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Masoumeh Azimirad,1,* YoungJae Jo,2,* Min-Sueng Kim,2 Minsoo Jeong,2 Shabnam Shahrokh,3 Hamid Asadzadeh Aghdaei,4 Mohammad Reza Zali,3 Seungjun Lee,5 Abbas Yadegar,1 Jae-Ho Shin2 1Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Department of Applied Biosciences, Kyungpook National University, Daegu, 41566, Republic of Korea; 3Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 4Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 5Department of Food Science and Nutrition, College of Fisheries Science, Pukyong National University, Busan, Republic of Korea*These authors contributed equally to this workCorrespondence: Abbas Yadegar; Jae-Ho Shin Tel +98-21-22432518; +82 53-950-5716Fax +98-21-22432527; +82 53-953-7233Email babak_y1983@yahoo.com; jhshin@knu.ac.krBackground and Purpose: Fecal microbiota transplantation (FMT) has emerged for the therapeutic treatment of recurrent Clostridioides difficile infection (rCDI) with concurrent inflammatory bowel disease (IBD). As the first Iranian population cohort, we examined how gut microbiota and their functional profiles change in Iranian rCDI patients with underlying IBD before and after FMT.Patients and Methods: FMT was performed to eight IBD patients via colonoscopy. Profiles of gut microbiota from donors and recipients were investigated using 16S rRNA gene sequence analysis.Results: Patients experienced no IBD flare-ups or other adverse effects, and all recovered to full health. Moreover, all rCDI patients lacked the Bacteroidetes present in donor samples. After FMT, the proportion of Bacteroidetes increased until a normal range was achieved. More specifically, the relative abundance of Prevotella was found to increase significantly following FMT. Prevotella was also found to correlate negatively with inflammation metrics, suggesting that Prevotella may be a key factor for resolving CDI and IBD. Gut microbiota diversity was found to increase following FMT, while dysbiosis decreased. However, the similarity of microbial communities of host and recipients did not increase, and wide variation in the extent of donor stool engraftment indicated that the gut bacterial communities of recipients do not shift towards those of donors.Conclusion: FMT leads to significant alterations of the community structure of gut bacteria in rCDI patients with IBD. The change in relative abundance of Proteobacteria and bacterial diversity indicated that FMT promotes recovery from intestinal permeability and inflammation in rCDI patients. Moreover, strong negative correlation between Prevotella and inflammation index, and decreased dysbiosis index advocate that the improvement of CDI is possibly due to gut microbiome alteration. Collectively, our findings show that FMT would be a promising therapy to help reprogram the gut microbiome of Iranian rCDI patients with IBD.Keywords: fecal microbiota transplantation, Clostridioides difficile infection, inflammatory bowel disease, gut microbiome, functional profiles, gut dysbiosis

Introduction: The microRNA-326 (miR-326) gene, by targeting ETS Proto-Oncogene 1 (ETS1), regulates the differentiation and interleukin-17A production of T helper 17 (Th17) cells. Celiac disease (CD) is an intestinal autoimmune disorder, in which the cascade of Th17 cells plays an important role in its pathogenicity. The aim of this study was to evaluate the expression changes of miR-326 and its two target genes ETS1 and IL-17A in celiac disease patients under a gluten-free diet (GFD). We expected the expression of miR-326 and IL-17A gene to decrease, and the expression of the ETS1 gene to increase, following the adherence to GFD.

Background: One of the main reasons for cancer resistance to chemotherapy is the presence of cancer stem cells (CSCs) in cancer tissues. It is also believed that CSCs are the unique originators of all tumor cells. On the other hand, the Epithelial-Mesenchymal Transition pathway (EMT) can act as the main agent of metastasis. Therefore, it is possible that targeting CSCs as well as the EMT pathway could help in cancer therapy. Considering that CSCs constitute only a small percentage of the total tumor mass, enrichment before study is necessary. In our previous study, CSCs were enriched in the human colon cancer cell line HT29 by induction of EMT. These CSC-enriched HT29 cells with mesenchymal morphology were named "HT29-shE". In the present study, these cells were used to investigate the effect of Pioglitazone (Pio) and Cetuximab (Cet) in order to find CSC and EMT targeting agents., Methods: The viability and IC 50 rate of cells treated with different concentrations of Pio and Cet were evaluated using the MTT test. EMT and CSC markers and cell morphology were assessed in Pio and Cet treated and untreated HT29-shE cells using flow cytometry, realtime PCR, immunocytochemistry, and microscopic monitoring., Results: The findings showed that Pio and Cet at concentrations of 250 μM and 40 μg/ml, respectively, decrease cell viability by 50%. Also, they were able to reduce the expression of CSC markers (CD133 and CD44) in the CSC enriched HT29 cell line. Furthermore, Pio and Cet could efficiently reduce the expression of vimentin as a mesenchymal marker and significantly upregulate the expression of E-cadherin as an epidermal marker of EMT and its reverse mesenchymal- toepithelial transition (MET). In addition, the mesenchymal morphology of HT29-shE changed into epithelial morphology after Cet treatment., Conclusion: Pio and Cet could inhibit EMT and reduce CSC markers in the EMT induced/CSC enriched cell line. We expect that focus on finding EMT/CSC-targeting agents like these drugs can be helpful for cancer treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: We aimed to elucidate the potential correlation between single-nucleotide polymorphisms (SNPs) in miRNA machinery genes and colorectal cancer (CRC) risk in an Iranian cohort., Methods: We conducted a robust case-control study involving 507 participants, which included 213 patients diagnosed with CRC and 294 healthy controls at Research Institute for Gastroenterology and Liver Diseases in Tehran Province, Iran in 2018. The study focused on genotyping four specific SNPs, RAN (rs14035), GEMIN3 (rs197412), GEMIN4 (rs2740348), and Dicer (rs3742330), using advanced ARMS-PCR and Tetra-primer ARMS-PCR techniques., Results: Notably, our investigation revealed the significant inverse association between the C/C genotype of rs197412 in the GEMIN3 gene and CRC risk (OR=0.54, 95% CI=0.33-0.87; P =0.0087). In stark contrast, the T/T genotype of rs14035 in the RAN gene was strongly associated with a heightened risk of developing CRC (OR=4.44, 95% CI=2.60-7.57, P <0.0001). Furthermore, we found that the G/G genotype of rs2740348 in GEMIN4 posed an increased risk for CRC (OR=2.9, 95% CI=1.44-5.85, P =0.0041) and it has a major effect on CRC risk in our population. The alleles and genotypes of rs3742330 in Dicer , however, did not exhibit a significant correlation with CRC., Conclusion: Our study provides compelling evidence that SNPs within miRNA processing genes significantly contribute to susceptibility to CRC among the Iranian population. Our research not only contributes to the growing body of miRNA-related genetic studies but also opens avenues for population-specific risk assessment and personalized medicine approaches in cancer therapy., (Copyright© 2024 Mobaraki et al. Published by Tehran University of Medical Sciences.)

Introduction: Helicobacter pylori causes stubborn infections and leads to a variety of stomach disorders, such as peptic ulcer, chronic atrophic gastritis, and gastric cancer. Although antibiotic-based approaches have been widely used against H. pylori , some challenges such as antibiotic resistance are increasing in severity. Therefore, simpler but more effective strategies are needed., Areas Covered: In this review, basic information on functionalized and non-functionalized micro/nano biomaterials and routes of administration for H. pylori inhibition are provided in an easy-to-understand format. Afterward, in vitro and in vivo studies of some promising bio-platforms including metal-based biomaterials, biopolymers, small-molecule saccharides, and vaccines for H. pylori inhibition are discussed in a holistic manner., Expert Opinion: Functionalized or non-functionalized micro/nano biomaterials loaded with anti- H. pylori agents can show efficient bactericidal activity with no/slight negative influence on the host gastrointestinal microbiota. However, this claim needs to be substantiated with hard data such as assessment of the biopharmaceutical parameters of anti- H. pylori systems and the measurement of diversity/abundance of bacterial genera in the host gastric/gut microbiota before and after H. pylori eradication.

