Mesenchymal stem cells (MSCs) are multipotent cells with high proliferative and self-renewal capacities, as well as immunomodulatory and neuroregenerative effects. Bone marrow and adipose tissues derived MSCs have been considered for the treatment of different diseases because not only they can be easily isolated from these tissues, but also a patient can be served as a donor for himself without the risk of rejection. More importantly, autologous MSCs carry a safer pattern without the risk of malignant transformation. Here, we will discuss the effectiveness of MSCs therapy for MS patients by reviewing of clinical trials.
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http://dx.doi.org/10.21037/sci.2019.10.06DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6987330PMC
December 2019

High prevalence of itraconazole resistance among isolated from Iran.

Curr Med Mycol 2019 Sep;5(3):43-46

Invasive Fungi Research Center, Mazandaran University of Medical Sciences, Sari, Iran.

Background And Purpose: Candida parapsilosis isolates usually have a low minimum inhibitory concentration (MIC) against azoles. Although Candida parapsilosis isolates usually have low MICs against azoles, recent studies candida invasive infections due to azole resistant-C. parapsilosis isolates . Regarding this, the main aim of this study was to determine the susceptibility pattern of Iranian clinical against available azole antifungal drugs.

Materials And Methods: This study was conducted on 105 previously-identified isolates of For the purpose of the study, the isolates were subjected to antifungal susceptibility testing against fluconazole (FLZ), itraconazole (ITZ), voriconazole (VRZ), and two new azole drugs, namely luliconazole (LUZU) and lanoconazole (LZN). The broth microdilution reference method adopted in this study was according to the Clinical & Laboratory Standards Institute M27-A3 and M27-S4 documents.

Results: According to the results, 89% (n=94) of isolates showed a MIC of ≥ 1 µg/ml, indicating resistance against ITZ. Multi-azole resistance was observed in 3.8% of the isolates. In addition, LUZU and LZN demonstrated the highest efficacy with the MIC values of 0.5 and 1 µg/ml, respectively.

Conclusion: The majority of the isolates showed high MIC values against ITZ. This may have been associated with the long-term ITZ prophylaxis/therapy in patients infected with candidiasis. Hence, the adoption of an appropriate antifungal agent is a crucial step for starting the treatment.
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http://dx.doi.org/10.18502/cmm.5.3.1746DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910713PMC
September 2019

A multi-centered study of colonization in patients with respiratory disorders: Is there a colonization trend in the elderly?

Curr Med Mycol 2019 Sep;5(3):19-25

Department of Molecular Pathology, National Research Institute of Tuberculosis and Lung Disease, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

Background And Purpose: colonization plays a key role in the progression of pulmonary infection. However, there are limited data regarding the colonization of these fungi in the patients residing in different regions of Iran. Regarding this, the present study was conducted to evaluate the prevalence of colonization in non-HIV-infected patients with respiratory failure introduced by physicians using nested polymerase chain reaction (PCR).

Materials And Methods: This study was conducted on 136 samples obtained from 136 patients with respiratory disorders referring to different hospitals in the capital and north of Iran during 2013-2015. The samples were collected using bronchoalveolar lavage (BAL; n=121) and sputum induction (n=15). Nested PCR method targeting mtLSU rRNA gene was used for the detection of DNA in the specimens.

Results: The nested PCR analysis resulted in the detection of DNA in 32 (23.5%) patients. The mean age of the participants was 49.04±11.94 years (age range: 14-90 years). The results revealed no correlation between colonization and gender. The studied patients were divided into two groups of immunocompromised and immunocompetent patients. In the regard, 25.4% of the patients with detectable DNA were immunocompromised and had cancer, organ transplantation, asthma, sarcoidosis, dermatomyositis, chronic obstructive pulmonary disease, bronchiectasis, and pulmonary vasculitis. On the other hand, DNA was detected in 21.8% of the immunocompetent patients. Frequencies of DNA detection in the patients with tuberculosis, hydatid cyst, and unknown underlying diseases were obtained as 20.8%, 25%, and 22%, respectively. The prevalence of colonization varied based on age. In this regard, colonization was more prevalent in patients aged above 70 years.

