Effect of Pioglitazone and Cetuximab on Colon Cancer Stem-like Cell (CCSLCs) Properties.

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. METHOD: The viability and IC50 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-- to-epithelial 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.

Future Nanotechnology-Based Strategies for Improved Management of Helicobacter pylori Infection.

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.

The critical role of gut-brain axis microbiome in mental disorders.

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.

Whole exome sequencing identifies MAP3K1, MSH2, and MLH1 as potential cancer-predisposing genes in familial early-onset colorectal cancer.

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.

Factors associated with treatment failure, and possible applications of probiotic bacteria in the arsenal against Helicobacter pylori.

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).

Exosome-mediated miR-200a delivery into TGF-ß-treated AGS cells abolished epithelial-mesenchymal transition with normalization of ZEB1, vimentin and Snail1 expression.

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-ß 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-ß 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 ß-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.

The interaction between autophagy, Helicobacter pylori, and gut microbiota in gastric carcinogenesis.

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.

Exosomes for angiogenesis induction in ischemic disorders.

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.

Imatinib suppresses activation of hepatic stellate cells by targeting STAT3/IL-6 pathway through miR-124.

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 (CCl4 )-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.

New insights into extracellular and intracellular redox status in COVID-19 patients.

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/O2• - 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/O2• - 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.

Up regulation of long non-coding RNAs BACE1 and down regulation of LINC-PINT are associated with CRC clinicopathological characteristics.

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 (ß-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.

High Prevalence Rate of Microbial Contamination in Patient-Ready Gastrointestinal Endoscopes in Tehran, Iran: an Alarming Sign for the Occurrence of Severe Outbreaks.

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 ß-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.

Obesity, a challenge in the management of inflammatory bowel diseases.

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.

Elevated interleukin-17A levels despite reduced microRNA-326 gene expression in celiac disease patients under gluten-free diet.

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. Methods: Peripheral blood samples of 40 CD patients under GFD (for more than 1 year) and 40 healthy individuals were collected. RNA was extracted, cDNA was synthesized and the miR-326, ETS1 and IL-17A gene expressions were evaluated by the quantitative polymerase real-time qPCR method. P-value ˂ 0.05 was considered statistically significant. Results: Although miR-326 mRNA expression was significantly lower in CD patients (P = 0.001), no significant difference was observed in ETS1 mRNA level between the two groups (P = 0.54), but IL-17A was significantly overexpressed in CD patients (P=0.002). No significant correlation was observed between the expression of the studied genes and the patients' symptoms and Marsh classification. Conclusion:Adherence to the GFD for one to two years did not have the expected effect on the expression of genes in this panel. The most important finding that contradicted our hypothesis was the observation of high IL-17A levels in CD patients despite dieting, which may be related to the protective effect of this cytokine on intestinal tight junctions, which needs to be confirmed in further studies.

Detection of SARS-CoV-2 Genome in Stool and Plasma Samples of Laboratory Confirmed Iranian COVID-19 Patients.

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.

DNA methylation biomarkers in colorectal cancer: Clinical applications for precision medicine.

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.

Detection and quantification of Epstein-Barr virus, cytomegalovirus, and human herpesvirus-6 in stomach frozen tissue of chronic gastritis and gastric cancer patients.

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.

The association of clinicopathological characterizations of colorectal cancer with membrane-bound mucins genes and LncRNAs.

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.

Fanconi Anemia Pathway in Colorectal Cancer: A Novel Opportunity for Diagnosis, Prognosis and Therapy.

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.