Publications by authors named "Malihe Talebi"

64 Publications

The effect of probiotics on respiratory tract infection with special emphasis on COVID-19: Systemic review 2010-20.

Int J Infect Dis 2021 Feb 9;105:91-104. Epub 2021 Feb 9.

Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Microbial Biotechnology Research Centre, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

To evaluate the effects of probiotics on respiratory tract infection (RTI) a systematic review of randomized controlled trials (RCTs) from January 2010 to January 2020 was conducted. The PubMed, Google Scholar, Embase, Scopus, Clinicaltrials.gov, and International Clinical Trials Registry Platform databases were systematically searched for the following keywords: respiratory tract infection, probiotics, viral infection, COVID-19, and clinical trial. A total of 27 clinical trials conducted on 9433 patients with RTI plus 10 ongoing clinical studies of probiotics intervention in Coronavirus disease 2019 (COVID-19) were reviewed. The review looked at the potency of probiotics for the hindrance and/or treatment of RTI diseases, this may also apply to COVID-19. The review found that probiotics could significantly increase the plasma levels of cytokines, the effect of influenza vaccine and quality of life, as well as reducing the titer of viruses and the incidence and duration of respiratory infections. These antiviral and immune-modulating activities and their ability to stimulate interferon production recommend the use of probiotics as an adjunctive therapy to prevent COVID-19. Based on this extensive review of RCTs we suggest that probiotics are a rational complementary treatment for RTI diseases and a viable option to support faster recovery.
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http://dx.doi.org/10.1016/j.ijid.2021.02.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871912PMC
February 2021

Analysis of virulence genes and molecular typing of Listeria monocytogenes isolates from human, food, and livestock from 2008 to 2016 in Iran.

Trop Anim Health Prod 2021 Jan 16;53(1):127. Epub 2021 Jan 16.

Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

The frequency of Listeria monocytogenes isolates collected from a total of 1150 samples including food (n = 300), livestock (n = 50), and human clinical (n = 800) was evaluated during 2008-2016. Antimicrobial resistance patterns, virulence factors, and molecular characteristics of these isolates were analyzed using disk diffusion method, sequencing, serotyping, and pulsed-field gel electrophoresis (PFGE). The analysis of 44 L. monocytogenes isolates showed that 72.7% (32 of 44) of all the isolates belonged to Serotype 1/2c, and 15.9% (7 of 44) belonged to Serotype 3c. All 44 isolates were resistant to one or more antimicrobial agents with the most frequent resistance to penicillin (75%) and tetracycline (47.7%). Of the 44 L. monocytogenes strains, 100, 69.2, and 62.5% of livestock, human, and food strains were resistant to penicillin, respectively. Using pulsed-field gel electrophoresis (PFGE) technique, the isolates' genetic diversity was determined, and 28 PFGE patterns with 8 common (CT) and 20 single types (ST) were identified. This study highlights the high prevalence of Serotype 1/2c in clinical and livestock samples, while different serotypes were observed in food samples. The presence of rare serotypes such as 4c, belonging to the Lineage III, as well as 4e and 1/2c which are infrequent in Iran indicates that paying attention to uncommon serotypes, especially 1/2c, during the listeriosis outbreaks is necessary.
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http://dx.doi.org/10.1007/s11250-021-02569-7DOI Listing
January 2021

Evaluation of the genetic relatedness of isolates by TRs analysis.

Iran J Basic Med Sci 2020 Oct;23(10):1323-1327

Microbial Biotechnology Research Center, Iran University of Medical Science, Tehran, Iran.

Objectives: Human gastrointestinal tract harbors a variety of bacteria with vital roles in human health. is considered one of the dominant constituents of gut microflora which can act as an opportunistic pathogen leading to various diseases, including colon cancer, diarrhea, uterine and intrathecal abscesses, septicemia, and pelvic inflammation. In this study, multiple locus variable number of tandem repeats analysis (MLVA) was performed to genetically differentiate 50 isolates.

Materials And Methods: Eight suitable tandem repeats (TRs) were selected by bioinformatics tools and were then subjected to PCR amplification using specific primers. Finally, MLVA profiles were clustered using BioNumerics 7.6 software package.

Results: All VNTR loci were detected in all isolates using the PCR method. Overall, isolates were differentiated into 27 distinct MLVA types. The highest diversity index was allocated to TR1, TR2, TR5, TR6, and TR8; with this taken into account, strain type 14 was the most prevalent with 12 strains belonging to this type. Clustering revealed three major clusters of A, B, and C. With regards to the pathogenicity of and the outcomes of infections related to this microorganism, it is imperative to study this microorganism isolated from both patients and healthy individuals.

Conclusion: This study aimed at evaluating the efficiency of MLVA for the genetic differentiation of . The results of this study indicate the promising efficiency of MLVA typing for cluster detection of this bacterium.
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http://dx.doi.org/10.22038/ijbms.2020.35816.8532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7585543PMC
October 2020

Polymorphisms in the genes encoding surface associated proteins of Clostridioides difficile isolates.

Infect Genet Evol 2020 12 17;86:104598. Epub 2020 Oct 17.

Division of Microbiology, Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; Food Microbiology Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Although the diversity of Clostridioides difficile toxins have been extensively studied, little is known about the variation in the surface associated proteins (SAPs) which are important in early steps of bacterial colonization and infection. Here, we examined 65C. difficile isolates to identify polymorphisms in the genes encoding SAPs.