Helicobacter pylori (H. pylori) is a recalcitrant pathogen, which can cause gastric disorders. During the past decades, polypharmacy-based regimens, such as triple and quadruple therapies have been widely used against H. pylori. However, polyantibiotic therapies can disturb the host gastric/gut microbiota and lead to antibiotic resistance. Thus, simpler but more effective approaches should be developed. Here, some recent advances in nanostructured drug delivery systems to treat H. pylori infection are summarized. Also, for the first time, a drug release paradigm is proposed to prevent H. pylori antibiotic resistance along with an IVIVC model in order to connect the drug release profile with a reduction in bacterial colony counts. Then, local delivery systems including mucoadhesive, mucopenetrating, and cytoadhesive nanobiomaterials are discussed in the battle against H. pylori infection. Afterward, engineered delivery platforms including polymer-coated nanoemulsions and polymer-coated nanoliposomes are poposed. These bioinspired platforms can contain an antimicrobial agent enclosed within smart multifunctional nanoformulations. These bioplatforms can prevent the development of antibiotic resistance, as well as specifically killing H. pylori with no or only slight negative effects on the host gastrointestinal microbiota. Finally, the essential checkpoints that should be passed to confirm the potential effectiveness of anti-H. pylori nanosystems are discussed., (© 2023 Wiley-VCH GmbH.)

The Gut-brain axis is a bidirectional neural and humoral signaling that plays an important role in mental disorders and intestinal health and connects them as well. Over the past decades, the gut microbiota has been explored as an important part of the gastrointestinal tract that plays a crucial role in the regulation of most functions of various human organs. The evidence shows several mediators such as short-chain fatty acids, peptides, and neurotransmitters that are produced by the gut may affect the brain's function directly or indirectly. Thus, dysregulation in this microbiome community can give rise to several diseases such as Parkinson's disease, depression, irritable bowel syndrome, and Alzheimer's disease. So, the interactions between the gut and the brain are significantly considered, and also it provides a prominent subject to investigate the causes of some diseases. In this article, we reviewed and focused on the role of the largest and most repetitive bacterial community and their relevance with some diseases that they have mentioned previously., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Chronic infection with Helicobacter pylori is the primary risk factor for the development of gastric cancer. Hindering our ability to comprehend the precise role of autophagy during H. pylori infection is the complexity of context-dependent autophagy signaling pathways. Recent and ongoing progress in understanding H. pylori virulence allows new frontiers of research for the crosstalk between autophagy and H. pylori. Novel approaches toward discovering autophagy signaling networks have further revealed their critical influence on the structure of gut microbiota and the metabolome. Here we intend to present a holistic view of the perplexing role of autophagy in H. pylori pathogenesis and carcinogenesis. We also discuss the intermediate role of autophagy in H. pylori-mediated modification of gut inflammatory responses and microbiota structure., Competing Interests: Declaration of interests There are no interests to declare., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The incidence of early-onset colorectal cancer (CRC), which affects people under 50, is increasing for unknown reasons. Additionally, no underlying genetic cause is found in 20%-30% of patients suspected of having familial CRC syndrome. Whole exome sequencing (WES) has generated evidence for new genes associated with CRC susceptibility, but many patients remain undiagnosed. This study applied WES in five early-onset CRC patients from three unrelated families to identify novel genetic variants that could be linked to rapid disease development. Furthermore, the candidate variants were validated using Sanger sequencing. Two heterozygote variations, c.1077-2A>G and c.199G>A, were found in the MSH2 and the MLH1 genes, respectively. Sanger sequencing analysis confirmed that these (likely) pathogenic mutations segregated in all the affected families' members. In addition, we identified a rare heterozygote variant (c.175C>T) with suspected pathogenic potential in the MAP3K1 gene; formally the variant is of uncertain significance (VUS). Our findings support the hypothesis that CRC onset may be oligogenic and molecularly heterogeneous. Larger and more robust studies are needed to understand the genetic basis of early-onset CRC development, combined with novel functional analyses and omics approaches., (© 2023 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Exosomes are small extracellular vesicles that can be derived from human cells such as mesenchymal stem cells (MSCs). The size of exosomes is at nano-scale range and owing to their biocompatibility and other characteristics, they have been promising candidates for delivery of bioactive compounds and genetic materials in disease therapy, especially cancer therapy. Gastric cancer (GC) is a leading cause of death among patients and this malignant disease affects gastrointestinal tract that its invasiveness and abnormal migration mediate poor prognosis of patients. Metastasis is an increasing challenge in GC and microRNAs (miRNAs) are potential regulators of metastasis and related molecular pathways, especially epithelial-to-mesenchymal transition (EMT). In the present study, our aim was to explore role of exosomes in miR-200a delivery for suppressing EMT-mediated GC metastasis. Exosomes were isolated from MSCs via size exclusion chromatography. The synthetic miR-200a mimics were transfected into exosomes via electroporation. AGS cell line exposed to TGF-β for EMT induction and then, these cells cultured with miR-200a-loaded exosomes. The transwell assays performed to evaluate GC migration and expression levels of ZEB1, Snail1 and vimentin measured. Exosomes demonstrated loading efficiency of 5.92 ± 4.6%. The TGF-β treatment transformed AGS cells into fibroblast-like cells expressing two stemness markers, CD44 (45.28%) and CD133 (50.79%) and stimulated EMT. Exosomes induced a 14.89-fold increase in miR-200a expression in AGS cells. Mechanistically, miR-200a enhances E-cadherin levels (P < 0.01), while it decreases expression levels of β-catenin (P < 0.05), vimentin (P < 0.01), ZEB1 (P < 0.0001) and Snail1 (P < 0.01), leading to EMT inhibition in GC cells. This pre-clinical experiment introduces a new strategy for miR-200a delivery that is of importance for preventing migration and invasion of GC cells., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Helicobacter pylori is a widespread helical Gram-negative bacterium, which causes a variety of stomach disorders, such as peptic ulcer, chronic atrophic gastritis, and gastric cancer. This microbe frequently colonizes the mucosal layer of the human stomach and survives in the inhospitable microenvironment, by adapting to this hostile milieu., Areas Covered: In this extensive review, we describe conventional antibiotic treatment regimens used against H. pylori including, empirical, tailored, and salvage therapies. Then, we present state-of-the-art information about reasons for treatment failure against H. pylori . Afterward, the latest advances in the use of probiotic bacteria against H. pylori infection are discussed. Finally, we propose a polymeric bio-platform to provide efficient delivery of probiotics for H. pylori infection., Expert Opinion: For effective probiotic delivery systems, it is necessary to avoid the early release of probiotics at the acidic stomach pH, to protect them against enzymes and antimicrobials, and precisely target H. pylori bacteria which have colonized the antrum area of the stomach (basic pH).

The activation of hepatic stellate cells is the primary function of facilitating liver fibrosis. Interfering with the coordinators of different signaling pathways in activated hepatic stellate cells (aHSCs) could be a potential approach in ameliorating liver fibrosis. Regarding the illustrated anti-fibrotic effect of imatinib in liver fibrosis, we investigated the imatinib's potential role in inhibiting HSC activation through miR-124 and its interference with the STAT3/hepatic leukemia factor (HLF)/IL-6 circuit. The anti-fibrotic effect of imatinib was investigated in the LX-2 cell line and carbon tetrachloride (CCl 4 )-induced Sprague-Dawley rat. The expression of IL-6, STAT3, HLF, miR-124, and α-smooth muscle actin (α-SMA) were quantified by quantitative real-time PCR (qRT-PCR) and the protein level of α-SMA and STAT3 was measured by western blot analysis both in vitro and in vivo. The LX-2 cells were subjected to immunocytochemistry (ICC) for α-SMA expression. After administering imatinib in the liver fibrosis model, histopathological examinations were done, and hepatic function serum markers were checked. Imatinib administration alleviated mentioned liver fibrosis markers. The expression of miR-124 was downregulated, while IL-6/HLF/STAT3 circuit agents were upregulated in vitro and in vivo. Notably, imatinib intervention decreased the expression of IL-6, STAT3, and HLF. Elevated expression of miR-124 suppressed the expression of STAT3 and further inhibited HSCs activation. Our results demonstrated that imatinib not only ameliorated hepatic fibrosis through tyrosine kinase inhibitor (TKI) activity but also interfered with the miR-124 and STAT3/HLF/IL-6 pathway. Considering the important role of miR-124 in regulating liver fibrosis and HSCs activation, imatinib may exert its anti-fibrotic activity through miR-124., (© 2023 International Federation for Cell Biology.)

