Influence of vitamin D receptor signaling and vitamin D on colonic epithelial cell fate decisions in ulcerative colitis.

BACKGROUND AND AIMS: Epidemiological studies have shown that subnormal levels of vitamin D (25(OH)D) are associated with a more aggravated clinical course of ulcerative colitis (UC). Despite an increased focus on the therapeutic importance of vitamin D and vitamin D receptor (VDR) signaling, the mechanisms underlying the effects of the vitamin D-VDR axis on UC remain elusive. Therefore, we aimed to investigate whether exposure to active vitamin D (1,25(OH)2D3)/VDR signaling in human organoids could influence the maintenance of the colonic epithelium. METHODS: Intestinal VDR expression was studied by immunohistochemistry, RNA expression arrays, and single-cell RNA sequencing of colonic biopsy specimens obtained from patients with UC and healthy individuals. To characterize the functional and transcriptional effects of 1,25(OH)2D3, we used patient-derived colonic organoids. The dependency of VDR was assessed by knocking out the receptor with CRISPR/Cas9. RESULTS: Our results suggest that 1,25(OH)2D3/VDR stimulation supports differentiation of the colonic epithelium and that impaired 1,25(OH)2D3/VDR signaling thereby may compromise the structure of the intestinal epithelial barrier, leading to flares of UC. Furthermore, a transcriptional response to VDR activity was observed primarily in fully differentiated cells at the top of the colonic crypt, and this response was reduced during flares of UC. CONCLUSIONS: We identified an important role of vitamin D signaling in supporting differentiated cell states in the human colonic epithelium, and thereby maintenance of the intestinal barrier integrity. This makes the vitamin D-VDR signaling axis an interesting target for therapeutic efforts to achieve and maintain remission in patients with UC.

Elevated levels of perfluoroalkyl substances in breast cancer patients within the Greater Manila Area.

Several studies have reported exposure of humans to various endocrine disrupting chemicals (EDCs) worldwide. However, there is a lack of data regarding EDC exposures in humans living in Southeast Asian countries, such as the Philippines. Hence, this study measured levels of 41 EDCs in women residing in the Greater Manila Area, home to the second largest city in Southeast Asia. Urine samples from women with versus without breast cancer were analyzed for 11 phthalate metabolites, 8 environmental phenols, and 10 bisphenols, while serum samples were analyzed for 12 perfluoroalkyl substances (PFAS). Out of the four groups of EDCs analyzed, PFAS were significantly associated with breast cancer (adjusted OR = 13.63, 95% CI: 3.24-94.88 p-trend = 0.001 for PFDoA; adjusted OR = 9.26, 95% CI 2.54-45.10, p-trend = 0.002 for PFDA; and adjusted OR = 2.66, 95% CI: 0.95-7.66, p-trend = 0.004 for PFHxA). Long-chain PFAS levels were positively correlated with age and were significantly higher in women from Region IV-A, a heavily industrialized region, than from the National Capital Region. Overall, this study showed baseline information regarding the level of EDCs in Filipinas, providing a glimpse of EDC exposure in women living in a megalopolis city in Southeast Asia.

Mapping Cellular Coordinates through Advances in Spatial Transcriptomics Technology.

Complex cell-to-cell communication underlies the basic processes essential for homeostasis in the given tissue architecture. Obtaining quantitative gene-expression of cells in their native context has significantly advanced through single-cell RNA sequencing technologies along with mechanical and enzymatic tissue manipulation. This approach, however, is largely reliant on the physical dissociation of individual cells from the tissue, thus, resulting in a library with unaccounted positional information. To overcome this, positional information can be obtained by integrating imaging and positional barcoding. Collectively, spatial transcriptomics strategies provide tissue architecture-dependent as well as position-dependent cellular functions. This review discusses the current technologies for spatial transcriptomics ranging from the methods combining mechanical dissociation and single-cell RNA sequencing to computational spatial re-mapping.

A Pilot Cancer-Phenome Biobanking System in a Low-Resource Southeast Asian Setting: The Philippine General Hospital Biobank Experience.

Biobanking has become an indispensable tool for translational research and health innovations. While the field of biobanking has progressed and evolved globally, biobanking in developing Association of Southeast Asian Nations (ASEAN) countries such as the Philippines remains underrepresented because of several challenges often encountered in these low- and middle-income countries. Recently, the Philippine government has undertaken enormous efforts to advancing research and development in the country, and one of the current research pursuits is the establishment of biobanks, with the hope of attaining more discoveries and innovations in the future. Given that cancer remains a leading cause of death in the Philippines, the Philippine government supported the establishment of a cancer biobank at the Philippine General Hospital (PGH). In this study, we present a specific use case of biobanking activity at the PGH Biobank, to build a cohort of biospecimens from Filipino patients with breast, endometrial, and ovarian cancer. This initiative is part of a biomonitoring study (1) to assess environmental exposures and possible risk factors in the Philippine population and (2) to develop a system of culturing human cells from Filipino patients for subsequent in vitro studies. We discuss issues faced and the solutions developed during the implementation of the biobank. Strong research collaboration, a funding source, basic infrastructure, and appropriate technology helped initiate this pilot biobank in the Philippines. Overall, the experiences of establishing the PGH Biobank may help other institutions in low-resource countries to set up cancer biobanks.