Methods: PCR was used to amplify slpA, fliC, fliD, cwp66 and cwp84 genes, followed by sequencing. In addition, the antigenicity and immunogenicity properties of different types of SlpA, FliC, FliD, Cwp66 and Cwp84 proteins were predicted in-silico by VaxiJen and BcePred online servers.

Results: The predominant slpA sequence type was gr-01 (42.37%), followed by hr-01 (11.86%) and 078-01 (10.16%). In addition, two new slpA subtypes of smz (smz-09-Ir and smz-010-Ir) and a new slpA sequence type (Ir-01) were identified among the isolates examined. Analysis of the nucleotide sequences of fliC, fliD, cwp66 and cwp84 genes revealed 7, 5,5,3 different sequence types, respectively. Insilico analysis of antigenicity of SAPs showed that FliC had the highest level of antigenicity whereas SlpA and Cwp66 proteins had the highest level of immunogenicity.

Conclusions: This study pointed to the nucleotide polymorphism in SAPs of C. difficile isolates and demonstrated noticeable diversity in antigenicity and immunogenicity of these proteins which need to be taken into consideration as promising therapeutic or vaccine targets.
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http://dx.doi.org/10.1016/j.meegid.2020.104598DOI Listing
December 2020

The effect of improved formulation of chitosan-alginate microcapsules of Bifidobacteria on serum lipid profiles in mice.

Microb Pathog 2020 Dec 17;149:104585. Epub 2020 Oct 17.

Department of Microbiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran; Microbial Biotechnology Research Center, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Probiotics have been associated with many beneficial effects in human digestive physiology. The aim of this study was to evaluate the effect of improved formulation of chitosan-alginate microcapsules of Bifidobacterium strains on serum triglycerides, cholesterol, HDL, and LDL in mice.

Methods: Five approved probiotic strains of Bifidobacterium were tested for anti-proliferative effect and interleukin-8 induction on HT-29 cell lines. Bifidobacterium strains plus five approved Lactobacillus were encapsulated in chitosan-alginate microcapsules and tested for its survival in simulated gastrointestinal conditions. These microcapsules were administered to 4 groups of mice (including 1. Bif (Bifidobacterium strains), 2. Lac (Lactobacillus strains), 3. Bif-Lac (Bifidobacterium plus Lactobacillus strains) and 4. Control) for 8 days. At eighth day, the blood of mice were taken and serum levels of triglycerides, cholesterol, HDL, and LDL of them were determined.

Results: All of the Bifidobacterium strains significantly (P < 0.001) reduced secretion of IL-8 in HT-29 cells as well as maximum antiproliferative effects (P < 0.001). In addition, all microcapsules showed impressive survival rate in bile (>%94.1) and gastrointestinal (>%78.28) conditions (P < 0.05). Only Bif-Lac group displayed significantly lower serum cholesterol and LDL levels than control group (P < 0.05). Besides, all groups indicate statistically significant weight loss of mice during the 8 days in comparison with the control group (P < 0.05).

Conclusion: The results of this study showed that the microencapsulated probiotics with alginate and chitosan had an effective mean of delivery of viable bacterial cells and non-pharmacological interventions use to reduce serum cholesterol and LDL levels in in-vivo condition.
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http://dx.doi.org/10.1016/j.micpath.2020.104585DOI Listing
December 2020

Changes in gut microbial flora after Roux-en-Y gastric bypass and sleeve gastrectomy and their effects on post-operative weight loss.

Updates Surg 2020 Oct 16. Epub 2020 Oct 16.

Minimally Invasive Surgery Research Center, Iran University of Medical Sciences, Rasool-E-Akram Hospital, Tehran, Iran.

Bariatric surgery affects gut microbial flora due to the anatomical and physiological changes it causes in the gastrointestinal tract. Understanding the interaction between the gut flora, the type of bariatric surgery and weight loss may help improve bariatric surgery outcomes. This study was designed to compare the effects of Roux-en-Y Gastric Bypass (RYGB) and Sleeve Gastrectomy (SG) on two main phyla of the gut microbiota in humans and evaluate their potential effect on weight changes. Thirty morbidly obese patients were divided into two groups and underwent laparoscopic SG or laparoscopic RYGB. The patients' weight changes and fecal samples were evaluated at baseline and 6 months after the surgery. A microbial flora count was carried out of the phyla Bacteroidetes and Firmicutes and Bacteroides Fragilis. Changes in the abundance of the flora and their correlation with weight loss were analyzed. After 6 months, the patients with a history of RYGB showed a significant decrease in stool Bacteroidetes while the reduction in the SG group was insignificant. Firmicutes abundance was almost unchanged following SG and RYGB. There was no significant change in Bacteroides Fragilis abundance in either of the two groups, but a positive correlation was observed between Bacteroides Fragilis and weight loss after SG and RYGB. Bariatric surgery can affect gut microbiota. It can be concluded that these changes are dependent on many factors and may play a role in weight loss.
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http://dx.doi.org/10.1007/s13304-020-00900-9DOI Listing
October 2020

The effect of selected Lactobacillus strains on dextran sulfate sodium-induced mouse colitis model.

Acta Microbiol Immunol Hung 2020 Jun 12;67(2):138-142. Epub 2020 Jun 12.

2Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Inflammatory bowel disease (IBD) comprises two major illnesses: Crohn's disease (CD) and ulcerative colitis (UC). Dextran sulfate sodium (DSS) mouse colitis model has been used in understanding the mechanism of IBD. This study was conducted to examine selected Lactobacillus spp. as potential IBD treatment in the DSS-induced animal model. Balb/c mice were used and colitis was induced by adding 5% dextran sodium sulfate into the drinking water for 8 days. Colon length, disease activity index (DAI) and histological analysis were measured as markers of inflammation in DSS colitis mice. The majority of the Lactobacillus species significantly prevented the shortening of the colon length compared with the DSS group. The DAI scores of mice were significantly reduced following usage of four Lactobacillus strains included: Lactobacillus plantarum 03 and 06, Lactobacillus brevis 02 and Lactobacillus rhamnosus 01. The histological analysis exhibited that oral administration of Lactobacillus strains had therapeutic effects on mice colitis. L. plantarum and L. brevis showed better therapeutic effect against DSS-induced acute colitis mice. The probiotic activities of these three isolates indicated that the probiotic effects were strain specific and none of these useful bacteria could exhibit all of the valued probiotic properties simultaneously.
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http://dx.doi.org/10.1556/030.2020.00834DOI Listing
June 2020

Lactobacillus species inhibitory effect on colorectal cancer progression through modulating the Wnt/β-catenin signaling pathway.

Mol Cell Biochem 2020 Jul 17;470(1-2):1-13. Epub 2020 May 17.

Department of Microbiology, Pasteur Institute of Iran, Tehran, Iran.

Probiotic bacteria are known to exert a wide range of anticancer activities on their animal hosts. In the present study, the anticancer effect of a cocktail of several potential probiotic Lactobacillus species (potential probiotic L.C) was investigated in vitro and in vivo. MTT and Flow cytometry tests results showed that administration of live potential probiotic L.C significantly decreased the HT-29 and CT-26 cells proliferation and induced late apoptotis in a time-dependent manner. In addition, quantitative real-time polymerase chain reaction (qPCR) results showed that exposure of potential probiotic L.C to both HT-29 and CT-26 cells during the incubation times resulted in the upregulation (apc and CSNK1ε for HT-29, CSNK1ε and gsk3β for CT-26) and downregulation (CTNNB1, CCND1, pygo2, axin2 and id2) of the Wnt/β- catenin pathway-related genes in a time-dependent manner. The significance of in vitro anticancer effect of potential probiotic L.C was further confirmed in an experimental tumor model. Data from the murine model of colorectal cancer (CRC) induced by Azoxymethane (AOM) and Dextran Sulfate Sodium (DSS) showed significantly alleviated inflammation and tumor development in AOM/DSS/L.C-injected mice compared to the AOM/DSS-injected mice. Tumor growth inhibition was accompanied by potential probiotic L.C-driven upregulation and downregulation of the Wnt/β-catenin pathway-related genes, similar to the in vitro results. These results showed that potential probiotic L.C inhibited the tumor growth, and that its anticancer activity was at least partially mediated through suppressing the Wnt/β-catenin pathway. Overall, the present study suggested that this probiotic could be used clinically as a supplement for CRC prevention and treatment.
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http://dx.doi.org/10.1007/s11010-020-03740-8DOI Listing
July 2020

Anti-cancer effects of Bifidobacterium species in colon cancer cells and a mouse model of carcinogenesis.

PLoS One 2020 13;15(5):e0232930. Epub 2020 May 13.

Microbial Biotechnology Research Centre, Iran University of Medical Sciences, Tehran, Iran.

Introduction: Probiotics are suggested to prevent colorectal cancer (CRC). This study aimed to investigate the anticancer properties of some potential probiotics in vitro and in vivo.

Materials And Methods: Anticancer effects of the following potential probiotic groups were investigated in LS174T cancer cells compared to IEC-18 normal cells. 1. a single strain of Bifidobacterium. breve, 2. a single strain of Lactobacillus. reuteri, 3. a cocktail of 5 strains of Lactobacilli (LC), 4. a cocktail of 5 strains of Bifidobacteria (BC), 5. a cocktail of 10 strains from Lactobacillus and Bifidobacterium (L+B). Apoptosis rate, EGFR, HER-2 and PTGS-2 (COX-2 protein) expression levels were assessed as metrics of evaluating anticancer properties. Effect of BC, as the most effective group in vitro, was further assessed in mice models.

Results: BC induced ~21% and only ~3% apoptosis among LS174T and IEC-18 cells respectively. BC decreased the expression of EGFR by 4.4 folds, HER-2 by 6.7 folds, and PTGS-2 by 20 folds among the LS174T cells. In all these cases, BC did not interfere significantly with the expression of the genes in IEC-18 cells. This cocktail has caused only 1.1 folds decrease, 1.8 folds increase and 1.7 folds decrease in EGFR, HER-2 and PTGS-2 expression, respectively. Western blot analysis confirmed these results in the protein level. BC significantly ameliorated the disease activity index, restored colon length, inhibited the increase in incidence and progress of tumors to higher stages and grades.

Conclusions: BC was the most efficient treatment in this study. It had considerable "protective" anti-cancer properties and concomitantly down regulated EGFR, HER-2 and PTGS-2 (COX-2), while having significant anti-CRC effects on CRC mice models. In general, this potential probiotic could be considered as a suitable nutritional supplement to treat and prevent CRC.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0232930PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219778PMC
July 2020

Screening for efficient nitrogen sources for overproduction of the biomass of the functionally probiotic L. plantarum strain RPR42 in a cane molasses-based medium.

AMB Express 2020 Mar 17;10(1):53. Epub 2020 Mar 17.

Department of Microbiology, Pasteur Institute of Iran, Tehran, Iran.

