Marjan Mohammadi

Pasteur Institute of Iran | IPI · Medical Biotechnology Department

Background Gastric cancer (GC) is considered a silent killer, taking more than three quarters of a million lives annually. Therefore, prior to further costly and invasive diagnostic approaches, an initial GC risk screening is desperately in demand. Methods In order to develop a simple risk scoring system, the demographic and lifestyle indices from...

Background The Naive Bayes (NB) classifier is a powerful supervised algorithm widely used in Machine Learning (ML). However, its effectiveness relies on a strict assumption of conditional independence, which is often violated in real-world scenarios. To address this limitation, various studies have explored extensions of NB that tackle the issue of...

Background: H. pylori are generally considered as extracellular organisms, with exclusive colonization of the gastric milieu. Yet, several extra gastric manifestations are associated with this infection. The aim of the present study was to investigate the feasibility of toxin transfer by extracellular vesicles, from bacterial and epithelial origin...

Background: The role of inflammatory cytokines, such as TNF-α and IL-8, in gastric carcinogenesis has been investigated, but their impact remains to be further elucidated. Methods: In this study, we measured the serum concentrations of these cytokines and H. pylori serostatus in dyspeptic patients, presenting with normal mucosa (NM = 53), chronic g...

Background The rates and routes of Helicobacter pylori transmission, in a high prevalent country like Iran, with gastric cancer as the leading cause of male cancer mortality is of essence. Here, we have studied the H. pylori-associated risk factors and the likelihood of interspousal transmission. Methods In a cohort of 686 young prewed couples, qu...

Background Intestinal metaplasia, gastric-to-intestinal transdifferentiation, occurs as a result of the misexpression of certain regulatory factors, leading to genetic reprogramming. Here, we have evaluated the H. pylori-induced expression patterns of these candidate genes. Methods The expression levels of 1)tissue-specific transcription factors (...

Alterations of mitochondria have been linked to several cancers. Also, the mitochondrial DNA copy number (mtDNA-CN) is altered in various cancers, including gastrointestinal tract (GIT) cancers, and several research groups have investigated its potential as a cancer biomarker. However, the exact causes of mtDNA-CN variations are not yet revealed. T...

Background: Intestinal metaplasia, gastric-to-intestinal transdifferentiation, occurs as a result of the misexpression of certain regulatory factors, leading to genetic reprogramming. Here, we have evaluated the H. pylori-induced expression patterns of these candidate genes. Methods: The expression levels of 1)tissue-specific transcription factors...

Background: Variations in mtDNA-CN of PBLs, as a potential biomarker for GC screening has currently been subject to controversy. Herein, we have assessed its efficiency in GC screening, in parallel and in combination with sPG I/II ratio, as an established indicator of gastric atrophy. Methods: The study population included GC (n = 53) and non-GC...

Background Amoxicillin-resistant H. pylori strains are increasing worldwide. To explore the potential resistance mechanisms involved, the 3D structure modeling and access tunnel prediction for penicillin-binding proteins (PBP1A) was performed, based on the Streptococcus pneumoniae , PBP 3D structure. Molecular covalent docking was used to determine...

We have performed a systematic review and meta-analysis for evaluation of mitochondrial DNA copy number (mtDNA-CN) alterations in peripheral blood leukocytes (PBL), and tumor tissues of gastrointestinal tract (GIT) cancers. Analysis of the PBL demonstrated a significant decrease [OR: 0.63 (0.53, 0.76)] and increase [OR: 1.52 (1.10, 2.10)] prior to...

Background Food insecurity can increase risks of health and nutritional problems, leading to difficulties in self-care and poor glycemic control in diabetic patients. This study assessed food insecurity and its association with diabetes control and self-care in type 2 diabetes patients. Methods In this cross sectional study, 148 adults with type 2...

Objectives Disruption of protein synthesis, by drug‐mediated restriction of the ribosomal nascent peptide exit tunnel (NPET), may inhibit bacterial growth. Here, we have studied the secondary and tertiary structures of domain V of the 23S rRNA in the wild‐type and mutant (resistant) H. pylori strains and their mechanisms of interaction with clarith...

Background: Food insecurity can increase risks of health and nutritional problems, leading to difficulties in self-care and poor glycemic control in diabetic patients. Purpose: This study assessed food insecurity and its association with diabetes control and self-care in type 2 diabetes patients. Methods: In this cross sectional study, 148 adults w...

Background: Antibiotic resistance is an ever-rising dilemma regarding the efficiency of Helicobacter pylori eradication. In parallel, multi-drug resistant (MDR) phenotypes have become a global health concern. Here, we have evaluated the prevalence of single and multidrug antibacterial resistance, against four commonly prescribed antibiotics. Method...

