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The soluble epoxide hydrolase (sEH; encoded by the EPHX2 gene) is an α/β hydrolase fold protein that is, widely distributed throughout the body. Recent studies have highlighted that sEH, in the metabolism of polyunsaturated fatty acids, plays a part in the pathogenesis of various diseases, including cardiovascular disease, Alzheimer's disease and intestine‐associated disease. This review discusses the current findings on the role of sEH in the development of intestine‐ and intestine‐associated diseases, including colitis, colorectal cancer, and other intestinal diseases, as well as the potential underlying mechanisms involved. [ABSTRACT FROM AUTHOR]

Intestinal dysbiosis is a major contributor to colorectal cancer (CRC) development, leading to bacterial translocation into the bloodstream. This study aimed to evaluate the presence of circulated bacterial DNA (cbDNA) in CRC patients (n = 75) and healthy individuals (n = 25). DNA extracted from peripheral blood was analyzed using PCR, with specific primers targeting 16S rRNA, Escherichia coli (E. coli), and Fusobacterium nucleatum (F. nucleatum). High 16S rRNA and E. coli detections were observed in all patients and controls. Only the detection of F. nucleatum was significantly higher in metastatic non-excised CRC, compared to controls (p < 0.001), non-metastatic excised CRC (p = 0.023), and metastatic excised CRC (p = 0.023). This effect was mainly attributed to the presence of the primary tumor (p = 0.006) but not the presence of distant metastases (p = 0.217). The association of cbDNA with other clinical parameters or co-morbidities was also evaluated, revealing a higher detection of E. coli in CRC patients with diabetes (p = 0.004). These results highlighted the importance of bacterial translocation in CRC patients and the potential role of F. nucleatum as an intratumoral oncomicrobe in CRC. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer is among the most common malignant tumors affecting the gastrointestinal tract. Liver metastases, a complication present in approximately 50% of colorectal cancer patients, are a considerable concern. Recently, studies have revealed the crucial role of miR-455 in tumor pathogenesis. However, the effect of miR-455 on the progression of liver metastases in colorectal cancer remains controversial. As an antagonist of bone morphogenetic protein(BMP), Gremlin 1 (GREM1) may impact organogenesis, body patterning, and tissue differentiation. Nevertheless, the role of miR-455 in regulating GREM1 in colorectal cancer liver metastases and how miR-455/GREM1 axis influences tumour immune microenvironment is unclear. Methods: Bioinformatics analysis shows that miR-455/GREM1 axis plays crucial role in liver metastasis of intestinal cancer and predicts its possible mechanism. To investigate the impact of miR-455/GREM1 axis on the proliferation, invasion, and migration of colorectal cancer cells, colony formation assay, wound healing and transwell assay were examined in vitro. The Dual-Luciferase reporter gene assay and RNA pull-down assay confirmed a possible regulatory effect between miR-455 and GREM1. In vivo, colorectal cancer liver metastasis(CRLM) model mice was established to inquiry the effect of miR-455/GREM1 axis on tumor growth and macrophage polarization. The marker of macrophage polarization was tested using immunofluorescence(IF) and quantitative real-time polymerase chain reaction(qRT-PCR). By enzyme-linked immunosorbent assay (ELISA), cytokines were detected in culture medium supernatants. Results: We found that miR-455 and BMP6 expression was increased and GREM1 expression was decreased in liver metastase compared with primary tumor. miR-455/GREM1 axis promotes colorectal cancer cells proliferation, migration, invasion via affected PI3K/AKT pathway. Moreover, downregulating GREM1 augmented BMP6 expression in MC38 cell lines, inducing M2 polarization of macrophages, and promoting liver metastasis growth in CRLM model mice. Conclusion: These data suggest that miR-455/GREM1 axis promotes colorectal cancer progression and liver metastasis by affecting PI3K/AKT pathway and inducing M2 macrophage polarization. These results offer valuable insights and direction for future research and treatment of CRLM. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most common cancer worldwide. The role of intestinal microbiota in carcinogenesis has also become an important research topic, and CRC is closely related to the intestinal microbiota. Selenium-containing compounds have attracted more attention as anticancer drugs as they can have minimal side effects. The purpose of this study was to determine and compare the effect of sodium selenite and selenomethionine on the microbial communities of nude mice with CRC. A CRC ectopic tumorigenesis model was established by subcutaneously injecting HCT116 cells into nude mice. The mice were then intraperitoneally injected with sodium selenite and selenomethionine for 24 days to regulate their intestinal microbiota. Compared with sodium selenite, selenomethionine resulted in a greater reduction in the richness and diversity of intestinal microbiota in nude mice with CRC, and the richness and diversity were closer to healthy levels. Selenomethionine also regulated a wider variety of flora. Additionally, sodium selenite and selenomethionine produced different microorganisms, changed function and metabolic pathways in the intestinal microbiota. Both sodium selenite and selenomethionine have certain effects on restoring the intestinal microbial diversity in nude mice with CRC, and the effect of selenomethionine is better than that of sodium selenite. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a type of intestinal cancer that causes more than 600,000 deaths every year. Overcoming the problems of metastasis requires detailed studies to reveal the potential molecular mechanisms. This study aims to reveal the molecular mechanism of CRC metastasis involving non-coding RNA regulation. The expression profile of FTH1P3 was analyzed based on the data of TCGA-COAD patient cohorts. Q-PCR analysis was performed to validate the expression of FTH1P3 in colorectal cancer cells. JASPR was used to screen transcription factors of FTH1P3. q-ChIP analysis was used to validate the target between FTH1P3 and transcription factor. Scratch assay and transwell assay were used to evaluate the migration and invasion ability of colorectal cancer cells. FTH1P3 is highly expressed in CRC patient cohort. FTH1P3 induced migration and invasion of SW480 cell through regulating epithelial-mesenchymal transition (EMT). In addition, FTH1P3 is a direct target of SNAI2. SNAI2 promotes the expression of FTH1P3. Both FTH1P3 and SNAI2 were directly targeted and repressed by miR-218-5p. Interestingly, ectopic FTH1P3 caused a decreased miR-218-5p level and an elevated nucleic SNAI2 protein expression level. Of note, only ectopic SNAI2 protein resulted in a repressed miR-218-5p and an increased FTH1P3, whereas SNAI2 3'UTR failed to affect the expression of miR-218-5p and FTH1P3. SNAI2 transcriptionally activates FTH1P3 expression. Both SNAI2 and FTH1P3 are targets of miR-218-5p. SNAI2/FTH1P3/miR-218-5p form a positive feedback loop in the regulation of CRC metastasis. [ABSTRACT FROM AUTHOR]

Copper, a trace element and vital cofactor, plays a crucial role in the maintenance of biological functions. Recent evidence has established significant correlations between copper levels, cancer development and metastasis. The strong redox‐active properties of copper offer both benefits and disadvantages to cancer cells. The intestinal tract, which is primarily responsible for copper uptake and regulation, may suffer from an imbalance in copper homeostasis. Colorectal cancer (CRC) is the most prevalent primary cancer of the intestinal tract and is an aggressive malignant disease with limited therapeutic options. Current research is primarily focused on the relationship between copper and CRC. Innovative concepts, such as cuproplasia and cuproptosis, are being explored to understand copper‐related cellular proliferation and death. Cuproplasia is the regulation of cell proliferation that is mediated by both enzymatic and nonenzymatic copper‐modulated activities. Whereas, cuproptosis refers to cell death induced by excess copper via promoting the abnormal oligomerisation of lipoylated proteins within the tricarboxylic acid cycle, as well as by diminishing the levels of iron‐sulphur cluster proteins. A comprehensive understanding of copper‐related cellular proliferation and death mechanisms offers new avenues for CRC treatment. In this review, we summarise the evolving molecular mechanisms, ranging from abnormal intracellular copper concentrations to the copper‐related proteins that are being discovered, and discuss the role of copper in the pathogenesis, progression and potential therapies for CRC. Understanding the relationship between copper and CRC will help provide a comprehensive theoretical foundation for innovative treatment strategies in CRC management. [ABSTRACT FROM AUTHOR]