Ischaemic disorders are leading causes of morbidity and mortality worldwide. While the current therapeutic approaches have improved life expectancy and quality of life, they are unable to "cure" ischemic diseases and instate regeneration of damaged tissues. Exosomes are a class of extracellular vesicles with an average size of 100-150 nm, secreted by many cell types and considered a potent factor of cells for paracrine effects. Since exosomes contain multiple bioactive components such as growth factors, molecular intermediates of different intracellular pathways, microRNAs and nucleic acids, they are considered as cell-free therapeutics. Besides, exosomes do not rise cell therapy concerns such as teratoma formation, alloreactivity and thrombotic events. In addition, exosomes are stored and utilized more convenient. Interestingly, exosomes could be an ideal complementary therapeutic tool for ischemic disorders. In this review, we discussed therapeutic functions of exosomes in ischemic disorders including angiogenesis induction through various mechanisms with specific attention to vascular endothelial growth factor pathway. Furthermore, different delivery routes of exosomes and different modification strategies including cell preconditioning, gene modification and bioconjugation, were highlighted. Finally, pre-clinical and clinical investigations in which exosomes were used were discussed., (© 2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: The imbalance of redox homeostasis induces hyper-inflammation in viral infections. In this study, we explored the redox system signature in response to SARS-COV-2 infection and examined the status of these extracellular and intracellular signatures in COVID-19 patients., Method: The multi-level network was constructed using multi-level data of oxidative stress-related biological processes, protein-protein interactions, transcription factors, and co-expression coefficients obtained from GSE164805, which included gene expression profiles of peripheral blood mononuclear cells (PBMCs) from COVID-19 patients and healthy controls. Top genes were designated based on the degree and closeness centralities. The expression of high-ranked genes was evaluated in PBMCs and nasopharyngeal (NP) samples of 30 COVID-19 patients and 30 healthy controls. The intracellular levels of GSH and ROS/O 2 •  - and extracellular oxidative stress markers were assayed in PBMCs and plasma samples by flow cytometry and ELISA. ELISA results were applied to construct a classification model using logistic regression to differentiate COVID-19 patients from healthy controls., Results: CAT, NFE2L2, SOD1, SOD2 and CYBB were 5 top genes in the network analysis. The expression of these genes and intracellular levels of ROS/O 2 •   -  were increased in PBMCs of COVID-19 patients while the GSH level decreased. The expression of high-ranked genes was lower in NP samples of COVID-19 patients compared to control group. The activity of extracellular enzymes CAT and SOD, and the total oxidant status (TOS) level were increased in plasma samples of COVID-19 patients. Also, the 2-marker panel of CAT and TOS and 3-marker panel showed the best performance., Conclusion: SARS-COV-2 disrupts the redox equilibrium in immune cells and the upper respiratory tract, leading to exacerbated inflammation and increased replication and entrance of SARS-COV-2 into host cells. Furthermore, utilizing markers of oxidative stress as a complementary validation to discriminate COVID-19 from healthy controls, seems promising., Competing Interests: Declaration of competing interest The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Alterations of the gut microbiome in cases of colorectal cancer (CRC) hint at the involvement of host-microbe interactions in the onset and progression of CRC and also, possibly, provide novel ways to detect and prevent CRC early. The aim of the present study was to evaluate whether the oral and fecal microbiomes of an individual can be suitable for CRC screening. Oral and fecal samples ( n = 80) were gathered in Taleghani hospital, affiliated with Shahid Beheshti University of Medical Sciences, Tehran-Iran, from CRC stage 0 and I patients and healthy controls (HCs), who were screened for the first time. Microbial metagenomics assays were performed for studying microbiota profiles in all oral and fecal samples gathered. An abundance of top bacterial genera from both types of specimens (fecal and saliva samples) revealed a distinction between CRC patients and HCs. In saliva samples, the α diversity index was different between the microbiome of HCs and CRC patients, while β diversity showed a densely clustered microbiome in the HCs but a more dispersed pattern in CRC cases. The α and β diversity of fecal microbiota between HCs and CRC patients showed no statistically significant differences. Bifidobacterium was identified as a potential bacterial biomarker in CRC saliva samples, while Fusobacterium , Dialister , Catonella , Tennerella , Eubacterium-brachy-group , and Fretibacterium were ideal to distinguish HCs from CRC patients. One of the reasons for the heterogeneity of CRC may be the gastrointestinal (GI) tract microbiota, which can also cause systematic resistance to CRC. Moreover, an evaluation of saliva microbiota might offer a suitable screening test for the early detection of this malignancy, providing more accurate results than its fecal counterpart.

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide that is attributed to gradual long-term accumulation of both genetic and epigenetic changes. To reduce the mortality rate of CRC and to improve treatment efficacy, it will be important to develop accurate noninvasive diagnostic tests for screening, acute and personalized diagnosis. Epigenetic changes such as DNA methylation play an important role in the development and progression of CRC. Over the last decade, a panel of DNA methylation markers has been reported showing a high accuracy and reproducibility in various semi-invasive or noninvasive biosamples. Research to obtain comprehensive panels of markers allowing a highly sensitive and differentiating diagnosis of CRC is ongoing. Moreover, the epigenetic alterations for cancer therapy, as a precision medicine strategy will increase their therapeutic potential over time. Here, we discuss the current state of DNA methylation-based biomarkers and their impact on CRC diagnosis. We emphasize the need to further identify and stratify methylation-biomarkers and to develop robust and effective detection methods that are applicable for a routine clinical setting of CRC diagnostics particularly at the early stage of the disease., (© 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Obesity, a morbid condition snowballing in the world, may cause many health issues in healthy and ill people. Many disorders are known to be influenced by obesity, mainly in a catastrophic way, including inflammatory bowel disease (IBD). Many studies sought to determine the effects that obesity prompts IBD. Some of them indicate that obesity is associated with poor outcomes. There is no consistency regarding the correlation between obesity and IBDs due to the equivocal nature of obesity and the shortage of extensive and reliable investigations. However, to a worldwide consensus, obesity has a unique disease burden and can cause poor prognosis when it accompanies other ailments. Here, we have reviewed some of the alterations and impacts that obesity may impose on the pathogenesis and clinical management of IBD. Conclusively, inflammatory processes of IBD are reinforced by obesity. Furthermore, as a two-way road, obesity can be caused by IBD. However, autoimmunity in IBD is not found to have a consistent relationship with obesity. Although, medical and surgical treatments of IBD are affected by obesity in terms of their efficacy and outcomes. The most important aspect of obesity that can influence the course of disease management is associated with significant disabilities that obesity may cause rather than a metabolic or molecular rationale., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Long non-coding RNAs (LncRNAs) are known to have regulatory consequences for aberrant gene expression in cancers. The aim of this study was to evaluate the expression levels of long non-encoding RNAs, BACE1 (β-secretase1) and LINC-PINT (Long Intergenic Non-Protein Coding RNA, P53 Induced Transcript), in colorectal cancer (CRC) with clinicopathological parameters., Methods and Results: Bioinformatics analysis defining effectual signalling pathways Wnt. A total of 130 tissue samples (50 fresh CRC tissues with parallel adjacent normal tissues (ADJ) accompanied with 30 normal healthy control tissue samples) were collected from the Iranian population. mRNA expression analysis was performed via Real Time Q-PCR. Statistical analysis for comparing CRC expression levels with ADJ and normal healthy tissues were carried out using Kruskal-Wallis tests. The Receiver Operating Characteristic (ROC) curve was plotted for each LNC, separately. We discovered that PINT and BACE1 expression levels were decreased and increased respectively in CRC tumour samples compared with ADJ normal and healthy tissues. Clinicopathological parameter assessment revealed a significant relationship between PINT expression, tumour location, staging and distant metastasis (p < 0.009, p < 0.014, p < 0.008, respectively). Also, BACE1 over expression was significantly associated with tumour site (p < 0.009), metastasis (p < 0.017) and histological differentiation (p < 0.028) and staging (p < 0.017). Furthermore, ROC curve plotting showed LINC-PINT LNC-BACE1 may distinguish between early and late-stage of CRC, highlighting the value of both BACE1 and PINT as CRC progression biomarkers., Conclusion: We investigated two LNCRNAs (PINT and BACE1) as potential CRC prognostic biomarkers, which are imperative for early and effective medical intervention in CRC. Expression levels of PINT and BACE1 in CRC tissue samples may serve to identify metastasis earlier, increasing patient survival rates and expediating clinical treatment options., (© 2022. The Author(s).)

