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Tissue regeneration after damage is generally thought to involve the mobilization of adult stem cells that divide and differentiate into progressively specialized progeny. However, recent studies indicate that tissue regeneration can be accompanied by reversion to a fetal-like state. During this process, cells at the injury site reactivate programs that operate during fetal development but are typically absent in adult homeostasis. Here, we summarize our current understanding of the molecular signals and epigenetic mediators that orchestrate "fetal-like reversion" during intestinal regeneration. We also explore evidence for this phenomenon in other organs and species and highlight open questions that merit future examination.

Regenerative cell therapy to replenish the missing neurons and glia in the aganglionic segment of Hirschsprung disease represents a promising treatment option. However, the success of cell therapies for this condition are hindered by poor migration of the transplanted cells. This limitation is in part due to a markedly less permissive extracellular environment in the postnatal gut than that of the embryo. Coordinated interactions between enteric neural crest-derived cells (ENCDCs) and their local environment drive migration along the embryonic gut during development of the enteric nervous system. Modifying transplanted cells, or the postnatal extracellular environment, to better recapitulate embryonic ENCDC migration could be leveraged to improve the engraftment and coverage of stem cell transplants. We compared the transcriptomes of ENCDCs from the embryonic intestine to that of postnatal-derived neurospheres and identified 89 extracellular matrix (ECM)-associated genes that are differentially expressed. Agrin, a heparin sulfate proteoglycan with a known inhibitory effect on ENCDC migration, was highly over-expressed by postnatal-derived neurospheres. Using a function-blocking antibody and a shRNA-expressing lentivirus, we show that inhibiting agrin promotes ENCDC migration in vitro and following cell transplantation ex vivo and in vivo. This enhanced migration is associated with an increased proportion of GFAP + cells, whose migration is especially enhanced.

Plasticity among cell lineages is a fundamental, but poorly understood, property of regenerative tissues. In the gut tube, the small intestine absorbs nutrients, whereas the colon absorbs electrolytes. In a striking display of inherent plasticity, adult colonic mucosa lacking the chromatin factor SATB2 is converted to small intestine. Using proteomics and CRISPR-Cas9 screening, we identify MTA2 as a crucial component of the molecular machinery that, together with SATB2, restrains colonic plasticity. MTA2 loss in the adult mouse colon activated lipid absorptive genes and functional lipid uptake. Mechanistically, MTA2 co-occupies DNA with HNF4A, an activating pan-intestinal transcription factor (TF), on colonic chromatin. MTA2 loss leads to HNF4A release from colonic chromatin, and accumulation on small intestinal chromatin. SATB2 similarly restrains colonic plasticity through an HNF4A-dependent mechanism. Our study provides a generalizable model of lineage plasticity in which broadly-expressed TFs are retained on tissue-specific enhancers to maintain cell identity and prevent activation of alternative lineages, and their release unleashes plasticity.

The composition of the microbial community in the intestine may influence the functions of distant organs such as the brain, lung, and skin. These microbes can promote disease or have beneficial functions, leading to the hypothesis that microbes in the gut explain the co-occurrence of intestinal and skin diseases. Here, we show that the reverse can occur, and that skin directly alters the gut microbiome. Disruption of the dermis by skin wounding or the digestion of dermal hyaluronan results in increased expression in the colon of the host defense genes Reg3 and Muc2, and skin wounding changes the composition and behavior of intestinal bacteria. Enhanced expression Reg3 and Muc2 is induced in vitro by exposure to hyaluronan released by these skin interventions. The change in the colon microbiome after skin wounding is functionally important as these bacteria penetrate the intestinal epithelium and enhance colitis from dextran sodium sulfate (DSS) as seen by the ability to rescue skin associated DSS colitis with oral antibiotics, in germ-free mice, and fecal microbiome transplantation to unwounded mice from mice with skin wounds. These observations provide direct evidence of a skin-gut axis by demonstrating that damage to the skin disrupts homeostasis in intestinal host defense and alters the gut microbiome.

BACKGROUND/AIMS: We investigated the clinical practice patterns of post-polypectomy colonoscopic surveillance among Korean endoscopists. METHODS: In a web-based survey conducted between September and November 2021, participants were asked about their preferred surveillance intervals and the patient age at which surveillance was discontinued. Adherence to the recent guidelines of the U.S. Multi-Society Task Force on Colorectal Cancer (USMSTF) was also analyzed. RESULTS: In total, 196 endoscopists completed the survey. The most preferred first surveillance intervals were: a 5-year interval after the removal of 1-2 tubular adenomas < 10 mm; a 3-year interval after the removal of 3-10 tubular adenomas < 10 mm, adenomas ≥ 10 mm, tubulovillous or villous adenomas, ≤ 20 hyperplastic polyps < 10 mm, 1-4 sessile serrated lesions (SSLs) < 10 mm, hyperplastic polyps or SSLs ≥ 10 mm, and traditional serrated adenomas; and a 1-year interval after the removal of adenomas with highgrade dysplasia, >10 adenomas, 5-10 SSLs, and SSLs with dysplasia. In piecemeal resections of large polyps ( > 20 mm), surveillance colonoscopy was mostly preferred after 1 year for adenomas and 6 months for SSLs. The mean USMSTF guideline adherence rate was 30.7%. The largest proportion of respondents (40.8%-55.1%) discontinued the surveillance at the patient age of 80-84 years. CONCLUSIONS: A significant discrepancy was observed between the preferred post-polypectomy surveillance intervals and recent international guidelines. Individualized measures are required to increase adherence to the guidelines.

The pig is an important translational model for studying intestinal physiology and disorders for its many homologies with humans, including the organization of the enteric nervous system (ENS), the major regulator of gastrointestinal functions. This study focused on the quantification and neurochemical characterization of substance P (SP) neurons in the pig ascending (AC) and descending colon (DC) in wholemount preparations of the inner submucosal plexus (ISP), outer submucosal plexus (OSP), and myenteric plexus (MP). We used antibodies for the pan-neuronal marker HuCD, and choline acetyltransferase (ChAT) and neuronal nitric oxide synthase (nNOS), markers for excitatory and inhibitory transmitters, for multiple labeling immunofluorescence and high-resolution confocal microscopy. The highest density of SP immunoreactive (IR) neurons was in the ISP (222/mm2 in the AC, 166/mm2 in the DC), where they make up about a third of HuCD-IR neurons, compared to the OSP and MP (19-22% and 13-17%, respectively, P

Introduction: Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. There is a significant burden of mortality from colorectal cancer in Africa. Due to the heterogeneity of dietary and lifestyle practices throughout Africa, our work sought to define risk factors for the development of CRC in the African continent. Methods: We systematically searched PubMed, Embase, Global Health, CINAHL, Cochrane CENTRAL, and African Index Medicus for studies written in English, examining the incidence and risk factors of CRC in Africa. A systematic analysis was done to compare different risk factors in constituent studies. A meta-analysis random effects model was fitted to estimate the pooled incidence of CRC. Results: Of 2471 studies screened, 26 were included for the quantitative analysis; 20 in the incidence analysis, and six in the risk factor analysis. The overall ASIR per 100,000 person-years of CRC for males and females was 7.51 and 6.22, respectively. The highest incidence rates were observed between 2012 and 2021. Risk factors for CRC in Africa include tobacco smoking, and consumption of red meat, butter, and alcohol. Protective factors included, regular consumption of fruits and regular physical activity. Conclusion: The incidence of CRC in Africa is higher than that suggested by previous studies. Our study shows that nonmodifiable and modifiable factors contribute to CRC in Africa. High-quality studies conducted on generalizable populations that examine risk factors in a comprehensive fashion are required to inform primary and secondary prevention initiatives for CRC in Africa. [ABSTRACT FROM AUTHOR]