Nitrogen source has a vital role for the efficient growth of lactobacilli. The effects of cheese whey, corn steep liquor, and wheat germ extract on the growth of L. plantarum strain RPR42 in cane molasses-based media was evaluated using various approaches of design of experiments. Our results showed that such protein-rich agricultural by-products significantly increase the biomass production of the strain RPR42 in cane molasses-based media. The most affecting nitrogenous material was cheese whey followed by CSL and the minor effect was reported for wheat germ extract as revealed in factorial and Box-Behnken design experiments. The replacement of costly beef extract and yeast extract with a defined mixtures of the above nitrogenous agricultural by-products in cane molasses-based medium led to production of up to 12.64 g/L/24 h of dry biomass of strain RPR42. A detectable cell density of strain RPR42 (~ 9.81 × 10 CFU/mL 24 h) which was observed in such an economic medium showed that the large-scale production of the strain RPR42 tend to be feasible at significantly low costs.
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http://dx.doi.org/10.1186/s13568-020-00976-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078425PMC
March 2020

High prevalence of Clostridiodes diffiicle PCR ribotypes 001 and 126 in Iran.

Sci Rep 2020 03 13;10(1):4658. Epub 2020 Mar 13.

Division of Microbiology, Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Clostridium difficile is a leading causative agent of hospital-acquired and community-acquired diarrhea in human. This study aims to characterize the predominant C. difficile strains, RT001 and 126, circulating in Iranian hospitals in relation to resistant phenotypes, the antibiotic resistance genes, and their genetic relatedness. A total number of 735 faecal specimens were collected from patients suspected of CDI in Tehran hospitals. Typing and subtyping of the strains were performed using CE-PCR ribotyping and MLVA, respectively, followed by PCR assays for ARGs and indicators of Tns. Minimum inhibitory concentrations (MICs) of five antibiotics were determined by MIC Test Strips. Among 65 strains recovered from CDI patients, RT001 (32.3%) and RT126 (9.2%) were found as the most frequent ribotypes, and 64 MLVA types were identified. Using MLVA, RT001 and RT126 were subtyped into 6 and 4 groups, respectively. The vanA, nim, tetM, gyrA, gyrB genes were detected in 24.6%, 0%, 89.2%, 95.3%, and 92.3% of the strains, respectively. The indicators of Tns including vanHAX, tndX, and int were found in 0%, 3% and 29.2% of the strains, respectively. The most common amino acid (AA) alterations of GyrA and GyrB were related to substitutions of Thr82 → Val and Ser366 → Val, respectively. Resistance rate to metronidazole, vancomycin, tetracycline, ciprofloxacin, and moxifloxacin was 81.5%, 30.7%, 85%, 79%, and 74%, respectively. This study, for the first time revealed the subtypes of circulating RT001 and RT126 in Iran. It is of importance that the majority of the strains belonging to RT001 were multidrug resistant (MDR). This study also pointed to the intra-hospital dissemination of the strains belonging to RT001 and RT126 for short and long periods, respectively, using MLVA. The most important resistance phenotypes observed in this study was vancomycin-resistant phenotypes. Resistance to metronidazole was also high and highlights the need to determine its resistance mechanisms in the future studies.
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http://dx.doi.org/10.1038/s41598-020-61604-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070088PMC
March 2020

Does biofilm formation have different pathways in

Iran J Basic Med Sci 2019 Oct;22(10):1147-1152

Microbial Biotechnology Research Center, Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Objectives: Biofilm formation is one of the most important factors in the development of infections caused by In this study, the expression levels of genes responsible for biofilm formation were studied in methicillin sensitive and methicillin resistant

Materials And Methods: A total of 100 meticillin-resistant (MRSA) and meticillin-sensetive s.aureus (MSSA) isolates were studied. Bacterial biofilm formation was evaluated phenotypically using microtiter plate method. Real-time PCR tests were conducted to determine the expression levels of genes involved in biofilm formation.

Results: Quantitative biofilm formation test was repeated three times for each specimen. The prevalence of weak, medium, and strong biofilm producers were 16%, 49%, and 35%, respectively. In MSSA isolates, expression levels of genes increased compared to the and genes. These results were different in MRSA isolates, and genes showed a decreased gene expression levels compared to the aforementioned genes.

Conclusion: Considering the results of this study, genes probably contribute to the same extent in both MRSA and MSSA isolates, and there is probably no significant difference in the role of these genes in these isolates. In addition, the results of this study indicated that MRSA may not use the conventional route for biofilm formation and may use independent pathways through Polysaccharide intercellular adhesion (PIA).
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http://dx.doi.org/10.22038/ijbms.2019.34888.8281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885392PMC
October 2019

The effects of probiotics on reducing the colorectal cancer surgery complications: A periodic review during 2007-2017.

Clin Nutr 2020 Aug 9;39(8):2358-2367. Epub 2019 Nov 9.

Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Background & Aims: To assess the effects of pro-/synbiotic treatment on patients with colorectal cancer (CRC), a systematic review was conducted on randomized controlled trials.

Methods: International databanks (ISI Web of Science, PubMed, Scopus, and Google Scholar) were searched from January 2007 to December 2017 using the following keywords: 'colorectal cancer' and 'probiotics'. The search was restricted to original articles published in English. Reference lists of all related studies were also reviewed to find other relevant publications. The statistical analysis was performed using SPSS software version 18.0 (IBM, NY, USA). Also, p < .05 was regarded as statistically significant.