Background: A safe and effective vaccine against Helicobacter pylori(Hp)is in high demand. Here, we have generated a recombinant H. pylori UreB-Lactobacillus casei (Lc) strain and evaluated the resulting antigen-specific immune responses and protective efficacy, in a mouse model. Methods: Recombinant UreB (rUreB) was cloned and expressed in E. coli...

Background: Fluoroquinolones hinder bacterial DNA replication by inhibiting DNA gyrase. However, mutations, in the QRDR segment of its A subunit (GyrA), cause antibiotic resistance. Here, the interactions of levofloxacin (LVX), gemifloxacin (GXN), and moxifloxacin (MXN) with Helicobacter pylori GyrA, in LVX-resistant vs -sensitive strains, were st...

Abstract: Background: Two of the Wnt signaling pathway target genes; tumor necrosis factor receptor family member (TROY) and leucine-rich G-protein coupled receptor (LGR5), are involved in the generation and maintenance of gastrointestinal epithelium. A negative modulatory role has recently been assigned to TROY, in this pathway. Here, we have exa...

Quantitation of the colonizing Helicobacter pylori (Hp) in the gastric tissue is essential for assessment of any trial vaccination and/or therapeutic regimens. To develop a qPCR method for Hp quantitation, the conserved glmM gene was amplified and cloned into pTG19T plasmid and linearized. Molecular masses of plasmid template (PT) and Hp genomic DN...

Background: Helicobacter pylori neutrophil-activating protein (HP-NAP) is a major virulence factor involved in H. pylori-induced chronic gastroduodenal inflammation and peptic ulcers. Here, we have developed a NapA deletion mutant strain and assessed its outcomes. Methods: A NapA deletion construct was created to facilitate homologous recombination...

Background: Fluoroquinolones are prescribed as a second line therapy, to rescue Helicobacter pylori (Hp) treatment failures. Resistance against this group of antibiotics is owed to point mutations in the Quinolone Resistance-Determining Region (QRDR), leading to amino acid changes causing dysfunctional DNA gyrase. Here, we have evaluated QRDR point...

Background: Stomach and the intestine share an endoderm-originated cell lineage. Their segregation and/or transdifferentiation (intestinal metaplasia) is controlled by a gradient of transcription factors. Helicobacter pylori (Hp) infection may lead to intestinal metaplasia. Here, we have evaluated this gradient of transcription factors, following i...

Background: Clarithromycin is a key component of Helicobacter pylori (Hp) treatment. Macrolides bind to the V domain of the bacterial 23srRNA in the 50S ribosomal subunit and inhibit peptide synthesis and elongation. Here, we have evaluated 23srRNA point mutations in clarithromycin-resistant clinical strains of Hp. Methods: Hp isolates from 100 dys...

Background: Amoxicillin is a component of first-line quadruple therapy. The penicillin binding proteins (PBPs) are the targets for beta lactam antibiotics, as inhibitors against bacterial cell wall synthesis. Point mutations, leading to amino acid substitutions in the PBPs, confer amoxicillin resistance. Here, we have evaluated these point mutation...

Background: Quantitation of Helicobacter pylori (Hp) in the gastric tissue is essential for assessment of vaccination/therapeutic regimens. Materials & results: Here, the inhibitory effect of mouse gastric DNA (MgDNA) on amplification of Hp genomic DNA (HpDNA) was evaluated by spiking HpDNA with serial dilutions of MgDNA, which yielded concentra...

Background Most two‐ dimensional in vitro models for studying host‐ H. pylori interactions rely on tumor‐derived cell lines, which harbor malignant alterations. The recent development of human gastric organoids has overcome this limitation and provides a highly sophisticated, yet costly, short‐term model for H. pylori infection, with restricted use...

Biobanking in the Developing World; Maximum Specimens, Minimum Infrastructure

There is an enormous number of astounding scientists, who have made their mark in science. Very few of them also serve as a true mentor, ready to provide a helping hand to young researchers, especially those in developing countries, who must constantly struggle to remain optimistic. Professor David Y. Graham is one of these rare characters. He rece...

Background: Helicobacter pylori (Hp) is a type one carcinogen, causing gastric cancer. Hp-mediated intestinal metaplasia in the stomach is perceived as a pre-requisite of intestinal-type gastric cancer. The process of gastric-to- intestinal trans-differentiation (as a cancer biomarker), can be traced through the expression of intestine-specific cau...

