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.

Colorectal cancer CRC remains one of the leading causes of cancer-related deaths worldwide, with chronic intestinal inflammation identified as a major risk factor. Notably, the tumor suppressor TP53 undergoes mutation at higher rates and earlier stages during human inflammation-driven colon tumorigenesis than in sporadic cases. We investigated whether deleting Trp53 affects inflammation-induced tumor growth and the expression of Lgr5+ cancer stem cells in mice. We examined azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon tumorigenesis in wild-type Trp53 (+/+), heterozygous (+/−), and knockout (−/−) mice. Trp53−/− mice showed increased sensitivity to DSS colitis and earlier accelerated tumorigenesis with 100% incidence. All groups could develop invasive tumors, but knockouts displayed the most aggressive features. Unlike wild-type CRC, knockouts selectively showed increased populations of Lgr5+ colon cancer stem-like cells. Trp53 loss also boosted laminin, possibly facilitating the disruption of the tumor border. This study highlights how Trp53 deletion promotes the perfect storm of inflammation and stemness, driving colon cancer progression. Trp53 deletion dramatically shortened AOM/DSS latency and improved tumor induction efficiency, offering an excellent inflammation-driven CRC model.

Background/Objectives: The Brazilian Unified Health System was established in 1988 as a public health system with principles of universality, equity, and integrality. One of Brazil’s main strategies to strengthen universal healthcare is the Family Health Strategy (FHS), a primary health care policy established in 1994 and fully incorporated in the country in 2006. This study aims to describe the time trends of FHS coverage in Brazil and its states from 2008 to 2023 and to correlate this coverage with the states’ Human Development Index (HDI). Methods: Data on the number of FHS teams, population, and HDI during the period were collected for each Brazilian state in the Brazilian Ministry of Health’s public-access databases. Prais–Winsten regression was used to conduct a time series analysis for each state and country. The annual percentage change (APC) was used to describe time trends in time series. Linear regression was used to identify a correlation between HDI and FHS coverage across states. Results: The FHS coverage in the country increased from 66.81% to 84.66% from 2009 to 2023. Disparities in coverage between regions are evident throughout the entire study period. The Northeast region (NE) exhibited higher FHS coverage but lower APC rates compared to other regions. Results suggest a negative correlation between HDI and FHS coverage in all Brazilian states for 2009, 2012, 2015, 2018, 2021, and 2023. Conclusions: The FHS coverage increased in Brazil and its states during the period. The highest coverages were found in states from the North (N) and NE regions, and the lowest were in the Southeast region. Nine federative units achieved full coverage (100%) and maintained it afterward, with seven from the N and NE. A negative correlation was found between FHS and HDI, suggesting that the expansion of FHS effectively targets vulnerable populations.