Conclusion: As the findings indicated, non-HIV-infected patients, especially the elderly, had a high prevalence of colonization. Therefore, these patients are probably a potential source of infection for others. Regarding this, it is of paramount importance to adopt monitoring and prophylactic measures to reduce this infection.
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http://dx.doi.org/10.18502/cmm.5.3.1742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910707PMC
September 2019

Genetic diversity and antifungal susceptibility patterns of Aspergillus nidulans complex obtained from clinical and environmental sources.

Mycoses 2020 Jan 3;63(1):78-88. Epub 2019 Nov 3.

Medical Mycology Reference Laboratory, National Center for Microbiology, Instituto de Salud Carlos III, Madrid, Spain.

The molecular epidemiology and antifungal susceptibility of Aspergillus nidulans species complex has not been well studied. To evaluate the genetic diversity and antifungal susceptibility patterns of clinical and environmental isolates of A. nidulans complex. Sixty clinical and environmental isolates of Aspergillus section Nidulantes were collected from five countries (Iran, The Netherlands, Spain, Portugal and Greece). The species were molecularly identified by sequencing of β-tubulin gene. The genetic diversity of A nidulans complex isolates (n = 54) was determined with a microsatellite genotyping assay. Antifungal susceptibility profile was determined using EUCAST method. The isolates were classified as A nidulans (46.7%), A spinulosporus (26.6%), A quadrilineatus (10%), A pachycristatus (3.3%), A rugulosus (3.3%), A unguis (5%), A creber, (1.7%), A olivicola (1.7%) and A sydowii (1.7%). Thirty-four sequence types (STs) were identified among the 54 A nidulans complex isolates. A high level of genetic diversity was found among A nidulans sensu stricto strains but low diversity was found among A spinulosporus strains. Amphotericin B showed high MICs to all species. The most active azole was posaconazole (GM = 0.64 mg/L), while itraconazole showed the highest MICs among azoles (GM = 2.95 mg/L). A spinulosporus showed higher MICs than A nidulans sensu stricto for all antifungals except for micafungin and anidulafungin. Interspecies variations may result in differences in antifungal susceptibility patterns and challenge antifungal therapy in infections caused by A nidulans. Differences in the distribution of STs or persistence of multiple STs might be related to the sources of isolation and niche specialisation.
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http://dx.doi.org/10.1111/myc.13019DOI Listing
January 2020

Discrimination of Aspergillus flavus from Aspergillus oryzae by matrix-assisted laser desorption/ionisation time-of-flight (MALDI-TOF) mass spectrometry.

Mycoses 2019 Dec 15;62(12):1182-1188. Epub 2019 Oct 15.

Invasive Fungi Research Center, Mazandaran University of Medical Sciences, Sari, Iran.

Background: Aspergillus flavus is a major cause of severe non-invasive fungal infections in the Middle Eastern countries. However, it is difficult to distinguish A flavus from A oryzae.

Objectives: To assess the potential of matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) in discriminating between A flavus and A oryzae and compare it with β-tubulin gene sequencing.

Methods: We used the Bruker Daltonik MALDI-TOF MS system to analyse 200 clinical and environmental A flavus isolates and one A pseudonomius and one A alliaceus (Aspergillus section Flavi) isolate a priori identified as such by sequencing of the β-tubulin gene.

Results: All 200 A flavus isolates were identified at the genus level and 176 (88%) at the species levels by MALDI-TOF MS based on the spectral log-scores (≥2.0 and 1.7-1.99, respectively); among them, only 18 (10.2%) were confirmed as A flavus, whereas 35 (19.9%) were identified as A oryzae and 123 (69.9%) as A flavus/A oryzae. Aspergillus pseudonomius and A alliaceus were misidentified as A flavus and A parasiticus with log-score values of 1.39 and 1.09, respectively.

