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In about 10-15% of patients with inflammatory bowel diseases (IBD) there is no clear definitive differential diagnosis between Crohn's disease (CD) and ulcerative colitis (UC) and the disease is classified as indeterminate colitis. Since pharmacological and surgical treatments differ in CD and UC, establishing a correct diagnosis is critical. The aim of this work was to access the expression profile of proteins involved in colonic inflammation and cancer in samples from CD and UC. For that, colon samples from 24 CD, 21 UC and 10 control patients were processed for immunohistochemistry using anti-phosphorylated RB at Ser(807/811) and anti-β-catenin. Crypts were blinded, analyzed and counted for phosphorylated RB-positive (phospho-RB) cells or scored for positive β-catenin staining. Western blot was used for confirming immuhistochemical results: RB phosphorylation was significantly greater in colon samples from patients with CD compared with UC (p<0.005). In contrast, the expression of β-catenin was significantly increased in UC compared with CD (p<0.005) samples. Phospho-RB and β-catenin are negatively correlated (CC: -0.573; p = 0.001). A positive phospho-RB test yielded high levels of sensitivity, specificity, negative and positive predictive values, and accuracy for the diagnosis of CD against UC. This work indicates that RB phosphorylation and β-catenin nuclear translocation are differently expressed in CD and UC, and provide novel insights into the pathogenic mechanisms of IBD. In particular, rates of phospho-RB-positive cells in mucosal samples emerge as a promising tool for the differential diagnosis of patients with IBD.

Innate immunity constitutes the first line of defense, fundamental for the recognition and the initiation of an inflammatory response against microorganisms. The innate immune response relies on the sensing of microbial-associated molecular patterns through specialized structures such as toll-like receptors (TLRs) and the nucleotide oligomerization domain- (NOD-) like receptors (NLRs). In the gut, these tasks are performed by the epithelial barrier and the presence of adaptive and innate immune mechanisms. TLRs and NLRs are distributed throughout the gastrointestinal mucosa, being more expressed in the epithelium, and in lamina propria immune and nonimmune cells. These innate immunity receptors exhibit complementary biological functions, with evidence for pathways overlapping. However, as tolerance is the predominant physiological response in the gastrointestinal mucosa, it appears that the TLRs are relatively downregulated, while NLRs play a critical role in mucosal defense in the gut. Over the past two decades, genetic polymorphisms have been associated with several diseases including inflammatory bowel disease. Special emphasis has been given to the susceptibility to Crohn’s disease, in association with abnormalities in the NOD2 and in the NLRP3/inflammasome. Nevertheless, the mechanisms underlying innate immune receptors dysfunction that result in the persistent inflammation in inflammatory bowel disease remain to be clarified.

The overall burden of cancer is rapidly increasing worldwide, reflecting not only population growth and aging, but also the prevalence and spread of risk factors. Gastrointestinal (GI) cancers, including stomach, liver, esophageal, pancreatic, and colorectal cancers, represent more than a quarter of all cancers. While smoking and alcohol use are the risk factors most commonly associated with cancer development, a growing consensus also includes dietary habits as relevant risk factors for GI cancers. Current evidence suggests that socioeconomic development results in several lifestyle modifications, including shifts in dietary habits from local traditional diets to less-healthy Western diets. Moreover, recent data indicate that increased production and consumption of processed foods underlies the current pandemics of obesity and related metabolic disorders, which are directly or indirectly associated with the emergence of various chronic noncommunicable conditions and GI cancers. However, environmental changes are not restricted to dietary patterns, and unhealthy behavioral features should be analyzed with a holistic view of lifestyle. In this review, we discussed the epidemiological aspects, gut dysbiosis, and cellular and molecular characteristics of GI cancers and explored the impact of unhealthy behaviors, diet, and physical activity on developing GI cancers in the context of progressive societal changes.

Background The prevalence of inflammatory bowel disease (IBD) is increasing globally, and the disease is frequently managed surgically. The aim of this study was to investigate the time trends and geographic distribution of IBD hospitalizations, surgeries and surgical-associated lethality. Methods Data from the Brazilian Health Public System were retrospectively collected regarding hospitalizations, in-hospital deaths, IBD-related surgical procedures and lethality from 2005 to 2015. Results This eleven-year period revealed decreases in the rates of hospitalization (24%), IBD-related surgeries (35%), and IBD-related surgical lethality (46%). Most surgeries were performed in Crohn’s disease patients, and the predominant procedure was small bowel resection, mostly in young adults. A higher prevalence of ulcerative was observed throughout the country. The highest hospitalization and surgical rates were observed in the more industrialized regions of the South and the Southeast and in the municipalities integrated with metropolitan regions (MRs). The highest surgical-related lethality rates were seen in the less-developed regions and in municipalities not integrated with MRs. The length of hospital stay showed a slight increase throughout the period. Conclusions Brazil follows the global trend of decreases in hospitalizations, lethality, surgeries, and surgical lethality associated with IBD. The unequal distribution of hospitalizations and surgeries, concentrated in the industrialized areas, but with a shift towards the Northeast and from urbanized to rural areas, indicates ongoing changes within the country. Reductions in the rates of IBD-related hospitalizations, surgeries and lethality suggest the effectiveness of decentralization and improvements in the quality of public health services and the advances in medical therapy during the study period.