Factors that reduce the risk of developing colorectal cancer include biologically active substances. In our previous research, we demonstrated the anti-inflammatory, immunomodulatory, and antioxidant effects of oat beta-glucans in gastrointestinal disease models. The aim of this study was to investigate the effect of an 8-week consumption of a diet supplemented with low-molar-mass oat beta-glucan in two doses on the antioxidant potential, inflammatory parameters, and colonic metabolomic profile in azoxymethane(AOM)-induced early-stage colorectal cancer in the large intestine wall of rats. The results showed a statistically significant effect of AOM leading to the development of neoplastic changes in the colon. Consumption of beta-glucans induced changes in colonic antioxidant potential parameters, including an increase in total antioxidant status, a decrease in the superoxide dismutase (SOD) activity, and a reduction in thiobarbituric acid reactive substance (TBARS) concentration. In addition, beta-glucans decreased the levels of pro-inflammatory interleukins (IL-1α, IL-1β, IL-12) and C-reactive protein (CRP) while increasing the concentration of IL-10. Metabolomic studies confirmed the efficacy of oat beta-glucans in the AOM-induced early-stage colon cancer model by increasing the levels of metabolites involved in metabolic pathways, such as amino acids, purine, biotin, and folate. In conclusion, these results suggest a wide range of mechanisms involved in altering colonic metabolism during the early stage of carcinogenesis and a strong influence of low-molar-mass oat beta-glucan, administered as dietary supplement, in modulating these mechanisms. [ABSTRACT FROM AUTHOR]

Background: There are some concerns about the higher risk of certain gastrointestinal (GI) cancers in patients with a history of bariatric metabolic surgery (BMS). The current study aimed to investigate the association of BMS with GI cancer hospital admission including esophageal, gastric, colorectal, small intestinal, liver, gallbladder, bile duct, and pancreatic cancers. Methods: The analysis utilized the US national inpatient sample (NIS) data from 2016 to 2020, employing ICD-10 codes. A propensity score matching in a 3:1 ratio was done to match the BMS and non-BMS groups. Results: A total of 328,369 patients with a history of BMS and 4,989,154 with obesity and without a history of BMS were included in this study. BMS was independently associated with a higher risk of gastric and pancreatic cancers hospital admission (OR: 1.69 (CI 95%: 1.42–2.01) and OR: 1.46 (CI 95%: 1.27–1.68)), respectively. In addition, BMS was independently associated with a lower risk of colorectal and liver cancer hospital admission (OR: 0.57 (CI 95%: 0.52–0.62) and OR: 0.72 (CI 95%: 0.52–0.98)), respectively. Besides, esophageal, gallbladder, bile duct, and small intestinal cancer were not significantly different between the two groups. In patients with GI cancer, although the BMS group had significantly lower total charges and length of hospital stay compared to the non-BMS group, the rate of in-hospital mortality was not significantly different. Conclusion: The current study showed that bariatric surgery may be associated with a higher risk of gastric and pancreatic cancer and a lower risk of colorectal and liver cancer hospital admission. Further research is needed to explore this association. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is the third most common cancer worldwide. One of the main causes of colorectal cancer is inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD). Intestinal epithelial cells (IECs), intestinal mesenchymal cells (IMCs), immune cells, and gut microbiota construct the main body of the colon and maintain colon homeostasis. In the development of colitis and colitis-associated carcinogenesis, the damage, disorder or excessive recruitment of different cells such as IECs, IMCs, immune cells and intestinal microbiota play different roles during these processes. This review aims to discuss the various roles of different cells and the crosstalk of these cells in transforming intestinal inflammation to cancer, which provides new therapeutic methods for chemotherapy, targeted therapy, immunotherapy and microbial therapy. [ABSTRACT FROM AUTHOR]

To explore the effects of anti‐programmed death‐1 (PD‐1) therapy on advanced colorectal cancer (CRC) based on the intestinal microecology. Ninety‐two patients with advanced CRC were selected. Patients were treated with Apatinib alone or anti PD‐1 treatment combined with Apatinib. The lactulose/mannitol (L/M) value of the urine was detected by high performance liquid chromatography. The changes of intestinal microflora were determined by real‐time fluorescence quantitative PCR. The risk factors were analyzed through multivariate logistic regression analysis. The curative effect of anti PD‐1 treatment combined with the Apatinib treatment (82.61%) was much higher than that of the Apatinib treatment alone (63.04%, p < 0.05). After treatment, the contents of Bifidobacterium, Lactobacillus, and Enterococcus faecalis were higher with lower levels of Escherichia coli in the observation group than the control (p < 0.05). The level of D‐lactic acid and urinary L/M value of the urine in the observation group was lower than that in control after treatment (p < 0.001). The patients had a 3‐year survival rate of 91.30%. Age >60 years old, histological types of mucinous adenocarcinoma and signet ring cell carcinoma, vascular tumor thrombus, nerve invasion, TNM stage of Ⅲ−Ⅳ were independent risk factors, and anti PD‐1 treatment was the protective factor (p < 0.05). In advanced CRC patients receiving anti PD‐1 treatment combined with the Apatinib treatment, the progression of advanced CRC was effectively controlled by maintaining the intestinal microflora balance. Anti PD‐1 therapy can improve the living quality of CRC patients. [ABSTRACT FROM AUTHOR]

Significance: Reactive oxygen species (ROS) are essential in maintaining normal intestinal physiology. Inflammatory bowel disease (IBD) is a relapsing chronic inflammatory disease of the intestine that is a major risk factor for colorectal cancer (CRC). Excess ROS are widely implicated in intestinal inflammation and cancer. Recent Advances: Clinical data have shown that targeting ROS broadly does not yield improved outcomes in IBD and CRC. However, selectively limiting oxidative damage may improve the efficacy of ROS targeting. An accumulation of lipid ROS induces a novel oxidative cell death pathway known as ferroptosis. A growing body of evidence suggests that ferroptosis is relevant to both IBD and CRC. Critical Issues: We propose that inhibition of ferroptosis will improve disease severity in IBD, whereas activating ferroptosis will limit CRC progression. Data from preclinical models suggest that methods of modulating ferroptosis have been successful in attenuating IBD and CRC. Future Directions: The etiology of IBD and progression of IBD to CRC are still unclear. Further understanding of ferroptosis in intestinal diseases will provide novel therapies. Ferroptosis is highly linked to inflammation, cell metabolism, and is cell-type dependent. Further research in assessing the inflammatory and tumor microenvironment in the intestine may provide novel vulnerabilities that can be targeted. Antioxid. Redox Signal. 39, 551–568. [ABSTRACT FROM AUTHOR]

Low-level laser irradiation (LLLI) is a novel approach that shows promise for the treatment of colorectal cancer (CRC). However, the molecular mechanisms underlying its biochemical effects and gene expression remain unclear. Here, LLLI (632.8 nm) was used to treat CRC RKO cells and normal small intestinal NCM460 cells. LLLI showed a significant dose- and time-dependent effect on cell viability, in which a single dose of irradiation at 15 J/cm2 selectively inhibited the growth of RKO cells but largely unaffected the activity of NCM460 cells. And then, LLLI produced an internal response, effectively reducing the level of H2O2 in tumor cells, downregulating the mitochondrial membrane potential, and improving the efficiency of apoptosis in CRC, but no internal response was observed in NCM460 cells under the same conditions. Furthermore, the expression of several important genes in the classical WNT pathway was significantly downregulated, and the pathway was inactivated after LLLI intervention, thereby inhibiting tumor cell growth. Simultaneously, TNF-α was effectively activated to stimulate the caspase family members of the death effector to initiate apoptosis led by the extrinsic pathway. LLLI successfully achieves tumor cell normalization while delivering a potent anticancer effect, expected to be a novel therapeutic modality for CRC. [ABSTRACT FROM AUTHOR]