This study aims to elucidate the surgical anatomy of the superior mesenteric vessels (SMV) and their relevance in colon and pancreatic surgeries. The superior mesenteric artery (SMA) and vein (SMV) play critical roles in the vascular supply and drainage of the intestines. Accurate knowledge of their anatomy is crucial for minimizing complications during surgical interventions. We conducted a detailed anatomical study using cadaveric dissections and imaging techniques to provide a comprehensive overview of the SMV's relationships with the colon and pancreas. The results are tabulated and analyzed to guide surgical practice. [ABSTRACT FROM AUTHOR]

Introduction: Immunoglobulin G (IgG) is important in mediating humoral immunity and in the maintenance of immune homeostasis in the intestinal mucosa. Oregano essential oil (OEO) is a natural herbal extract that possesses antimicrobial, antioxidant, anti-inflammatory, and immunomodulatory properties. As the effects of OEO on intestinal mucosal immunity in Holstein dairy bulls remained unclear, we investigated the effect of dietary supplementation of OEO on IgG levels and IgG+ cells residing in the intestinal tract in Holstein dairy bulls. Methods: Twelve Holstein bulls in good health of approximately 10 months of age were selected for the experiment and randomly equally divided into two groups. The control (CK) group was fed a basal ration, and in the OEO group, the basal ration was supplemented with OEO (20 g/head/day). After 300 days of feeding, tissue samples of the jejunum, ileum, and colon of the bulls in each group were collected for histopathological analysis, immunohistochemistry, and enzyme-linked immunosorbent assays, respectively. Results: The jejunum, ileum, and colon of bulls in the CK group had obvious pathological damage, whereas the structure of each intestinal segment was clear and intact. In the OEO group, pathological damage was significantly reduced. IgG+ plasma cells were diffusely distributed in the lamina propria of the jejunum, ileum, and colon in the CK and OEO groups, with no significant difference between the groups. OEO supplementation significantly reduced the number of IgG+ plasma cells in each intestinal segment, with the highest decrease rate being noted for the ileum (22.87%), followed by the colon (19.45%) and jejunum (8.52%). ELISA test results and immunohistochemical results were mutually verified. The change in IgG content was consistent with the trend of change in the number of IgG+ plasma cells. Discussion: Our findings suggest that OEO supplementation does not alter the diffuse spatial distribution of IgG+ plasma cells in the intestines of Holstein dairy bulls, but lowers immunoglobulin levels to normal levels, significantly reduces intestinal damage, and may enhance mucosal immune defence barrier function by inhibiting inflammatory reactions. [ABSTRACT FROM AUTHOR]

We describe cases of three infants who developed acquired colonic atresia presumed secondary to significant systemic cardiovascular compromise and in the absence of necrotizing enterocolitis. An acquired colonic atresia may present as feed intolerance and should be investigated with a lower gastrointestinal contrast study. We would also recommend routine lower gastrointestinal contrast study prior to stoma closure in an infant with history of significant cardiovascular compromise, even in the absence of significant widespread colonic inflammation such as necrotizing enterocolitis. [ABSTRACT FROM AUTHOR]

Background Incidence of early-onset colorectal cancer (CRC) has increased globally in recent decades. We examined early-onset CRC incidence trends worldwide for potential cohort effects, defined as changes associated with time of birth (eg, early-life exposure to carcinogens), and period effects, defined as changes associated with calendar periods (eg, screening programs). Methods We obtained long-term incidence data for early-onset CRC diagnosed in patients aged 20 to 49 years through the year 2012 for 35 countries in the Cancer Incidence in Five Continents database. We used a smoothing method to help compare cohort and period trends of early-onset CRC and used an age-period-cohort model to estimate cohort and period effects. Results Cohort effects had a more dominant role than period effects in the early-onset CRC incidence in Shanghai (China), the United Kingdom, Australia, New Zealand, Canada, the United States, and Osaka (Japan). The smoothed trends show the specific birth cohorts when early-onset CRC began to increase: the 1940s-1950s birth cohorts in the United States; the 1950s-1960s birth cohorts in other Western countries; the 1960s birth cohorts in Osaka; and the 1970s-1980s birth cohorts in Shanghai. Such increases occurred earlier for early-onset cancers of the rectum than of the colon. For the other countries, the results were less clear. Conclusions Recent birth cohorts may have been exposed to risk factors different from earlier cohorts, contributing to increased early-onset CRC incidence in several developed countries or regions in the West and Asia. Such increases began in earlier birth cohorts in Western countries than in developed regions of Asia. [ABSTRACT FROM AUTHOR]

The aim of this study is to compare the diagnostic performance of magnetic resonance imaging (MRI) against computed tomography (CT) in various aspects of local staging in colon cancer patients. This study was a prospective single arm diagnostic accuracy study. All consecutive adult patients with confirmed colon cancer that met the current criteria for surgical resection were considered as eligible. Diagnostic performance assessment included T (T1/T2 vs T3/T4 and < T3ab vs > T3cd) and N (N positive) staging, serosa and retroperitoneal surgical margin (RSM) involvement and extramural vascular invasion (EMVI). Imaging was based on a 3 Tesla MRI system and the evaluation of all sequences (T1, T2 and diffusion-weighted imaging-DWI series) by two independent readers. CT scan was performed in a 128 row multidetector (MD) CT scanner (slice thickness: 1 mm) with intravenous contrast. Pathology report was considered as the gold standard for local staging. Sensitivity (SE), specificity (SP), and area under the curve (AUC) were calculated for both observers. MRI displayed a higher diagnostic performance over CT in terms of T1/T2 vs T3/T4 (SE: 100% vs 83.9%, SP: 96.6% vs 81%, AUC: 0.825 vs 0.983, p < 0.001), N positive (p < 0.001) and EMVI (p = 0.023) assessment. An excellent performance of MRI was noted in the T3ab vs T3cd (CT AUCReader1: 0.636, AUCReader2: 0.55 vs MRI AUCReader1: 0.829 AUCReader2 0.846, p = 0.01) and RSM invasion diagnosis. In contrast to these, MRI did not perform well in the identification of serosa invasion. MRI had a higher diagnostic yield than CT in several local staging parameters. [ABSTRACT FROM AUTHOR]

