7 research outputs found
Primary Malignant Melanoma of the Gastric Antrum: A Case Report
Primary melanoma of the antrum is a rare and aggressive disease. Diagnosis requires a correlation between the patient's history, tumor histopathology, and immunohistochemistry. Surgery and mutation‐targeted treatments may improve overall survival
De Novo Pediatric Ulcerative Colitis Triggered by SARS-CoV-2 Infection: a Tale of 2 Sisters
Calcium-induced differentiation in normal human colonoid cultures: Cell-cell / cell-matrix adhesion, barrier formation and tissue integrity.
Background and aimsThe goal of the study was to assess calcium alone and Aquamin, a multi-mineral natural product that contains magnesium and detectable levels of 72 trace elements in addition to calcium, for capacity to affect growth and differentiation in colonoid cultures derived from histologically-normal human colon tissue.MethodsColonoid cultures were maintained in a low-calcium (0.25 mM) medium or in medium supplemented with an amount of calcium (1.5-3.0 mM), either from calcium alone or Aquamin for a period of two weeks. This was shown in a previous study to induce differentiation in colonoids derived from large adenomas. Changes in growth, morphological features and protein expression profile were assessed at the end of the incubation period using a combination of phase-contrast and scanning electron microscopy, histology and immunohistology, proteomic assessment and transmission electron microscopy.ResultsUnlike the previously-studied tumor-derived colonoids (which remained un-differentiated in the absence of calcium-supplementation), normal tissue colonoids underwent differentiation as indicated by gross and microscopic appearance, a low proliferative index and high-level expression of cytokeratin 20 in the absence of intervention (i.e., in control condition). Only modest additional changes were seen in these parameters with either calcium alone or Aquamin (providing up to 3.0 mM calcium). In spite of this, proteomic analysis and immunohistochemistry revealed that both interventions induced strong up-regulation of proteins that promote cell-cell and cell-matrix adhesive functions, barrier formation and tissue integrity. Transmission electron microscopy revealed an increase in desmosomes in response to intervention.ConclusionsThese findings demonstrate that colonoids derived from histologically normal human tissue can undergo differentiation in the presence of a low ambient calcium concentration. However, higher calcium levels induce elaboration of proteins that promote cell-cell and cell-matrix adhesion. These changes could lead to improved barrier function and improved colon tissue health
Ulcerative Colitis-Derived Colonoid Culture: A Multi-Mineral-Approach to Improve Barrier Protein Expression
PMCID: PMC7719760Background: Recent studies demonstrated that Aquamin®, a calcium-, magnesium-rich, multi-mineral natural product, improves barrier structure and function in colonoids obtained from the tissue of healthy subjects. The goal of the present study was to determine if the colonic barrier could be improved in tissue from subjects with ulcerative colitis (UC).
Methods: Colonoid cultures were established with colon biopsies from 9 individuals with UC. The colonoids were then incubated for a 2-week period under control conditions (in culture medium with a final calcium concentration of 0.25 mM) or in the same medium supplemented with Aquamin® to provide 1.5 - 4.5 mM calcium. Effects on differentiation and barrier protein expression were determined using several approaches: phase-contrast and scanning electron microscopy, quantitative histology and immunohistology, mass spectrometry-based proteome assessment and transmission electron microscopy.
Results: Although there were no gross changes in colonoid appearance, there was an increase in lumen diameter and wall thickness on histology and greater expression of cytokeratin 20 (CK20) along with reduced expression of Ki67 by quantitative immunohistology observed with intervention. In parallel, upregulation of several differentiation-related proteins was seen in a proteomic screen with the intervention. Aquamin®-treated colonoids demonstrated a modest up-regulation of tight junctional proteins but stronger induction of adherens junction and desmosomal proteins. Increased desmosomes were seen at the ultrastructural level. Proteomic analysis demonstrated increased expression of several basement membrane proteins and hemidesmosomal components. Proteins expressed at the apical surface (mucins and trefoils) were also increased as were several additional proteins with anti-microbial activity or that modulate inflammation. Finally, several transporter proteins that affect electrolyte balance (and, thereby affect water resorption) were increased. At the same time, growth and cell cycle regulatory proteins (Ki67, nucleophosmin, and stathmin) were significantly down-regulated. Laminin interactions, matrix formation and extracellular matrix organization were the top three up-regulated pathways with the intervention.
Conclusion: A majority of individuals including patients with UC do not reach the recommended daily intake for calcium and other minerals. To the extent that such deficiencies might contribute to the weakening of the colonic barrier, the findings employing UC tissue-derived colonoids here suggest that adequate mineral intake might improve the colonic barrier.http://deepblue.lib.umich.edu/bitstream/2027.42/174691/2/fcell-08-577221_Aslam_2020.pdfPublished versionDescription of fcell-08-577221_Aslam_2020.pdf : Published versio
Knowledge, attitudes and practices survey on organ donation among a selected adult population of Pakistan
<p>Abstract</p> <p>Background</p> <p>To determine the knowledge, attitudes and practices regarding organ donation in a selected adult population in Pakistan.</p> <p>Methods</p> <p>Convenience sampling was used to generate a sample of 440; 408 interviews were successfully completed and used for analysis. Data collection was carried out via a face to face interview based on a pre-tested questionnaire in selected public areas of Karachi, Pakistan. Data was analyzed using SPSS v.15 and associations were tested using the Pearson's Chi square test. Multiple logistic regression was used to find independent predictors of knowledge status and motivation of organ donation.</p> <p>Results</p> <p>Knowledge about organ donation was significantly associated with education (p = 0.000) and socioeconomic status (p = 0.038). 70/198 (35.3%) people expressed a high motivation to donate. Allowance of organ donation in religion was significantly associated with the motivation to donate (p = 0.000). Multiple logistic regression analysis revealed that higher level of education and higher socioeconomic status were significant (p < 0.05) independent predictors of knowledge status of organ donation. For motivation, multiple logistic regression revealed that higher socioeconomic status, adequate knowledge score and belief that organ donation is allowed in religion were significant (p < 0.05) independent predictors. Television emerged as the major source of information. Only 3.5% had themselves donated an organ; with only one person being an actual kidney donor.</p> <p>Conclusion</p> <p>Better knowledge may ultimately translate into the act of donation. Effective measures should be taken to educate people with relevant information with the involvement of media, doctors and religious scholars.</p