Biology subjects

Bialkowska, A. B.

Publications and source records attributed to Bialkowska, A. B..

4 recordsLinked to original sources

bioRxiv2026

Comparison studies between Cesium-137 and X-ray irradiators in epithelial injury using in vitro and in vivo models

Radiation-induced intestinal injury is a widely used model for studying mechanisms regulating tissue injury and regeneration. Traditionally, Cesium (137Cs) radiation has been used in research applications, but over the past decade, X-ray irradiation has become increasingly favored due to its improved safety and non-radioactive profile. Since each type of radiation has distinct physical characteristics that drive its performance, we sought to systematically compare the effects of the X-ray and 137Cs irradiators on intestinal epithelial injury and regeneration. Using established in vitro models, including colorectal cancer cell lines such as HCT116, RKO, and DLD-1, and mouse intestinal organoids, alongside an in vivo model, Bmi1-CreER;Rosa26eYFP, we evaluated differences in transcriptional, protein, and histopathological responses to irradiation. Our results demonstrate that X-ray produced intestinal injury and regenerative responses comparable to those induced by 137Cs, supporting its reliability as an alternative modality for studying intestinal radiation.

cell biology↗

bioRxiv2023

A Titratable Necrotizing Enterocolitis Mouse Model

BackgroundNecrotizing enterocolitis (NEC) is an inflammatory gastrointestinal process that afflicts approximately 10% of preterm infants born in the United States each year, with a mortality rate of 30%. NEC severity is graded using Bells classification system, from stage I mild NEC to stage III severe NEC. Over half of NEC survivors present with neurodevelopmental impairment during adolescence, a long-term complication that is poorly understood but can occur even after mild NEC. Although multiple animal models exist, none allow the experimenter to control nor represent the gradient of symptom severities seen in NEC patients. We bridge this knowledge gap by developing a graded murine model of NEC and studying its relationship with neuroinflammation across a range of NEC severities. MethodsPostnatal day 3 (P3) C57BL/6 mice were fed a formula containing different concentrations (0% control, 0.25%, 1%, 2%, and 3%) of dextran sodium sulfate (DSS). P3 mice were fed every 3 hours for 72-hours. We collected data on weight gain and behavior (activity, response, body color) during feeding. At the end of the experiment, we collected tissues (intestine, liver, plasma, brain) for immunohistochemistry, immunofluorescence, and cytokine and chemokine analysis. ResultsThroughout NEC induction, mice fed higher concentrations of DSS died sooner, lost weight faster, and became sick or lethargic earlier. Intestinal characteristics (dilation, color, friability) were worse in mice fed with higher DSS concentrations. Histology revealed small intestinal disarray among mice fed all DSS concentrations, while higher DSS concentrations resulted in reduced small intestinal cellular proliferation and increased hepatic and systemic inflammation. In the brain, IL-2, G-CSF, and CXCL1 concentrations increased with higher DSS concentrations. Although the number of neurons and microglia in the CA1 hippocampal region did not differ, microglial branching was significantly reduced in DSS-fed mice. ConclusionWe characterize a novel graded model of NEC that recapitulates the full range of NEC severities. We show that mild NEC is sufficient to initiate neuroinflammation and microglia activation. This model will facilitate studies on the neurodevelopmental effects of NEC.

physiology↗

bioRxiv2022

Deep learning-based approach for the characterization and quantification of histopathology in mouse models of colitis

Inflammatory bowel disease (IBD) is a chronic immune-mediated disease of the gastrointestinal tract. While therapies exist, response can be limited within the patient population. As such, researchers have studied mouse models of colitis to further understand its pathogenesis and identify new treatment targets. Although bench methods like flow cytometry and RNA-sequencing can characterize immune responses with single-cell resolution, whole murine colon specimens are processed at once. Given the simultaneous presence of colonic regions that are involved or uninvolved with abnormal histology, processing whole colons may lead to a loss of spatial context. Detecting these regions in hematoxylin and eosin (H&E)-stained colonic tissues offers the downstream potential of quantifying immune populations in areas with and without disease involvement by immunohistochemistry on serially sectioned slides. This could provide a complementary, spatially-aware approach to further characterize populations identified by other methods. However, detection of such regions requires expert interpretation by pathologists and is a tedious process that may be difficult to perform consistently across experiments. To this end, we have trained a deep learning model to detect Involved and Uninvolved regions from H&E-stained colonic slides across controls and three mouse models of colitis - the dextran sodium sulfate (DSS) chemical induction model, the recently established intestinal epithelium-specific, inducible Klf5{Delta}IND (Villin-CreERT2;Klf5fl/fl) genetic model, and one that combines both induction methods. The trained classifier allows for extraction of Involved colonic regions across mice to cluster and identify histological classes. Here, we show that quantification of Involved and Uninvolved image patch classes in swiss rolls of colonic specimens can be utilized to train a linear determinant analysis classifier to distinguish between mouse models. Such an approach has the potential for revealing histological links and improving synergy between various colitis mouse model studies to identify new therapeutic targets and pathophysiological mechanisms.

immunology↗

bioRxiv2019

Loss of the Krppel-like factor 4 tumor suppressor is associated with epithelial-mesenchymal transition in colorectal cancer

Colorectal cancer (CRC) is the third leading cancer-related cause of death due to its propensity to metastasize. Epithelial-mesenchymal transition (EMT) is a multistep process important for invasion and metastasis of CRC. Kruppel-like factor 4 (KLF4) is a zinc finger transcription factor highly expressed in differentiated cells of the intestinal epithelium. KLF4 has been shown to play a tumor suppressor role during CRC tumorigenesis - its loss accelerates development and progression of cancer. The present study examines the relationship between KLF4 and markers of EMT in CRC.\n\nMethodsImmunofluorescence staining for KLF4 and EMT markers was performed on archived patient samples after colorectal cancer resection and on colonic tissues of mice with colitis-associated cancer.\n\nResultsWe found that KLF4 expression is lost in tumor sections obtained from CRC patients and in those of mouse colon following azoxymethane and dextran sodium sulfate (AOM/DSS) treatment when compared to their respective normal appearing mucosa. Importantly, in CRC patient tumor sections we observed a negative correlation between KLF4 levels and mesenchymal markers including TWIST, {beta}-catenin, claudin-1, N-cadherin, and vimentin. Similarly, in tumor tissues from AOM/DSS-treated mice KLF4 levels were negatively correlated with mesenchymal markers including SNAI2, {beta}-catenin, and vimentin and positively correlated with the epithelial marker E-cadherin.\n\nConclusionThese findings suggest that the loss of KLF4 expression is a potentially significant indicator of EMT in CRC.

cancer biology↗