Introduction: Mixed neuroendocrine-nonendocrine neoplasms (MiNENs) of the digestive tract are rare. They contain both neuroendocrine and nonendocrine components. We here report a rare case of a metastatic MiNEN originating in the ascending colon. Case Presentation: An 80-year-old man presented with abdominal pain and vomiting. Colonoscopy showed an obstructing mass in the ascending colon, and a biopsy resulted in diagnosis of an adenocarcinoma. A CT scan revealed multiple liver metastases. Thus, our diagnosis was stage IV colon adenocarcinoma (cT4aN1bM1a according to TNM Classification of Malignant Tumors). The primary lesion was resected to alleviate symptoms. Histopathological and immunohistochemical examination revealed a well-differentiated adenocarcinoma and a small-cell neuroendocrine carcinoma, leading to the diagnosis of a MiNEN. The patient declined postoperative treatment and died approximately 2 months after the surgery. Conclusion: The incidence of MiNENs may be underestimated because they lack typical symptoms or imaging features and are therefore often only diagnosed after resection. Awareness of colonic MiNENs and further accumulation of cases are necessary to improve the outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer care is being increasingly driven by biomarker testing. Many biomarkers are traditionally measured on a sample from a patient tumor such as a biopsy. More recently, "liquid biopsy" has emerged as a blood test to complement or replace traditional tissue-based testing. In this report, we explore one of the first case series of rapid liquid biopsy performed within a hospital setting. The results include a median 3-day time to results, compared to approximately 14 days using traditional centralized reference labs. Additional details of the cohort are shared to highlight the utility of point of care liquid biopsy. Liquid biopsy is rapidly becoming an indispensable tool in the oncologist's arsenal; however, this technique remains elusive in a publicly funded healthcare system, and real-world evidence is needed to demonstrate utility and feasibility. Here, we describe the first experience of an in-house point of care liquid biopsy program at a Canadian community hospital. A retrospective review of consecutive cases that underwent plasma-based next-generation sequencing (NGS) was conducted. Liquid biopsy was initiated at the discretion of clinicians. Sequencing followed a point of care workflow using the Genexus™ integrated sequencer and the Oncomine precision assay, performed by histotechnologists. Results were reported by the attending pathologist. Eligible charts were reviewed for outcomes of interest, including the intent of the liquid biopsy, results of the liquid biopsy, and turnaround time from blood draw to results available. A total of 124 cases, with confirmed or suspected cancer, underwent liquid biopsy between January 2021 and November 2023. The median turnaround time for liquid biopsy results was 3 business days (range 1–12 days). The sensitivity of liquid biopsies was 71%, compared to tissue testing in cases with matched tissue results available for comparison. Common mutations included EGFR (29%), in 86 lung cancer patients, and PIK3CA (22%), identified in 13 breast cancer patients. Healthcare providers ordered liquid biopsies to inform diagnostic investigations and treatment decisions, and to determine progression or resistance mechanisms, as these reasons often overlapped. This study demonstrates that rapid in-house liquid biopsy using point of care methodology is feasible. The technique facilitates precision treatment and offers many additional advantages for cancer care. [ABSTRACT FROM AUTHOR]

Cancer cells require substantial amounts of energy and substrates for their metabolic hyperactivity, enabling the synthesis of new cells at the expense of healthy ones. Preliminary in vitro data suggest that a mix of free essential amino acids (EAA-mix) can promote cancer cell apoptosis by enhancing autophagy. This study aimed to confirm, both in vitro and in vivo, whether EAA intake could influence the development of colon cancer in mice. We investigated changes in cancer proliferation in CT26 cells treated with EAA-mix and in mice fed with EAA-rich modified diets (EAARD) as compared to those on a standard laboratory diet (StD). CT26 cells were injected subcutaneously (s.c.) or intraperitoneally (i.p.). After 21 days, tumors were removed and measured. In vitro data corroborated that EAA-mix impairs cancer growth by inducing apoptosis. In vivo data revealed that mice on StD developed significantly larger (s.c.) and more numerous (i.p.) cancers than those on EAARD. EAA administration appears to influence cancer cell survival with notable antiproliferative properties. [ABSTRACT FROM AUTHOR]

Early detection of the adenocarcinoma cancer in colon tissue by means of explainable deep learning, by classifying histological images and providing visual explainability on model prediction. Considering that in recent years, deep learning techniques have emerged as powerful techniques in medical image analysis, offering unprecedented accuracy and efficiency, in this paper we propose a method to automatically detect the presence of cancerous cells in colon tissue images. Various deep learning architectures are considered, with the aim of considering the best one in terms of quantitative and qualitative results. As a matter of fact, we consider qualitative results by taking into account the so-called prediction explainability, by providing a way to highlight on the tissue images the areas that from the model point of view are related to the presence of colon cancer. The experimental analysis, performed on 10,000 colon issue images, showed the effectiveness of the proposed method by obtaining an accuracy equal to 0.99. The experimental analysis shows that the proposed method can be successfully exploited for colon cancer detection and localisation from tissue images. [ABSTRACT FROM AUTHOR]

Postoperative colorectal imaging studies play an important role in the detection of surgical complications and disease recurrence. In this pictorial essay, we briefly describe methods of surgery, imaging findings of their early and late complications, and postsurgical recurrence of cancer and inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Background/Aims: Appropriate tissue tension and clear visibility of the dissection area using traction are essential for effective and safe endoscopic submucosal dissection (ESD). In this study, we developed a retractable robot-assisted traction device and evaluated its performance in colorectal ESD. Methods: An experienced endoscopist performed ESD 18 times on an ex vivo porcine colon using the robot and 18 times using the conventional method. The outcome measures were procedure time, dissection speed, procedure-related adverse events, and blind dissection rate. Results: Thirty-six colonic lesions were resected from ex vivo porcine colon samples. The total procedure time was significantly shorter in robot-assisted ESD (RESD) than in conventional ESD (CESD) (20.1±4.1 minutes vs 34.3±8.3 minutes, p<0.05). The submucosal dissection speed was significantly faster in the RESD group than in the CESD group (36.8±9.2 mm2 /min vs 18.1±4.7 mm2 /min, p<0.05). The blind dissection rate was also significantly lower in the RESD group (12.8%±3.4% vs 35.1%±3.9%, p<0.05). In an in vivo porcine feasibility study, the robotic device was attached to a colonoscope and successfully inserted into the proximal colon without damaging the colonic wall, and ESD was successfully performed. Conclusions: The dissection speed and safety profile improved significantly with the retractable RESD. Thus, our robotic device has the potential to provide simple, effective, and safe multidirectional traction during colonic ESD. [ABSTRACT FROM AUTHOR]

Colorectal neoplasms are prevalent in patients with chronic kidney disease (CKD); however, the safety and efficacy of colorectal endoscopic submucosal dissection (ESD) are not well understood. This retrospective analysis included ESD procedures performed in 1266 patients with CKD across five tertiary medical institutions from January 2015 to December 2020. Patients were categorized based on their estimated glomerular filtration rate (eGFR), which ranged from CKD1 to CKD5 (including those on dialysis). We found that en bloc resection rates remained high across all CKD stages, affirming the procedural efficacy of ESD. Notably, the prevalence of cardiovascular comorbidities, such as ischemic heart disease and diabetes mellitus, significantly increased with an advancing CKD stage, with a corresponding increase in the Charlson Comorbidity Index, highlighting the complexity of managing these patients. Despite these challenges, the complete resection rate was lower in the CKD5 group (50%) than in the CKD1 group (83.4%); however, procedural complications, such as perforation and bleeding, did not significantly differ among the groups. The predictive models for complete resection and major complications showed no significant changes with a decreasing eGFR. These findings underscore that ESD is a feasible and safe treatment for colorectal neoplasms in patients with CKD, successfully balancing the inherent procedural risks with clinical benefits. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Primary leiomyosarcoma of the colon is a very rare tumor entity. Because of unspecific findings, diagnostic can be challenging. Most cases are diagnosed in advanced stages with poor overall survival. Unclear histological findings of smooth muscle cell tissue in colon biopsies together with a tumor of the colon wall in computed tomography (CT) imaging should lead to the differential diagnosis of primary colonic leiomyosarcoma and further diagnostic procedures. Primary colonic leiomyosarcoma is an extremely rare tumor entity arising from smooth muscle cells in the colon wall. Only 0.1% of all colorectal malignancies are leiomyosarcomas. Most patients are diagnosed in advanced disease stages. The overall survival rates are low, and recurrence rates are high. Only few data regarding the outcome in localized early disease stages are available. We report the case of an early‐stage primary leiomyosarcoma of the sigmoid colon treated with surgical resection. We present the case of a 53‐year‐old male patient who underwent a colonoscopy due to intermittent rectal bleeding. Colonoscopy revealed an intraluminal polypoid growing tumor in the sigmoid colon. A biopsy was performed with inconclusive histological results. A CT scan revealed a process in the sigmoid colon with wall thickening; there was no evidence of metastatic lesions. After laparoscopic oncological resection of the sigmoid colon, histological examination surprisingly revealed a localized high‐grade leiomyosarcoma. Primary leiomyosarcoma of the colon is a rare tumor entity and diagnostic can be challenging. Only a few patients with colonic leiomyosarcoma diagnosed in localized early disease stages and treated with complete surgical resection have been reported in the literature. These patients seem to have a better prognosis with longer overall survival. Because of unspecific diagnostic findings and the lack of symptoms in early disease stages, interdisciplinary collaborations between gastroenterologists, radiologists, pathologists, and surgeons are crucial for early diagnosis and treatment. [ABSTRACT FROM AUTHOR]