Objective: The relationship between intestinal microbiome and colorectal cancer (CRC) progression is unclear. This study aims to identify the intestinal microbiome associated with CRC progression and construct predictive labels to support the accurate assessment and treatment of CRC. Method: The 192 patients included in the study were divided into stage I-II and stage III-IV CRC patients according to the pathological stages, and preoperative stools were collected from both groups for 16S rDNA sequencing of the intestinal microbiota. Pearson correlation and Spearman correlation coefficient analysis were used to analyze the differential intestinal microbiome and the correlation with tumor microenvironment and to predict the functional pathway. XGBoost model (XGB) and Random Forest model (RF) were used to construct the microbiome-based signature. The total RNA extraction from 17 CRC tumor simples was used for transcriptome sequencing. Result: The Simpson index of intestinal microbiome in stage III-IV CRC were significantly lower than those in stage I-II CRC. Proteus, Parabacteroides, Alistipes and Ruminococcus etc. are significantly enriched genus in feces of CRC patients with stage III-IV. ko00514: Other types of O − glycan biosynthesis pathway is relevant with CRC progression. Alistipes indistinctus was positively correlated with mast cells, immune activators IL-6 and IL6R, and GOBP_PROTEIN_FOLDING_IN_ENDOPLASMIC_RETICULUM dominantly. The Random Forest (RF) model and eXtreme Gradient Boosting (XGBoost) model constructed with 42 CRC progression-associated differential bacteria were effective in distinguishing CRC patients between stage I-II and stage III-IV. Conclusions: The abundance and diversity of intestinal microbiome may increase gradually with the occurrence and progression of CRC. Elevated fetal abundance of Proteus, Parabacteroides, Alistipes and Ruminococcus may contribute to CRC progression. Enhanced synthesis of O − glycans may result in CRC progression. Alistipes indistinctus may play a facilitated role in mast cell maturation by boosting IL-6 production. Alistipes indistinctus may work in the correct folding of endoplasmic reticulum proteins in CRC, reducing ER stress and prompting the survival and deterioration of CRC, which may owe to the enhanced PERK expression and activation of downstream UPR by Alistipes indistinctus. The CRC progression-associated differential intestinal microbiome identified in our study can be served as potential microbial markers for CRC staging prediction. [ABSTRACT FROM AUTHOR]

Objective: This study aims to evaluate the diagnostic value of human serum cysteine protease inhibitors (cystatin 4 [CST4]) in colorectal cancer (CRC) patients. Methods: A total of 291 patients who were admitted to Zhuzhou Central Hospital for colonoscopy from January 2020 to December 2021 and met the inclusion criteria were selected. Serum samples of the patients were collected, and CST4 was detected by double-antibody sandwich enzyme-linked immunosorbent assay. Simultaneously, CEA and CA19-9 were detected, and the patients were divided into the CRC group, benign lesion group, and healthy control group. An attempt was made to construct a CRC prediction model including CST4 and draw a subject working characteristic curve as a diagnostic threshold for CRC prediction, and evaluate the diagnostic efficacy of the above indicators. At the same time, the expression analysis of CST4, CEA, and CA19-9 was verified by combining the data of CRC in the Tumor Genome Atlas (TCGA). Results: In this study, the levels of serum CST4, CEA, and CA19-9 in the CRC group were higher than those in the colorectal benign lesion group and healthy control group, with statistical significance (P <.001). The analysis results of the receiver operating characteristic curve showed that the area under the receiver operator characteristic curve (AUC) of CST4 was 0.7739, which was obviously larger than the AUC of CA19-9 and CEA. CRC data from the TCGA expression database showed that CST4 expression and CEA expression were higher in CRC patients than in normal samples. The combined model based on CST4 was successfully constructed, and the AUC for predicting the occurrence of CRC was 0.7851. Conclusion: CST4 is a novel and improved diagnostic marker for CRC. The combined model based on CST4 has a certain potential value in terms of predicting the occurrence of intestinal cancer. [ABSTRACT FROM AUTHOR]

Acrolein, a highly reactive α,β-unsaturated aldehyde, is a compound involved in the pathogenesis of many diseases, including neurodegenerative diseases, cardiovascular and respiratory diseases, diabetes mellitus, and the development of cancers of various origins. In addition to environmental pollution (e.g., from car exhaust fumes) and tobacco smoke, a serious source of acrolein is our daily diet and improper thermal processing of animal and vegetable fats, carbohydrates, and amino acids. Dietary intake is one of the main routes of human exposure to acrolein, which is a major public health concern. This review focuses on the molecular mechanisms of acrolein activity in the context of its involvement in the pathogenesis of diseases related to the digestive system, including diabetes, alcoholic liver disease, and intestinal cancer. [ABSTRACT FROM AUTHOR]

Research on the associations between structural variation and the appearance of endogenous and exogenous factors common in tumorigenesis allows for a better understanding of the causes of structural variants present in tumor genomes. Analysis of genomic variations from 2600 whole genomes compared to various cancer-inducing factors has found a moderate correlation between the development of structural variants and the increase in TP53 mutations and SBS4 mutational signatures in patients with Lung Adenocarcinoma or Squamous Cell Carcinoma. [ABSTRACT FROM AUTHOR]

The extract from Lycopodium clavatum (LC), a vascular plant, is traditionally used as a homeopathic medication to aid in digestive, urinary, liver, and neural disorders. Recently, LC has been shown to have potential anti-cancer effects on cervical and colon cancer cells. LC is believed to activate the CASP3 gene and affect the BCL-2 and p53 genes. These genes are involved in inducing apoptosis, regulating apoptosis, and suppressing the proliferation of tumor cells, respectively. Therefore, it was hypothesized that treating SW480 colorectal cancer cells with higher concentrations of LC would increase the expression of the CASP3 and p53 genes while decreasing the expression of the BCL-2 gene, thus resulting in cellular death. The hypothesis was tested by treating SW480 cells with two different concentrations of LC and counting every 24 hours (for three days), measuring cell proliferation and death. In addition, the expressions of CASP3, BCL-2, and p53 were measured with a qPCR test. Overall, the experiment demonstrated that LC could increase the gene expression of the CASP3, BCL-2, and p53 genes. Additionally, both LC concentrations resulted in a similar arrest of population growth, with 0.05 mg/ml of LC being the optimal concentration to induce apoptosis. [ABSTRACT FROM AUTHOR]

Background: Intestinal cancer the third most prevalent malignancy and leading cause of cancer mortality worldwide, is colorectal cancer (CRC). More than one-third of colorectal cancer cases in Egypt include people under the age of 40 who are found to have the disease at an advanced stage. Due to its function in human tumours, cyclooxygenase (COX), a crucial enzyme in the prostanoid biosynthesis pathway, has drawn a lot of interest. COX-2 regulates cell proliferation, cell transformation, tumour growth, metastasis, and invasion, and so plays an important role in the origin and development of metaplastic and dysplastic tissues, as well as the beginning and progression of cancer. Increased COX-2 expression has been linked to a variety of epithelial-based premalignant and malignant lesions in the gastrointestinal system, including the colorectal area. Objectives: To investigate the probable link between COX-2 gene polymorphism and colorectal cancer risk. Methods: This is a case-control study with 100 participants. Were selected 50 with colorectal cancer (case group) from Inpatient and Outpatient Oncology Clinic, Faculty of Medicine, Menoufia University and 50 participants without colorectal neoplasia (control group) matched in age and gender with case group. With the use of the usual literature approach, the polymorphism -765G/C COX2 gene was being identified using molecular genetic analysis. Clinical and pathological data from the patient were also examined. The findings demonstrated a link between the existence of the COX2 gene polymorphism and susceptibility to colorectal cancer in this pattern, with a significant incidence of GC and CC genotype in those with colorectal cancer. Additionally, there were variations in allele frequencies between the groups. There was a greater incidence of polymorphism in the left colon when cancer patients were divided based on the location of their tumours. Results: The comparison between the two studied groups indicated the genotype distribution of COX 2 gene polymorphisms in CRC patients that was 42%, 50%, and 8% with GG, GC, and CC respectively whereas in control group, it was 76% with GG, 22% with GC, and 2% with CC. The genotypic distribution revealed statistical difference (p=0.003). The allelic frequencies were 67% who had the wild allele G and the remaining 33% had the variant allele C in CRC group while in control group there were 87% with G and 13% with C allele. The difference was statistically significant (p=0.001). The GC genotype revealed a significant risk of CRC as compared to GG genotype. Subjects carrying the C allele had a significant risk of CRC compared to those carrying the allele G Conclusion: The COX2 gene polymorphism is linked to an increased risk of colorectal cancer, particularly rectosigmoid tumours. [ABSTRACT FROM AUTHOR]