An alarmingly increasing number of outbreaks caused by contaminated gastrointestinal (GI) endoscopes are being reported as a particularly concerning issue. This study is the first large-scale multicenter survey to evaluate the contamination of GI endoscopes in Tehran, Iran. This multicenter study was conducted among 15 tertiary referral and specialized gastrointestinal settings. Reprocessed GI endoscopes were sampled by the sequence of the flush-brush-flush method. Bacterial and viral contamination, as well as antimicrobial resistance, were explored by culture and molecular assays. A total of 133 reprocessed and ready-to-use GI endoscopes were investigated. In phase I and phase II, 47% and 32%, respectively, of the GI endoscopes were determined to be contaminated. GI flora was the most prevalent contaminant isolated from GI endoscopes, in which the most predominant bacteria were Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae, in both phase I and II evaluations. The majority of the isolated bacteria in the current study were considered multidrug-resistant organisms (MDROs). More importantly, we recovered carbapenem-resistant nonfermentative Gram-negative bacilli (CRNFGNB), carbapenem-resistant Enterobacterales (CRE), extended-spectrum β-lactamase (ESBL)-producing Enterobacterales (ESBL-E), multidrug-resistant Clostridioides difficile, vancomycin-resistant Enterococcus (VRE), and drug-resistant Candida spp. Disconcertingly, our molecular assays revealed contamination of some reprocessed GI endoscopes with hepatitis B virus (HBV), hepatitis C virus (HCV), and even HIV. This multicenter study indicates a higher-than-expected contamination rate among reprocessed and ready-for-patient-use GI endoscopes, which suggests a higher-than-expected endoscopy-associated infection (EAI) risk, and potentially, morbidity and mortality rate, associated with endoscopy procedures in Tehran, Iran. IMPORTANCE In the light of severe outbreaks caused by multidrug-resistant microorganisms due to contaminated GI endoscopes, understanding to what extent GI endoscopes are inadequately reprocessed is crucial. Several studies assessed contamination of GI endoscopes with various outcomes across the world; however, the prevalence and risk factors of contaminated GI endoscopes and potential subsequent nosocomial spread are still unknown in Iran. The present study is the first large-scale multicenter survey to evaluate the microbial contamination of repossessed and ready-to-use GI endoscopes in Tehran, Iran. Our study showed a higher-than-expected contamination rate among reprocessed GI endoscopes, which suggests potential seeding of deadly but preventable outbreaks associated with endoscopy procedures in Iran. These results suggest that the current reprocessing and process control guidelines do not suffice in Iran. The current study is of particular importance and could provide insights into unrecognized and unidentified endoscopy-associated outbreaks in Iran.

Human herpes viruses (HHVs) are among the most common infectious agents detected in the gastrointestinal tract that might be involved in oncogenesis and other gastrointestinal disorders. Although the link between the Epstein-Barr virus (EBV) and gastric cancer (GC) has been established, the role of the viruses in various stomach diseases remains unknown. The frequencies and viral copy number of EBV, cytomegalovirus (CMV), and human herpesvirus 6 (HHV-6) among 50 gastric cancer tumors and 105 chronic gastritis tissues were measured by quantitative real-time PCR. In the tumor specimens and the adjacent normal tissues EBV was found in 60% and 30.9%, CMV in 14% and 4.7%, and HHV-6 in 18%, and 14.2%, respectively. The detection rate of EBV and CMV was found to be significantly higher in tumor tissues relative to the adjacent normal tissues. Also, in chronic gastritis, the frequency of EBV, CMV, and HHV-6 was 19%, 12.3%, and 15.2%, respectively, compared with 16.4%, 1.1%, and 8.2% in their corresponding normal tissues. Here, the CMV frequency was found to be significantly higher in gastritis tissues relative to the adjacent normal tissues. Furthermore, viral load in both gastric cancer and gastritis groups was higher in either tumor or gastritis lesion compared with matched adjacent normal tissue. This study showed a clear association between gastric cancer with both EBV and CMV. Meanwhile, analyses revealed a strong association between the EBV, CMV, and HHV-6 viral loads with gastritis (P = 0.0026, P < 0.0001, and P = 0.0405, respectively). Our results suggest that these three viruses might contribute to the induction and development the gastritis and gastric cancer., (© 2022 The Societies and John Wiley & Sons Australia, Ltd.)

Coronavirus disease 2019 (COVID19), caused by the severe acute respiratory syndrome coronavirus 2 (SARSCoV2), was first discovered in China in late 2019 and quickly spread worldwide. Although nasopharyngeal swab sampling is still the most popular approach identify SARS-CoV-2 carriers, other body samples may reveal the virus genome, indicating the potential for virus transmission via non-respiratory samples. In this study, researchers looked at the presence and degree of SARS-CoV-2 genome in stool and plasma samples from 191 Iranian COVID-19 patients, and looked for a link between these results and the severity of their disease. SARS-CoV-2 RNA shedding in feces and plasma of COVID-19 patients was assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Medical data were collected and evaluated, including Clinical features, demographics, radiological, and laboratory findings of the patients. Plasma samples from 117 confirmed laboratory patients were evaluated and 24 out of 117 patients (20.51%) tested positive for SARS-COV-2 RNA. Besides, 20 out of 74 patients (27.03%) tested positive for SARS-COV-2 RNA in stool samples. There seems to be no relationship between the presence of SARS-CoV-2 genome in fecal and plasma samples of Covid-19 patients and the severity of illness. We provide evidence of the SARS-CoV-2 genome presence in stool and plasma samples of Iranian COVID-19 patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Makhmalbaf, Hosseini, Aghdaei, Niasar, Shoraka, Yadegar, Baradaran Ghavami, Shahrokh, Moshari, Malekpour, Zali and Mohebbi.)

Background: Colorectal cancer (CRC) is one of the most common malignancies in the world and has a high mortality rate. It is believed that dysfunction in the expression of mucins and aberrant expression of some lncRNAs are associated with the occurrence and development of CRC. Therefore, the aim of the present study was to investigate the expression of MUC15, MUC16, MUC20, PCAT1, CCAT1 and HOTAIR genes in colorectal cancer and its relationship with clinicopathological variables., Materials and Methods: This research was prospective case-control study. Tumors from CRC patients were collected from the Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran. RNA extraction and cDNA synthesis were performed using the corresponding kits. The gene primer was designed and RT-PCR was used to evaluate gene expression. The t-test and ANOVA were employed to examine the differences between groups. Data analysis was performed using Prism8 software., Results: The results of the present study showed that the expression of MUC15 (P = 0.0012), MUC20 (P = 0.009) and CCAT1 (P = 0.001) genes in patients with colorectal cancer were significantly different from tumor margin samples. There were also associations between the expression of the studied genes and clinicopathological variables such as grade and stage of colorectal cancer tumor as well as the age of the patients. The area under the curves (AUC) for the MUC15 0.953 (95% CI 7565-0.9897, P = 0.0003), MUC20 0.782 (95% CI 0.6163-0.9482, P = 0.008) and CCAT1 0.917 (95% CI 0.8015-1, P = 0.0003) were calculated by ROC analysis., Conclusion: The current experiment revealed changes in expression level of mucin genes and lncRNAs in CRC and its different stages, showing that they can be considered as biomarkers for diagnosis of this cancer., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Long non-coding RNAs have been proposed as biomarkers for the detection, prevention and screening of various malignancies. In this study, two lncRNAs (ANRIL and BANCR) were assessed for biomarker application in the early detection of colorectal cancer (CRC) through stool specimen testing, as a non-invasive and cost-effective methodology. A total of 40 stool samples were collected from patients referred to the hospital with colorectal cancer or adenomatous polyps as pre-cancerous lesions; patients were diagnosed using colonoscopy and pathology reports were available. Twenty control samples were also obtained from healthy subjects for comparison. RNA extraction and cDNA synthesis were followed by real-time PCR to evaluate lncRNA expression. The up-regulation of ANRIL in 20% of samples taken from polyp patients, combined with up-regulation in 65% of patients with CRC, confirmed the potential usefulness of ANRIL as a prognostic biomarker (AUC 0.95; P < 0.0001). BANCR relative expression analysis illustrated significant up-regulation in polyp (P < 0.04) and tumoural participants (P < 0.03) compared with normal control individuals. The expression patterns of ANRIL and BANCR in polyp cases were significantly correlated according to correlation analysis (r = 0.45, P < 0.045). ANRIL expression patterns in stool specimens of polyp and tumour cases supported the use of ANRIL as a prognostic biomarker for screening patients in the early stages of CRC. Up-regulation of BANCR in pre-cancerous lesions as well as down-regulation of ANRIL may also be a specific marker pair for easy, convenient and fast CRC prognosis.

