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Background and Aim: Colorectal cancer (CRC) originates from pre-existing polyps in the colon. The development of different subtypes of CRC is influenced by various genetic and epigenetic characteristics. CpG island methylator phenotype (CIMP) is found in about 15-20% of sporadic CRCs and is associated with hypermethylation of certain gene promoters. This study aims to find prognostic genes and compare their expression and methylation status as potential biomarkers in patients with serrated sessile adenomas/polyps (SSAP) and CRC, in order to evaluate which, one is a better predictor of disease., Method: This study employed a multi-phase approach to investigate genes associated with CRC and SSAP. Initially, two gene expression datasets were analyzed using R and Limma package to identify differentially expressed genes (DEGs). Venn diagram analysis further refined the selection, revealing four genes from the Weissenberg panel with significant changes. These genes, underwent thorough in silico evaluations. Once confirmed, they proceeded to wet lab experimentation, focusing on expression and methylation status. This comprehensive methodology ensured a robust examination of the genes involved in CRC and SSAP., Result: This study identified cancer-specific genes, with 8,351 and 1,769 genes specifically down-regulated in SSAP and CRC tissues, respectively. The down-regulated genes were associated with cell adhesion, negative regulation of cell proliferation, and drug response. Four highly downregulated genes in the Weissenberg panel, including CACNA1G, IGF2, MLH1, and SOCS1. In vitro analysis showed that they are hypermethylated in both SSAP and CRC samples while their expressions decreased only in CRC samples., Conclusion: This suggests that the decrease in gene expression could help determine whether a polyp will become cancerous. Using both methylation status and gene expression status of genes in the Weissenberg panel in prognostic tests may lead to better prognoses for patients., (© 2024. The Author(s).)

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.)

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.)

Angiotensin-converting enzyme 2 (ACE2) acts as a key receptor for the spike of SARS-CoV-2. Two main microRNAs (miRs), miR-200c-3p and miR-421-5p, are considered to modulate the expression of ACE2 gene and alterations in the expression of these miRNAs may influence the outcomes of COVID-19 infection. Accordingly, we examined whether miRNAs directing ACE2 expression altered in the SARS-CoV-2 infection. 30 patients with COVID-19 included in the study. At the time of admission and discharge, the expression of miR-200c-3p and miR-421-5p, inflammatory cytokine IL-6, and regulatory T cells' expression profiles (CD4, CD25, and Foxp3) were examined using quantitative real-time PCR method. At the time of admission, the expression levels of miR-200c-3p and miR-421-5p as well as CD4, CD25, and Foxp3 significantly decreased while IL-6 expression notably enhanced. However, by the time of discharge, the expression levels of the genes were opposite to the time of admission. Moreover, Pearson correlation analysis indicated that IL-6 expression negatively correlated with Foxp3 and miR-200c-3p expressions despite miR-421-5p and miR-200c-3p positively correlated at admission time. By manipulating miR-200c-3p and miR-421-5p expressions and controlling the ACE2 level, it is plausible to modulate the inflammation by reducing IL-6 and maintenance tolerance hemostasis during COVID-19 infection., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Colorectal cancer (CRC) is one of the most common cancers in the world and has a high mortality rate. It is accepted that dysfunction in the expression of mucins are associated with the occurrence and development of CRC. Therefore, the present study aimed to investigate the expression of MUC2, MUC5A, and MUC5B genes in CRC and their relationship with clinicopathological variables., Materials and Methods: The population included 28 patients after a colonoscopy and confirmation of the results. Tumors and parallel adjacent normal tissues from CRC patients were collected. 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 used to examine the differences between the different groups. Data analysis was performed using Prism8 software. Tumors from CRC patients were retrospectively collected from Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran., Results: The results showed that the expression of MUC2, MUC5A, and MUC5B genes was lower in patients with CRC aged 50 years or younger than was in older patients (P<0.05). Only the MUC5B gene expression was associated with tumor grades, which was higher in poorly differentiated tumors. The expression of MUC5A and MUC2 genes was higher in stage IV of the tumor than in other stages (P<0.05). Conclusion: Among the changes in the expression of MUC secretory genes, including MUC2, MUC5A, and MUC5B and clinicopathological variables, there was a relationship that could have prognostic and diagnostic value in CRC., Conclusion: None., (Copyright© 2021, Galen Medical Journal.)

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.