• Increased IDH2 expression strongly associated with the progression of colorectal cancer (CRC) • Decreased IDH2 promotes α-ketoglutarate (α-KG) deposition by suppression of reductive citrate cycle. • Inhibitory IDH2-mediated deposition of α-KG dysregulate energy metabolism in CRC cells. • IDH2 promotes HIF-1A stabilization and facilitates CRC-liver metastasis. • Pharmacotherapy of IDH2 confers protection against CRC in vitro and in vivo. Changes in isocitrate dehydrogenases (IDH) lead to the production of the cancer-causing metabolite 2-hydroxyglutarate, making them a cause of cancer. However, the specific role of IDH in the progression of colon cancer is still not well understood. Our current study provides evidence that IDH2 is significantly increased in colorectal cancer (CRC) cells and actively promotes cell growth in vitro and the development of tumors in vivo. Inhibiting the activity of IDH2, either through genetic silencing or pharmacological inhibition, results in a significant increase in α-ketoglutarate (α-KG), indicating a decrease in the reductive citric acid cycle. The excessive accumulation of α-KG caused by the inactivation of IDH2 obstructs the generation of ATP in mitochondria and promotes the downregulation of HIF-1A, eventually inhibiting glycolysis. This dual metabolic impact results in a reduction in ATP levels and the suppression of tumor growth. Our study reveals a metabolic trait of colorectal cancer cells, which involves the active utilization of glutamine through reductive citric acid cycle metabolism. The data suggests that IDH2 plays a crucial role in this metabolic process and has the potential to be a valuable target for the advancement of treatments for colorectal cancer. [ABSTRACT FROM AUTHOR]

Cancer is one of the most common causes of death worldwide. A strong predisposition to cancer is generally only observed in colorectal cancer (5% of cases) and breast cancer (2% of cases). Colorectal cancer is the most common cancer with a strong genetic predisposition, but it includes dozens of various syndromes. This group includes familial adenomatous polyposis, attenuated familial adenomatous polyposis, MUTYH-associated polyposis, NTHL1-associated polyposis, Peutz–Jeghers syndrome, juvenile polyposis syndrome, Cowden syndrome, Lynch syndrome, and Muir–Torre syndrome. The common symptom of all these diseases is a very high risk of colorectal cancer, but depending on the condition, their course is different in terms of age and range of cancer occurrence. The rate of cancer development is determined by its conditioning genes, too. Hereditary predispositions to cancer of the intestine are a group of symptoms of heterogeneous diseases, and their proper diagnosis is crucial for the appropriate management of patients and their successful treatment. Mutations of specific genes cause strong colorectal cancer predispositions. Identifying mutations of predisposing genes will support proper diagnosis and application of appropriate screening programs to avoid malignant neoplasm. [ABSTRACT FROM AUTHOR]

Objective: The gut microbiota and its metabolites are important for host physiological homeostasis, while dysbiosis is related to diseases including the development of cancers such as colorectal cancer (CRC). In this study, we characterized the relationship of an altered gut microbiome with the fecal metabolome in CRC patients in comparison with volunteers having a normal colorectal mucous membrane (NC). Methods: The richness and composition of the microbiota in fecal samples of 30 CRC patients and 36 NC controls were analyzed through 16S rRNA gene sequencing, and the metabolome was determined by ultra-performance liquid chromatography coupled to tandem mass spectrometry. Spearman correlation analysis was to determine the correlation between the gut microbiome and fecal metabolome in CRC patients. Results: There were significant alterations in the gut microbiome and fecal metabolome in CRC patients compared with NC controls. Bacteroidetes, Firmicutes, Actinobacteriota, and Proteobacteria dominated the gut microbial communities at the phylum level in both groups. Compared with NC controls, CRC patients had a lower frequency of Blautia and Lachnospiracaea but a higher abundance of Bacteroides fragilis and Prevotella. Regarding the fecal metabolome, twenty-nine metabolites were identified as having significantly changed, showing increased levels of adrenic acid, decanoic acid, arachidonic acid, and tryptophan but a reduction in various monosaccharides in the fecal samples of CRC patients. Moreover, increased abundance of Bacteroides fragilis was strongly associated with decreased levels of monosaccharides, while Blautia was positively associated with the production of monosaccharides in the fecal samples. Conclusion: These results highlight alterations of gut microbiota in association with certain metabolites in CRC progression, implying potential diagnostic and intervention potential for CRC. [ABSTRACT FROM AUTHOR]

Purpose: CT colonography (CTC) is growing in its utilization as a nationally approved colorectal cancer screening test. After colonic polyps, lipomas are the second most common colonic lesions and their accurate and rapid recognition are important. Methods: This retrospective Institutional Review Board approved study was performed at two large academic university-based institutions. 1044 patients underwent CTC at Institution A from 2010 to 2018 and 1094 patients underwent CTC at Institution B from 2003 to 2015. All CTC examinations with at least one colonic lipoma in their report were evaluated by a fellowship-trained abdominal imaging radiologist. 47 CTC examinations containing 59 colonic lipomas were detected and included. Segmental location, sessile versus pedunculated morphology, multiplicity, average attenuation, and largest lesion diameter were evaluated. A review of the current literature on colonic lipomas is entailed. Results: The overall incidence of colonic lipoma was 2.2% in women and 2.3% in men. Mean age for detection of colonic lipomas on CTC was 66.9 years. Segmental locations of colonic lipomas include ascending colon (39%), transverse colon (19%), ileocecal valve (12%), cecum (12%), descending colon (10%), and rectosigmoid (8%). 9% of colonic lipomas were multiple, 42% were pedunculated, and 58% were sessile. The mean (range) size of detected lipomas was 19 (6–59) mm. The mean (range) attenuation was − 132 (− 41 to − 258) HU. Conclusion: Most colonic lipomas are located in the ascending colon. Although they are typically solitary, just under 10% are multiple, and although they are most often sessile, slightly under half are pedunculated mimicking polyps. CTC detects smaller lipomas than optical colonoscopy. [ABSTRACT FROM AUTHOR]

Purpose: The study aimed to evaluate the relationship between intra-tumor metabolic heterogeneity parameters of 18F-FDG and KRAS mutation status in colorectal cancer (CRC) patients and which threshold heterogeneity parameters could better reflect the heterogeneity characteristics of colorectal cancer. Methods: Medical data of 101 CRC patients who underwent 18F-FDG PET/CT and KRAS mutation analysis were selected. On PET scans, 18F-FDG traditional indices maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), total lesion glycolysis (TLG), and heterogeneity parameters coefficient of variation with a threshold of 2.5 (CV2.5), CV40%, heterogeneity index-1 (HI-1), and HI-2 of the primary lesions were obtained. We inferred correlations between these 18F-FDG parameters and KRAS mutation status. Results: 41 patients (40.6%) had KRAS gene mutation. Assessment of FDG parameters showed that SUVmax (19.00 vs. 13.16, p < 0.001), MTV (11.64 vs. 8.83, p = 0.001), and TLG (102.85 vs. 69.76, p < 0.001), CV2.5 (0.55 vs. 0.46, p = 0.006), and HI-2 (14.03 vs. 7.59, p < 0.001) of KRAS mutation were higher compared to wild-type (WT) KRAS. CV40% (0.22 vs. 0.24, p = 0.001) was lower in the KRAS mutation group, while HI-1 had no significant difference between the two groups. Multivariate analysis showed that MTV (OR = 4.97, 1.04–23.83, p = 0.045) was the only significant predictor in KRAS mutation, using a cut-off of 7.62 (AUC = 0.695), and MTV showed a sensitivity of 90.2% and specificity of 45.0%. However, the PET parameters were not independent predictors in KRAS mutation. Conclusion: KRAS gene mutant CRC patients had more 18F-FDG uptake (SUVmax, MTV, TLG) and heterogeneity (CV2.5, HI-2) than WT KRAS. MTV was the only independent predictor of KRAS gene mutation in colorectal cancer patients. [ABSTRACT FROM AUTHOR]