Results: A total of 21 clinical trials were retrieved, involving 1831 patients subjected to elective colorectal surgery. The studies included in this review have investigated the effects of probiotics on different aspects of colorectal cancer treatment (p < .05). According to the present study results, probiotics could significantly decrease inflammatory factors, chemotherapy side effects, severe diarrhea, postoperative infectious complications, and duration of antibiotic therapy; shift fecal microbiota in favor of Actinobacteria; and change the tumor tissue microbiota (p < .05).

Conclusion: Based on the present review, the preoperative use of pro-/synbiotics as prophylaxis for patients with CRC could improve clinical outcomes. More detailed data about the types of probiotic species and the optimal consumption dose of pro-/synbiotics should be taken in to account in future meta-analysis reviews.
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http://dx.doi.org/10.1016/j.clnu.2019.11.008DOI Listing
August 2020

Correction to: ABCA7 and EphA1 Genes Polymorphisms in Late-Onset Alzheimer's Disease.

J Mol Neurosci 2020 Feb;70(2):174

Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran.

The original version of this article unfortunately contained a mistake in the Authorgroup section. Author Azra Delpak's given name was misspelled as "Azar".
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http://dx.doi.org/10.1007/s12031-019-01442-5DOI Listing
February 2020

Inhibitory effects of Lactobacilli cocktail on HT-29 colon carcinoma cells growth and modulation of the Notch and Wnt/β-catenin signaling pathways.

Microb Pathog 2020 Feb 2;139:103829. Epub 2019 Nov 2.

Department of Microbiology, Pasteur Institute of Iran, Tehran, Iran. Electronic address:

Probiotics could be considered as attractive candidates for preventing tumor growth through maintaining homeostasis. The aim of this study was to evaluate the inhibitory effect of a cocktail of five Lactobacillus species on human colorectal carcinoma cell line HT-29. The anti-proliferative and apoptotic effects of Lactobacilli cocktail were evaluated using MTT and flow cytometry tests, respectively. Quantitative real-time polymerase chain reaction (qPCR) was used to analyze the expression of several genes in the Notch (notch, hes1, msi1, and numb) and Wnt/β-catenin (CTNNB1 and CCND1) pathways, following the treatment of HT-29 cells with Lactobacilli cocktail. The treatment by Lactobacilli cocktail induced a significant anti-proliferative effect and late stage apoptosis among the cancer cells (p < 0.05). Compared to the untreated cells, Lactobacilli cocktail induced the down-regulation of notch, hes1, and msi1 genes and up-regulation of numb gene in the Notch pathway as well as the down-regulation of CTNNB1 and CCND1 genes in the Wnt/β-catenin pathway in a time-dependent manner (p < 0.05). CONCLUSION: Lactobacilli cocktail was shown to have beneficial anti-tumor effects on HT-29 cells by modulating the Notch and Wnt/β-catenin pathways; therefore, the use of Lactobacilli probiotics as nutritional supplements may prevent the incidence of colon cancer.
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http://dx.doi.org/10.1016/j.micpath.2019.103829DOI Listing
February 2020

ABCA7 and EphA1 Genes Polymorphisms in Late-Onset Alzheimer's Disease.

J Mol Neurosci 2020 Feb 28;70(2):167-173. Epub 2019 Oct 28.

Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran.

Large-scale genome-wide studies have revealed the role of several genes and their respective single-nucleotide polymorphisms (SNPs) in the pathophysiology of late-onset Alzheimer's disease (LOAD). Here, the frequencies of ABCA7 SNPs rs3764650 and rs4147929 and EphA1 SNP rs11771145 were assessed and compared in LOAD patients and healthy subjects. In a case-control study, 110 patients with LOAD (case) and 88 healthy unrelated age- and gender-matched individuals (control), both from Azeri descent, were enrolled. DNA was extracted from blood samples using the salting out method, and the genotyping was performed by RFLP-PCR for rs3764650, rs4147929, and rs11771145 polymorphisms. Electrophoresis was carried out on agarose gel. Sequencing was utilized for confirmation of the results. No differences were found in the frequencies of ABCA7 SNP rs3764650 and EphA1 SNP rs11771145 between healthy subjects and LOAD patients. However, a significant difference was revealed in the frequencies of AA (p = 0.042, OR = 0.150; 95%CI = 0.005-1.410) and GG (p = 0.009, OR = 1.716; 95%CI = 0.918-3.218) genotypes of ABCA7 SNP rs4147929 between the mentioned groups. This study showed that ABCA7 SNP rs4147929 might be a predisposing factor for LOAD. However, such an association was not found between ABCA7 SNP rs3764650 as well as EphA1 SNP rs11771145 and LOAD. These results must be confirmed in other ethnic groups.
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http://dx.doi.org/10.1007/s12031-019-01420-xDOI Listing
February 2020

Characterization of Clostridioides difficile isolates recovered from hospitalized patients and the hospitals environment and air: A multicenter study.

Anaerobe 2019 Oct 25;59:154-158. Epub 2019 Jun 25.

