A prediction of the CRNDE role by modulating NF-κB pathway in inflammatory bowel disease (IBD).

Long non-coding RNAs (lncRNAs) regulate multiple pathways and cellular mechanisms. Recent research has emphasized their involvement in the pathogenesis of complex diseases, such as Inflammatory Bowel Disease (IBD) which is characterized by chronic inflammation of the intestines. The two most common types of IBD are ulcerative colitis and Crohn's disease. CRNDE lncRNA was initially detected in colorectal cancer (CRC) and found to be involved in the tumorigenesis pathways. Further studies revealed the role of CRNDE in activating inflammation and promoting the release of inflammatory cytokines. This study utilizes the RNA-seq data analysis and bioinformatics tools to clarify the role of CRNDE in the IBD pathogenesis and confirms its expression in inflamed HT-29 and Caco-2 cell lines and also colonic and blood samples of UC patients and controls ex vivo. Based on our results, CRNDE was significantly upregulated in IBD samples compared to controls in RNA-seq data analysis and Real-time PCR of inflamed HT-29 cell line and colonic biopsies from UC patients. Additionally, predicted that its expression is positively correlated with the pro-inflammatory cytokines production. CRNDE interactions was investigated with several inflammation-related miRNAs and regulatory proteins computationally. Thus, CRNDE upregulation in the colon of IBD patients could be involved in IBD pathogenesis by promoting inflammatory pathways and targeting anti-inflammatory miRNAs.

A Simple High Yield Technique for Isolation of Wharton's Jelly-derived Mesenchymal Stem Cell.

Background: The isolation of Mesenchymal Stem Cells (MSCs) from various tissues is possible, with the umbilical cord emerging as a competitive alternative to bone marrow. In order to fulfill the demands of cell therapy, it is essential to generate stem cells on a clinical scale while minimizing time, cost, and contamination. Here is a simple and effective protocol for isolating MSC from Wharton's Jelly (WJ-MSC) using the explant method with various supplements. Methods: Utilizing the explant method, small fragments of Wharton's jelly from the human umbilical cord were cultured in a flask. The multipotency of the isolated cells, were confirmed by their differentiation ability to osteocyte and adipocyte. Additionally, the immunophenotyping of WJ-MSCs showed positive expression of CD73, CD90, and CD105, while remaining negative for hematopoietic markers CD34 and CD45, meeting the criteria for WJ-MSC identification. Following that, to evaluate cells' proliferative capacity, various supplements, including basic Fibroblast Growth Factor (bFGF), Non-Essential amino acids (NEA), and L-Glutamine (L-Gln) were added to either alpha-Minimal Essential Medium (α-MEM) or Dulbecco's Modified Eagle's Medium-F12 (DMEM-F12), as the basic culture media. Results: WJ-MSCs isolated by the explant method were removed from the tissue after seven days and transferred to the culture medium. These cells differentiated into adipocyte and osteocyte lineages, expressing CD73, CD90, and CD105 positively and CD34 and CD45 negatively. The results revealed that addition of bFGF to α-MEM or DMEMF12 media significantly increased the proliferation of MSCs when compared to the control group. However, there were no significant differences observed when NEA or LGln were added. Conclusion: Although bFGF considerably enhances cell proliferation, our study demonstrates that MSCs can grow and expand when properly prepared Wharton's jelly tissues of the human umbilical cord.

Management of Malignant Gastric Outlet Obstruction: A Comprehensive Review on the Old, the Classic and the Innovative Approaches.

Gastrojejunostomy is the principal method of palliation for unresectable malignant gastric outlet obstructions (GOO). Gastrojejunostomy was traditionally performed as a surgical procedure with an open approach butrecently, notable progress in the development of minimally invasive procedures such as laparoscopic gastrojejunostomies have emerged. Additionally, advancements in endoscopic techniques, including endoscopic stenting (ES) and endoscopic ultrasound-guided gastroenterostomy (EUS-GE), are becoming more prominent. ES involves the placement of self-expandable metal stents (SEMS) to restore luminal patency. ES is commonly the first choice for patients deemed unfit for surgery or at high surgical risk. However, although ES leads to rapid improvement of symptoms, it carries limitations like higher stent dysfunction rates and the need for frequent re-interventions. Recently, EUS-GE has emerged as a potential alternative, combining the minimally invasive nature of the endoscopic approach with the long-lasting effects of a gastrojejunostomy. Having reviewed the advantages and disadvantages of these different techniques, this article aims to provide a comprehensive review regarding the management of unresectable malignant GOO.