Background: Leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5) and a member of the tumor necrosis factor receptor superfamily (TROY) are two of the recently introduced stem cell markers, the latter of which has an inhibitory effect on the former. Methods: Tumor and paired adjacent tissue of gastric cancer (GC) patients (N=36), at di...

Background: Helicobacter pylori (Hp) infection is believed to upregulate the expression of gastric stemness marker (LGR5), which has been associated with the process of gastric carcinogenesis. On the other hand, a member of the tumor necrosis factor receptor superfamily (TROY) is known to inversely affect LGR5 activity. Methods: Female C57BL/6 mice...

Background: Helicobacter pylori (Hp) infection is associated with a range of gastrointestinal diseases including gastric cancer, which is initiated by atrophic gastritis, particularly in its intestinal subtype. This study has addressed the combination of antibody responses to different Hp virulence factors in reflecting gastric atrophy. Methods: Fo...

Background: Treatment success of H. pylori eradication therapy has declined worldwide largely because of increased antimicrobial resistance. New therapeutic approaches are needed, especially for countries like Iran, where resistance to commonly used drugs is already widespread and traditional H. pylori therapies produce poor cure rates. Aim: To...

Gastric cancer is the fourth most prevalent cancer worldwide, which claims more than 700,000 lives every year. However, the current chemical and surgical management of this mortal cancer remains far from successful. A recent safe approach to preventing or treating tumorigenesis has been the re-introduction of traditional herbal medicine, taking adv...

Persistent bacterial infections cause persistent irritation of the host’s defense systems, which when ineffective in eradication of the infection, result in a multitude of self-destructive damages. This in some cases occurs to such severity that the resulting cellular hyper-proliferation provides grounds for increased chances of writing errors (gen...

Purpose Helicobacter pylori secretory peptidyl prolyl isomerase, HP0175, is progressively identified as a pro-inflammatory and pro-carcinogenic protein, which serves to link H. pylori infection to its more severe clinical outcomes. Here, we have analyzed host HP0175-specific antibody responses in relation to the severity of gastritis. Methods The H...

Background BabA is a Helicobacter pylori cell surface adhesin, which binds to the ABO/Leb histo-blood group antigens (Leb) and serves as a virulence factor. Methods H. pylori single colonies were isolated from 156 [non-ulcer dyspepsia (NUD) = 97, duodenal ulcer (DU) = 34, gastric cancer (GC) = 25)] patients. babA and babB genes were evaluated by ge...

Background: Gastric cancer arises, mainly, on an inflammatory background. Helicobacter pylori neutrophil activating (HP-NAP) protein functions as a potent pro-inflammatory mediator. Similarly, IL-4 plays a critical role in the inflammation pathway, the levels of which are altered by C to T transition at position -590 in its promoter region. Here, w...

Introduction : Intestinal metaplasia, induced by Helicobacter pylori (Hp) infection, increases the risk of gastric cancer. This metaplastic state marks a “point of no return”, after which the presence of Hp becomes dispensable. Here, we have depicted a time- map of this process via tracing key biomarkers. Methods : RT- PCR was used to assess gastri...

Introduction : The ATP- binding cassette (ABC) transporters create unidirectional channels in various cell membranes, including those of the gastrointestinal epithelial lining. These channels function to efflux drugs and toxins, as a protective measure. Here, we have explored the impact of functional SNPs in two of its prominent members (ABCB1 and...

Purpose Helicobacter pylori secretory peptidyl prolyl isomerase, HP0175, is progressively identified as a proinflammatory and pro-carcinogenic protein, which serves to link H. pylori infection to its more severe clinical outcomes. Here, we have analyzed host HP0175-specific antibody responses in relation to the severity of gastritis. Methods The HP...

Helicobacter pylori (H. pylori) is a common infection responsible for considerable morbidity and mortality worldwide. It is now recommended that all H. pylori infections be cured unless there are compelling reasons not to. Like other infectious diseases, the most reliable method to achieve high cure rates is to base therapy on the results of patien...

INTRODUCTION Helicobacter pylori (H. pylori) infect more than half of the adult population worldwide, causing a variety of gastrointestinal disorders, ranging from gastritis to peptic ulcer diseases and in the worst case scenario, the fatal cancer of the stomach [1]. Although the stomach is exposed to an array of ingested external ingredients, incl...

Introduction: Promoter hypermethylation is an important mechanism of gene silencing. Several aberrant methylations have been reported in the promoter region of tumor suppressor genes, including p16, DAPK and E-cad, in associa- tion with solid tumors. P16 tumor suppressor gene is an essential regulator of the cell cycle. Our aim was to determine the...

