Evaluating CD4 and Foxp3 mRNA Expression in Tissue Specimens of Celiac Disease and Colorectal Cancer Patients.

OBJECTIVE: Celiac disease (CD) and colorectal cancer (CRC) are distinct gastrointestinal conditions with a debated association. This study aimed to evaluate the mRNA expression of CD4 and Foxp3 in tissue specimens of CD and CRC patients. The findings can provide valuable insights into the complex connection between these different gastrointestinal conditions. METHODS: Tissue samples from 100 CRC patients, 50 CD patients, and 50 healthy controls (HCs) were collected. RNA extraction, cDNA synthesis, and quantitative real-time PCR were performed. Statistical analysis was conducted using ANOVA and Pearson's correlation test. RESULT: CD4 mRNA expression was significantly higher in CRC patients compared to CD patients and HCs (P<0.0001 for both). Foxp3 mRNA expression was significantly higher in CD patients compared to CRC patients and HCs (P<0.0001 for both). Clinicopathological characteristics did not correlate significantly with gene expression levels. CONCLUSION: This study reveals differential expression patterns of CD4 and Foxp3 mRNA in CRC and CD patients. Upregulated CD4 mRNA suggests its potential role in promoting tumor growth, while increased Foxp3 mRNA expression may reflect an immunosuppressive mechanism in CD pathogenesis. These findings provide insights into the molecular and immunological aspects of CRC and CD, warranting further studies for potential therapeutic strategies.

Evaluation of long non-coding RNAs EGOT, NRAV, NRIR and mRNAs ISG15 and IFITM3 expressions in COVID-19 patients.

Individuals with Coronavirus Disease 2019 (COVID-19) may show no symptoms to moderate or severe complications. This variation may be due to differences in the strength of the immune response, including a delayed interferon (IFN) response in asymptomatic patients and higher IFN levels in severe patients. Some long non-coding RNAs (lncRNAs), as regulators of the IFN pathway, may contribute to the emergence of different COVID-19 symptoms. This study aimed to comparatively investigate the relationship between lncRNAs (eosinophil granule ontogeny transcript (EGOT), negative regulator of antiviral response (NRAV), and negative regulator of interferon response (NRIR)), alongside interferon-stimulated genes (ISGs) like ISG-15 and interferon-induced transmembrane protein 3 (IFITM3) in COVID-19 patients with asymptomatic, moderate, and severe symptoms. Buffy coat samples were collected from 17 asymptomatic, 23 moderate, 22 severe patients, and 44 healthy controls. Quantitative real-time PCR was utilized to determine the expression levels. In a comparison between COVID-19 patients and healthy individuals, higher expression levels of EGOT and NRAV were observed in severe and moderate patients. NRIR expression was increased across all patient groups. Meanwhile, ISG15 expression decreased in all patient groups, and the moderate group showed a significant decrease in IFITM3 expression. Comparing COVID-19 patient groups, EGOT expression was significantly higher in moderate COVID-19 patients compared to asymptomatic patients. NRAV was higher in moderate and severe patients compared to asymptomatic. NRIR levels did not differ significantly between the COVID-19 patient groups. ISG15 was higher in moderate and severe patients compared to asymptomatic. IFITM3 expression was significantly higher in severe patients compared to the moderate group. In severe COVID-19 patients, EGOT expression was positively correlated with NRAV levels. EGOT and NRAV showed a significant positive correlation in asymptomatic patients, and both were positively correlated with IFITM3 expression. This study suggests that EGOT, NRAV, NRIR, ISG15, and IFITM3 may serve as diagnostic biomarkers for COVID-19. The lncRNA NRAV may be a good biomarker in a prognostic panel between asymptomatic and severe patients in combination with other high-sensitivity biomarkers. EGOT, NRAV, and ISG15 could also be considered as specific biomarkers in a prognostic panel comparing asymptomatic and moderate patients with other high-sensitivity biomarkers.

Long non-coding RNAs ANRIL, THRIL, and NEAT1 as potential circulating biomarkers of SARS-CoV-2 infection and disease severity.

The current outbreak of coronavirus disease 2019 (COVID-19) is a global emergency, as its rapid spread and high mortality rate, which poses a significant threat to public health. Innate immunity plays a crucial role in the primary defense against infections, and recent studies have highlighted the pivotal regulatory function of long non-coding RNAs (lncRNAs) in innate immune responses. This study aims to assess the circulating levels of lncRNAs namely ANRIL, THRIL, NEAT1, and MALAT1 in the blood of moderate and severe SARS-CoV-2 infected patients, in comparison to healthy individuals. Additionally, it aims to explore the potential of these lncRNAs as biomarkers for determining the severity of the disease. The blood samples were collected from a total of 38 moderate and 25 severe COVID-19 patients, along with 30 healthy controls. The total RNA was extracted and qPCR was performed to evaluate the blood levels of the lncRNAs. The results indicate significantly higher expression levels of lncRNAs ANRIL and THRIL in severe patients when compared to moderate patients (P value = 0.0307, P value = 0.0059, respectively). Moreover, the expression levels of lncRNAs ANRIL and THRIL were significantly up-regulated in both moderate and severe patients in comparison to the control group (P value < 0.001, P value < 0.001, P value = 0.001, P value < 0.001, respectively). The expression levels of lncRNA NEAT1 were found to be significantly higher in both moderate and severe COVID-19 patients compared to the healthy group (P value < 0.001, P value < 0.001, respectively), and there was no significant difference in the expression levels of NEAT1 between moderate and severe patients (P value = 0.6979). The expression levels of MALAT1 in moderate and severe patients did not exhibit a significant difference compared to the control group (P value = 0.677, P value = 0.764, respectively). Furthermore, the discriminative power of ANRIL and THRIL was significantly higher in the severe patient group than the moderate group (Area under curve (AUC) = 0.6879; P-value = 0.0122, AUC = 0.6947; P-value = 0.0093, respectively). In conclusion, the expression levels of the lncRNAs ANRIL and THRIL are correlated with the severity of COVID-19 and can be regarded as circulating biomarkers for disease progression.