Emodin, a natural anthraquinone, has been shown to have antitumorigenic properties and may be an effective therapy for colorectal cancer (CRC). However, its clinical development has been hampered by a poor understanding of its mechanism of action. The purpose of this study was to 1) evaluate the efficacy of emodin in mouse models of intestinal/colorectal cancer and 2) to examine the impact of emodin on macrophage behavior in the context of CRC. We used a genetic model of intestinal cancer (ApcMin/+) and a chemically induced model of CRC [azoxymethane/dextran sodium sulfate (AOM/DSS)]. Emodin was administered orally (40 or 80 mg/kg in AOM/DSS and 80 mg/kg in ApcMin/+) three times a week to observe its preventative effects. Emodin reduced polyp count and size in both rodent models (P < 0.05). We further analyzed the colon microenvironment of AOM/DSS mice and found that mice treated with emodin exhibited lower protumorigenic M2-like macrophages and a reduced ratio of M2/M1 macrophages within the colon (P < 0.05). Despite this, we did not detect any significant changes in M2-associated cytokines (IL10, IL4, and Tgfb1) nor M1-associated cytokines (IL6, TNFα, IL1β, and IFNγ) within excised polyps. However, there was a significant increase in NOS2 expression (M1 marker) in mice treated with 80 mg/kg emodin (P < 0.05). To confirm emodin's effects on macrophages, we exposed bone marrow-derived macrophages (BMDMs) to C26 colon cancer cell conditioned media. Supporting our in vivo data, emodin reduced M2-like macrophages. Overall, these data support the development of emodin as a natural compound for prevention of CRC given its ability to target protumor macrophages. [ABSTRACT FROM AUTHOR]

Objective: To investigate the role of METTL3 in 5-fluorouracil resistance. Methods: High-dose intermittent inductionmethod was used to establish 5-FU resistant cell lines. Knockdown of METTL3 or EZH2 inhibitor GSK343 treatment were performed indrug-resistant cells. qPCR and Western blot were used to detect the expression of METTL3 and EZH2. CCK-8 was used to detect cell proliferation in each group. The m6A methylated RNA immunoprecipitation was used to analyze the modification of EZH2 mRNA m6A. Results: There was no significant difference in the proliferation activity of the drug-resistant group and the untreated cells under the treatment of various drug concentrations (P>0.05), however the primary cell group of intestinal cancer cells had a significant decreased proliferation activity compared to untreated cells under 0.5-10 μg/mL. Compared with the primary cell group, the expression levels of METTL3 and EZH2 in the drug-resistant group were significantly higher (P<0.01). After knockdown of METL3 or GSK343 in the drug-resistant group, the proliferation activity of cells at a concentration of 0.5 μg/mL-10 μg/mL was significantly lower than that of cells treatedwith 0 μg/mL (P<0.05). Compared with the control cells, the expression of EZH2 in the METTL3 knockdown cells of the drug resistancegroup was significantly down-regulated (P<0.01). The m6A methylated RNA immunoprecipitation experiment showed that the EZH2mRNA m6A modification level (m6A enrichment of 6361.95± 67.47%) of the METL3 knockdown cells in the drug-resistant group wassignificantly lower than that of the non-knockdown cells (396.30± 57.74)(P<0.01). Conclusion: METL3 plays a key role in 5-FU resistance of colorectal cancer cells. Targeted inhibition of METL3 is expected to become an important molecular target for alleviating resistance of colorectal cancer. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) is a progressive monogenetic disorder that causes persistent pulmonary disease, but also affects other organ systems, including the digestive tract. Recent advances in treatment and care of patients with CF, including the use of new and highly effective CF transmembrane conductance regulator modulators, have led to a dramatic increase in survival. Young patients with CF now can expect to live to or beyond middle age, when cancer is more frequent. Patients with CF now are known to face an increased risk of digestive tract cancer, particularly cancer of the colon. The risk, which could be triggered by associated CF-related conditions or other genetic mechanisms, is even greater in patients who received a transplant. Also some evidence suggests that adenomatous polyps develop more frequently in patients with CF and at an earlier age than in patients without CF. To reduce the excess risk of intestinal cancer in patients with CF, the Cystic Fibrosis Foundation has developed colonoscopy-based guidelines. For nontransplanted patients, colonoscopy should begin at 40 years of age, with rescreening at 5-year intervals; the screening interval should be shortened to 3 years if adenomatous polyps are discovered. For transplanted patients, screening should start at 30 years of age, or within 2 years of the transplant operation. Before colonoscopy, it is essential for patients with CF to undergo a special, more intensive bowel preparation than normally used for those without CF. Whether the new drugs that have dramatically improved morbidity and mortality for patients with CF will alter the risk of cancer is unknown and needs to be assessed in future studies. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Patients with serrated polyposis syndrome (SPS) and their first-degree relatives (FDRs) have increased colorectal cancer (CRC) risk. Patients with sporadic sessile serrated lesion (SSL) have risk for progression to CRC. Yet familial risks of common extracolonic cancers and even CRC in these cohorts are poorly understood. Our aim was to examine cancer risk for patients with SPS and sporadic SSL and their close and more distant relatives using a large population database. METHODS: Patients with SPS (n = 59) from hereditary patient registries were eligible for study. Sporadic SSL (n = 754) and sex- and age-matched normal colonoscopy controls (n = 1,624) were selected from clinical data linked to the Utah Population Database. Cox models adjusting for the number of relatives, degree of relatedness, and person-years at risk were used to estimate CRC, extracolonic, and any-site adenocarcinoma/carcinoma cancer risk in patients and their relatives. RESULTS: Compared with controls, CRC risk was elevated 10-fold in patients with SPS (P = 0.04) and 5-fold in their FDRs (P = 0.001). Any-site adenoma/carcinoma risk was increased 2.6-fold in FDRs of patients with SPS. No elevated risks of other common extracolonic cancers were observed in SPS and family members. The FDRs, second-degree relatives, and third-degree relatives of patients with both SSL and adenomatous polyps exhibited a 50% increased CRC risk. DISCUSSION: Patients with SPS and their FDRs have an increased CRC risk, confirming other reports. Interestingly, patients with SSL were noted to have an increased risk of prostate cancer. Relatives of individuals with both sporadic SSL and adenomas, irrespective of size or dysplasia on examination, may have an elevated CRC risk, suggesting closer colonoscopy surveillance in this population. [ABSTRACT FROM AUTHOR]

Lynch syndrome (LS), Lynch‐like syndrome (LLS) and familial colorectal cancer type X (FCCX) are different entities of familial cancer predisposition leading to an increased risk of colorectal cancer (CRC). The aim of this prospective study was to characterise and to compare the risks for adenoma and CRC in these three risk groups. Data was taken from the registry of the German Consortium for Familial Intestinal Cancer. Patients were prospectively followed up in an intensified colonoscopic surveillance programme that included annual examinations. Cumulative risks for adenoma and CRC were calculated separately for LS, LLS and FCCX, and then for males and females. Multivariate Cox regression was used to analyse the independent contributions of risk group, mismatch repair gene (within LS), sex and previous adenoma. The study population comprised 1448 individuals (103 FCCX, 481 LLS and 864 LS). The risks were similar for colorectal adenomas, but different for first and metachronous CRC between the three risk groups. CRC risk was highest in LS, followed by LLS and lowest in FCCX. Male sex and a prevalent adenoma in the index colonoscopy were associated with a higher risk for incident adenoma and CRC. In patients with LS, CRC risks were particularly higher in female MSH2 than MLH1 carriers. Our study may support the development of risk‐adapted surveillance policies in LS, LLS and FCCX. What's new? While associations between colorectal cancer (CRC) risk and Lynch syndrome (LS) are well‐described, less is known about CRC risks linked to the closely related Lynch‐like syndrome (LLS) and familial colorectal cancer type X (FCCX). In this prospective follow‐up study of patients with LS, LLS, and FCCX, risks were similar for colorectal adenomas but considerably different for first and metachronous CRCs. In addition, LS females who carried MSH2 mutations had notably higher CRC risks than female MLH1 mutation carriers. The identification of variations in carcinogenic pathways between LS, LLS, and FCCX could enable risk‐adapted CRC surveillance for these syndromes. [ABSTRACT FROM AUTHOR]

