Accumulating evidence indicates that breakdown of the+ protective mucosal barrier of the gut plays a role in colorectal cancer (CRC) development. Inflammation and oxidative stress in the colonic epithelium are thought to be involved in colorectal carcinogenesis and the breakdown of the integrity of the colonic barrier may increase the exposure of colonocytes to toxins from the colonic milieu, enhancing inflammatory processes and release of Reactive Oxygen Species (ROS). The aetiological importance of the gut microbiome and its composition – influenced by consumption of processed meats, red meats and alcoholic drinks, smoking, physical inactivity, obesity - in CRC development is also increasingly being recognized. The gut microbiome has diverse roles, such as in nutrient metabolism and immune modulation. However, microbial encroachment towards the colonic epithelium may promote inflammation and oxidative stress and even translocation of species across the colonic lumen. Recent research suggests that factors that modify the above mechanisms, e.g., obesity and Western diet, also alter gut microbiota, degrade the integrity of the gut protective barrier, and expose colonocytes to toxins. However, it remains unclear how obesity, lifestyle and metabolic factors contribute to gut-barrier integrity, leading to metabolic disturbance, colonocyte damage, and potentially to CRC development. This review will discuss the interactive roles of gut-barrier dysfunction, microbiome dysbiosis, and exposure to endogenous toxins as another mechanism in CRC development, and how biomarkers of colonic mucosal barrier function may provide avenues for disease, prevention and detection.

Objective: Physicians play a key role in performing and referring patients for cancer screening. A paucity of data exists for breast cancer screening (BCS) recommendations, demographic characteristics, screening practices, and barriers of screening among physicians. The purpose of this project is to examine physicians’ characteristics, practices, and beliefs about BCS recommendations and its barriers. Methods: The study used a descriptive correlational design and 110 surveys were completed. Data was analyzed using descriptive and inferential statistics generated with Statistical Packages for Sciences (SPSS) 26.0 version.Results: Most of the surveyed Chinese physicians worked in the community, were females, and between 30-39 years of age. Participants reported working in collaboration on numerous aspects of BCS, and also reported the recommendation of starting screening at younger ages in contrast to existing guidelines. A higher percentage of participants recommended more clinical breast exams compared to mammograms or ultrasounds. Several perceived barriers in working with patients and lower physician comfort levels with aspects of BCS were identified. Graduate degree-holding physicians reported higher physician comfort levels, and lower screening and follow-up practice. Increased familiarity with screening guidelines resulted in higher screening and follow-up practice but also higher physician-patient barrier scores. Increased perceived importance in using guidelines correlated to higher screening and follow-up practice scores.Conclusion: The results of this study point to the potential utility and importance in understanding the demographic factors that influence physician beliefs and practices. Results also highlighted the need for evidence-based guidelines for physician education and culturally tailored materials to address communication barriers and physician comfort. Furthermore, when studying physician screening practices and beliefs, context-specific considerations, as well as interprofessional collaboration are essential to improve patient outcomes. Physicians hold a salient role in ensuring that patients have access to cancer screening. Focusing on this group provides a critical focal point in addressing disparities in breast cancer screening and improving outcomes amongst Chinese women.

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Macrophages adopt a pro-inflammatory phenotype in response to environmental challenges in a process that often coincides with the formation of transient cytosolic p62/SQSTM1 inclusions containing ubiquitinated proteins in structures known as aggresome-like induced structures (ALIS). Although described as stress-induced inclusions that accumulate aggregated proteins, little direct evidence supports their hypothesized structural role in the context of immune stimulation. Here, we showed that these structures in primary macrophages are induced by multiple microbial-based ligands, including exposure to cytosolic double-stranded DNA. Rather than accumulating aggregated proteins, we observed that ubiquitinated proteins form a ring-shaped structure around the perimeter of these circular foci. We identified that different microbial stimuli induced the formation of ubiquitin-positive foci with distinct characteristics and we observed selective recruitment of context-dependent immune regulators. Our findings are consistent with a model where these ubiquitin-containing structures act as adaptable organizing centers for innate immune signaling.