This case report presents the findings of colon adenocarcinoma in a young adult male who presented with vague abdominal pain as his only complaint, suspicious of appendicitis. The patient underwent abdominal computed tomography (CT) imaging for further evaluation of his abdominal pain. CT findings showed pericecal fat stranding and prominent lymph nodes concerning for acute appendicitis, but the appendix could not be adequately visualized; due to the indeterminate CT findings, general surgery proceeded to perform an exploratory laparotomy on the patient and removed an appendiceal mass-like structure that was revealed to be invasive adenocarcinoma of the colon per pathology. This case report details the radiological and pathological findings of colorectal adenocarcinoma presenting similarly to acute appendicitis and demonstrates that colorectal adenocarcinoma must be considered on the list of differentials in young adults presenting with abdominal pain and unclear CT imaging.

Abstract Background A multitude of mouse models are utilized to emulate and study intestinal inflammation. T‐cell receptor alpha chain (TCRα)‐deficient mice are used as a model of spontaneous colitis that has similarities with human ulcerative colitis. However, colitis is triggered late in the life of the mouse (age: 4–5 months), and inflammation does not develop at the same time in different mice. A previously conducted study reported that the administration of the drug piroxicam triggered predictable and early colitis in TCRα‐deficient mice at the age of 6–8 weeks. However, a detailed characterization of ensuing inflammation was not provided. Methods We conducted an in‐depth examination of piroxicam‐triggered colitis in TCRα‐deficient mice, with emphasis on spatial histopathologic changes and analysis of expression of inflammatory markers. Furthermore, we tested amelioration of colitis with dexamethasone. Results We confirmed that piroxicam induced a time‐prescribed colitis and did so in the proximal colon as well as the cecum of TCRα‐deficient mice. Piroxicam administration was observed to induce epithelial hyperplasia, goblet cell loss, and leukocyte infiltration with occasional ulceration. A Swiss roll technique was used to examine the colon and cecum in its entirety. Importantly, we observed that inflammation was multifocal segmental, with areas of tissue damage in between healthy tissue. In addition, we observed variability in the severity of inflammation among replicate animals and treatments, and that the administration of dexamethasone only partially ameliorated inflammation in the proximal colon. Conclusions Piroxicam consistently induced multifocal segmental colitis in the proximal colon and cecum, although the degree of inflammation was reduced in the latter. Importantly, spatial variability in inflammation in the large intestine and the inter‐replicate variation in the severity of inflammation must be taken into consideration when utilizing this murine model of synchronized colitis.

Postoperative colorectal imaging studies play an important role in the detection of surgical complications and disease recurrence. In this pictorial essay, we briefly describe methods of surgery, imaging findings of their early and late complications, and postsurgical recurrence of cancer and inflammatory bowel disease.

Abstract The aim of this study is to compare the diagnostic performance of magnetic resonance imaging (MRI) against computed tomography (CT) in various aspects of local staging in colon cancer patients. This study was a prospective single arm diagnostic accuracy study. All consecutive adult patients with confirmed colon cancer that met the current criteria for surgical resection were considered as eligible. Diagnostic performance assessment included T (T1/T2 vs T3/T4 and T3cd) and N (N positive) staging, serosa and retroperitoneal surgical margin (RSM) involvement and extramural vascular invasion (EMVI). Imaging was based on a 3 Tesla MRI system and the evaluation of all sequences (T1, T2 and diffusion-weighted imaging-DWI series) by two independent readers. CT scan was performed in a 128 row multidetector (MD) CT scanner (slice thickness: 1 mm) with intravenous contrast. Pathology report was considered as the gold standard for local staging. Sensitivity (SE), specificity (SP), and area under the curve (AUC) were calculated for both observers. MRI displayed a higher diagnostic performance over CT in terms of T1/T2 vs T3/T4 (SE: 100% vs 83.9%, SP: 96.6% vs 81%, AUC: 0.825 vs 0.983, p

Metastatic colorectal cancers with BRAF mutation are a class of tumors that have a poor prognosis compared to wild type patients. Even if this group has found some hope in targeted therapy with multi-targeted blockade of the mitogen-activated protein kinase (MAPK) signalling pathway, more work must be done to increase treatment efficacy, particularly for the microsatellite stability/DNA proficient mismatch repair (MSS/pMMR) subtype. Patients with BRAF mutant colorectal cancer and high microsatellite instability/DNA deficient mismatch repair (MSI-H/dMMR) are considered to have a high tumor mutation load and a lot of neoantigen, which makes immunotherapy likely to be effective. It is generally accepted that MSS/pMMR colorectal cancer is an immunologically “cold” tumor that is resistant to immunotherapy. Then, patients with BRAF mutant colorectal cancer appear to find hope with targeted therapy paired with immune checkpoint blockade therapy. The clinical effectiveness and developing new approaches of immune checkpoint blockade therapy for MSI-H/dMMR and MSS/pMMR BRAF mutant metastatic colorectal cancer are reviewed in this paper. We also address possible biomarkers in the tumor immune microenvironment for predicting immunotherapeutic response in BRAF mutant colorectal cancer.

Introduction: Mixed neuroendocrine-nonendocrine neoplasms (MiNENs) of the digestive tract are rare. They contain both neuroendocrine and nonendocrine components. We here report a rare case of a metastatic MiNEN originating in the ascending colon. Case Presentation: An 80-year-old man presented with abdominal pain and vomiting. Colonoscopy showed an obstructing mass in the ascending colon, and a biopsy resulted in diagnosis of an adenocarcinoma. A CT scan revealed multiple liver metastases. Thus, our diagnosis was stage IV colon adenocarcinoma (cT4aN1bM1a according to TNM Classification of Malignant Tumors). The primary lesion was resected to alleviate symptoms. Histopathological and immunohistochemical examination revealed a well-differentiated adenocarcinoma and a small-cell neuroendocrine carcinoma, leading to the diagnosis of a MiNEN. The patient declined postoperative treatment and died approximately 2 months after the surgery. Conclusion: The incidence of MiNENs may be underestimated because they lack typical symptoms or imaging features and are therefore often only diagnosed after resection. Awareness of colonic MiNENs and further accumulation of cases are necessary to improve the outcomes.