Background: The intestinal flora is correlated with the occurrence of colorectal cancer. We evaluate a new predictive model for the non-invasive diagnosis of colorectal cancer based on intestinal flora to verify the clinical application prospects of the intestinal flora as a new biomarker in non-invasive screening of colorectal cancer. Methods: Subjects from two independent Asian cohorts (cohort I, consisting of 206 colorectal cancer and 112 healthy subjects; cohort II, consisting of 67 colorectal cancer and 54 healthy subjects) were included. A probe-based duplex quantitative PCR (qPCR) determination was established for the quantitative determination of candidate bacterial markers. Results: We screened through the gutMEGA database to identify potential non-invasive biomarkers for colorectal cancer, including Prevotella copri (Pc), Gemella morbillorum (Gm), Parvimonas micra (Pm), Cetobacterium somerae (Cs), and Pasteurella stomatis (Ps). A predictive model with good sensitivity and specificity was established as a new diagnostic tool for colorectal cancer. Under the best cutoff value that maximizes the sum of sensitivity and specificity, Gm and Pm had better specificity and sensitivity than other target bacteria. The combined detection model of five kinds of bacteria showed better diagnostic ability than Gm or Pm alone (AUC = 0.861, P < 0.001). These findings were further confirmed in the independent cohort II. Particularly, the combination of bacterial markers and fecal immunochemical test (FIT) improved the diagnostic ability of the five bacteria (sensitivity 67.96%, specificity 89.29%) for patients with colorectal cancer. Conclusion: Fecal-based colorectal cancer-related bacteria can be used as new non-invasive diagnostic biomarkers of colorectal cancer. Simultaneously, the molecular biomarkers in fecal samples are similar to FIT, have the applicability in combination with other detection methods, which is expected to improve the sensitivity of diagnosis for colorectal cancer, and have a promising prospect of clinical application. [ABSTRACT FROM AUTHOR]

Resveratrol (RES) and Vitamin E (VE) are anti-cancer active ingredients with relatively high content in peanut seeds and sprouts. This study aimed to determine the synergistic inhibitory effect of RES and VE on colorectal cancer. Using 5-FU as a positive drug control, the effect of RES combined with VE on HCT-8 cells was determined, and cell viability was detected using the cell-counting kit 8 (CCK8) method. Cell morphology changes were observed using optical microscopy. Cell migration ability was evaluated by the scratch test, while cell colonies were determined by the cloning test formation ability. Apoptosis status was assessed by flow cytometry and nuclear staining by DAPI, and the expression level of apoptosis-related proteins was determined by western blotting. Compared with the single component group, the RES combined with VE group significantly inhibited the growth and proliferation of HCT-8 intestinal cancer cells in vitro. The RES combined with VE group had a greater impact on cell morphology changes and cell colony formation and significantly reduced cell migration ability and intestinal cancer cell apoptosis (p < 0.05). Additionally, combined treatment with RES and VE significantly upregulated the expression of pro-apoptotic proteins BAX, caspase-3, caspase-8, and caspase-9, and downregulated the expression of anti-apoptotic protein BCL-2, compared to the single component treatment. RES combined with VE is effective in promoting intestinal cancer cell apoptosis. This study demonstrated the significant positive synergy of RES and VE on HCT-8 cells, providing a new perspective for more effective use of RES. [ABSTRACT FROM AUTHOR]

Surgery for colorectal cancer (CRC) can cause damage to the intestinal mucosal barrier and lead to bacterial invasion. This study mainly analyzed whether propofol (PPF) could protect the intestinal mucosal barrier damage caused by CRC surgery, and explored its molecular mechanism. A mouse CRC model was constructed using azomethane and dextran sulfate sodium. During anesthesia, continuous intravenous injection of PPF was used for intervention. The influences of PPF on intestinal mucosal permeability and bacterial invasion were detected. The levels of microRNA (miR)-155, Toll-like receptor 4 (TLR4)/NF-κB in the intestinal mucosa, and the location of miR-155 were detected by fluorescence in situ hybridization (FISH). Mouse macrophages were used to analyze the regulation of miR-155 on the secretion of inflammatory cytokines through the TLR4/NF-κB pathway. PPF treatment promoted the expression of tight junction protein in the intestinal mucosa, protected the intestinal barrier, inhibited the translocation of intestinal bacteria, and increased the level of the beneficial bacterium Lactobacillus on the mucosal surface. In addition, PPF treatment could inhibit the expression of miR-155, TLR4/NF-KB, and reverse inflammatory response. miR-155 was expressed in macrophages of intestinal mucosa tissue. Overexpression of miR-155 promoted the nuclear translocation of NF-κB and the expression of inflammatory cytokines in macrophages. The use of VIPER to inhibit TLR4 reversed the pro-inflammatory effects of miR-155. PPF might inhibit the activation of the NF-κB pathway by downregulating miR-155 expression, thereby reducing the secretion of inflammatory cytokines. This might be the mechanism by which PPF protected the intestinal barrier of CRC surgical model mice. [ABSTRACT FROM AUTHOR]

Introduction: Oxidative stress and lipid peroxidation are pointed as possible factors in the development of colorectal cancer (CRC). The aim of this study was to assess the serum malondialdehyde (MDA) and non-enzymatic antioxidants concentration (albumin, bilirubin, uric acid, and ferritin) and their relation with the stage and histopathologic size (pT) of CRC. Methods: One hundred and twenty patients with clinically and histopathologically confirmed CRC and the need for surgical treatment were included in a cross-sectional study. All patients were divided into groups according to the disease stage and depth of tumor invasion. The control group included 30 subjects with no signs of malignant and inflammatory bowel disease. The patients and controls did not receive vitamin supplementation. Peripheral venous blood was sampled before the surgical treatment of CRC patients and on the day of the examination of control subjects for determination of serum MDA and the concentration of the non-enzymatic antioxidants. Results: The serum levels of MDA were progressively increased in CRC patients with the highest level in the fourth stage of disease and pT4 group. Ferritin levels increased significantly with the CRC stage and decreased with the depth of bowel wall invasion. Serum albumin concentration significantly decreased with increasing stage and increasing depth of tumor invasion of the intestinal wall, while serum bilirubin level showed no change compared to the control group. Serum uric acid concentration was significantly higher in CRC patients, but no difference was observed with CRC progression. It was confirmed that serum albumin significantly negatively correlated with the CRC stage (rho = -0.649, p < 0.001), while serum MDA significantly positively correlated with the CRC stage (rho = 0.750, p < 0.001). Conclusion: These results indicate that serum MDA concentrations are related to the progression of CRC, to which the imbalance in non-enzymatic antioxidants also contributes. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Gender preferences have been reported as a barrier to colorectal cancer screening, particularly among women. We aim to identify the role of patients' gender preferences for endoscopists and endoscopy team members, with the effect of age-related and regional differences. METHODS: We conducted an anonymous, voluntary survey of all adult outpatients presenting at our endoscopy centers before their procedures. RESULTS: We received 2,138 (1,207 women, 905men, and 26 undisclosed; 50% urban and 50% rural) completed surveys. The majority of the patients (89%) did not have an endoscopist gender preference, while 8% preferred a same-gender endoscopist, and 2% preferred an opposite gender endoscopist. Among patients who expressed a gender preference, men more commonly preferred a same-gender endoscopist than women (91% vs 67%, P < 0.05). More patients preferred a same-gender endoscopy team member than a same-gender endoscopist (17% vs 8%, P < 0.05), and women more commonly preferred a same-gender endoscopy team member than men (26% vs 6%, P < 0.05). Most patients who expressed same-gender endoscopist preference were between the ages of 50-69 years as compared to other age groups (P < 0.05). Of the urban patients, 9%expressed a same-gender endoscopist preference and3%expressed an opposite gender preference, compared with 7% and 2% of rural patients (P < 0.05). Among patients with any endoscopist gender preference, rural patients were more willing to wait longer (41% vs 21%, P < 0.05), whereas urban patients were willing to pay more (64% vs 14%, P < 0.05) to have their preferences met. DISCUSSION: Contrary to previous studies, most patients did not have an endoscopist gender preference. Interestingly, men had more same-gender endoscopist preference, whereas women had more same-gender endoscopy team member preference. Age-related and regional differences exist among patients' gender preferences for their endoscopist and endoscopy team member, and addressing these preferences while creating an environment of a multigender endoscopy team may be beneficial in improving colorectal cancer screening. [ABSTRACT FROM AUTHOR]