Division of Microbiology, Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran; Food Microbiology Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

In healthcare settings, contamination of environment with toxigenic and hypervirulent Clostridioides difficile strains is a serious concern. Here, we assessed whether patients with C. difficile have a role to play in the dissemination of C. difficile in our settings or other sources are implicated in its circulation. A total of 700 fecal specimens and 1435 environmental samples from surfaces, equipment and air of rooms occupied by patients suspected of C. difficile infection were taken from 4 tertiary hospitals in Tehran, Iran between April 2016 and August 2017. Antibiotic susceptibility testing and detection of resistance genes were performed for the environmental isolates. The clinical and environmental isolates of C. difficile were subjected to Pulsed Field Gel Electrophoresis (PFGE) analysis. Forty three (6.14%) and 2 (0.13%) isolates of C. difficile were recovered from the clinical and environmental samples, respectively. In the clinical settings, 2 patients were suspected of recurrent C. difficile infection. Thirty distinct pulsotypes were found among the C. difficile isolates including 28 singletons and 2 common types. One of the two environmental isolates was isolated from floor in the Medical ward, of pulsotype/ribotype/toxinotype PT10/New ribotype/toxinotype V, harbored cdtA/B and tcdC-A, and resistant to ciprofloxacin. The other one was isolated from air of a room in ICU, assigned to PT11/RT001/toxinotype 0, belonged to tcdC-sc3 genotypes and resistant to metronidazole. The environmental isolates did not generate amplicons in PCR assays targeting vanA and nim genes. This study provided evidence for dissemination of genetically diverse strains of C. difficile in hospitalized patients, presence of C. difficile in hospital air, existence of binary toxin positive/antibiotic-resistant isolate on the floor and intra-hospital dissemination of this pathogen.
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http://dx.doi.org/10.1016/j.anaerobe.2019.06.012DOI Listing
October 2019

Rapid Simultaneous Molecular Stool-Based Detection of Toxigenic Clostridioides difficile by Quantitative TaqMan Real-Time PCR Assay.

Clin Lab 2019 Apr;65(4)

Background: Clostridioides difficile is a major cause of nosocomial infectious diarrhea in hospitalized patients throughout the world.

Methods: A multiplex real-time PCR assay was developed and evaluated in comparison with toxigenic culture (TC) (as gold standard method) for direct detection of toxigenic C. difficile in fecal specimens. The multiplex real-time PCR assay simultaneously detected glutamate dehydrogenase (gluD), toxin A (tcdA), toxin B (tcdB), and binary toxin (cdtB) genes in stool samples.

Results: The results of multiplex real-time PCR were compared to those of the TC method in 250 patients suspected of C. difficile infection. The prevalence of positive TC was 13.6%. Forty-two stool samples (16.8%) were determined to be gluD+ using multiplex real-time PCR. These included 35 (83.3%) toxigenic (32 tcdA+, tcdB+ and three tcdB+) and 7 (20.0%) were cdtB+. The multiplex real-time PCR assay had a sensitivity of 91.45%, specificity of 99.54%, and positive and negative predictive values of 97% and 98.6%, respectively, compared to the TC method for diagnosis of C. difficile. The analytical sensitivity of the multiplex real-time PCR assay was estimated to be 102 CFU/g of stools and 0.0200 pg of genomic DNA from culture. The analytical specificity was determined to be 100% by using enteric and non-C. difficile standard bacterial strains.

Conclusions: The molecular method developed in the study was rapid, sensitive, and specific for detection of toxigenic C. difficile. It is applicable to be performed in clinical laboratories and correlated well with the results obtained by TC.
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http://dx.doi.org/10.7754/Clin.Lab.2018.180735DOI Listing
April 2019

Molecular typing of Clostridioides difficile isolates from clinical and non-clinical samples in Iran.

APMIS 2019 Apr;127(4):222-227

Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Clostridioides difficile is a major cause of nosocomial infectious diarrhea in hospitalized patients throughout the world. We aimed to characterize C. difficile isolates among hospitalized patients, hospital staffs, and hospital environment samples obtained in three tertiary care hospitals of Iran with regard to their molecular types between June 2016 and November 2017. The toxigenicity of C. difficile isolates was determined by toxigenic culture and multiplex-PCR. Toxigenic C. difficile isolates collected were ribotyped using capillary gel electrophoresis-based PCR and the database of WEBRIBO (http://webribo.ages.at). Of 500 clinical and non-clinical samples, toxigenic C. difficile were identified in 35 of 250 stool samples (14%) and in 3 of 250 swabs (1.2%). The most frequently found ribotypes (RTs) were 039, AI-12, and AI-21 (15.8, 10.52, and 10.52% of all isolates, respectively). Further RTs were: 017, 001, AI-3, AI-15, AI-18, AI-10, AI-4, and PR21195 (as new ribotype). The epidemic RTs (027 and 078) seen in the Europe, North America, and Asia were completely absent in this study.
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http://dx.doi.org/10.1111/apm.12937DOI Listing
April 2019

High Rate of Serotype Switching and Genetic Variations Indicates Widespread Recombination Between Clinical and Commensal Penicillin-Nonsusceptible in Tehran.

Microb Drug Resist 2019 Jul/Aug;25(6):865-873. Epub 2019 Feb 20.

3 Department of Microbiology, Pasteur Institute of Iran, Tehran, Iran.

A total of 161 were collected between 2013 and 2015 in Tehran, Iran. The strains were tested for antimicrobial susceptibility and minimum inhibitory concentrations, serotyped, and genotyped by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). Penicillin-binding proteins (PBPs) were also typed by restriction fragment length polymorphism (PBP-RFLP). Out of 161 strains, 32 isolates (20%) were highly resistant to penicillin. The most frequent serotypes among the penicillin-nonsusceptible (PNSP) were 14 (24%), 23F (18%), and 19F (17%). RFLP of , , and genes revealed 8, 6, and 7 different patterns, respectively. Analysis of 93 PNSP isolates displayed 80 PFGE types with 8 common types constituting 21 (23%) isolates. The remaining 72 isolates (77%) were single types. MLST indicated a high degree of genetic diversity among the 93 PNSP with 36 different sequence types. Six internationally known penicillin resistant clones were identified in our isolates among which Spain-1 (ST81), Spain-2 (ST90), and Spain-3 (ST156) were the predominant clones. The results indicated international identifiable clones of especially Spain-1 with high penicillin resistance could play a major role in spread of antimicrobial resistance in Iran. The extensive sequence variation in PBP2x, PBP2b, and PBP1a in resistant strains of clinical and commensal was suggestive of a widespread homologous recombination within populations.
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http://dx.doi.org/10.1089/mdr.2018.0336DOI Listing
December 2019

The emergence of metronidazole and vancomycin reduced susceptibility in Clostridium difficile isolates in Iran.