Abstract Early detection of the adenocarcinoma cancer in colon tissue by means of explainable deep learning, by classifying histological images and providing visual explainability on model prediction. Considering that in recent years, deep learning techniques have emerged as powerful techniques in medical image analysis, offering unprecedented accuracy and efficiency, in this paper we propose a method to automatically detect the presence of cancerous cells in colon tissue images. Various deep learning architectures are considered, with the aim of considering the best one in terms of quantitative and qualitative results. As a matter of fact, we consider qualitative results by taking into account the so-called prediction explainability, by providing a way to highlight on the tissue images the areas that from the model point of view are related to the presence of colon cancer. The experimental analysis, performed on 10,000 colon issue images, showed the effectiveness of the proposed method by obtaining an accuracy equal to 0.99. The experimental analysis shows that the proposed method can be successfully exploited for colon cancer detection and localisation from tissue images.

BACKGROUND: Enteric neuropathies, which result from abnormalities of the enteric nervous system, are associated with significant morbidity and high health-care costs, but current treatments are unsatisfactory. Cell-based therapy offers an innovative approach to replace the absent or abnormal enteric neurons and thereby restore gut function. METHODS: Enteric neuronal stem cells (ENSCs) were isolated from the gastrointestinal tract of Wnt1-Cre;R26tdTomato mice and generated neurospheres (NS). NS transplants were performed via injection into the mid-colon mesenchyme of nNOS-/- mouse, a model of colonic dysmotility, using either 1 (n = 12) or 3 (n = 12) injections (30 NS per injection) targeted longitudinally 1-2 mm apart. Functional outcomes were assessed up to 6 weeks later using electromyography (EMG), electrical field stimulation (EFS), optogenetics, and by measuring colorectal motility. RESULTS: Transplanted ENSCs formed nitrergic neurons in the nNOS-/- recipient colon. Multiple injections of ENSCs resulted in a significantly larger area of coverage compared to single injection alone and were associated with a marked improvement in colonic function, demonstrated by (1) increased colonic muscle activity by EMG recording, (2) faster rectal bead expulsion, and (3) increased fecal pellet output in vivo. Organ bath studies revealed direct neuromuscular communication by optogenetic stimulation of channelrhodopsin-expressing ENSCs and restoration of smooth muscle relaxation in response to EFS. CONCLUSIONS: These results demonstrate that transplanted ENSCs can form effective neuromuscular connections and improve colonic motor function in a model of colonic dysmotility, and additionally reveal that multiple sites of cell delivery led to an improved response, paving the way for optimized clinical trial design.

Colonic duplication constitutes a rare congenital anomaly, characterized by the presence of hollow cystic or tubular structures exhibiting an epithelial-lined intestinal wall. Diagnostic challenges persist due to its low incidence and manifestation of nonspecific symptoms such as abdominal pain or constipation, resulting in a reluctance to pursue surgical resection. As associated malignancies in colonic duplication are rare, the inherent malignant potential of these anomalies remains undetermined. Additionally, despite reported instances of associated malignancies in colonic duplication, there is an absence of reports in the literature detailing tubular adenoma within these cases. The histologic features of the presented case are particularly noteworthy, situated at the precancerous stage, intimating potential progression towards adenocarcinoma within colonic duplication.

Abstract Ischemic colitis (IC) and sarcopenia are associated with aging and multiple comorbidities. We aimed to investigate the prevalence and predictive role of sarcopenia in patients with IC. We retrospectively analyzed 225 hospitalized patients (median age, 72 years; women, 67.1%; severe IC, 34.2%) who were diagnosed with IC between January 2007 and February 2022. Sarcopenia was defined as the skeletal muscle index at the third lumbar vertebra determined by computed tomography. It was present in 49.3% (n = 111) of the patients and was significantly associated with severe IC compared to those without sarcopenia (48.6% vs. 20.2%, P

Background: No studies have appeared in the literature evaluating the intraluminal volume of injected saline in the canine colon for performing leak tests in colotomy incisions. Aim: To determine the volume of the injected intraluminal saline necessary to achieve an intraluminal pressure of 17.3 cm H2O in 10 cm colonic segments containing a closed colotomy occluded with intestinal forceps or by digital pressure. Methods: Fresh colon was obtained from 8 canine cadavers and divided into 10cm segments. A 3cm antimesenteric colonic incision was performed at each intestinal segment which was closed using a 3-0 polydioxanone suture in a simple continuous pattern. Each colonic construct was occluded with Doyen intestinal forceps or by digital pressure and a leak test was performed by saline infusion. The saline volume needed to achieve a predetermined intraluminal pressure of 17.3 cm H2O, following occlusion was recorded. Results: The mean volume of injected saline with the Doyen intestinal forceps occlusion (20.4 ± 8.2 ml) was significantly larger than that of the digital occlusion technique (17.5 ± 6.8 ml) [ P=0.021]. Conclusion: For 10 cm canine colonic constructs containing a closed colotomy, saline volumes of 20.4 ml with Doyen occlusion and 17.5 ml with digital occlusion can be utilized to achieve intraluminal pressures of 17.3 cm H2O. [Open Vet J 2024; 14(5.000): 1130-1134]

The aim of this study was to evaluate the findings of CT scans in patients with pathologically confirmed primary colorectal squamous-cell carcinoma (SCC). The clinical presentation and CT findings in eight patients with pathologically confirmed primary colorectal squamous-cell carcinoma were retrospectively reviewed by two gastrointestinal radiologists. Hematochezia was the most common symptom (n = 5). The tumors were located in the rectum (n = 7) and sigmoid colon (n = 1). The tumors showed circumferential wall thickening (n = 4), bulky mass (n = 3), or eccentric wall thickening (n = 1). The mean maximal wall thickness of the involved segment was 29.1 mm ± 13.4 mm. The degree of tumoral enhancement observed via CT was well enhanced (n = 4) or moderately enhanced (n = 4). Necrosis within the tumor was found in five patients. The mean total number of metastatic lymph nodes was 3.1 ± 3.3, and the mean short diameter of the largest metastatic lymph node was 16.6 ± 5.7 mm. Necrosis within the metastatic node was observed in six patients. Invasions to adjacent organs were identified in five patients (62.5%). Distant metastasis was detected in only one patient. In summary, primary SCCs that arise from the colorectum commonly present as marked invasive wall thickening or a bulky mass with heterogeneous well-defined enhancement, internal necrosis, and large metastatic lymphadenopathies.

Abstract Enterochromaffin (EC) cells located within the intestinal mucosal epithelium release serotonin (5-HT) to regulate motility tones, barrier function and the immune system. Electroanalytical methodologies have been able to monitor steady state basal extracellular 5-HT levels but are unable to provide insight into how these levels are influenced by key regulatory processes such as release and uptake. We established a new measurement approach, amperometry approach curve profiling, which monitors the extracellular 5-HT level at different electrode–tissue (E–T) distances. Analysis of the current profile can provide information on contributions of regulatory components on the observed extracellular 5-HT level. Measurements were conducted from ex vivo murine ileum and colon using a boron-doped diamond (BDD) microelectrode. Amperometry approach curve profiling coupled with classical pharmacology demonstrated that extracellular 5-HT levels were significantly lower in the colon when compared to the ileum. This difference was due to a greater degree of activity of the 5-HT transporter (SERT) and a reduced amount of 5-HT released from colonic EC cells. The presence of an inhibitory 5-HT4 autoreceptor was observed in the colon, where a 40% increase in extracellular 5-HT was the half maximal inhibitory concentration for activation of the autoreceptor. This novel electroanalytical approach allows estimates of release and re-uptake and their contribution to 5-HT extracellular concentration from intestinal tissue be obtained from a single series of measurements.