This study aimed to evaluate humoral responses after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of patients with inflammatory bowel disease (IBD). Patients with IBD enrolled in a tertiary outpatient unit were followed up between September 2021 and September 2022 via serial blood collection. Immunoglobulin G antibody titers against SARS-CoV-2 were measured before administration and 1 and 6 months after the administration of two doses of different vaccination regimens. The results were compared with those of a healthy control group obtained during the same period. The mean pre-vaccination antibody titers were 452.0 and 93.3 AU/mL in the IBD (n = 42) and control (n = 89) groups, respectively. After two doses of the vaccine, the titers significantly increased in both groups (IBD, 8568.0 AU/mL; control, 7471.0 AU/mL; p < 0.001). One month after the second dose, no significant differences were observed between the two groups (p = 0.955). Significant differences between vaccination schemes in the IBD group were observed, with higher titers in those who received Pfizer, younger patients (p < 0.005), and those with a previous coronavirus disease 2019 (COVID-19) infection (p < 0.012). The use of immunosuppressants and immunobiologicals did not affect the overall humoral response to COVID-19 vaccine in patients with IBD, but specific vaccine regimens, age, and previous coronavirus infection significantly did. This study reinforces the positive impact of booster doses and the safety of SARS-CoV-2 vaccination.

Mutations of the p53 tumor suppressor gene have been associated with abnormalities in cell cycle regulation, DNA repair and synthesis, apoptosis, and it has been implicated in the prognosis of advanced gastric cancer. The aim of this study was to evaluate the occurrence of p53 gene mutation and its possible prognostic implications in early gastric cancer. In a retrospective study, we studied 80 patients with early gastric cancer treated surgically between 1982 and 2001. Mutation of p53 gene was investigated in surgical gastric specimens by immunohistochemistry, and results were analyzed in relation to gender, age, macroscopic appearance, size and location of tumor, presence of lymph nodes, Lauren’s histological type, degree of differentiation, and the 5-year survival. The expression of p53 was more frequent among the intestinal type ( p = 0.003), the differentiated ( p = 0.007), and the macroscopically elevated tumors ( p = 0.038). Nevertheless, the isolated expression of p53 was not associated with the 5-year survival, or with the frequency of lymph node involvement. The degree of differentiation was detected as an independent factor related to the outcome of patients (0.044). Significantly shorter survival time was found in p53-negative compared with p53-positive patients, when considering the degree of differentiation of tumors, as assessed by Cox regression analysis (0.049). The association of p53 with the intestinal type, the degree of differentiation and morphological characteristics, may reflect the involvement of chronic inflammatory process underlying early gastric cancer. In this population sample, the expression of p53 alone has no prognostic value for early gastric cancer. However, the significant difference in p53 expression between subgroups of degree of differentiation of tumors can influence post-operative outcome of patients and may be related to possible distinct etiopathogenic subtypes.

Aberrant signaling through damage-associated molecular patterns (DAMPs) has been linked to several health disorders, attracting considerable research interest over the last decade. Adenosine triphosphate (ATP), a key extracellular DAMP, activates the purinergic receptor P2X7, which acts as a danger sensor in immune cells and is implicated in distinct biological functions, including cell death, production of pro-inflammatory cytokines, and defense against microorganisms. In addition to driving inflammation mediated by immune and non-immune cells, the persistent release of endogenous DAMPs, including ATP, has been shown to result in epigenetic modifications. In intestinal diseases such as inflammatory bowel disease (IBD) and colorectal cancer (CRC), consequent amplification of the inflammatory response and the resulting epigenetic reprogramming may impact the development of pathological changes associated with specific disease phenotypes. P2X7 is overexpressed in the gut mucosa of patients with IBD, whereas the P2X7 blockade prevents the development of chemically induced experimental colitis. Recent data suggest a role for P2X7 in determining gut microbiota composition. Regulatory mechanisms downstream of the P2X7 receptor, combined with signals from dysbiotic microbiota, trigger intracellular signaling pathways and inflammasomes, intensify inflammation, and foster colitis-associated CRC development. Preliminary studies targeting the ATP−P2X7 pathway have shown favorable therapeutic effects in human IBD and experimental colitis.