Background and Objective: Non-invasive body contouring devices have fewer side effects and are the new techniques for the treatment of obesity. The present study aimed to evaluate the effects of microwave technology on the abdominal obesity and anthropometric indices of overweight adults., Materials and Methods: This clinical trial was conducted on 53 overweight adults aged 18-65 years who referred to Behbood Clinic in Tehran, Iran. The participants were exposed to microwave technology (radiofrequency: 2.5 GHz) based on a standard treatment protocol at three intervals (0, 20, and 40 days). Abdominal obesity, body mass index, waist-to-hip ratio, body fat mass, and fat thickness were measured at the beginning and 20, 40, and 60 days after the study. In addition, three-day dietary records were collected at intervals., Results: In total, 77.6% of the subjects were female and 22.4% were male. The mean calorie intake of the participants was 2245.14 ± 1981.16 kcal/day. Microwave shock significantly reduced fat thickness in four abdominal areas (p < 0.001). Moreover, waist circumference (p < 0.001) and total fat thickness of the abdomen decreased (p = 0.003 and p = 0.002, respectively)., Conclusion: According to the results, microwave technology and radiofrequency could effectively reduce anthropometric indices. In general, the reduction of these indicators and weight may be more significant in men compared to women., (© 2021 Wiley Periodicals LLC.)

Helicobacter pylori as a class I carcinogen is correlated with a variety of severe gastroduodenal diseases; therefore, H. pylori eradication has become a priority to prevent gastric carcinogenesis. However, due to the emergence and spread of multidrug and single drug resistance mechanisms in H. pylori , as well as serious side effects of currently used antibiotic interventions, achieving successful H. pylori eradication has become exceedingly difficult. Recent studies expressed the intention of seeking novel strategies to improve H. pylori management and reduce the risk of H. pylori -associated intestinal and extragastrointestinal disorders. For which, vitamin supplementation has been demonstrated in many studies to have a tight interaction with H. pylori infection, either directly through the regulation of the host inflammatory pathways or indirectly by promoting the host immune response. On the other hand, H. pylori infection is reported to result in micronutrient malabsorption or deficiency. Furthermore, serum levels of particular micronutrients, especially vitamin D, are inversely correlated to the risk of H. pylori infection and eradication failure. Accordingly, vitamin supplementation might increase the efficiency of H. pylori eradication and reduce the risk of drug-related adverse effects. Therefore, this review aims at highlighting the regulatory role of micronutrients in H. pylori -induced host immune response and their potential capacity, as intrinsic antioxidants, for reducing oxidative stress and inflammation. We also discuss the uncovered mechanisms underlying the molecular and serological interactions between micronutrients and H. pylori infection to present a perspective for innovative in vitro investigations, as well as novel clinical implications., Competing Interests: None declared., (Copyright © 2022 Ali Nabavi-Rad et al.)

Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and has the second highest mortality rate globally. Thanks to the advent of next-generation sequencing technologies, several novel candidate genes have been proposed for CRC susceptibility. Germline biallelic mutations in one or more of the 22 currently recognized Fanconi anemia (FA) genes have been associated with Fanconi anemia disease, while germline monoallelic mutations, somatic mutations, or the promoter hypermethylation of some FANC genes increases the risk of cancer development, including CRC. The FA pathway is a substantial part of the DNA damage response system that participates in the repair of DNA inter-strand crosslinks through homologous recombination (HR) and protects genome stability via replication fork stabilization, respectively. Recent studies revealed associations between FA gene/protein tumor expression levels (i.e., FANC genes) and CRC progression and drug resistance. Moreover, the FA pathway represents a potential target in the CRC treatment. In fact, FANC gene characteristics may contribute to chemosensitize tumor cells to DNA crosslinking agents such as oxaliplatin and cisplatin besides exploiting the synthetic lethal approach for selective targeting of tumor cells. Hence, this review summarizes the current knowledge on the function of the FA pathway in DNA repair and genomic integrity with a focus on the FANC genes as potential predisposition factors to CRC. We then introduce recent literature that highlights the importance of FANC genes in CRC as promising prognostic and predictive biomarkers for disease management and treatment. Finally, we represent a brief overview of the current knowledge around the FANC genes as synthetic lethal therapeutic targets for precision cancer medicine.

Introduction: Primary sclerosing cholangitis (PSC) is a rare, chronic, and progressive cholestatic disease involving intra- and/or extrahepatic bile ducts. PSC in many patients results in end-stage liver diseases. Nearly 60% of the PSC patients suffer from concomitant inflammatory bowel diseases (IBDs). Classically, IBDs are divided into two principle types: Crohn's disease (CD) and ulcerative colitis (UC). However, with growing knowledge, PSC-associated IBD (PSC-IBD) seems to be a rather distinct entity with specific genetics, clinical, and microbiota characteristics., Areas Covered: In this article, we aim to review the unique characteristics of PSC-IBD from clinical, genetic, and microbiota point of view., Expert Opinion: PSC-IBD's unique characteristics contribute to the notion that it could be a distinct entity. Acknowledgment of PSC-IBD as a novel entity necessitates designing new clinical guidelines for diagnosis and developing novel therapies.

Different molecular signaling pathways have been involved in the incidence and progression of CRC. We aimed to examine the correlation between eight candidate genes, including TFGβ, SMAD2, SMAD4, RhoA, EGFR, MAP2K1, MTA1, and LEF1 in the progression of colorectal cancer (CRC) and their association with clinicopathological variables and CRC patients prognosis. Immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) analysis 2 -ΔΔct , were performed to assess the expression of eight genes in 64 and 122 patients with CRC, respectively and 20 normal samples were added for verification. We showed a positive correlation between SMAD2 and MAP2K1 (r = 0.337, P < 0.001), MAP2K1 and LEF1 (r = 0.187, P = 0.03), SMAD4 and RhoA (r = 0.214, P = 0.01) and as well, a negative correlation between SMAD2 and TGFβ (r =  - 0.197, P = 0.02), and RhoA and LEF1 (r =  - 0.180, P = 0.04) in tumor tissues. A decrease in RhoA mRNA expression was associated with the advanced TNM stage (P = 0.01), while the EGFR and SMAD2 mRNA expression upregulated in advanced stages (P = 0.03, P = 0.03), respectively. Also, an increase in EGFR and SMAD4 protein expression was significantly associated with the advanced TNM stage (P = 0.000) (P = .002), respectively. Perceiving the connections between canonical and non-canonical Transforming growth factor (TGF-β) signaling pathway along with the epidermal growth factor receptor (EGFR) and WNT cascades may trigger the development of novel approaches for CRC prediction., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The aim, as proof of concept, was to optimize niosomal formulations of tamoxifen in terms of size, morphology, encapsulation efficiency, and release kinetics for further treatment of the breast cancer (BC). Different assays were carried out to evaluate the pro-apoptotic and cytotoxicity impact of tamoxifen-loaded niosomes in two BC cells, MDA-MB-231 and SKBR3. In this study, tamoxifen was loaded in niosomes after optimization in the formulation. The formulation of niosomes supported maximized drug entrapment and minimized their size. The novel formulation showed improvement in storage stability, and after 60 days only, small changes in size, polydispersity index, and drug entrapment were observed. Besides, a pH-dependent release pattern of formulated niosomes displayed slow release at physiological pH (7.4) and a considerable increase of release at acidic pH (5.4), making them a promising candidate for drug delivery in the BC treatment. The cytotoxicity study exhibited high biocompatibility with MCF10A healthy cells, while remarkable inhibitory effects were observed after treatment of cancerous lines, MDA-MB-231, and SKBR3 cells. The IC50 values for the tamoxifen-loaded niosomes were significantly less than other groups. Moreover, treatment with drug-loaded niosomes significantly changed the gene expression pattern of BC cells. Statistically significant down-regulation of cyclin D, cyclin E, VEGFR-1, MMP-2, and MMP-9 genes and up-regulation of caspase-3 and caspase-9 were observed. These results were in correlation with cell cycle arrest, lessoned migration capacity, and increased caspase activity and apoptosis induction in cancerous cells. Optimization in the formulation of tamoxifen-loaded niosomes can make them a novel candidate for drug delivery in BC treatment., (© 2022. The Author(s), under exclusive licence to American Association of Pharmaceutical Scientists.)