Abstract Introduction Mantle cell lymphoma is a rare lymphoma of the gastrointestinal tract that may present as multiple lymphomatous polyposis. We report a case of lymphomatous polyposis with a review of the literature. Case report A 56-year-old man of Black ethnicity and Ivorian nationality with no relevant past medical history, consulted for a sudden onset symptoms of gastrointestinal obstruction, which evolved over 2 days. Macroscopic examination revealed the presence of multiple polyploid formations of the colonic mucosa. Histology showed diffuse lymphomatous proliferation of submucosa consisting off small lymphoid cells with a hyperchromatic crenelated nucleus, suggesting lymphomatous polyposis. Immunohistochemical examination showed expression by the tumor cells of antibodies to CD20, CD5, Bcl2, and cyclin D1. They did not express antibodies to CD10 and CD23. The Ki67 proliferation index was 25%. We have thus retained the diagnosis of mantle cell lymphomatous polyposis. Conclusion Multiple lymphomatous polyposis is a rare entity characterized by the presence of numerous gastrointestinal polyploid lesions sometimes involving several segments of the gastrointestinal tract. Typical lymphoma presenting as lymphomatous polyposis is mantle cell lymphoma; although, other tumors may have this aspect.

We describe herein the findings from postmortem computed tomography (PMCT) of barium peritonitis due to descending colon perforation. The patient was a woman in her 60s who underwent upper gastrointestinal series with barium swallow for the purpose of physical examination. The patient developed abdominal pain the next day and visited a clinic, but was sent home for later follow-up. She was found dead at home 8 days after upper gastrointestinal series. Based on the corpse phenomena and police investigations of the scene of death, the patient was estimated to have died 6 days after the upper gastrointestinal series. PMCT revealed free gas within the peritoneal cavity. Barium and fat stranding were also observed around a diverticulum in the descending colon. A large amount of residual barium was seen in the ascending colon and was considered to represent antemortem constipation and delayed barium excretion. No gas was detected in the abdominal wall, cardiac chambers or hepatic vasculature. The pancreas and adrenal glands had a normal appearance. We diagnosed barium peritonitis due to descending colon perforation as the cause of death. Diverticular perforation was suspected because barium retention and fat stranding were particularly noticeable around the descending colon diverticulum. In conclusion, we have presented a rare case of postmortem diagnosis of barium peritonitis. In PMCT interpretation, distinguishing between ante- and postmortem intestinal perforations is important.

The tremendous plastic production and poor post-use management are current and future sources of environmental and human contamination due to their degradation products: microplastics and nanoplastics (MNPLs). Methodological developments have allowed MNPLs to be detected in an increasing variety of human foods, as well as in stool and colonic mucosa. It was suggested early that the direct contact between MNPLs and intestinal tissues could represent a potential risk for human health. In order to assess this, over the last 3 years, numerous studies have evaluated the impact of MNPL ingestion on intestinal homeostasis in rodents. This comprehensive review reports the preclinical studies published between January 2021 and January 2024, and analyzes their contributions as well as their shortcomings. It shows that evidence is accumulating of the intestinal toxicity of spherical MNPLs, which lead to pro-inflammatory, pro-oxidative, barrier-disruptive and dysbiotic effects. However, the available literature has addressed only a minor part of the potential health issues of MNPLs. Many parameters contributing to MNPL toxicity need to be better taken into account in future studies. Particular attention should be paid to improve the representativeness of MNPLs, as well as to better consider the susceptibility factors of MNPL toxicity, generated especially by an underlying pathology or pathological imprinting.

Colorectal cancer (CRC) is highly prevalent among Saudi males and females. Understanding its symptoms, risk factors, and screening is vital. This study aims to gauge CRC awareness in Taif City, Saudi Arabia, based on demographics. An observational study in Taif City surveyed awareness on colorectal screening, gathering data from March-April 2023 via a questionnaire covering demographics, screening knowledge, symptoms, and risk factors. Involving 551 participants, most were 19-40 years old (59.2%), female (65.9%), and had a bachelor’s degree (71.3%). Notably, 49.2% hadn’t visited a family doctor. Awareness on CRC screening was low. 37.7% knew about fecal occult blood tests, 32.7% about sigmoidoscopy, and 34.8% about colonoscopy. Only 27.6% knew the recommended screening age, and 2.4% the frequency. Participants sought information mainly online (45.7%) or from friends (24.1%). Recognized risk factors included family history (57.0%), blood in stool (58.8%), and abdominal pain (47.9%). The study highlights inadequate awareness about CRC screening in Taif. It underscores the necessity for targeted education campaigns, collaboration with healthcare professionals, and diverse information sources to improve understanding among the population.

Abstract As an important immune stimulator and modulator, IFNγ is crucial for gut homeostasis and its dysregulation links to diverse colon pathologies, such as colitis and colorectal cancer (CRC). Here, we demonstrated that the epigenetic regulator, CBX3 (also known as HP1γ) antagonizes IFNγ signaling in the colon epithelium by transcriptionally repressing two critical IFNγ-responsive genes: STAT1 and CD274 (encoding Programmed death-ligand 1, PD-L1). Accordingly, CBX3 deletion resulted in chronic mouse colon inflammation, accompanied by upregulated STAT1 and CD274 expressions. Chromatin immunoprecipitation indicated that CBX3 tethers to STAT1 and CD274 promoters to inhibit their expression. Reversely, IFNγ significantly reduces CBX3 binding to these promoters and primes gene expression. This antagonist effect between CBX3 and IFNγ on STAT1/PD-L1 expression was also observed in CRC. Strikingly, CBX3 deletion heightened CRC cells sensitivity to IFNγ, which ultimately enhanced their chemosensitivity under IFNγ stimulation in vitro with CRC cells and in vivo with a syngeneic mouse tumor model. Overall, this work reveals that by negatively tuning IFNγ-stimulated immune genes’ transcription, CBX3 participates in modulating colon inflammatory response and CRC chemo-resistance.

Background. Colorectal cancer is a commonly diagnosed neoplasia in men and women worldwide. This study aims to rigorously map the arterial distribution of the colon in order to assess the implications of vascular patterns in surgical resection. Methods. Cadaveric dissections were performed to explore the arterial distribution (including collateral blood flow) of the colon. The study used standard dissection tools and photographic documentation to detail the vascular architecture supporting the large intestine. Results. The dissection revealed important arterial branches and anastomoses in the area of the superior and inferior mesenteric arteries, which are able to ensure continuous local blood supply especially in cases of arterial ischemia. An important arterial anastomosis was identified between the right branch of the middle colic artery and the ascending branch of the right colic artery, as well as the specific distribution of the marginal artery of Drummond and Haller-Riolan anastomotic arch. Conclusions. The blood supply of the colon derived from both mesenteric arteries includes redundant arterial anastomoses, but which are critical in specific situations such as the approach and results of surgical resection. Understanding these vascular patterns and collateral pathways, as well as careful intraoperative surgical exploration, are essential for oncologic surgeons to ensure successful colic resections with minimal complications and morbidity.