Principles of Molecular Utility for CMS Classification in Colorectal Cancer Management.

Colorectal cancer (CRC) is the second cause of cancer-related deaths in both sexes globally and presents different clinical outcomes that are described by a range of genomic and epigenomic alterations. Despite the advancements in CRC screening plans and treatment strategies, the prognosis of CRC is dismal. In the last two decades, molecular biomarkers predictive of prognosis have been identified in CRC, although biomarkers predictive of treatment response are only available for specific biological drugs used in stage IV CRC. Translational clinical trials mainly based on "omic" strategies allowed a better understanding of the biological heterogeneity of CRCs. These studies were able to classify CRCs into subtypes mainly related to prognosis, recurrence risk, and, to some extent, also to treatment response. Accordingly, the comprehensive molecular characterizations of CRCs, including The Cancer Genome Atlas (TCGA) and consensus molecular subtype (CMS) classifications, were presented to improve the comprehension of the genomic and epigenomic landscapes of CRCs for a better patient management. The CMS classification obtained by the CRC subtyping consortium categorizes CRC into four consensus molecular subtypes (CMS1-4) characterized by different prognoses. In this review, we discussed the CMS classification in different settings with a focus on its relationships with precursor lesions, tumor immunophenotype, and gut microbiota, as well as on its role in predicting prognosis and/or response to pharmacological treatments, as a crucial step towards precision medicine.

Detection of SARS-CoV-2 RNA in selected agricultural and food retail environments in Tehran, Iran.

The SARS-CoV-2 pandemic has and continues to impose a considerable public health burden. Although not likely foodborne, SARS-CoV-2 transmission has been well documented in agricultural and food retail environments in several countries, with transmission primarily thought to be worker-to-worker or through environmental high touch surfaces. However, the prevalence and degree to which SARS-CoV-2 contamination occurs in such settings in Iran has not been well documented. Furthermore, since SARS-CoV-2 has been observed to be shed in the feces of some infected individuals, wastewater has been utilized as a means of surveilling the occurrence of SARS-CoV-2 in some regions. This study aimed to investigate the presence of SARS-CoV-2 RNA along the food production and retail chain, from wastewater and irrigation water to vegetables in field and sold in retail. From September 2020 to January 2021, vegetables from different agricultural areas of Tehran province (n = 35), their irrigated agricultural water (n = 8), treated wastewater mixed into irrigated agricultural water (n = 8), and vegetables collected from markets in Tehran (n = 72) were tested for the presence of SARS-CoV-2 RNA. The vegetable samples were washed with TGBE buffer and concentrated with polyethylene glycol precipitation, while water samples were concentrated by an adsorption-elution method using an electronegative filter. RT-qPCR targeting the SARS-CoV-2 N and RdRp genes was then conducted. SARS-CoV-2 RNA was detected in 51/123 (41.5%) of the samples overall. The presence of SARS-CoV-2 RNA in treated wastewater, irrigation water, field vegetables, and market produce were 75, 37.5, 42.85, and 37.5%, respectively. These results indicate that SARS-CoV-2 RNA is present in food retail and may also suggest that produce can additionally be contaminated with SARS-CoV-2 RNA by agricultural water. This study demonstrates that SARS-CoV-2 RNA was detected in waste and irrigation water, as well as on produce both in field and at retail. However, more evidence is needed to understand if contaminated irrigation water causes SARS-CoV-2 RNA contamination of produce, and if there is a significant public health risk in consuming this produce.

Lack of association between interleukin 28B gene polymorphisms (rs8099917G/T, rs12979860 C/T) and susceptibility to chronic hepatitis C virus infection, Tehran, Iran.

AIM: Chronic Hepatitis C infection is a critical health problem worldwide, which caused by hepatitis C virus (HCV). Interleukin 28B (IL28B) is a determinant factor in disease progression and also susceptibility to chronic HCV infection. BACKGROUND: The most significant aim of this study is to analyze the association between IL28B gene polymorphisms with susceptibility to chronic HCV infection in Iranian population. METHODS: This study follows a case- control study design, in which, 288 patients with chronic hepatitis C and 250 healthy individuals were genotyped for IL28B polymorphisms (rs12979860 C/T and rs8099917 G/T). Studied population collected from Taleghani Haospital, Tehran. Genotyping of IL28B gene polymorphisms were performed using PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) method. 10 percent of the studied population was sequenced to validate the results. RESULTS: rs8099917 G/T and rs12979860 C/T were differently distributed in hepatitis C patients and healthy controls in the female gender. TT, TG and GG genotypes distribution in the female gender were 56.7%, 39.8% and 4.5% in cases and 67%, 31.6% and 1.4% in controls (p=0.54). Also CC, CT and TT genotypes distribution were 31.8%, 61.4% and 6.8% in cases and 51.7%, 44.9% and 3.4% in controls (p=0.2). However, there was no significant difference in the allelic frequency and genotype distribution of rs12979860 C/T and rs8099917 T/G in both HCV patients with genotype 1a and 3a. CONCLUSION: It seems that rs8099917 G/T polymorphism plays a significant role in susceptibility to chronic HCV infection in Iranian population. On the other hand, no association was found between rs12979860 C/T polymorphisms and chronic hepatitis C.