• Provide an overview of the CGAS-STING signaling pathway and activation mechanism, and explore the interaction of this signaling pathway with other pathways. • Exploring the role of the cGAS-STING signaling pathway in various intestinal diseases and research advances. • Summarize current natural products and other substances that target the cGAS-STING signaling pathway for therapeutic effects. • Exploring the effect of gut flora on this signaling pathway. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signal has drawn much consideration due to its sensitivity to DNA in innate immune mechanisms. Activation of the cGAS-STIN signaling pathway induces the production of interferon and inflammatory cytokines, resulting in immune responses, or inflammatory diseases. The intestinal tract is a vital organ for the body's nutrition absorption, recent studies have had various points of view on the job of cGAS-STING pathway in various intestinal sicknesses. Therefore, understanding its role and mechanism in the intestinal environment can help to develop new strategies for the treatment of intestinal diseases. This article examines the mechanism of the cGAS-STING pathway and its function in inflammatory bowel disease, intestinal cancer, and long-injury ischemia-reperfusion, lists the current medications that target it for the treatment of intestinal diseases, and discusses the impact of intestinal flora on this signaling pathway, to offer a theoretical and scientific foundation for upcoming targeted therapies for intestinal disorders via the cGAS-STING pathway. [ABSTRACT FROM AUTHOR]

Inhibition of K-RAS effectors like B-RAF or MEK1/2 is accompanied by treatment resistance in cancer patients via re-activation of PI3K and Wnt signaling. We hypothesized that myotubularin-related-protein-7 (MTMR7), which inhibits PI3K and ERK1/2 signaling downstream of RAS, directly targets RAS and thereby prevents resistance. Using cell and structural biology combined with animal studies, we show that MTMR7 binds and inhibits RAS at cellular membranes. Overexpression of MTMR7 reduced RAS GTPase activities and protein levels, ERK1/2 phosphorylation, c- FOS transcription and cancer cell proliferation in vitro. We located the RAS-inhibitory activity of MTMR7 to its charged coiled coil (CC) region and demonstrate direct interaction with the gastrointestinal cancer-relevant K-RASG12V mutant, favouring its GDP-bound state. In mouse models of gastric and intestinal cancer, a cell-permeable MTMR7-CC mimicry peptide decreased tumour growth, Ki67 proliferation index and ERK1/2 nuclear positivity. Thus, MTMR7 mimicry peptide(s) could provide a novel strategy for targeting mutant K-RAS in cancers. • RAS mutations underlie resistance of gastrointestinal cancers to clinical therapies. • We identified the lipid phosphatase MTMR7 as a novel physiological inhibitor of mutant RAS. • MTMR7 peptide derived from its coiled coil domain stabilized the inactive form of GDP bound K-RAS G12V. • Cell permeable MTRM7-derived peptide mitigated growth of gastric and colorectal cancer in mice. • We may develop new treatments based on the MTMR7-derived peptide for patients with RAS mutant cancers. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Anti-PD-1 therapy for advanced colorectal cancer based on intestinal microecology." The correction addresses an error in the funding information section of the article, where the incorrect grant and award numbers were provided. The correct grant and award numbers should be "First Batch, No. 202201020571 and Grant/Award Number: 202201020571." The correction notice apologizes for the error. [Extracted from the article]

The life on earth is driven by energy, supplied by the tiny organelles of the cell called mitochondria and they are usually stated as the powerhouses of the cell. In population genetics, Mitochondrial DNA (mtDNA) is used extensively to categorize individuals or populations. The mutation sites observed in human mtDNA by comparing with the reference sequence (rCRS) are termed into definite human mtDNA haplogroups. Previous studies showed that mtDNA specific haplogroups and polymorphisms were established to be linked with various human diseases, including cancer in numerous populations. Furthermore, it is also known that several mitochondrial DNA polymorphisms are implicated in enhanced production of Reactive Oxygen Species (ROS) which are known to be an increased risk cause for several cancers, including colorectal cancer in Indian patients. Hence in our study, we made high resolution examination on mtDNA hypervariable region to trace the association of specific mtDNA haplogroup with colorectal cancer in south Indian populations. We report that mtDNA Haplogroup M was observed in 60% of the colorectal cancer patients and around 55% in the studied control samples. Haplogroup M is the most frequent mtDNA cluster found among south Indian populations. We further sub-lineated macro haplogroup M and found sub haplogroups (M8, M7, M6, M5, M3 and M2) in varied frequencies. In particular, we found significant association of haplogroup M5 with colorectal cancer patients (p = 0.026). Haplogroup M5 was observed in 12% of colorectal cancer patients in south Indian patients and in 3.3% of the control populations. These results suggest that individuals with haplogroup M5 may have significant risk to develop colorectal cancer. [ABSTRACT FROM AUTHOR]

The intestine is the well-acknowledged important organ where the nutritional molecules are absorbed. Meanwhile, intestinal ailments, including intestinal mucosal atrophy, barrier dysfunction (leaky gut), inflammation bowel disease (ulcerative colitis and Crohn's disease), irritable bowel syndrome (IBS), dysbacteriosis, and cancers (sporadic and colitis-associated intestinal cancers), have always been the top-ranking diseases that we are confronting. However, although there are several reports on the intestinal modulatory effects for the food macromolecular components (polysaccharides and prebiotics), the effects of low-molecular-weight phytochemicals from foods, especially those from functional foods, on intestinal ailments have not been methodically understood. Various functional foods and their low-molecular-weight phytochemicals that help protect intestinal homeostasis have been demonstrated. The preliminary in vitro results are not included due to the uncertainty of their in vivo efficacy. This review compiles only in vivo bioactive reports and findings with solid pieces of evidence (both human and animal-based ones) to demonstrate the practical use of the food and its low-molecular-weight phytochemicals as complementary therapies or dietary supplements for intestinal health and their underlying mechanism of action. Functional foods (both the whole food and extracts) and their low-molecular-weight phytochemicals can benefit intestinal health of both small and large intestines at different stages of intestinal ailments through promoting intestinal epithelial renewal and barrier function, restoring intestinal flora, inhibiting intestinal inflammation and tumor growth, and exerting intestinal-cancer preventive effects. Therefore, depending on the circumstances of the intestinal ailment, intake of certain functional foods or their low-molecular-weight phytochemicals can relieve the symptom of intestinal ailments and contribute to the maintenance of intestinal homeostasis at different levels. • The effects of foods and their phytochemicals on intestinal homeostasis are summarized. • Only clinical and in vivo results are compiled to assure the credibility of the conclusion in this paper. • Recommendations are suggested with respect to different intestinal ailments. [ABSTRACT FROM AUTHOR]