16S rRNA sequencing analysis of the oral and fecal microbiota in colorectal cancer positives versus colorectal cancer negatives in Iranian population.

BACKGROUND: Colorectal cancer (CRC) poses a significant healthcare challenge, accounting for nearly 6.1% of global cancer cases. Early detection, facilitated by population screening utilizing innovative biomarkers, is pivotal for mitigating CRC incidence. This study aims to scrutinize the fecal and salivary microbiomes of CRC-positive individuals (CPs) in comparison to CRC-negative counterparts (CNs) to enhance early CRC diagnosis through microbial biomarkers. MATERIAL AND METHODS: A total of 80 oral and stool samples were collected from Taleghani Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran, encompassing both CPs and CNs undergoing screening. Microbial profiling was conducted using 16S rRNA sequencing assays, employing the Nextera XT Index Kit on an Illumina NovaSeq platform. RESULTS: Distinct microbial profiles were observed in saliva and stool samples of CPs, diverging significantly from those of CNs at various taxonomic levels, including phylum, family, and species. Saliva samples from CPs exhibited abundance of Calothrix parietina, Granulicatella adiacens, Rothia dentocariosa, and Rothia mucilaginosa, absent in CNs. Additionally, Lachnospiraceae and Prevotellaceae were markedly higher in CPs' feces, while the Fusobacteria phylum was significantly elevated in CPs' saliva. Conversely, the non-pathogenic bacterium Akkermansia muciniphila exhibited a significant decrease in CPs' fecal samples compared to CNs. CONCLUSION: Through meticulous selection of saliva and stool microbes based on Mean Decrease GINI values and employing logistic regression for saliva and support vector machine models for stool, we successfully developed a microbiota test with heightened sensitivity and specificity for early CRC detection.

The anti-inflammatory and anti-apoptotic effects of Achillea millefolium L. extracts on Clostridioides difficile ribotype 001 in human intestinal epithelial cells.

BACKGROUND: Clostridioides difficile infection (CDI) is one of the most common health care-acquired infections. The dramatic increase in antimicrobial resistance of C. difficile isolates has led to growing demand to seek new alternative medicines against CDI. Achillea millefolium L. extracts exhibit strong biological activity to be considered as potential therapeutic agents. In this work, the inhibitory effects of A. millefolium, its decoction (DEC) and ethanol (ETOH) extracts, were investigated on the growth of C. difficile RT001 and its toxigenic cell-free supernatant (Tox-S) induced inflammation and apoptosis. METHODS: Phytochemical analysis of extracts was performed by HPLC and GC analysis. The antimicrobial properties of extracts were evaluated against C. difficile RT001. Cell viability and cytotoxicity of Caco-2 and Vero cells treated with various concentrations of extracts and Tox-S were examined by MTT assay and microscopy, respectively. Anti-inflammatory and anti-apoptotic effects of extracts were assessed in Tox-S stimulated Caco-2 cells by RT-qPCR. RESULTS: Analysis of the phytochemical profile of extracts revealed that the main component identified in both extracts was chlorogenic acid. Both extracts displayed significant antimicrobial activity against C. difficile RT001. Moreover, both extracts at concentration 50 µg/mL had no significant effect on cell viability compared to untreated cells. Pre-treatment of cells with extracts (50 µg/mL) significantly reduced the percentage of Vero cells rounding induced by Tox-S. Also, both pre-treatment and co-treatment of Tox-S stimulated Caco-2 cells with extracts significantly downregulated the gene expression level of IL-8, IL-1ß, TNF-α, TGF-ß, iNOS, Bax, caspase-9 and caspase-3 and upregulated the expression level of Bcl-2. CONCLUSION: The results of the present study for the first time demonstrate the antimicrobial activity and protective effects of A. millefolium extracts on inflammatory response and apoptosis induced by Tox-S from C. difficile RT001 clinical strain in vitro. Further research is needed to evaluate the potential application of A. millefolium extracts as supplementary medicine for CDI prevention and treatment in clinical setting.

