Colorectal cancer is a notorious disease, with almost half of the patients succumbing to the disease. The prevalence and incidence rates of colorectal cancer are increasing in many parts of the world, highlighting the need to discover new biomarkers for diagnosis and therapy. Caldesmon (CaD), an actin-binding protein that plays a significant role in controlling cell motility, has emerged as a promising biomarker. The CALD1 gene encodes CaD as multiple transcripts that mainly encode two protein isoforms: High-molecular-weight (h-CaD), expressed in smooth muscle, and low-molecular-weight (l-CaD), expressed in nonsmooth muscle cells. Most studies have suggested an oncogenic role of CaD in colorectal cancer, but the exact subcellular localization of the two CaD isoforms in tumor cells and stroma have not been clarified yet. Here, we analyzed tissue samples from 262 colorectal cancer patients by immunohistochemistry analysis using specific antibodies for l-CaD and h-CaD. The results showed elevated cytoplasmic expression levels of l-Cad in 187/262 (71.4%) cases. l-Cad was expressed at low levels in the normal colon mucosa and was also consistently expressed in the cancer-associated stroma of all cases, suggesting that it could play a role in modulating the tumor microenvironment. l-CaD expression in cancer cells was associated with preinvasive stages of cancer. Survival analysis indicated that patients with high l-CaD expression in tumor cells could respond poorly to selective chemotherapeutic 5FU, but not combination chemotherapy. h-CaD was expressed in colonic and vascular smooth muscle cells as expected and to a lesser extent in the tumor-associated stroma, but it was not expressed in the cancer cells or normal colon mucosal epithelial cells. Collectively, these data clarify how the expression patterns of CaD isoforms in colorectal cancer can have applications in the management of colorectal cancer patients.

Background: Butyrate is a microbiota-derived short-chain fatty acid with established roles in maintaining intestinal barrier integrity and regulating immune responses. Although its effects have been extensively investigated in immunocompetent models, systemic immune homeostasis in severely immunodeficient hosts remains incompletely understood. This exploratory study evaluated the impact of sodium butyrate (NaB) supplementation on tissue-associated microbial antigen detection and immune marker distribution along different organs in athymic nude mice. Methods: Female NU/J athymic mice were administered either regular drinking water (H₂O, n = 10) or NaB-supplemented water (150 mM, n = 5) for six weeks. Intestinal, liver, lung, and kidney tissues were collected for histopathological and immunohistochemical analyses. Expression of microbial antigens, including lipopolysaccharide (LPS) and lipoteichoic acid (LTA), as well as immune-associated markers (CD3, CD8a, CD68, CD278, and transglutaminase-2 [TGM2]), was assessed using a semiquantitative scoring system. Results: NaB supplementation did not significantly affect organ morphology but was associated with better weight gain. Histological examination revealed preserved tissue architecture in all organs, with only mild condensation of small intestinal crypts in NaB-treated mice. Immunohistochemical analysis showed consistently lower LPS expression in NaB-treated animals compared with controls in the small intestine, liver, and kidney, with a borderline reduction in the lungs. Reduced LPS detection was accompanied by significantly lower expression of the macrophage marker CD68 in the kidney. Conclusions: Oral NaB supplementation was associated with lower detection of bacterial antigens in tissues and reduced innate immune expression across multiple organs. These findings support a potential role for butyrate in limiting microbial expression and systemic inflammatory signaling in athymic mice.