Like other noncoding RNAs (ncRNAs), dysregulation of long ncRNAs (lncRNAs) has been associated with various clinicopathological features of colorectal cancer (CRC) patients such as lymph node metastasis (LNM). Recently, three aberrant expressed oncogenic lncRNA (onco-lncRNAs), including HOXA transcript at the distal tip (HOTTIP), plasmacytoma variant translocation 1 (PVT1), and urothelial carcinoma associated 1 (UCA1) have been reported in LNM. Herein, we compared the diagnostic performance of these lncRNAs as individual biomarkers and as a discriminating panel between LNM CRC patients, nonmetastatic lymph nodes (NLN) and normal healthy subjects. The lncRNAs expression level was measured by quantitative real-time PCR and analyzed by the Mann-Whitney U test. The receiver operating characteristic (ROC) curve analysis was applied to evaluate the diagnostic power. The Kaplan-Meier survival analysis was performed to outline the overall survival (OS) of CRC patients with an abnormal level of lncRNAs. The area under the ROC curve (AUC) of the overexpressed HOTTIP (0.7817; 95% CI, 0.6809-0.8824), PVT1 (0.8559; 95% CI, 0.7737-0.9382), and UCA1 (0.8135; 95% CI, 0.722-0.9051) introduced them as individual CRC biomarkers. As a predictive panel, the AUC values of the HOTTIP, PVT1, and UCA1 for training set were 0.9256 (95% CI, 0.8634-0.9879; all CRCs), 0.8708 (95% CI, 0.7709-0.9378; NLN) and 0.9804 (95% CI, 0.9585-0.9998; LNM), and for validation set were 0.9286 (95% CI, 0.8752-0.9820; all CRCs), 0.8911 (95% CI, 0.8238-0.9585; NLN), and 0.9833 (95% CI, 0.9642-1.002; LNM), respectively. Also, HOTTIP/PVT1/UCA1 panel dysregulation had a marked correlation with patient's OS in training set (logrank test P = 0.0121; hazard ratio [HR], 0.1225; 95% confidence interval [CI], 0.02376-0.6312), and in validation set (logrank test P < 0.0001, HR, 0.2003; 95% CI, 0.08942-0.4486). These data showed that the combination of HOTTIP, PVT1, and UCA1 as a predictive panel, has a better diagnostic performance than each of these lncRNAs individually, and could be used for the screening of patients with advanced CRC., (© 2019 Wiley Periodicals, Inc.)

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Genetic variations in cytokine genes and their receptors lead to the severity of the disease. The interleukin-1 receptor antagonist (IL1RN) is a cytokine that inhibits interleukin-1 (IL-1) activity by binding to IL-1 receptors. Also, interleukin-4 (IL-4) is an anti-inflammatory cytokine that can play an important role in several cancers. The present case-control study was aimed to evaluate the association of IL-4 and IL1RN VNTR polymorphisms with the susceptibility to CRC in a sample of Iranian population provided by the Research Center for Gastroenterology and Liver Disease at Taleghani Hospital, Tehran. A total of 123 patients diagnosed with CRC and 152 healthy controls were recruited in the present study. Genomic DNA was extracted by salting out method from whole blood and genotyping of IL1RN and IL-4 VNTR polymorphisms were determined by PCR-based technology. Our study manifested the frequency of 1/2 and 2/4 genotypes of IL1RN 68bp VNTR polymorphism are significantly different between both groups (p = 0.0001 and p = 0.01 respectively). However, we could not find any correlation between IL-4 VNTR polymorphism and CRC cancer. It seems that 1/2 and 2/4 genotypes of IL1RN are correlated with CRC susceptibility in our population, although, more studies are needed to confirm our results.

In Iran, both Plasmodium vivax and P. falciparum malaria have been detected, but P. vivax is the predominant species. Point mutations in dihydrofolate reductase (dhfr) gene in both Plasmodia are the major mechanisms of pyrimethamine resistance. From April 2007 to June 2009, a total of 134 blood samples in two endemic areas of southern Iran were collected from patients infected with P. vivax and P. falciparum. The isolates were analyzed for P. vivax dihydrofolate reductase (pvdhfr) and P. falciparum dihydrofolate reductase (pfdhfr) point mutations using various PCR-based methods. The majority of the isolates (72.9%) had wild type amino acids at five codons of pvdhfr. Amongst mutant isolates, the most common pvdhfr alleles were double mutant in 58 and 117 amino acids (58R-117N). Triple mutation in 57, 58, and 117 amino acids (57L/58R/117N) was identified for the first time in the pvdhfr gene of Iranian P. vivax isolates. All the P. falciparumsamples analyzed (n = 16) possessed a double mutant pfdhfrallele (59R/108N) and retained a wild-type mutation at position 51. This may be attributed to the fact that the falciparum malaria patients were treated using sulfadoxine-pyrimethamine (SP) in Iran. The presence of mutant haplotypes in P. vivax is worrying, but has not yet reached an alarming threshold regarding drugs such as SP. The results of this study reinforce the importance of performing a molecular surveillance by means of a continuous chemoresistance assessment.