Rare single-nucleotide variants of MLH1 and MSH2 genes in patients with Lynch syndrome.

BACKGROUND: Approximately 5% of colorectal cancers (CRCs) are hereditary. Lynch syndrome (LS), also known as hereditary nonpolyposis colorectal cancer (HNPCC), is the most common form of recognized hereditary CRC. Although Iran, as a developing country, has a high incidence of CRC, the spectrum of variants has yet to be thoroughly investigated. AIMS: This study aimed to investigate pathogenic and non-pathogenic variants in MLH1 and MSH2 genes in Iranian patients with suspected Lynch syndrome (sLS). METHODS AND RESULTS: In the present study, 25 peripheral blood samples were collected from patients with sLS and high microsatellite instability (MSI-H). After DNA extraction, all samples underwent polymerase chain reaction and Sanger sequencing to identify the variants in the exons of MLH1 and MSH2 genes. The identified variants were interpreted using prediction tools, and were finally reported under ACMG guidelines. In our study population, 13 variants were found in the MLH1 gene and 8 in the MSH2 gene. Interestingly, 7 of the 13 MLH1 variants and 3 of the 8 MSH2 variants were novel, whereas the remaining variants were previously reported or available in databases. In addition, some patients with sLS did not have variants in the exons of the MLH1 and MSH2 genes. The variants detected in the MLH1 and MSH2 genes had specific characteristics regarding the number, area of occurrence, and their relationship with demographic and clinicopathologic features. CONCLUSION: Overall, our results suggest that analysis of MLH1 and MSH2 genes alone is insufficient in the Iranian population, and more comprehensive tests are recommended for detecting LS.

Expression Analysis of Long Noncoding RNA-MALAT1 and Interleukin-6 in Inflammatory Bowel Disease Patients.

 Inflammatory bowel disease (IBD) manifests as chronic inflammation within the gastrointestinal tract. The study focuses on a long noncoding RNA (lncRNA) known as Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1). MALAT1's misregulation has been linked with various autoimmune diseases and regulates proinflammatory cytokines. The role of IL6 in immune-triggered conditions, including IBD, is another focal point. In this research, the expression of MALAT1 and IL6 in IBD patients was meticulously analyzed to uncover potential interactions. The study involved 33 IBD patients (13 with Crohn's disease and 20 with ulcerative colitis) and 20 healthy counterparts. Quantitative real-time polymerase chain reaction determined the MALAT1 and IL6 gene expression levels. The competitive endogenous RNA (ceRNA) regulatory network was constructed using several tools, including LncRRIsearch and Cytoscape. A deep dive into the Inflammatory Bowel Disease database was undertaken to understand IL6's role in IBD. Drugs potentially targeting these genes were also pinpointed using DGIdb. Results indicated a notable elevation in the expression levels of MALAT1 and IL6 in IBD patients versus healthy controls. MALAT1 and IL6 did not show a direct linear correlation, but IL6 could serve as MALAT1's target. Analyses unveiled interactions between MALAT1 and IL6, regulated by hsa-miR-202-3p, hsa-miR-1-3p, and has-miR-9-5p. IL6's pivotal role in IBD-associated inflammation, likely interacting with other cytokines, was accentuated. Moreover, potential drugs like CILOBRADINE for MALAT1 and SILTUXIMAB for IL6 were identified. This research underscored MALAT1 and IL6's potential value as targets in diagnosis and treatment for IBD patients.

Low incidence of microsatellite instability in gastric cancers and its association with the clinicopathological characteristics: a comparative study.