Background/Aims We investigated the clinical practice patterns of post-polypectomy colonoscopic surveillance among Korean endoscopists. Methods In a web-based survey conducted between September and November 2021, participants were asked about their preferred surveillance intervals and the patient age at which surveillance was discontinued. Adherence to the recent guidelines of the U.S. Multi-Society Task Force on Colorectal Cancer (USMSTF) was also analyzed. Results In total, 196 endoscopists completed the survey. The most preferred first surveillance intervals were: a 5-year interval after the removal of 1–2 tubular adenomas < 10 mm; a 3-year interval after the removal of 3–10 tubular adenomas < 10 mm, adenomas ≥ 10 mm, tubulovillous or villous adenomas, ≤ 20 hyperplastic polyps < 10 mm, 1–4 sessile serrated lesions (SSLs) < 10 mm, hyperplastic polyps or SSLs ≥ 10 mm, and traditional serrated adenomas; and a 1-year interval after the removal of adenomas with highgrade dysplasia, >10 adenomas, 5–10 SSLs, and SSLs with dysplasia. In piecemeal resections of large polyps ( > 20 mm), surveillance colonoscopy was mostly preferred after 1 year for adenomas and 6 months for SSLs. The mean USMSTF guideline adherence rate was 30.7%. The largest proportion of respondents (40.8%–55.1%) discontinued the surveillance at the patient age of 80–84 years. Conclusions A significant discrepancy was observed between the preferred post-polypectomy surveillance intervals and recent international guidelines. Individualized measures are required to increase adherence to the guidelines.

Although single-incision laparoscopic surgery (SILS) has gained some attention as a feasible alternative to conventional multiport laparoscopic surgery (MPLS) in colonic surgery, it became less prevalent than expected. Hence, we conducted this systematic review to evaluate the feasibility, safety, and oncological outcomes of single-incision laparoscopic colectomy (SILC) with meta-analysis and discussion of the future prospect of SILS. The search was conducted from September to October 2023 using PubMed and the Cochrane Central Register of Controlled Trials. Articles on colorectal cancer comparing SILC with multiport laparoscopic colectomy (MPLC) from all randomized controlled trials and comparative studies with 50 patients or more per arm were examined. The primary outcomes were the intra- and postoperative complication rates, and the secondary outcomes were the perioperative and oncological outcomes. The trends of the SILS number in Japan and the trends of the number of articles on SILS in PubMed were also reviewed. There were no significant differences in perioperative complication rates, operative factors, and oncological outcomes between SILC and MPLC, although heterogeneity was observed mainly in operative factors and the total length of the skin incision was significantly shorter in SILC. Therefore, SILC is technically and oncologically feasible and safe when performed by experienced laparoscopic surgeons. The case number of SILS was gradually increasing but the rate of SILS was decreasing in Japan. The number of articles on SILS was also decreasing. SILS has gained foothold to some extent but has plateaued. The emerging new robotic platform may reappraise the concept of SILS.

Abstract Background Due to faster recovery and lower morbidity rates, laparoscopy has become the gold standard in elective colorectal surgery for both the benign and malignant forms of the disease. A substantial proportion of colorectal operations are, however, carried out in emergency settings, and most of the emergency resections are still performed open. The aim of this study is to compare the laparoscopic versus open approach for emergency colorectal surgery. Method/design This is a multicenter prospective randomized controlled trial including adult patients presenting with a condition requiring emergency colorectal resection. Discussion Previous studies cautiously recommend wider use of laparoscopy in emergency colorectal resections, but all earlier reports are retrospective, are mostly single-center studies, and have limited numbers of patients. Laparoscopy may involve some unpredictable risks that have not yet been reported because of the infrequent use of the techniqueded to assess the safety of laparoscopy as well as the advantages and disadvantages of open compared with laparoscopic emergency surgery. Trial registration Trial registration number: ClinicalTrials.gov NCT05005117 . Registered on August 12, 2021.

The tremendous plastic production and poor post-use management are current and future sources of environmental and human contamination due to their degradation products: microplastics and nanoplastics (MNPLs). Methodological developments have allowed MNPLs to be detected in an increasing variety of human foods, as well as in stool and colonic mucosa. It was suggested early that the direct contact between MNPLs and intestinal tissues could represent a potential risk for human health. In order to assess this, over the last 3 years, numerous studies have evaluated the impact of MNPL ingestion on intestinal homeostasis in rodents. This comprehensive review reports the preclinical studies published between January 2021 and January 2024, and analyzes their contributions as well as their shortcomings. It shows that evidence is accumulating of the intestinal toxicity of spherical MNPLs, which lead to pro-inflammatory, pro-oxidative, barrier-disruptive and dysbiotic effects. However, the available literature has addressed only a minor part of the potential health issues of MNPLs. Many parameters contributing to MNPL toxicity need to be better taken into account in future studies. Particular attention should be paid to improve the representativeness of MNPLs, as well as to better consider the susceptibility factors of MNPL toxicity, generated especially by an underlying pathology or pathological imprinting. [ABSTRACT FROM AUTHOR]

Myeloid sarcoma, a rare extramedullary manifestation of acute myeloid leukemia (AML), can occur in various anatomic sites but seldom involves the gastrointestinal tract. We report the unusual case of a 49-year-old man with a history of AML who initially presented with abdominal pain and imaging findings suggestive of a paracolic abscess. However, the lesion rapidly progressed to a large descending colon mass with peritoneal involvement over five weeks. Surgical resection and histopathological examination confirmed a diagnosis of myeloid sarcoma. This case highlights the potential of myeloid sarcoma to mimic an inflammatory colonic process at initial presentation prior to manifesting as an overt mass lesion. Although exceedingly rare, myeloid sarcoma should be considered in patients with a history of AML presenting with colon lesions, particularly in those with an aggressive clinical course. Early recognition may expedite appropriate treatment and prevent unnecessary procedures. This report also underscores the importance of correlating imaging findings with clinical history and histopathology findings to establish an accurate diagnosis. [ABSTRACT FROM AUTHOR]

To optimize and characterize xanthan gum multi-particulate formulation for colon targeting, which increases the residence time at the absorbing surface of the colon. Xanthan gum was dispersed in cold water containing drug and was permitted to expand for 2 h. Sodium alginate was blended well in 10 ml of water. Xanthan gum solution containing the drug was added to sodium alginate solution and 0.3 ml of glutaraldehyde was added to the dispersion, with constant stirring. Then, polymer-drug solution was added dropwise into 5% w/v calcium chloride solution with continuous stirring, producing microspheres filtered by Whatman filter paper and dried at 30 °C-40 ℃. Microspheres were performed by chemical cross-linking with glutaraldehyde, which increased the maximum drug entrapment efficiency up to 73.63 ± 0.65% with an increasing concentration of xanthan gum polymer 0.7% w/v for the optimized F6 batch. Better results were found by increasing the polymer concentration along with the glutaraldehyde concentration. The kinetics of drug release for the F6 batch was considered as an optimized batch because the regression value was found to be 0.997 in the peppas model. The accelerated stability study on the optimized F6 batch performed to learn whether the drug has any change during its period of usability. The polysaccharide remains intact in the stomach and intestine and the drug was released in the colon with low toxicity and biodegradability. The present studies showed that optimizing and characterizing xanthan gum multiparticulate formulation for colon targeting gives metronidazole the most effective and controlled delivery. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is an autoimmune disorder caused by uncontrolled immune activation and the subsequent destruction of the colon tissue. Quercetin (Qt) is a natural antioxidant and anti-inflammatory agent proposed as an alternative to mitigate IBD. However, its use is limited by its low oral bioavailability. This study aimed to develop nanoemulsions (NEs) based on a soluble chenopodin/alginate (QPA) complex and Tween 80 (T80), intended for the colonic release of Qt, activated by the pH (5.4) and bacteria present in the human colonic microbiota. NEs with different ratios of QPA/Tw80 (F1-F6) were prepared, where F4Qt (60/40) and F5Qt (70/30) showed sizes smaller than 260 nm, PDI < 0.27, and high encapsulation efficiency (>85%). The stability was evaluated under different conditions (time, temperature, pH, and NaCl). The DSC and FTIR analyses indicated hydrophobic and hydrogen bonding interactions between QPA and Qt. F4Qt and F5Qt showed the greater release of Qt in PBS1X and Krebs buffer at pH 5.4 (diseased condition), compared to the release at pH 7.4 (healthy condition) at 8 h of study. In the presence of E. coli and B. thetaiotaomicron, they triggered the more significant release of Qt (ƒ2 < 50) compared to the control (without bacteria). The NEs (without Qt) did not show cytotoxicity in HT-29 cells (cell viability > 80%) and increased the antioxidant capacity of encapsulated Qt. Therefore, these NEs are promising nanocarriers for the delivery of flavonoids to the colon to treat IBD. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) stands as a significant global health concern, ranking second in mortality and third in frequency among cancers worldwide. While only a small fraction of CRC cases can be attributed to inherited genetic mutations, the majority arise sporadically due to somatic mutations. Emerging evidence reveals gut microbiota dysbiosis to be a contributing factor, wherein polyketide synthase-positive Escherichia coli (pks+ E. coli) plays a pivotal role in CRC pathogenesis. pks+ bacteria produce colibactin, a genotoxic protein that causes deleterious effects on DNA within host colonocytes. In this review, we examine the role of the gut microbiota in colon carcinogenesis, elucidating how colibactin-producer bacteria induce DNA damage, promote genomic instability, disrupt the gut epithelial barrier, induce mucosal inflammation, modulate host immune responses, and influence cell cycle dynamics. Collectively, these actions foster a microenvironment conducive to tumor initiation and progression. Understanding the mechanisms underlying pks+ bacteria-mediated CRC development may pave the way for mass screening, early detection of tumors, and therapeutic strategies such as microbiota modulation, bacteria-targeted therapy, checkpoint inhibition of colibactin production and immunomodulatory pathways. [ABSTRACT FROM AUTHOR]