Background: Colorectal cancer (CRC) and inflammatory bowel disease (IBD) are closely interrelated. However, the effect of having a family history of one disease on the risk of another remains undetermined., Aim: The purpose of this meta-analysis was to estimate the prevalence of a family history of CRC among patients with IBD, as well as the prevalence of a family history of IBD among patients with CRC., Methods: PubMed, Scopus, Embase, Web of Science, and Google Scholar were searched to identify studies reporting the prevalence of family history of IBD among patients with CRC, in addition to the prevalence of family history of CRC among IBD patients. Criteria for study inclusion consisted of the following: (1) studies that evaluated either IBD or CRC and dysplasia, (2) included all age groups, and (3) evaluated the family history effects for IBD or CRC. The total number of IBD patients and IBD patients with a family history of CRC and the total number of CRC patients and CRC patients with a family history of IBD were reviewed. The pooled prevalence of diseases was also estimated according to degree of relatives and geographical area. Random-effects models were used for estimating pooled prevalence., Results: A total of 27 studies were included with 26,576 IBD and 9,181 CRC or dysplasia patients. Eligible studies included 13 case-control, 10 cohort, and 4 cross-sectional types. The pooled prevalence of a family history of CRC among patients with IBD was 6% (95% CI: 4-9%). The pooled prevalence for first- and second-degree relatives (11%, 95% CI: 0-37%) was more than that for the other relative subgroups of relatedness degree. The prevalence in the American regions (8% (95% CI: 5-13%)) was higher than that in the others. The pooled prevalence for a family history of IBD among CRC or dysplasia patients was 11% (95% CI: 6-16%). The pooled prevalence for first-degree relatives (13% (95% CI: 3-28%) was higher than that for the other relative subgroups of relatedness degree; it was also greater in American countries (15%, 95% CI: 8-23%)., Conclusion: This study emphasizes the relationship between a family history of IBD and CRC development. Additionally, there was notable prevalence for a family history of CRC among IBD patients. American countries and first-degree relatives were identified to have a higher prevalence for both disease processes., Competing Interests: All authors have no potential conflict of interest relevant to this article., (Copyright © 2021 Hadis Najafimehr et al.)

Inflammatory bowel disease is a chronic, relapsing-remitting gastrointestinal disorder which has become a serious global concern, and it imposes a great degree of health and economic burdens on communities worldwide. Although the presence of non-Helicobacter pylori Helicobacter (NHPH) microorganisms has been reported in various gastrointestinal disorders, their putative role in the pathogenesis of IBD has been a matter of controversy. The present study aimed to investigate the existence of gastric and enterohepatic NHPHs and their probable coinfection with H. pylori in IBD. Totally, 168 clinical specimens including 70 colonic biopsies and 98 fecal specimens were obtained from IBD patients. Genomic DNA was extracted from all samples, and its quality and concentration were assessed by β-globin PCR and spectrophotometry. The Helicobacter genus-specific PCR was performed using 16S rRNA gene. All samples were also tested for H. pylori infection by PCR of ureC gene fragment (glmM). The presence of NHPH was examined by using species-specific PCR assays. Based on PCR results, H. pylori was detected in 12.9% and 3.1% of colonic biopsies and fecal specimens, respectively. However, no statistically significant correlation was observed (P value > 0.05). We failed to find NHPH in both colonic biopsies and fecal specimens from IBD patients. Despite the fact that none of the IBD patients harbored the NHPH in the current work, further cohorts with larger sample size are required to determine the possible relationship between NHPH infection and IBD pathogenesis., (© 2021. Institute of Microbiology, Academy of Sciences of the Czech Republic, v.v.i.)

Recently, adaptive NK cell therapy has become a promising treatment but has limited efficacy as a monotherapy. The identification of immune checkpoint inhibitor (ICI) molecules has opened a new horizon of immunotherapy. Herein, we aimed to demonstrate the cytotoxic effects of a polytherapy consisting of ex vivo expanded IL-2-activated NK cells combined with human anti-PD-1 antibody as an important checkpoint molecule in a xenograft gastric cancer mouse model. EBV-LCL cell is used as a feeder to promote NK cell proliferation with a purity of 93.4%. Mice (NOG, female, 6-8 weeks old) with xenograft gastric tumors were treated with PBS, ex vivo IL-2-activated NK cells, IL-2-activated NK cell along with human anti-PD-1 (Nivolumab), and IL-2-activated pretreated NK cells with anti-PD-1 antibody. The cytotoxicity of ex vivo expanded NK cells against MKN-45 cells was assessed by a lactate dehydrogenase (LDH) assay. Tumor volume was evaluated for morphometric properties, and tumor-infiltrating NK cells were assessed by immunohistochemistry (IHC) and quantified by flow cytometry. Pathologic responses were considered by H and E staining. Ex vivo LDH evaluation showed the cytotoxic potential of treated NK cells against gastric cancer cell line. We indicated that the adoptive transfer of ex vivo IL-2-activated NK cells combined with anti-PD-1 resulted in tumor growth inhibition in a xenograft gastric cancer model. Mitotic count was significantly decreased (* p < 0.05), and the tumor was associated with improved infiltration of NK cells in the NK-anti-PD-1 pretreated group (* p < 0.05). In conclusion, the combination approach of activated NK cells and anti-PD-1 therapy results in tumor growth inhibition, accompanied by tumor immune cell infiltration in the gastric tumor model., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Abdolahi, Ghazvinian, Muhammadnejad, Ahmadvand, Aghdaei, Ebrahimi-Barough, Ai, Zali, Verdi and Baghaei.)

Background: Regarding the controversial role of Blastocystis in inflammatory bowel diseases (IBD) patients, it seems that this protozoan may lead to an overgrowth of some non-beneficial bacteria. The current study aimed to investigate the co-existence of Blastocystis and Clostridioides difficile in IBD patients., Methods: Stool samples of 102 IBD patients were collected and cultivated for C. difficile and Blastocystis. DNA extraction was performed on positive samples and C. difficile and Blastocystis were toxinotyped and subtyped, respectively. Fisher's exact test and logistic regression were employed to calculate the correlation between the existence of Blastocystis and its subtypes (ST) with C. difficile and its type of toxins. Also, the co-existence of Blastocystis and C. difficile with the frequency of defecations was evaluated., Results: Blastocystis and C. difficile were observed in 17 (16.7%) and 26 (25.5%) of stool samples, respectively. From 26 C. difficilepositive isolates, 24 (92.3%) and 2 (7.7%) were tcdA+/B+ and tcdA+/B-, respectively. Also, 10 (58.8%) and 7 (41.2%) were Blastocystis ST1 and ST3, respectively. Statistically significant correlations between co-existence of Blastocystis and C. difficile and co-existence of these microorganisms and frequency of defecation (P < .035) were seen. There was no statistically significant correlation between subtypes of Blastocystis and colonization of C. difficile or its toxinotypes., Conclusion: The co-existence of Blastocystis and C. difficile in IBD patients was observed in the current study. Moreover, it can be proposed that these microorganisms may have synergistic effects on their colonization in the gastrointestinal tract.

Background: The projection studies are imperative to satisfy demands for health care systems and proper response to the public health problems such as inflammatory bowel disease (IBD)., Methods: To accomplish this, we established an illness-death model based on available data to project the future prevalence of IBD in Asia, Iran in particular, separately from 2017 to 2035. We applied two deterministic and stochastic approaches., Results: In 2035, as compared to 2020, we expected a 2.5-fold rise in prevalence for Iran with 69 thousand cases, a 2.3-fold increment for North Africa and the Middle East with 220 thousand cases, quadrupling of the prevalence for India with 2.2 million cases, a 1.5-fold increase for East Asia region with 4.5 million cases, and a 1.6-fold elevation in prevalence for high-income Asia-Pacific and Southeast Asia regions with 183 and 199 thousand cases respectively., Conclusions: Our results showed an emerging epidemic for the prevalence of IBD in Asia regions and/or countries. Hence, we suggest the need for immediate action to control this increasing trend in Asia and Iran. However, we were virtually unable to use information about age groups, gender, and other factors influencing the evolution of IBD in our model due to lack of access to reliable data.