Objective: The purpose of this study was to evaluate the potential association between single nucleotide polymorphisms (SNPs) in microRNA (miRNA) binding sites in the NOD2 and IL12B gene 3.-untranslated regions and colorectal cancer (CRC) susceptibility in an Iranian population., Methods: We genotyped NOD2 rs3135500 [3. untranslated region (UTR) A/G] and IL12B rs1368439 (3.UTR G /T) in a hospital-based study of 92 colorectal cancer cases and 105 healthy controls. All samples were genotyped by TaqMan assay via an ABI 7500 Real Time PCR System (Applied Biosystems) with DNA from FFPE tissue and peripheral blood., Results: our results showed similar distribution of genotype and allelic frequencies of the NOD2 and IL12B polymorphisms between patients and controls. When the more common rs3135500 AA genotype was used as the reference, the rs3135500 AG and rs3135500 GG genotypes were not significantly associated with the risk of CRC (OR = 1.294, 95% CI: 0.524 -3.197; and OR = 2.230, 95% CI: 0.87 - 5.715, respectively), and The IL12B rs1368439 TG and IL12B rs1368439 GG genotypes were not significantly associated with the risk of CRC compared with the IL12B rs1368439 TT genotype (OR = 1.547 95% CI: 0.187- 12.771; and OR = 1.753, 95% CI: 0.217-14.157, respectively)., Conclusion: NOD2 rs3135500 and IL12B rs1368439 SNPs were not genetic risk factors for colorectal cancer in the studied Iranian population.

Mitochondrial genes have more power than nuclear genes in reconstructing phylogenetic relationships among closely related species because of their faster sequence evolution. The aim of this study was to use the complete or near-complete sequences from three mitochondrial genes (cox1, nad1 and atp6) and partial sequences of the 12S rRNA gene to infer relationships among isolates of Echinococcus granulosus from Iran. Two hundred and twenty-nine isolates of E. granulosus were collected from cattle, camels, sheep, buffalo and goats from different geographical areas. Most individuals were found to possess the G1 genotype but some of the camel samples belonged to the G6 genotype. Newly designed primers for cox1, nad1 and atp6 genes amplified bands of 1830, 708 and 1157 bp for the G1 genotype and 1856, 705, 1054 bp for the G6 genotype, respectively. The result of this survey showed that atp6 and nad1 genes are good molecular markers for identifying E. granulosus isolates from a range of hosts in Iran.

Blastocystis is an unusual enteric protozoan parasite of humans and many animals whose pathogenic potential is still controversial. To increase the understanding of the molecular epidemiology of this emerging parasite and due to its potential impact on public health, its subtypes (STs) in Iranian symptomatic and asymptomatic individuals were determined. A total of 100 Blastocystis isolates by microscopy and culture methods were obtained. DNA was extracted from the positive culture isolates, and the Blastocystis subtypes were identified using seven subtype-specific sequenced-tagged site (STS) primers. Four subtypes, ST3 as dominant (53 %), followed by ST1 (48 %), ST5 (33 %), and ST2 (7 %) were identified. In this study, ST1 in gastrointestinal patients compared to asymptomatic individuals was significantly dominant (p = 0.001). From 33 (33 %) mixed subtype infections, ST1, 3 (14 %) was significantly related to GI symptoms (p = 0.045), and eight mixed infections with three different STs, which are under reported, were also identified.

Background: Geothermal waters could be suitable niches for thermophilic free living amoebae including Naegleria and Hartmannella. Ardebil Province, northwest Iran is popular for having many hot springs for recreational and health purposes activity. The present research is the first molecular based investigation regarding the presence of Naegleria and Hartmannella in the hot springs of Ardebil Province in Iran., Methods: Overall, 30 water samples were taken from waters of thermal hot springs in Ardebil Province, Iran during 2010-2011. All collected samples were transferred to Dept. of Parasitology and Mycology, Shahid Beheshti University of Medical Sciences, Tehran, Iran. Cultivation of concentrated water samples was performed using culture-enrichment method. Cloning of the target amoebae was obtained and morphological and molecular analysis was done using page key combined with two sets of primers, respectively. Sequence analysis and homology search was used for strains identification., Results: Of 30 water samples, 8 (26.7%) were positive for thermotolerant Vahlkampfiids and Hartmannella based on morphological characteristics of vegetative form and double walled cysts. Cloning of the target amoebae were done successfully. Sequencing of the positive isolates revealed that the strains belonged to Naegleria (N. carteri and N. spp) and H. vermiformis., Conclusion: The result highlights a need for improved filtration and disinfection and periodic monitoring of recreational thermal waters in order to prevent disease related to free- living amoebae. This is the first comprehensive molecular study of thermophilic Naegleria and Hartmannella in hot springs of Iran.