Introduction: Helicobacter pylori (Hp) CagA is a highly polymorphic protein, due to its sequence diversities at the C-terminus. This diversity has been associ- ated with the geographic origin of Hp strains, resulting in their designation as Eastern versus Western types. Methods: Genomic DNA was extracted from single colonies of Hp strains from 170...

Background: Helicobacter pylori (Hp) adhesion, BabA, is localized on the bacte- rial cell surface, binds to the fucosylated Lewis b histo-blood group antigen on gastric epithelial cells and is responsible for bacterial colonization in the gastric milieu. The diverse roles of this bacterial adhesion in Hp-induced pathogenesis remain understudied. Me...

Introduction: Helicobacter pylori (Hp) infection is mostly acquired during childhood, in the developing world. This is generally owed to poor socio-eco- nomic status and family crowding, resulting in intrafamilial transmission. Sero- logic detection of Hp infection remains as the most suitable method of population screening. The aim of this study w...

Gastric cancer is the second cause of cancer related mortality worldwide. Helicobacter pylori (Hp) infection is now established as the leading risk factor for gas- tric cancer (GC). The aim of the present study was to identify the potential serum biomarkers associated with Hp-associated GC. Methods: We used a serum prefractionation strategy, based...

Purpose: To evaluate a home-made ELISA kit for detection of Helicobacter pylori (Hp) infection and comparison of its immunologic criteria with those of foreign commercial kits. Methods: A home-made IgG ELISA kit was developed using soluble antigenic fractions of Hp proteins. Confirmed sera were tested and serological criteria were evaluated through...

Gastric cancer is a silent killer, claiming more than seven hundred thousand lives every year. This heavy burden creates an irrefutable need for accurate, noninvasive methods of population screening and early detection as well as disease monitoring and management. Gastric cancer is a multi-factorial disease with an uneven geographic distribution, m...

Background: Cytokine gene single nucleotide polymorphisms (SNPs) are widely used to study susceptibility to complex diseases and as a tool for anthropological studies. Materials and Methods: To investigate cytokine SNPs in an Iranian multi‑ethnic population, we have investigated 10 interleukin (IL) SNPs (IL‑1β (C‑511T, T‑31C), IL‑2 (G‑384T), IL‑4 (...

Serologic screening of gastric cancer (GC) by serum pepsinogens (sPG) levels and Helicobacter pylori (Hp) sero-status, though highly informative, has provided heterogeneous results. Here, we have evaluated the modifying effects of demographic factors on the risk impact of Hp sero-status/sPG levels in gastric cancer, with particular emphasis on age....

Gastric cancer is the second cause of cancer related mortality worldwide. Helicobacter pylori (Hp) infection is now established as the leading risk factor for gas- tric cancer (GC). The aim of the present study was to identify the potential serum biomarkers associated with Hp-associated GC. Methods: We used a serum prefractionation strategy, based...

Gastric cancer is the second cause of cancer related mortality worldwide. Helicobacter pylori (Hp) infection is now established as the leading risk factor for gas- tric cancer (GC). The aim of the present study was to identify the potential serum biomarkers associated with Hp-associated GC. Methods: We used a serum prefractionation strategy, based...

Background: Serum screening of antigen-specific antibodies can ideally be used as a non-invasive and cost-effective method of monitoring H. pylori-mediated histopathologic changes. For this purpose, we have, herein, evaluated this hypothesis using three H. pylori recombinant proteins in association with H. pylori infection and its clinical outcomes...

Background: Variation in cancer incidence in geographical locations is partly owed to diverse lifestyle factors. Among these modifiable dietary habits require more detailed investigations. Methods: Personal interviews with 559 gastric cancer (GC) and 811 non-ulcer dyspeptic (NUD) patients using comprehensive questionnaires produced extensive inform...

Background: Secreted peptidyl prolyl cis-, trans-isomerase, HP0175 activates tumor infiltrating lymphocytes through activation of pro-inflammatory cytokines, which are thought to be responsible for pre-cancerous gastric histopathologic changes. This study has evaluated the association between HP0175-specific antibody response and grade of gastric i...

Background: Intestinal type of gastric cancer (GC) is believed to initiate with H. pylori-mediated gastric inflammation. On the other hand, functional single nucleotide polymorphisms (SNPs) in cytokine genes significantly affect recruitment of inflammatory cells into the gastric mucosal lining. Here we have measured the risk enhancing role of singl...

Background: MicroRNAs (miRNAs) expression is deregulated in Helicobacter pylori-infected gastric mucosa and gastric cancer tissue. Recent studies have demonstrated that these non-coding small RNA molecules are also released into the circulation and can reflect the presence of tumors. The aim of this study was to investigate serum miR-21 levels in p...