Gastric cancer is a complex heterogeneous disease with different molecular subtypes that have clinical implications. It is characterized by high mortality rates and limited effective therapies. Microsatellite instability (MSI) has been recognized as a subgroup with a good prognosis based on TCGA and ACRG categorizations. Besides its prognostic and predictive value, gastric cancers with high MSI exhibit different clinical behaviors. The prevalence of high MSI has been assessed in gastric cancer worldwide, especially in East Asia, but there is a lack of such information in the Middle East. Therefore, this study aimed to investigate the incidence and status of MSI in Iranian gastric cancer patients using 53 samples collected from 2015 to 2020 at Taleghani Hospital Medical Center. DNA from tumoral and normal tissues were extracted and assessed through multiplex-PCR based on five mononucleotide repeats panel. Clinicopathological variables, including age, sex, Lauren classification, lymph node involvement, TNM stage, differentiation, localization, and tumor size, were also analyzed. With 2 males and 2 females, high microsatellite instability represented a small subgroup of almost 7.5% of the samples with a median age of 60.5 years. High microsatellite instability phenotypes were significantly associated with patients aged 68 years and older (p­value of 0.0015) and lower lymph node involvement (p­value of 0.0004). Microsatellite instability was also more frequent in females, with distal gastric location, bigger tumor size, and in the intestinal type of gastric cancer rather than the diffuse type.

Identification of antisense and sense RNAs of intracrine fibroblast growth factor components as novel biomarkers in colorectal cancer and in silico studies for drug and nanodrug repurposing.

INTRODUCTION: Colorectal cancer (CRC) is one of the most malignant tumors and in which various efforts for screening is inconclusive.The intracrine FGF panel, the non-tyrosine kinase receptors (NTKR) FGFs and affiliated antisenses play a pivotal role in FGF signaling.The expression levels of coding and non-coding intracrine FGFs were assessed in CRC donors.Also, substantial costs and slow pace of drug discovery give high attraction to repurpose of previously discovered drugs to new opportunities. OBJECTIVES: The aim of present study was to evaluate the potential role of the coding and non-coding intracrine FGFs as a new biomarkers for CRC cases and defining drug repurposing to alleviate FGF down regulation. METHODS: RNA-seq data of colon adenocarcinomas (COAD) was downloaded using TCGA biolinks package in R.The DrugBank database (https://go.drugbank.com/) was used to extract interactions between drugs and candidate genes. A total of 200 CRC patients with detailed criteria were enrolled.RNAs were extracted with TRIzol-based protocol and amplified via LightCycler® instrument.FGF11 and FGF13 proteins validation was performed by used of immunohistochemistry technique in tumor and non-tumoral samples.Pearson's correlation analysis and ROC curve plotted by Prism 8.0 software. RESULTS: RNA-seq data from TCGA was analyzed by normalizing with edgeR.Differentially expressed gene (DEG) analysis was generated. WCC algorithm extracted the most significant genes with a total of 47 genes. Expression elevation of iFGF antisenses (12AS,13As,14AS) compared with the normal colon tissue were observed (P = 0.0003,P = 0.042,P = 0.026, respectively). Moreover,a significant decrease in expression of the corresponding sense iFGF genes was detected (P < 0.0001).Plotted receiver operating characteristic (ROC) curves for iFGF components' expression showed an area of over 0.70 (FGF11-13: 0.71% and FGF12-14: 0.78%, P < 0.001) for sense mRNA expression, with the highest sensitivity for FGF12 (92.8%) and lowest for FGF11 (61.41%).The artificial intelligence (AI) revealed the valproic acid as a repurposing drug to relief the down regulation of FGF12 and 13 in CRC patients. CONCLUSION: Intracrine FGFs panel was down regulated versus up regulation of dependent antisenses. Thus, developing novel biomarkers based on iFGF can be considered as a promising strategy for CRC screening.In advanced, valporic acid detected by AI as a repurposing drug which may be applied in clinical trials for CRC treatment.

Chemo-immune cell therapy by intratumoral injection of adoptive NK cells with capecitabine in gastric cancer xenograft model.