Aim: We aimed to describe the epidemiological and clinical characteristics of Iranian patients with COVID-19., Methods: In this single-center and retrospective study, patients with confirmed COVID-19 infections were enrolled. Univariate and multivariate logistic regression methods were used to explore the risk factors associated with outcomes., Results: Of 179 patients with confirmed COVID-19 infection, 12 remained hospitalized at the end of the study and 167 were included in the final analysis. Of these, 153 (91.6%) were discharged and 14 (8.38%) died in hospital. Approximately half (50.9%) of patients suffered from a comorbidity, with diabetes or coronary heart disease being the most common in 20 patients. The most common symptoms on admission were fever, dyspnea, and cough. The mean durations from first symptoms to hospital admission was 8.64 ± 4.14 days, whereas the mean hospitalization time to discharge or death was 5.19 ± 2.42 and 4.35 ± 2.70 days, respectively. There was a significantly higher age in non-survivor patients compared with survivor patients. Multivariate regression showed increasing odds ratio (OR) of in-hospital death associated with respiratory rates >20 breaths/min (OR: 5.14, 95% CI: 1.19-22.15, p = 0.028) and blood urea nitrogen (BUN) >19 mg/dL (OR: 4.54, 95% CI: 1.30-15.85, p = 0.017) on admission. In addition, higher respiratory rate was associated with continuous fever (OR: 4.08, 95% CI: 1.18-14.08, p = 0.026) and other clinical symptoms (OR: 3.52, 95% CI: 1.05-11.87, p = 0.04)., Conclusion: The potential risk factors including high respiratory rate and BUN levels could help to identify COVID-19 patients with poor prognosis at an early stage in the Iranian population.

Clostridioides difficile infection (CDI) remains a major healthcare problem worldwide, however, little is known about CDI epidemiology in Iran. Between December 2004 and November 2018, 3649 stool samples were collected from patients in 69 hospitals and medical centres in Tehran and were cultured for the presence of C. difficile ; isolates were characterized by PCR ribotyping and toxin genes detection. A total of 582 C. difficile isolates were obtained and the overall CDI prevalence was 15.9%; 290 (49.8%) cases were healthcare-associated (HA) and 292 (50.2%) cases were community-associated (CA). Of these, DNA of 513 isolates submitted for ribotyping. The ribotype and/or WEBRIBO type could be assessed in 366 (62.9%) isolates. The most frequent RTs were 001 ( n  = 75, 12.9%), 126 ( n  = 65, 11.2%) and 084 ( n  = 19, 3.3%); the toxin gene profile tcdA + B isolates (2.6%) did not carry any toxin genes. There was no difference between frequently found RTs in HA-CDI and CA-CDI, except for RT 029 which was more likely to be associated with healthcare origin (12/15, + /cdtA + B + ( n  = 112, 19.2%) was the most common. Fifteen C. difficile isolates (2.6%) did not carry any toxin genes. There was no difference between frequently found RTs in HA-CDI and CA-CDI, except for RT 029 which was more likely to be associated with healthcare origin (12/15, p -value = 0.02). No isolate of RTs 027 or 078 was identified. Importantly, RTs 031, 038, 039, 084, 085 reported previously as RTs with an absence of toxin genes, revealed the presence of toxin genes in our study. Using Simpson's reciprocal index of diversity, we found that RT diversity decreased as the prevalence of the RT 084 increased ( R  = -0.78, p -value = 0.041). Different patterns in CDI epidemiology underscore the importance of local surveillance and infection control measures in Tehran healthcare settings.

Abnormal activation of Toll-like receptor (TLRs) signaling can result in colon cancer development. The aim of this study was to investigate the expression of important TLRs in different histological types of colorectal polyps and evaluate their relationship with intestinal microbiota. The expression levels of TLR2, 3, 4, and 5 were analyzed in intestinal biopsy specimens of 21 hyperplastic polyp (HP), 16 sessile serrated adenoma (SSA), 29 tubular adenoma (TA), 21 villous/tubulovillous (VP/TVP) cases, and 31 normal controls. In addition, selected gut bacteria including Streptococcus bovis , Enterococcus faecalis , Enterotoxigenic Bacteroides fragilis (ETBF), Fusobacterium nucleatum , Porphyromonas spp., Lactobacillus spp., Roseburia spp., and Bifidobacterium spp. were quantified in fecal samples using absolute qRT PCR, and, finally, the association between TLRs and these gut microbiota- was evaluated by Spearman's correlation coefficient. Higher expression of TLR2 and TLR4 in VP/TVP and TA, and lower expression levels of TLR3 and TLR5 in all type of polyps were observed. The differences in TLR expression patterns was not only dependent on the histology, location, size, and dysplasia grade of polyps but also related to the intestinal microbiota patterns. TLR2 and TLR4 expression was directly associated with the F. nucleatum, E. faecalis , S. bovis , Porphyromonas , and inversely to Bifidobacterium , Lactobacillus , and Roseburia quantity. Furthermore, TLR3 and TLR5 expression was directly associated with Bifidobacterium , Roseburia , and Lactobacillus quantity. Our results suggest a possible critical role of TLRs during colorectal polyp progression. An abnormal regulation of TLRs in relation to gut microbial quantity may contribute to carcinogenesis.

Considering the global increase in the prevalence of hepatic fibrosis and ineffective disease treatment, novel therapies are urgently needed. The current study is focused on comparing the therapeutic effects of mesenchymal stem cells (MSC)/imatinib combination therapy to single (MSCs or imatinib) therapy, in a rat model of carbon tetrachloride (CCL4)-induced liver fibrosis. Using rats, hepatic fibrosis was induced by injection of CCL4. Rats were divided into 5 groups: CCL4-induced hepatic fibrosis, phosphate buffered saline (PBS) treatment (vehicle control), Bone marrow-MSCs (BM&#95;MSCs), imatinib, and bone marrow-MSCs/imatinib co-treatment. The therapeutic impact of these approaches was determined using histopathology, sirius-red staining, serum markers, and qRT-PCR for over expression of matrix components. IHC and Western blot were conducted for further confirmation of the results. Single treatment with MSCs or imatinib and the combination therapy, all significantly reduced serum levels of ALT, AST, and ALP concomitant with down-regulation of α-SMA, pro-collagen I, pro-collagen III, collagen IV, and laminin. A significant reduction of ECM components deposits and a decrease in α-SMA expression were detected in all treatment groups. Pathological observations demonstrated that 20% and 40% of the rats in the MSC and MSC/imatinib group were in grade F0 respectively, while 80% of the rats of the imatinib group were in grade 2. Even though all treatment strategies studied resulted in an equally potent reduction in the mRNA and protein expression levels of pro-fibrotic markers, in aspect of pathological observations, our results demonstrate the highest therapeutic potential of utilizing combination of BM-MSCs and imatinib., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In inflammatory bowel diseases (IBD), the therapeutic benefit and mucosal healing from specific probiotics may relate to the modulation of dendritic cells (DCs). Herein, we assessed the immunomodulatory effects of four probiotic strains including Lactobacillus salivarius , Bifidobacterium bifidum , Bacillus coagulans and Bacillus subtilis natto on the expression of co-stimulatory molecules, cytokine production and gene expression of signal-transducing receptors in DCs from IBD patients. Human monocyte-derived DCs from IBD patients and healthy controls were exposed to four probiotic strains. The expression of co-stimulatory molecules was assessed and supernatants were analyzed for anti-inflammatory cytokines. The gene expression of toll-like receptors (TLRs), IL-12p40 and integrin αvβ8 were also analyzed. CD80 and CD86 were induced by most probiotic strains in ulcerative colitis (UC) patients whereas only B. bifidum induced CD80 and CD86 expression in Crohn's disease (CD) patients. IL-10 and TGF-β production was increased in a dose-independent manner while TLR expression was decreased by all probiotic bacteria except B. bifidum in DCs from UC patients. TLR-4 and TLR-9 expression was significantly downregulated while integrin ß8 was significantly increased in the DCs from CD patients. IL-12p40 expression was only significantly downregulated in DCs from CD patients. Our findings point to the general beneficial effects of probiotics in DC immunomodulation and indicate that probiotic bacteria favorably modulate the expression of co-stimulatory molecules, proinflammatory cytokines and TLRs in DCs from IBD patients.