The features of Helicobacter pylori adhesins, their interactions with their host counterparts, regulated and selective gene expressions are amongst the many clever strategies this microorganism undertakes to survive the otherwise sterile gastric milieu. The ingenious crafting of these interactions and the respective host reactions govern, in part,...

Introduction: H. pylori infection induces chronic inflammation associated with induction of pro-inflammatory cytokines, such as tumor necrosis factor-a, the key cytokine in tumor promotion. One of the TNF-a inducing protein (Tip-a) gene family in H. pylori genome is Tip-a, which acts as a carcinogenic factor by induction of TNF-a gene expression. W...

Introduction: Helicobacter pylori hom gene encodes an outer membrane protein with allelic divergence; homB and its nearly 90% similar allele, homA. In this study, we have evaluated the association of gastric cancer with hom gene status and other virulence factors including cagA and vacA in an Iranian casecontrol study. Methods: A total of 241 H. py...

Introduction: Promoter hypermethylation is an important mechanism of gene silencing. Several aberrant methylations have been reported in the promoter region of tumor suppressor genes (including p16, DAPK and E-cad) in association with gastric carcinogenesis. Methods: The association of promoter hypermethylation of p16, DAPK and Ecad was assessed th...

Background: Multiple etiologic factors are suspected to cause gastric cancer, the most important of which is infection with virulent types of Helicobacter pylori. Materials and methods: We have compared 102 gastric cancer patients with 122 non-ulcer, non-cancer dyspeptic patients. Gastric specimens were evaluated for H. pylori infection by tissu...

Background and aims: Helicobacter pylori is a highly diverse pathogen, which encounters epithelial cells as the initial defense barrier during its lifelong infection. The structure of epithelial cells can be disrupted through cleavage of microfilaments. Cytokeratin 18 (CK18) is an intermediate filament, the cleavage of which is considered an early...

Background: Attempts for early detection of gastric cancer have recently focused on host's genetic susceptibility factors and gene-environment interactions. We have, herein, studied the association of MTHFR C677T single nucleotide polymorphism (SNP) and its interaction with Helicobacter pylori infection, smoking, age and gender on the risk of gast...

Helicobacter pylori is a well-recognized gastroduodenal pathogen (National Institute of Health Consensus Conference, JAMA 272:65–9, 1994) and a class I carcinogen (International Agency for Research on Cancer, IARC Monograph on the Evaluation of Carcinogenic Risk to Humans 61:177–240, 1994) which successfully colonizes the harsh acidic environment o...

Interleukins depending on their tumor promoting or suppressing functions are known to affect cancer risk. IL-2 and IL-4 are respectively known as pro and antiinflammatory cytokines which are affected by H. pylori infection and involved in predisposition to gastric cancer. We have, herein, investigated the risk of gastric cancer associated with of I...

IL-8 is a well-studied pro-inflammatory cytokine which is known to potentiate gastritis in response to H. pylori infection. Furthermore, its elevated circulatory levels are associated with poor prognosis of gastric cancer patients. IL-8 -251T/A single nucleotide polymorphism (SNP) results in higher production of this cytokine among its carriers. We...

The high incidence and mortality rate of gastric cancer (GC) in Iran and the poor survival rate due to its late detection are the major incentives in seeking non invasive approaches for early screening of high risk populations. Serum pepsinogen (PG) levels have long been established as potential indicators of the gastric mucosal integrity, abnormal...

Three hundred and eighty-two GC patients (cases), 626 non ulcer dyspeptic patients (NUD) and 179 healthy blood donors were enrolled as hospital and population based controls, respectively. Fasting blood samples were taken for measuring serum PG I, PG II. GC cases were categorized according to tumor subsite and subtype. PMN/neutrophil infiltrations,...

Conclusions: Results of our studies show the difficulty in interpreting cross-sectional studies. Results of the cohort study show a slightly increased incidence in HCWs compared to non-exposed controls. Abstract no.: P04.04 We carried out a hospital based case-control study, including 382 cases with confirmed gastric cancer and 645 gastric cancer f...

Objectives: Several studies have shown that beside Helicobacter pylori (Hp) and its virulence factors, host genetic and protein content as well as environmental factors are involved in gastric carcinogenesis. In this study we aimed to estimate the risk of gastric cancer development associated with serum anti-Hp and its cytotoxin associated gene A p...

Objectives: Gastric cancer is the most severe manifestation of chronic H. pylori (Hp) infection. HP-induced carcinogenesis is mediated mostly through two potent polymorphic toxins; vacA and cagA. The aim of this study was to determine associations between different cagA/vacA genotypes and functions with gastrointestinal complications and evaluate w...