Background: Given the role of the P2X7 receptor (P2X7R) in inflammatory bowel diseases (IBD), we investigated its role in the development and progression of colitis-associated colorectal cancer (CA-CRC). Methods: CA-CRC was induced in P2X7R+/+ and P2X7R−/− mice with azoxymethane (AOM) combined with dextran sodium sulfate (DSS). In a therapeutic protocol, P2X7R+/+ mice were treated with a P2X7R-selective inhibitor (A740003). Mice were evaluated with follow-up video endoscopy with endoluminal ultrasound biomicroscopy. Colon tissue was analyzed for histological changes, densities of immune cells, expression of transcription factors, cytokines, genes, DNA methylation, and microbiome composition of fecal samples by sequencing for 16S rRNA. Results: The P2X7R+/+ mice displayed more ulcers, tumors, and greater wall thickness, than the P2X7R−/− and the P2X7R+/+ mice treated with A740003. The P2X7R+/+ mice showed increased accumulation of immune cells, production of proinflammatory cytokines, activation of intracellular signaling pathways, and upregulation of NLRP3 and NLRP12 genes, stabilized after the P2X7R-blockade. Microbial changes were observed in the P2X7R−/− and P2X7R+/+-induced mice, partially reversed by the A740003 treatment. Conclusions: Regulatory mechanisms activated downstream of the P2X7R in combination with signals from a dysbiotic microbiota result in the activation of intracellular signaling pathways and the inflammasome, amplifying the inflammatory response and promoting CA-CRC development.

Abstract Background The epidemiology of inflammatory bowel disease (IBD) in developing countries may uncover etiopathogenic factors. We investigated IBD prevalence in Brazil by investigating its geographic, spatial, and temporal distribution, and attempted to identify factors associated with its recent increase. Methods A drug prescription database was queried longitudinally to identify patients and verify population distribution and density, race, urbanicity, sanitation, and Human Development Index. Prevalence was calculated using the number of IBD patients and the population estimated during the same decade. Data were matched to indices using linear regression analyses. Results We identified 162 894 IBD patients, 59% with ulcerative colitis (UC) and 41% with Crohn’s disease (CD). The overall prevalence of IBD was 80 per 100 000, with 46 per 100 000 for UC and 36 per 100 000 for CD. Estimated rates adjusted to total population showed that IBD more than triplicated from 2008 to 2017. The distribution of IBD demonstrated a South-to-North gradient that generally followed population apportionment. However, marked regional differences and disease clusters were identified that did not fit with conventionally accepted IBD epidemiological associations, revealing that the rise of IBD was variable. In some areas, loss of biodiversity was associated with high IBD prevalence. Conclusions When distribution is considered in the context of IBD prevalence, marked regional differences become evident. Despite a background of Westernization, hotspots of IBD are recognized that are not explained by population density, urbanicity, sanitation, or other indices but apparently are explained by biodiversity loss. Thus, the rise of IBD in developing countries is not uniform, but rather is one that varies depending on yet unexplored factors like geoecological conditions. Lay Summary The analysis of a large population of inflammatory bowel disease (IBD) patients in a developing country reveals that the rising prevalence of IBD is not uniform and is linked to factors not traditionally associated with IBD, such as geosocial features and loss of biodiversity.

Purpose Endoscopic ultrasound (EUS) imaging of the colon is an important diagnostic tool for early neoplasia, although usually restricted to the rectum in inflammatory bowel disease (IBD). This study aimed to evaluate the ability of an endoluminal ultrasound biomicroscopic (eUBM) system to detect and characterize lesions simulating Crohn’s disease in the colon of rats in vivo. Methods Colitis was induced with trinitrobenzene sulfonic acid instillated in the distal colon. Eighteen Wistar rats were submitted to eUBM in three time points: week 1 group (18 animals examined on day 3 after colitis induction), week 2 group (12 animals on days 3 and 10), and week 3 group (7 animals on days 3, 10, and 17). This design yielded distinct inflammation intensities. Three untreated rats were used for acquisition of control images. Scores were used for comparison with histology. Results Scores for eUBM and histology in the different moments of examination achieved a Spearman’s rank correlation coefficient of 0.87 ( p  < 0.001). Findings of wall thickening presented positive predictive value (PPV) and sensitivity of 94 and of 100 %, respectively. Superficial and deep ulcers presented a PPV of 89 and 80 %, respectively, and negative predictive values of 100 and 85 %, respectively. Conclusion Accurate detection and analysis of the lesions was achieved. The model is essential for the clinical development of the technique and a reproducible method for the evaluation of experimental colitis. eUBM might be applicable in different segments of the gut, developing into a novel adjunct method for IBD evaluation.