J Glob Antimicrob Resist 2019 09 28;18:28-33. Epub 2019 Jan 28.

Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Objectives: Clostridium difficile (C. difficile) is the main causative agent of antibiotic-associated diarrhoea (AAD) and pseudomembranous colitis. The accumulation of antimicrobial resistance in C. difficile strains can drive C. difficile infection (CDI) epidemiology. This study was undertaken to evaluate the antimicrobial resistance patterns of toxigenic C. difficile isolates cultured from diarrhoeal stool samples of hospitalised patients with suspected CDI in three tertiary care hospitals in Tehran, Iran.

Methods: Two hundred and fifty diarrhoeal stool samples were investigated by toxigenic culture using cycloserine-cefoxitin-fructose agar and the VERO cell line. Antimicrobial susceptibility to metronidazole, vancomycin, clindamycin, tetracycline, and moxifloxacin was performed by disk diffusion and Etest methods on Brucella Blood Agar supplemented with hemin and vitamin K.

Results: Thirty-five stool samples (14.0%) proved positive using C. difficile toxigenic culture. According to Clinical and Laboratory Standards Institute breakpoints, the following resistance was identified in C. difficile isolates: metronidazole (2 of 35); moxifloxacin (7 of 35); clindamycin (18 of 35); and tetracycline (5 of 35). Using European Committee on Antimicrobial Susceptibility Testing breakpoints, three of 35 isolates showed reduced-susceptibility for vancomycin and 14 of 35 for metronidazole. In addition, the results showed a good correlation between the inhibition zone diameter (disk diffusion) and MIC values (Etest); Pearson correlation coefficient 0.7400.95 (P< 0.001).

Conclusions: Multidrug resistance was observed in Iranian clinical toxigenic C. difficile isolates, including reduced susceptibility to first-line CDI treatment drugs. In addition, disk diffusion can be used as a cost-effective option for the antimicrobial susceptibility testing of C. difficile isolates.
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http://dx.doi.org/10.1016/j.jgar.2019.01.027DOI Listing
September 2019

Correction to: A review on anti-adhesion therapies of bacterial diseases.

Infection 2019 02;47(1):25-26

Department of Microbiology and Virology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

The presentation of Table  was incorrect. The corrected table is given below.
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http://dx.doi.org/10.1007/s15010-018-1240-3DOI Listing
February 2019

A review on anti-adhesion therapies of bacterial diseases.

Infection 2019 Feb 1;47(1):13-23. Epub 2018 Oct 1.

Department of Microbiology and Virology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

Background: Infections caused by bacteria are a foremost cause of morbidity and mortality in the world. The common strategy of treating bacterial infections is by local or systemic administration of antimicrobial agents. Currently, the increasing antibiotic resistance is a serious and global problem. Since the most important agent for infection is bacteria attaching to host cells, hence, new techniques and attractive approaches that interfere with the ability of the bacteria to adhere to tissues of the host or detach them from the tissues at the early stages of infection are good therapeutic strategies.

Methods: All available national and international databanks were searched using the search keywords. Here, we review various approaches to anti-adhesion therapy, including use of receptor and adhesion analogs, dietary constituents, sublethal concentrations of antibiotics, and adhesion-based vaccines.

Results: Altogether, the findings suggest that interference with bacterial adhesion serves as a new means to fight infectious diseases.

Conclusion: Anti-adhesion-based therapies can be effective in prevention and treatment of bacterial infections, but further work is needed to elucidate underlying mechanisms.
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http://dx.doi.org/10.1007/s15010-018-1222-5DOI Listing
February 2019

Trends in the discovery of new drugs for Mycobacterium tuberculosis therapy with a glance at resistance.

Tuberculosis (Edinb) 2018 03 9;109:17-27. Epub 2017 Dec 9.

Department of Microbiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Despite the low expensive and effective four-drug treatment regimen (isoniazid, rifampicin, pyrazinamide and ethambutol) was introduced 40 years ago, TB continues to cause considerable morbidity and mortality worldwide. In 2015, the WHO estimated a total of 10.4 million new tuberculosis (TB) cases worldwide. Currently, the increased number of multidrug-resistant (MDR-TB), extensively-drug resistant (XDR-TB) and in some recent reports, totally drug-resistant TB (TDR-TB) cases raises concerns about this disease. MDR-TB and XDR-TB have lower cure rates and higher mortality levels due to treatment problems. Novel drugs and regimens for all forms of TB have emerged in recent years. Moreover, scientific interest has recently increased in the field of host-directed therapies (HDTs) in order to identify new treatments for MDR-TB. In this review, we offer an update on the discovery of new drugs for TB therapy with a glance at molecular mechanisms leading to drug resistance in Mycobacterium tuberculosis.
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http://dx.doi.org/10.1016/j.tube.2017.12.002DOI Listing
March 2018

Characterization of bacteriocin production in Lactobacillus spp. isolated from mother's milk.