As an important immune stimulator and modulator, IFNγ is crucial for gut homeostasis and its dysregulation links to diverse colon pathologies, such as colitis and colorectal cancer (CRC). Here, we demonstrated that the epigenetic regulator, CBX3 (also known as HP1γ) antagonizes IFNγ signaling in the colon epithelium by transcriptionally repressing two critical IFNγ-responsive genes: STAT1 and CD274 (encoding Programmed death-ligand 1, PD-L1). Accordingly, CBX3 deletion resulted in chronic mouse colon inflammation, accompanied by upregulated STAT1 and CD274 expressions. Chromatin immunoprecipitation indicated that CBX3 tethers to STAT1 and CD274 promoters to inhibit their expression. Reversely, IFNγ significantly reduces CBX3 binding to these promoters and primes gene expression. This antagonist effect between CBX3 and IFNγ on STAT1/PD-L1 expression was also observed in CRC. Strikingly, CBX3 deletion heightened CRC cells sensitivity to IFNγ, which ultimately enhanced their chemosensitivity under IFNγ stimulation in vitro with CRC cells and in vivo with a syngeneic mouse tumor model. Overall, this work reveals that by negatively tuning IFNγ-stimulated immune genes' transcription, CBX3 participates in modulating colon inflammatory response and CRC chemo-resistance. Synopsis: The epigenetic regulator CBX3 (also known as HP1γ) antagonized IFNγ/STAT1/PD-L1 axis and thereby decreased IFNγ-stimulated immune genes transcription, which ultimately modulated colon inflammatory response and CRC chemo-resistance. CBX3 deletion resulted in chronic mouse colon inflammation, accompanied by upregulated STAT1 and PD-L1 levels in the colon epithelium. CBX3 deletion heightened CRC cells' sensitivity to IFNγ stimulation and increased STAT1/PD-L1 expression. CBX3 antagonized IFNγ signaling by tethering to the promotors of Stat1 and Cd274, and transcriptionally repressing their expression. IFNγ stimulation reduced CBX3 binding and primed gene expression. Re-sensitizing CRC cells to IFNγ by deletion CBX3 enhanced their chemosensitivity under IFNγ stimulation in vitro as well as in vivo. The epigenetic regulator CBX3 (also known as HP1γ) antagonized IFNγ/STAT1/PD-L1 axis and thereby decreased IFNγ-stimulated immune genes transcription, which ultimately modulated colon inflammatory response and CRC chemo-resistance. [ABSTRACT FROM AUTHOR]

The main objective of this study was observe the distribution and expression of tau in the distal colonic muscle layers using opioid-induced constipation (OIC) rat model and to explore the mechanistic correlation between the tau phosphorylation and occurrence of OIC. The rat model of OIC was generated by intraperitoneal (i.p) injection of loperamide hydrochloride (Lop; 5mg/kg), and was evaluated by examining the fecal properties, intestinal propulsion mobility, immunohistochemistry (IHC), western blot (WB) and ELISA for detecting levels of Tau, P-Ser396-tau, P-Ser404-tau, protein kinase C (PKC), p38 MAPK (p38), p-p38 MAPK (p-p38) and µ-opioid receptors (MORs) in the colonic samples. The gene sequencing approach was used to detect alternatively spliced tau isoforms in the distal colonic muscle layer. Sequencing analysis revealed that 3 isoforms of tau, namely 2N4R, 1N4R and 0N4R were expressed in the distal colonic myocardium tissue. OIC rats had small, dry and hard feces, and intestinal propulsion velocity was significantly slower, especially in the distal colon. P-Ser396-Tau, P-Ser404-Tau, PKC, p-p38, p38, and Tau positive cells were distributed in the intestinal muscle plexus of the distal colon, and all of them were colocalized with MORs; though the expressions levels of tau and p38 remained unchanged, others indexes above significantly increased in the distal colonic muscle layer of OIC rats. However, after the administration of p38 blocker SB203580, OIC rats had salami-like feces, with an increase in colonic propulsion velocities; although the expressions levels of Tau and p38 didn't change significantly in distal colonic muscle layers, the expressions levels of P-Ser396-Tau, P-Ser404-Tau, and p-p38 significantly reduced. To conclude there is a unique distribution pattern of tau within the distal colonic musculature of OIC rats. The abnormal activation of MORs contributes to the hyperphosphorylation of tau protein, which in turn induces the development of OIC. [ABSTRACT FROM AUTHOR]

Crohn's disease (CD) is a subtype of inflammatory bowel disease (IBD) characterized by transmural disease. The concept of transmural healing (TH) has been proposed as an indicator of deep clinical remission of CD and as a predictor of favorable treatment endpoints. Understanding the pathophysiology involved in transmural disease is critical to achieving these endpoints. However, most studies have focused on the intestinal mucosa, overlooking the contribution of the intestinal wall in Crohn's disease. Multi-omics approaches have provided new avenues for exploring the pathogenesis of Crohn's disease and identifying potential biomarkers. We aimed to use transcriptomic and proteomic technologies to compare immune and mesenchymal cell profiles and pathways in the mucosal and submucosa/wall compartments to better understand chronic refractory disease elements to achieve transmural healing. The results revealed similarities and differences in gene and protein expression profiles, metabolic mechanisms, and immune and non-immune pathways between these two compartments. Additionally, the identification of protein isoforms highlights the complex molecular mechanisms underlying this disease, such as decreased RTN4 isoforms (RTN4B2 and RTN4C) in the submucosa/wall, which may be related to the dysregulation of enteric neural processes. These findings have the potential to inform the development of novel therapeutic strategies to achieve TH. [ABSTRACT FROM AUTHOR]