INTRODUCTION: During the COVID-19 pandemic, both the channelling of manpower into the COVID-19 services and efforts to limit viral spreading of the disease have led to rescheduling and prioritizing oncological cases that are considered as cases of emergency and any postponement of the cases can lead to health problems. In this study, we aimed to show that the surgical treatment of COVID-19 (-) colorectal cancer patients can be performed in a hospital which was declared as a pandemic hospital. METHOD: In our study, we included patients who underwent surgery for colorectal cancer in the general surgery clinic between the dates 03.20.2020 and 05.20.2020, when the hospital was declared COVID-19 pandemic hospital. Emergency colorectal cancer surgeries such as ileus and perforation were excluded from the study. RESULTS: While in the status of pandemic hospital, 80 COVID-19 (+) and 563 COVID-19 (+) suspicious patients were treated. Between 10 March 2020 and 15 May 2020, 12 colorectal cancer patients were operated in the General Surgery Clinic of BAIBU Faculty of Medicine, as well. CONCLUSION: We think that with our study we have shown that during the COVID-19 pandemic, the surgical treatment can be performed for patients with colorectal cancer by eliminating COVID-19 suspicions. [ABSTRACT FROM AUTHOR]

The current study was designed to clarify the histochemical changes in the types of mucin that develop in colorectal carcinoma, as well the changes in the types and amount of mucin seen in different grading of colorectal cancer which is marked reduction that has seen in poorly differentiated subtype. Mucin histochemical changes clarified by applying special stain (Periodic acid shiff and alcian blue) and (Orcein /Alcian blue) on 40 biopsies selected from patients who had colorectal cancer of different staging and first we reviewed the H&E slides then select those 40 cases blocks to be stained with special stains on those colorectal biopsies and we used 13 cases of normal colonic tissue considered as control cases, those patients biopsies had obtained from Teaching Laboratories in Medical city in Baghdad Medical College teaching Hospital. There is marked reduction in the amount of normal mucin in colorectal cancer biopsies in addition to the changes of the type of mucin from sulphated mucin to sialomucin when comparing with normal colonic biopsy specimen that used as control and stained with same special stains with significant reduction or sometimes complete absence of mucin in poorly differentiated grade. In conclusion, in this study, we could demonstrate that there is a progressive decline of acid mucin from low-graded to high graded adenocarcinoma of colorectal with corresponding decrease in neutral mucins. [ABSTRACT FROM AUTHOR]

Transforming growth factor‐β (TGF‐β) plays a dual role acting as tumor promoter or suppressor. Along with cyclooxygenase‐2 (COX‐2) and oncogenic Ras, this multifunctional cytokine is deregulated in colorectal cancer. Despite their individual abilities to promote tumor growth and invasion, the mechanisms of cross regulation between these pathways is still unclear. Here, we investigate the effects of TGF‐β, Ras oncogene and COX‐2 in the colorectal cancer context. We used colon adenocarcinoma cell line HT‐29 and Ras‐transformed IEC‐6 cells, both treated with prostaglandin E2 (PGE2), TGF‐β or a combined treatment with these agents. We demonstrated that PGE2 alters the subcellular localization of E‐cadherin and β‐catenin and enhanced the tumorigenic potential in HT‐29 cells. This effect was inhibited by TGF‐β, indicating a tumor suppressor role. Conversely, in Ras‐transformed IEC‐6 cells, TGF‐β induced COX‐2 expression and increased invasiveness, acting as a tumor promoter. In IEC‐6 Ras‐transformed cells, TGF‐β increased nuclear β‐catenin and Wnt/β‐catenin activation, opposite to what was seen in the PGE2 and TGF‐β joint treatment in HT‐29 cells. Together, our findings show that TGF‐β increases COX‐2 levels and induces invasiveness cooperating with Ras in a Wnt/β‐catenin activation‐dependent manner. This shows TGF‐β dual regulation over COX‐2/PGE2 tumor promotion depending on the H‐Ras and Wnt/β‐catenin pathways activation status in intestinal cancer cells. [ABSTRACT FROM AUTHOR]

Personalised treatment which is a dynamically developing branch of medicine, is based on individualisation of diagnostic and therapeutic procedures. Its aim is to optimise treatment by increasing therapy effectiveness, while minimising side effects. It is designed both for patients with a diagnosed hereditary cancer syndrome, as well as those with sporadic cancers. In the case of a diagnosed colorectal cancer, personalised treatment requires patient selection based on predictive factors. This involves determination of the genetic status within the epidermal growth factor receptor (EGFR) signalling pathway, including assessment of the cancer tissue genotype with respect to RAS gene mutations (KRAS, NRAS) and BRAF gene mutations. In patients who do not respond to anti-EGFR targeted therapy, chemotherapy aimed at vascular endothelial growth factor (VEGF) is introduced. In personalised medicine it is also essential to introduce prophylactic and therapeutic measures, both in carriers of germline mutations, and members of their families who have not been diagnosed with this mutation, but who meet family history and clinical criteria of hereditary cancer syndrome. [ABSTRACT FROM AUTHOR]

Purpose: This study assessed population awareness of colorectal cancer and the attitude toward screening and its determinants in the Aseer region of Saudi Arabia. Patients and methods: A descriptive cross-sectional approach was used to identify all accessible populations in the Aseer region of southern Saudi Arabia. Data were collected from participants using an online pre-structured questionnaire. The tool assessed participants' biodemographic data, medical and family history, awareness regarding colorectal cancer and attitude toward screening. Results: A total of 1,296 respondents completed the survey. Participants' ages ranged from 18 to 65 years, with a mean age of 29.6±13.8 years. The majority of participants were female (66.7%; 864). A total of 1,018 (78.5%) of the participants had heard about colorectal cancer, and 648 (50%) correctly defined it as large intestine cancer. Regarding symptoms, participants mostly reported abdominal pain (80.3%), blood in the stool (77.2%), and a change in bowel habits (76.7%). A good awareness level was established in nearly one-fifth of the participants. A total of 1,236 participants (95.4%) reported that they would undergo screening if they had any risk factor for colorectal cancer. The main barrier to undergo screening was that participants did not have any symptoms (31.7%). Conclusion: This survey revealed that the public awareness of colorectal cancer in the Aseer region was overall poor. Participants had some knowledge regarding individual aspects but lacked knowledge of others. We recommend that healthcare staff should pay more attention to improving public awareness of the recommended screening for colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC), a type of highly occurred intestinal cancer at present, is prone to metastasis at the later stage of chemotherapy. Looking for the anti-metastatic agents from natural compounds attracted much concern. Here, it aims to demonstrate whether oxymatrine, an anti-cancer natural compound, has anti-metastatic activity and its potential significance in clinic. Materials and Methods: Wound healing assay and transwell assay were for evaluating the effect of oxymatrine on cell migration and invasion in vitro. Anti-metastatic action in vivo was determined by hepatic metastasis of colorectal cancer cells in mice. Results: Oxymatrine can significantly inhibit cancer cell migration and invasion in vitro. The production of ATP, pyruvate, and lactate was suppressed in CRC cells under the treatment of oxymatrine, as well as the glucose consumption. Meantime, extracellular acidification rates (ECR) were evidently attenuated although the oxygen consumption rates (OCR) were not affected. Both clued that oxymatrine inhibition of metastasis is possibly related to blocking aerobic glycolysis. Subsequent results indicated that pyruvate kinase M2 (PKM2) not hexokinase (HK) and phosphofructokinase (PFK) were involved in oxymatrine blocking glycolysis as the PKM2 kinase activity and expression were inhibited by oxymatrine and the PKM2 activator, TEPP-46, can reverse in part the effect of oxymatrine induced in CRC cells. Furthermore, this process was also mediated by inhibition of glucose transporter 1 (GLUT1). Finally, the in vivo metastatic model in mice showed both 20 mg/kg and 40 mg/kg oxymatrine significantly inhibit liver metastasis of CRC cells in mice, and PKM2 and GLUT1 expression in liver of the oxymatrine-treated group is declined. Conclusion: Oxymatrine exerted anti-metastatic activity dependent on inhibition of PKM2-mediated aerobic glycolysis. It is not only an anti-cancer agent but also a potential anti-metastatic compound with clinical application significance. [ABSTRACT FROM AUTHOR]