Introduction: Gastric cancer is one of the most commonly known malignancies and is the fifth cancer-related death globally. Whereas natural killer (NK) cells play a critical role in tumor elimination; therefore, adoptive NK cell therapy has become a promising approach in cancer cytotherapy. Hence, this study investigated the chemo-immune cell therapy in MKN-45 derived xenograft gastric cancer model. Methods: Three groups of animals have received the following treatments separately: activated NK cells, capecitabine, the combination of capecitabine and activated NK cells, and one was considered as the control group. Morphometric properties of tumor samples were evaluated at the end of the study. NK cells infiltration was evaluated by immunohistochemistry (IHC) of hCD56. Mitotic count and treatment response was assessed by hematoxylin and eosin (H&E) staining. The proliferation ratio to apoptosis was determined by IHC assessment of Ki67 and caspase 3. Results: The results indicated that the NK cell therapy could effectively decrease the mitotic count in pathology assessment, but the tumor was not completely eradicated. In combination with metronomic chemotherapy (MC) of capecitabine, NK cell therapy demonstrated a significant difference in tumor morphometric properties compared to the control group. The proliferation ratio to apoptosis was also in line with pathology data. Conclusion: Although NK cell therapy could effectively decrease the mitotic count in vivo, the obtained findings indicated lesser potency than MC despite ex vivo activation. In order to enhance NK cell therapy effectiveness, suppressive features of the tumor microenvironment and inhibitory immune checkpoints blockade should be considered.

The possible role of viral infections in acute pancreatitis: a review of literature.

Acute pancreatitis, a potentially fatal disease, with symptoms including nausea and/or vomiting, indigestion, and abdominal pain, is known to range from a mild self-limiting state up to a more severe and lethal form. This review aims to provide a clearer picture to improve understanding the role of viral agents in the development of acute pancreatitis. Common databases including PubMed, Google Scholar, and Scopus were used for the literature search. In this review search terms including virus, viral, infection, and specific descriptive terms for a virus were considered in different combinations. Various causative agents are recognized in the development of acute pancreatitis as one of the most frequent gastrointestinal diseases, such as gallstones, alcoholism, and hypertriglyceridemia. Microbial pathogens with about 10% of acute pancreatitis cases, mainly viruses, among other factors, are thought to play a role in this regard. Once the pancreatitis diagnosis has been made, depending on the causative agent, the management approach and specific interventions affect the final outcome. Virus-induced acute pancreatitis in patients should be considered. Advanced diagnostic tests such as PCR, in situ hybridization, and biopsy can help for a better understanding of the role of viruses in causing acute pancreatitis. Improvement in the tests will lead to timely diagnosis, treatment, and better management of pancreatitis.

A novel stop codon mutation in STK11 gene is associated with Peutz-Jeghers Syndrome and elevated cancer risk: a case study.

Based on the analysis of patients with Peutz-Jeghers syndrome (PJS), Serine threonine kinase11 (STK11) is known as a tumor suppressor gene, which is involved in cell polarization, regulation of apoptosis, and DNA damage response. In this case report study, we examined STK11 gene sequencing in a 42-year-old woman with mucocuta neous pigmentation and positive family history. Endoscopy and colonoscopy showed >1000 polyps throughout the stomach/colon (PJ-type hamartomas). The larger polyp in the stomach was resected and the small bowel imaging detected multiple jejunum/ileum small polyps. The data released from the sequencing results revealed five alterations in exons 1 to 5. The major mutation in stop codon was reported as converted to the amino acid tryptophan (TRP) to tyrosine (TER). The TGG codon was converted to TAG by mutation. Finally, another novel mutation in STK11 stop codon as a 'de novo' variant was seen. It is predicted that stop codon mutations make the affected person susceptible to developing colorectal cancer.

Combination of pioglitazone and dendritic cell to optimize efficacy of immune cell therapy in CT26 tumor models.