Background: Patients with inflammatory bowel disease (IBD) are at greater risk for Clostridioides difficile infection (CDI). There remain controversial issues about the association of infliximab therapy in IBD patients and CDI., Objective: The present work aimed to investigate the potential association between infliximab therapy and the risk of CDI in a group of Iranian patients with IBD., Patients and Methods: A total of 140 IBD patients were enrolled, their fresh stool specimens were obtained and used for C. difficile detection. The presence of toxin-encoding genes of C. difficile isolates were examined by PCR. Demographic data, frequency of defecation, antibiotic usage, and IBD therapy were recorded., Results: About half of the IBD patients had a history of antibiotic usage, mostly metronidazole (11.4 %) alone, and metronidazole + ciprofloxacin (16.4 %) as drug combination. C. difficile was isolated from 17.1 % (24/140) of the IBD patients, and more than 90 % of the isolates were found to be toxigenic having genotypes of tcdA + /tcdB + (18/22, 81.8 %), tcdA + /tcdB - (3/22, 13.6 %) and tcdA - /tcdB + (1/22, 4.5 %). Interestingly, we only found a significant relationship between the emergence of CDI and the use of infliximab in combinations with other drugs (P = 0.023)., Conclusions: In conclusion, there was a considerable incidence of CDI in Iranian patients with IBD. Our study also demonstrated that anti-TNF containing regimens in combinations with other immunosuppressive medications potentially may influence susceptibility to CDI in a group of patients with underlying IBD. Furthermore, our findings recommend avoiding the prolonged use of infliximab along with other corticosteroids or immunomodulators. Further validation studies are needed to better understand the mechanisms that regulate TNF-mediated pathways in CDI pathogenesis among IBD patients., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Aim: The prognostic and predictive value of Elevated Microsatellite Alterations at Selected Tetranucleotide (EMAST) has been reported in colorectal cancer (CRC). The prevalence of EMAST in CRC varied across the literature. We conducted a meta-analysis to determine the prevalence of EMAST in CRC. Materials & methods: Three international databases including PubMed, ISI and Scopus were searched to identify related articles that described the frequency of EMAST. Results: Analysis was performed on 16 eligible studies including 4922 patients. The overall EMAST prevalence among CRCs patients was 33% (95% CI: 23-43%, I 2  = 98%). Conclusion: This study indicated that approximately a third of the CRC patients are diagnosed with EMAST, hereupon EMAST as a prognostic and predictive biomarker should be more studied clinically.

To date, there is no licensed treatment or approved vaccine to combat the coronavirus disease of 2019 (COVID-19), and the number of new cases and mortality multiplies every day. Therefore, it is essential to develop an effective treatment strategy to control the virus spread and prevent the disease. Here, we summarized the therapeutic approaches that are used to treat this infection. Although it seems that antiviral drugs are effective in improving clinical manifestation, there is no definite treatment protocol. Lymphocytopenia, excessive inflammation, and cytokine storm followed by acute respiratory distress syndrome are still unsolved issues causing the severity of this disease. Therefore, immune response modulation and inflammation management can be considered as an essential step. There is no doubt that more studies are required to clarify immunopathogenesis and immune response; however, new therapeutic approaches including mesenchymal stromal cell and immune cell therapy showed inspiring results.

Colorectal cancer (CRC) is a common intestinal cancer with a high mortality rate. Early detection of this type of cancer is fundamental to the prevention of the disease, which results in improved survival rates. In the human colon tissue, transition from normal epithelium to adenoma is considered to be caused by unknown molecular incidents occurring over 5-10 years. The detection of CRC has proved problematic when in the early stages of disease. In addition, identifying suitable biomarkers for the detection of CRC progress in patients remains one of the most significant challenges. Long non-coding RNAs have been demonstrated to contribute to the promotion of CRC. The aim of the present study was to investigate the clinical and biological significance of long intergenic non-coding (linc)RNA-p21, lincRNA-regulator of reprogramming (ROR) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in the colon tumor and polyp tissue, and the association that these have with the expression of p53 at the mRNA level. Neoplastic and paired adjacent normal tissue samples were obtained from 72 patients (46 polyps and 26 tumors). Reverse transcription-quantitative PCR was performed to determine the relative fold changes in the expression of lincRNA-p21, lincRNA-RoR, MALAT1 and p53 in the samples. A significant association was observed between the levels of MALAT1 and p53 in neoplasm tissues (R=0.073; P<0.05). The relative expression of the MALAT1 gene revealed a statistically significant difference between the different polyp types and number of polyps (P=0.0028 and 0.022, respectively). Adjuvant therapy in patients with tumors revealed an association between the levels of lincRNA-ROR and lincRNA-p21 expression (P=0.015 and 0.038, respectively). MALAT1 may be selected as an early detection biomarker for CRC. Furthermore, lincRNA-ROR and lincRNA-p21 may serve as prognostic and therapeutic biomarkers in patients with CRC., (Copyright: © Chaleshi et al.)

Pancreatic cancer (PC) is a malignancy with little/no warning signs before the disease reaches its ultimate stages. Currently early detection of PC is very difficult because most patients have non-specific symptoms leading to postponing the correct diagnosis. In this study, using multiple bioinformatics tools, we integrated various serum expression profiles of miRNAs to find the most significant miRNA signatures helpful in diagnosis of PC and constructed novel miRNA diagnosis models for PC. Altogether, 27 differentially expressed miRNAs (DEMs) showed area under curve (AUC) score >80%. The most promising miRNAs, miR-1469 and miR-4530, were individually able to distinguish two groups with the highest specificity and sensitivity. By using multivariate cox regression analyses, 5 diagnostic models consisting of different combinations of miRNAs, based on their significant expression algorithms and functional properties were introduced. The correlation model consisting of miR-125a-3p, miR-5100 and miR-642b-3p was the most promising model in the diagnosis of PC patients from healthy controls with an AUC of 0.95, Sensitivity 0.98 and Specificity 0.97. Validation analysis was conducted for considered miRNAs on a final cohort consist of the microarray data from two other datasets (GSE112264 & GSE124158) . These results provide some potential biomarkers for PC diagnosis after testing in large case-control and cohort studies.

Clostridioides difficile and Staphylococcus aureus are two well-known pathogens both causing hospital- and community-acquired infections. However, their intestinal coexistence was not well investigated in inflammatory bowel disease (IBD). Herein, we explored the prevalence of C. difficile, S. aureus and their coexistence in the gut of Iranian patients with IBD. Fecal and colon specimens were obtained from 70 outpatients with underlying IBD, and investigated for the presence of C. difficile and S. aureus. C. difficile isolates were characterised by CE-ribotyping. PCR was used for detection of toxin-encoding genes of C. difficile and S. aureus isolates. The antimicrobial susceptibility testing of C. difficile and S. aureus isolates were examined by agar dilution and Kirby-Bauer disk diffusion methods, respectively. Totally, C. difficile and S. aureus were detected in only 5.7% and 15.8% of IBD flares. Coexistence of C. difficile and S. aureus was detected in 5.7% of IBD flares. Two different C. difficile ribotypes including RT 126 and RT 017 were identified showing toxin profiles of tcdA + B + /cdtA + B + and tcdA + B + , respectively. In S. aureus isolates, only positivity for the presence of sea enterotoxin was detected. C. difficile isolates were susceptible to metronidazole, ceftazidime and fidaxomicin. The highest resistance of S. aureus isolates was observed against penicillin (92.3%), following amoxicillin-clavulanate (38.5%) and amikacin (30.8%). Our findings demonstrated that patients with IBD flare are more sensitive to acquire coinfection of C. difficile and S. aureus than remission. However, more robust data is required to study the crosstalk between these enteric infections and their clinical relevance in patients with IBD flare., Competing Interests: Declaration of competing interest The authors declare that they have no conflicts of interest., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Aim: rs2585428 and rs4809960 polymorphisms were significantly associated with overall cancer risk, but there is no evidence regarding the overall colorectal cancer (CRC) risk. Materials & methods: A total of 505 subjects, including 246 patients with CRC and 259 noncancer controls participated in the study. The genotyping was performed using tetra-primer amplification refractory mutation systems PCR. Results: Analysis of genotypes revealed that CYP24A1 rs4809960 CC genotype decreased the risk of CRC (p = 0.009). In addition, the genotype frequencies showed a significant difference under the dominant and recessive inheritance models (p = 0.019 and p = 0.02, respectively). Conclusion: Our findings indicate that the CYP24A1 rs4809960 polymorphism decreased the risk of CRC in the studied population.