Microb Pathog 2018 May 15;118:242-246. Epub 2018 Mar 15.

Department of Microbiology, Pasteur Institute of Iran, Tehran, Iran. Electronic address:

The purpose of the present study was to isolate Lactobacillus bacteria from mother's milk and to assess their probiotic potential. Sixty breast milk samples were collected from the volunteered mothers aged from 19 to 35 and from rural areas of Lorestan and Markazi Provinces, Iran. At first, 970 bacill-shaped bacterial colonies were isolated from these samples and stored in proper condition. Two hundred isolates were randomly selected and investigated for their ability to tolerate acidic condition and to tolerate bile salt as well. Only 33 isolates could withstand the exposure to low pH and bile salt. The isolates were identified using PCR primer specific to Lactobacillus and it was demonstrated that eighteen of thirty-three isolates were belonged to the Lactobacillus. Among the isolates, 16 and 2 of them were Lactobacillus reuteri and L. gasseri, respectively. In addition, the antibiotic resistance of the isolates was determined using disc diffusion method and all of the isolates were shown to be sensitive to eight out of the twelve investigated antibiotics. Moreover, the antagonistic effect of the isolates was inspected on ten indicator pathogens. Interestingly, all of the pathogenic bacteria were inhibited by Lactobacillus isolates. In addition, to partially understand the nature of inhibition mechanism, well diffusion deployed for two randomly-selected indicator bacteria and the resulting halos of three isolates were statistically significant compared to other lactobacillus (p < 0.05). Subsequently, bacteriocin genes (plnS, Laf, gasA) were identified by PCR among the isolates. The results showed that only 2 isolates possessed the gasA gene which were in accordance with well diffusion test. Consequently, eighteen Lactobacillus isolated from breast milk samples which all of them were able to tolerate low pH and bile salt. Similarly, all of the Lactobacillus isolates were proved to inhibit the growth of pathogen strains and two of them possess a bacteriocin-related gene.
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http://dx.doi.org/10.1016/j.micpath.2018.03.020DOI Listing
May 2018

Improvement of semen parameters after antibiotic therapy in asymptomatic infertile men infected with Mycoplasma genitalium.

Infection 2018 Feb 9;46(1):31-38. Epub 2017 Nov 9.

Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Objectives: To elucidate the association between asymptomatic infections caused by Mycoplasma genitalium and male infertility, and evaluate the role of antibiotic therapy in treatment of this failure.

Methods: A total of 165 infertile males having abnormal semen parameters (study group) and 165 healthy fertile men (control group) were included. Semen samples were taken from all participants and after analyzing for semen parameters, undergone real-time PCR, microbial culture, and reactive oxygen species (ROS), as well as total antioxidant capacity (TAC) assays. Infected individuals of study group were treated with antibiotic. One month after the treatment completion, second semen samples were taken and subjected to all the tests mentioned. The data were analyzed using SPSS statistical software, version 22.0.

Results: The frequency of M. genitalium was significantly higher in the infertile men compared with the fertile ones (9.7% vs. 1.2%; p = 0.001). Mean cycle threshold (C ) value was lower in infected infertile than infected fertile men (p < 0.001). All semen parameters, except volume, pH, and viscosity, were improved (p < 0.05), most of which reached their normal range; leukocytes in seminal fluid decreased (p = 0.02), the level of TAC was elevated (p = 0.002), and ROS level as well as ROS/TAC ratio reduced after antibiotic treatment (p = 0.03). Wives of seven infected infertile men (43.8%) became pregnant 4 months after the treatment completion.

Conclusions: Asymptomatic infection caused by M. genitalium is correlated with male infertility and antibiotic therapy can improve the semen quality and be used to treat male infertility.
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http://dx.doi.org/10.1007/s15010-017-1075-3DOI Listing
February 2018

Isolates of Lactobacillus plantarum and L. reuteri display greater antiproliferative and antipathogenic activity than other Lactobacillus isolates.

J Med Microbiol 2017 10 13;66(10):1416-1420. Epub 2017 Sep 13.

Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.

Purpose: Lactic acid bacteria (LAB) have been associated with many beneficial effects in human digestive physiology. The aim of this study was to evaluate such effect, including attachment, antiproliferation and anti-pathogenic/antibacterial/antimicrobial properties of LAB isolated from healthy humans.

Methodology: Thirteen isolates, obtained from fecal samples of healthy individuals, were identified by phenotypic and molecular methods. Human colon adenocarcinoma cell line HT-29 and the cell proliferation kit II (XTT) assay were used for examination of the Lactobacillus adherence and antiproliferative activity, respectively. In addition, the inhibitory effect of Lactobacillus isolates against pathogenic bacteria was examined.

Results: Out of 13 Lactobacillus isolates, 5 (38 %) isolates were non-adhesive, 4 (31 %) were adhesive and 4 (31 %) were strongly adhesive. Amongst the isolated lactobacilli, L. reuteri showed the highest degree of inhibitory effect against the attachment of the enteropathogens. The XTT assay showed that 3 different isolates had the strongest antiproliferative activity with the maximum effect observed by L. plantarum isolates.

Conclusion: Our results described that different Lactobacillus species isolated from normal fecal samples had different degrees of antiproliferative and anti-pathogenic/antibacterial/antimicrobial activities. However, no isolates showed all of the examined properties concurrently, suggestive that a combination of Lactobacillus species is needed for an active biological defense system.
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http://dx.doi.org/10.1099/jmm.0.000591DOI Listing
October 2017