Introduction: The maturation faith of dendritic cells is restrained by the inflammatory environment and cytokines, such as interleukin-6 and its downstream component. Therefore, introducing the suitable antigen to dendritic cells is crucial. However, reducing the severity of the suppressive tumor microenvironment is indispensable. The present study examined the combination therapy of lymphocyte antigen 6 family member E (LY6E) pulsed mature dendritic cells (LPMDCs) and pioglitazone against colorectal cancer (CRC) to elevate the effectiveness of cancer treatment through probable role of pioglitazone on inhibiting IL-6/STAT3 pathway. Methods: Dendritic cells were generated from murine bone marrow and were pulsed with lymphocyte antigen 6 family member E peptide to assess antigen-specific T-cell proliferation and cytotoxicity assay with Annexin/PI. The effect of pioglitazone on interleukin (IL)-6/STAT3 was evaluated in vitro by real-time polymerase chain reaction (PCR). Afterward, the CRC model was established by subcutaneous injection of CT26, mouse colon carcinoma cell line, in female mice. After treatment, tumor, spleen, and lymph nodes samples were removed for histopathological, ELISA, and real-time PCR analysis. Results: In vitro results revealed the potential of lysate-pulsed dendritic cells in the proliferation of double-positive CD3-8 splenocytes and inducing immunogenic cell death responses, whereas pioglitazone declined the expression of IL-6/STAT3 in colorectal cell lines. In animal models, the recipient of LPMDCs combined with pioglitazone demonstrated high tumor-infiltrating lymphocytes. Elevating the IL-12 and interferon-gamma (IFN-γ) levels and prolonged survival in lysate-pulsed dendritic cell and combination groups were observed. Conclusion: Pioglitazone could efficiently ameliorate the immunosuppressive feature of the tumor microenvironment, mainly through IL-6. Accordingly, applying this drug combined with LPMDCs provoked substantial CD8 positive responses in tumor-challenged animal models.

Characterisation of extracellular vesicles isolated from hydatid cyst fluid and evaluation of immunomodulatory effects on human monocytes.

Hydatidosis is a disease caused by the larval stage of Echinococcus granulosus, which involves several organs of intermediate hosts. Evidence suggests a communication between hydatid cyst (HC) and hosts via extracellular vesicles. However, a little is known about the communication between EVs derived from HC fluid (HCF) and host cells. In the current study, EVs were isolated using differential centrifugation from sheep HCF and characterized by western blot, electron microscope and size distribution analysis. The uptake of EVs by human monocyte cell line (THP-1) was evaluated. The effects of EVs on the expression levels of pro- and anti-inflammatory cytokines were investigated using quantitative real-time PCR (RT-PCR), 3 and 24 h after incubation. Moreover, the cytokine level of IL-10 was evaluated in supernatant of THP-1 cell line at 3 and 24 h. EVs were successfully isolated and showed spherical shape with size distribution at 130.6 nm. After 3 h, the expression levels of pro-inflammatory cytokine genes (IL1Β, IL15 and IL8) were upregulated, while after 24 h, the expression levels of pro-inflammatory cytokines were decreased and IL13 gene expression showed upregulation. A statistically significant increase was seen in the levels of IL-10 after 24 h. The main mechanism of the communication between EVs derived from HCF and their host remains unclear; however, time-dependent anti-inflammatory effects in our study suggest that HC may modulate the immune responses via EVs.

Accuracy of the Discriminatory Ability of Combined Fecal Microbiota Panel in the Early Detection of Patients with Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) screening and detecting it at an early stage is an effective way to decrease mortality from CRC. Colonoscopy, considered the gold standard (GS) for diagnosing the disease in many countries, has several limitations. Therefore, the main focus of this literature is to investigate the ability of combining candidate gut microbiota for early diagnosis of CRC, both in the presence and absence of GS test outcomes. METHODS: We analyzed the data derived from a case-control study, including 83 screening colonoscopies conducted on subjects aged 18-92 years in Tehran, Iran. The candidate gut microbiota including, ETBF, Enterococcus faecalis, and Porphyromonas gingivalis were quantified in samples using absolute qRT PCR. The Bayesian latent class model (LCM) was employed to combine the values from the multiple bacterial markers in order to optimize the discriminatory ability compared with a single marker. RESULTS: Based on Bayesian logistic regression, we discovered that family history of CRC, physical activity, cigarette smoking, and food diet were all significantly associated with an increased risk of CRC. When comparing ETBF and E. faecalis to P. gingivalis, we have observed that P. gingivalis exhibited greater predictive power in detecting high-risk individuals with CRC. As such, the sensitivity, specificity, and the area under the receiver-operating characteristics curve of combining ETBF, E. faecalis, and P. gingivalis were 98%, 96%, and 0.97, respectively. CONCLUSIONS: This study suggests that the combined use of the three markers markedly improves classification performance compared to pairwise combinations, as well as individual markers, both with and without GS test outcomes. Noticeably, the triple composition of the fecal markers may serve as a reliable non-invasive indicator for the early prediction of CRC.