Conclusions: The results indicate that the commercially available Bruker Daltonik MALDI-TOF MS score database cannot separate A flavus and A oryzae species. We also showed that establishment of an in-house library is a useful tool to discriminate closely related Aspergillus species, including A flavus and A oryzae.
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http://dx.doi.org/10.1111/myc.13010DOI Listing
December 2019

National trends in incidence, prevalence and disability-adjusted life years of invasive aspergillosis in Iran: a systematic review and meta-analysis.

Expert Rev Respir Med 2019 11 26;13(11):1121-1134. Epub 2019 Aug 26.

The University of Manchester , Manchester , NH , USA.

: We aimed to study the epidemiology, prevalence, incidence, clinical manifestations, underlying diseases, treatments, outcomes, and societal impact through disability-adjusted life years (DALYs) of IA in Iran. : A random-effect meta-analytic model was fitted to estimate the prevalence and incidence of IA in Iran. We also calculated DALYs. : Out of 79 published studies during the past 25 years from Iran, 23 met the inclusion criteria. A total of 2947 patients were included, of whom 396 (13.4%) patients were diagnosed with IA according to EORTC/MSG and ICU criteria. The main underlying condition for IA was hematologic disorders (39.4%). 86 (43%) was the most common isolate. The pooled prevalence and incidence rates were 20.5 (95% CI 12.5 to 29.9) and 4.8 (95% CI 2.3-8.2) per 100,000 population, respectively. Total DALYs was estimated 164.13 per 100,000 population. YLLs constitute the majority of IA burden compared to YLDs (162.80 YLLs/100,000 population vs 1.33 YLDs per 100,000 population). The highest YLL rates were found in people aged 45-49 (62.9 YLLs/100,000 population) and 30-34 years (45.2 YLLs/100,000 population), respectively. : This study indicates an increasing burden of IA in Iran, despite the extensive use of prophylaxis, challenging the public health, especially immunocompromised patients.
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http://dx.doi.org/10.1080/17476348.2019.1657835DOI Listing
November 2019

In vitro activities of 15 antifungal drugs against a large collection of clinical isolates of Microsporum canis.

Mycoses 2019 Nov 1;62(11):1069-1078. Epub 2019 Oct 1.

Invasive Fungi Research Center, School of Medicine, Mazandaran University of Medical Sciences.

Background: Microsporum canis is a zoophilic species, found to be the most frequently isolated species in animals. M. canis causes sporadic outbreaks of infections in humans, such as the one that occurred in Canada, where more than 1000 human cases were detected over an 8-year period. Despite the medical importance of M. canis infections, there are limited in vitro data on the antifungal susceptibility to antifungal drugs, including new generation triazoles and imidazoles.

Objective: The aim of the current study was to comprehensively evaluate the in vitro activity of new azoles and comparator drugs against a large panel of M. canis isolates using a microdilution assay.

Methods: The in vitro susceptibility to novel triazoles and imidazoles was compared to that of other antifungal drugs using a large collection of M. canis clinical isolates (n = 208) obtained from patients and animals with dermatophytosis in Iran, France and Turkey.

Results: All isolates exhibited high susceptibility to the majority of the tested antifungal agents. However, luliconazole, lanoconazole and efinaconazole, as well as econazole, demonstrated superior activity against all strains in comparis on with the other drugs.

Conclusion: FDA-approved antifungal drugs, that is luliconazole, efinaconazole and lanoconazole, showed the highest antifungal activity and should be promising candidates for the treatment of dermatophytosis caused by M canis. However, their therapeutic effectiveness remains to be determined in clinical settings.
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http://dx.doi.org/10.1111/myc.12986DOI Listing
November 2019

Identification of clinical dermatophyte isolates obtained from Iran by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Curr Med Mycol 2019 Jun;5(2):22-26

Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Background And Purpose: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is widely used to discriminate among pathogenic microorganisms in clinical laboratories. The aim of this study was to assess the utility of MALDI-TOF MS in the routine identification of clinical dermatophyte isolates obtained from various geographical regions of Iran.

Materials And Methods: A total of 94 isolates, including (n=44), (n=40), (n=4), (n=4), and (=1), were analyzed in this study. The identity of each isolate was determined by polymerase chani reaction amplification and sequencing of the internal transcribed spacer (ITS) region of nuclear-encoded ribosomal DNA and also MALDI-TOF MS. The obtained data by molecular approach were compared with MALDI-TOF MS.