Global long-term trends and spatial cluster analysis of pancreatic cancer incidence and mortality over a 30-year period using the global burden of disease study 2019 data.

INTRODUCTION: Pancreatic cancer (PC) is one of the most fatal malignancies, and its incidence and mortality rates are growing annually throughout the world. In this research, we aimed to investigate the time trends and identify the spatial clusters of incidence and mortality on a global scale over the last 30 years, using the Global Burden of Disease (GBD) study 2019 data. METHODS: Age-standardized incidence and mortality data due to PC were extracted from the GBD study, which was carried out from 1990 to 2019. A Joinpoint regression analysis was utilized to examine trends in the incidence and mortality of PC over the past three decades. As such, spatial analyses were undertaken to detect the spatial distribution and clustering of the metrics globally. RESULTS: It was observed that both the incidence and mortality rates were higher in males than in females worldwide. The global mortality and incidence rates significantly increased by 0.8% per year over the time of follow-up period (p<0.05). By spatial cluster analysis for mortality, European and North African countries, as well as Greenland were explored as hot spots; while South African and Southeast Asian countries were explored as cold spots. Regarding incidence, hot spots were found in European countries, Southern America, and Greenland; whilst cold spots were determined in Southern Africa and Madagascar. CONCLUSIONS: Collectively, the temporal trends disclosed a gradual rise in PC incidence and mortality rates over the period 1990-2019, reflecting the global health concern. We further found geographical variations in the patterns and identified high- and low-risk areas for incidence and mortality. These findings facilitate the design and implementation of more resource-efficient and geographically targeted treatments. Given the results of the current study, a practical approach to minimizing the future PC burden involves planned population-wide interventions, as well as primary prevention through healthier lifestyles.

The impact of COVID-19 on national program of colorectal cancer screening in Tehran, Iran: a multicenter study.

BACKGROUND: The COVID-19 pandemic has affected all aspects of the healthcare system, including prevention, treatment, rehabilitation of diseases and health education; access to essential therapies; allocation of finance & facilities to health issues, and governance of diseases, including COVID-19 and other diseases. Consequently, the burden of COVID-19 was not only attributable to the multiorgan involvement and detailed presentation of the disease but also to the inadequate management of other diseases resulting from the exclusive allocation of resources and medical personnel to the pandemic crisis. Over the mentioned period, one observed deficiency was the lack of public and official favor for conventional screening protocols. To this end, this study aims to evaluate the impact of the COVID-19 pandemic on colorectal cancer (CRC) screening protocols at Shahid Beheshti University of Medical Sciences in Tehran, Iran, in an effort to identify individuals at risk for CRC and provide them with intensive screening and therapy. METHODS: This is an observational study comparing the number of candidates for CRC screening referred to primary, secondary, and tertiary health-care centers under supervision of Shahid Beheshti University of Medical Sciences (SBMU), Tehran, Iran in a 2-year interval before and after COVID-19 pandemics. Patients with intermediate- and high-risk criteria for colorectal cancer were included in the study and were screened by fecal immunochemical test. Patients with positive or indeterminate fecal test results were further evaluated with colonoscopy in research institute for gastroenterology and liver diseases where is a tertiary referral center for CRC screening. Finally, the decrease percentage of screening tests and endoscopic findings during the pandemic period compared to pre-pandemic period was calculated and interpreted. RESULTS: A significant decrease in the number of performed fecal immunochemical tests (FITs), referred positive FITs, and referred patients with positive alarm signs to the Research Institute of Gastroenterology and Liver Diseases (RIGLD) center inevitably led to a considerable decrease in the number of endoscopic findings, including high-risk adenomas, sessile serrated polyps, and even early-stage colorectal cancers (CRCs). CONCLUSION: The disruption of screening protocols caused by the COVID-19 pandemic appears to increase the number of patients with high-grade and end-stage CRCs referred in the near future.

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.

A systematic review and meta-analysis for the association of the insulin-like growth factor1 pathway genetic polymorphisms with colorectal cancer susceptibility.

Background: The receptors, ligands, and associated proteins of the insulin-like growth factor (IGF) family are involved in cancer development. The IGF1 receptor and its accompanying signaling cascade are a crucial growth-regulatory mechanism that plays an important role in colorectal cancer (CRC) proliferation and differentiation. IRS1 (Insulin receptor substrate-1), a major substrate for the IGF1R, is involved in cell growth and promotes tumorigenesis. There are shreds of evidence from prior research suggesting that IGF system polymorphisms may influence susceptibility to CRC. However, the findings in this area were contradictory. Accordingly, we carried out a systematic literature search to identify all case-control, cross-sectional, and cohort studies on the association between various polymorphisms across four IGF1 pathway genes (IGF1, IGF1R, IRS1, and IRS2) and the risk of CRC. Methods: We performed a comprehensive search strategy in PubMed, Scopus, and Web of Science databases for articles available until Aug 30, 2022. A total of 26 eligible studies with IGF1/IGF1R, IRS1 and IRS2 polymorphisms; met the inclusion criteria. All case-control studies for IGF1 rs6214C>T, IRS1 rs1801278G>A, and IRS2 rs1805097G>A comprising 22,084 cases and 29,212 controls were included in the current meta-analysis. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate relationships between the polymorphisms and CRC susceptibility. All statistical analyses were performed using STATA software version 14.0. Results: The meta-analysis of available data for rs6214C>T, rs1801278G>A, and rs1805097G>A showed a significant association between these polymorphisms and an increased CRC risk in some of the comparisons studied (rs6214C>T, pooled OR for CC = 0.43, 95% CI 0.21- 0.87, P = 0.019; rs1801278G>A, OR for GA = 0.74, 95% CI 0.58-0.94, P = 0.016; rs1805097G>A, OR for GA = 0.83, 95% CI 0.71-0.96, P = 0.013). Nevertheless, the meta-analysis did not include other genetic variations in IGF1, IGF1R, IRS1, and IRS2 due to heterogeneity and limited sample size. Conclusions: This systematic review and meta-analysis provide evidence that genetic variants in IGF1 rs6214C>T, IRS1 rs1801278G>A, and IRS2 rs1805097G>A are associated with an increased risk of CRC. These findings may contribute to a better understanding of the complex genetic mechanisms involved in CRC development and could inform future research on prevention and treatment strategies for this disease.

Effect of bariatric surgery on atherogenicity and insulin resistance in patients with obesity class II: a prospective study.

OBJECTIVE: Enormous efforts have been made to evaluate reliable, simple and practical indicators for predicting patients at risk of progression of cardiovascular disease events, whereby bariatric surgery has remained understudied. Thus, we performed this study to assess the effect of bariatric surgery procedures on atherogenicity and insulin resistance indicators. DESIGN: Cohort study. SETTING, PARTICIPANTS AND OUTCOME MEASURES: Four hundred and forty-three class II obese (severely obese) patients who underwent sleeve gastrectomy, Roux-en-Y gastric bypass, or one anastomosis gastric bypass were followed up for 12 months after surgery. Atherosclerosis-related indicators were evaluated at baseline, as well as 6 and 12 months after surgery. RESULTS: Atherogenic index of plasma, lipoprotein combine index, atherogenic coefficient, cholesterol index, Castelli's risk indices I and II, and triglyceride to high-density lipoprotein-cholesterol ratio (p<0.01) improved after 12 months. Additionally, bariatric surgery yielded a significantly reduced triglyceride glucose index. There was no significant difference between procedures in terms of indicators. The Spearman correlation test showed a significant inverse correlation between weight plus fat mass and atherosclerosis-related indicators as well as a positive correlation between percentage of excess weight loss and these indicators. CONCLUSIONS: This study demonstrated three bariatric surgery procedures' ability to improve atherogenicity and insulin resistance in patients with obesity class II. The anti-atherogenicity effects can be partly assigned to the reduction of body weight and adipose tissue. Nevertheless, further studies with larger sample sizes and longer follow-ups are required to confirm our results.