Results: The MALDI-TOF MS led to the identification of 44 (47%) isolates at the species level by generating the spectral score values of ≥ 2.0. However, there was not sufficient agreement between the results of the molecular-based ITS identification methods and MALDI-TOF MS in the species identification of 16 (17%) isolates. The Bruker Daltonics database was also not able to identify protein spectra related to 12 isolates (13%), including . (n=5), . (n=4), . (n=2), and . (n=1).

Conclusion: According to the results, the utility of MALDI-TOF MS as a routine diagnostic tool for the accurate and reliable identification of dermatophytes can be justified whenever the protein spectra of a large set of worldwide clinical isolates are included in the commercial libraries. In addition, MALDI-TOF MS can be alternatively used to construct an in-house reference database.
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http://dx.doi.org/10.18502/cmm.5.2.1157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6626716PMC
June 2019

Using chemical chaperones to increase recombinant human erythropoietin secretion in CHO cell line.

Prep Biochem Biotechnol 2019 16;49(6):535-544. Epub 2019 Apr 16.

g Department of Quality Control , Production and Research Complex, Pasteur Institute of Iran , Tehran , Iran.

In recombinant protein production, over-expressed genes induce unfolded protein response (UPR), overloaded protein aggregation in endoplasmic reticulum and its expansion. In this study, we have used 16 chemicals to improve erythropoietin production in engineered CHO cells and tried to study the mechanism of reducing protein aggregation in each treatment. Endoplasmic reticulum expansion was studied through endoplasmic reticulum specific labeling with utilizing fluorescent glibenclamide and its molecular chaperones expression were studied by real-time polymerase chain reaction. The increase in the mRNA level of EPO and endoplasmic reticulum chaperones GRP78/BiP, XBP1, ATF6, and ATF4 in different chemical treatments were not related to ER expansion. On the other hand, ER expansion in beta alanine, beta cyclodextrin and taurine treatments resulted in increased EPO secretion. Dramatically increase in EPO expression in conjugated linoleic acid, spermidine, trehalose, and maltose (19, 20, 16, and 19-fold, respectively) did not increase erythropoietin productivity, but betaine which did not caused ER expansion, with minor increase in EPO gene expression increase EPO productivity. The results indicated that betaine increase EPO secretion in engineered CHO cell line without relation to ER expansion and molecular chaperones expression.
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http://dx.doi.org/10.1080/10826068.2018.1479865DOI Listing
July 2019

In vitro interactions of crocin with fluconazole against isolates.

Curr Med Mycol 2018 Dec;4(4):25-30

Invasive Fungi Research Centre, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Background And Purpose: The incidence of invasive fungal infections has been increased in recent years. The growing use of azole drugs for prophylactic and therapeutic purposes has resulted in the gradual emergence of azole-resistant species. Accordingly, the introduction of a new strategy to improve the management of infections is an urgent need. Regarding this, the present study was performed to evaluate the antifungal activities of crocin (Cro) alone and in combination with fluconazole.

Materials And Methods: clinical isolates of four different species. The identity of the isolates was confirmed using the internal transcribed spacer identification system. The interactions of Cro with fluconazole were investigated using a microdilution checkerboard method based on the Clinical and Laboratory Standards Institute reference technique with 96-well microtiter plates. Furthermore, the assessment of the interaction of drug combinations was accomplished using the fractional inhibitory concentration index (FICI) based on the Loewe additivity theory.

Results: According to the results, Cro alone showed a relatively high MIC50 value (1 g/ml) against species. Our results demonstrated indifferent interactions between Cro and fluconazole with a FICI range of 0.5-4 against strains.

Conclusion: The high MIC value for Cro against species indicated its failure to show appropriate antifungal activity against this species. The MIC of this agent was not significantly reduced even by the addition of fluconazole. Therefore, other mechanisms which are not related to the mechanism of azole drugs are involved at high concentration of Cro.
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http://dx.doi.org/10.18502/cmm.4.4.383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386508PMC
December 2018