Biology subjects

Campen, M. J.

Publications and source records attributed to Campen, M. J..

4 recordsLinked to original sources

bioRxiv2025

Chronic Cadmium Exposures and Hyperglycemia Additively Drive Mitochondrial Dysfunction in Hepatic Cells: Key Implications for MASLD Etiopathogenesis

Effects of chronic heavy metal stress on hepatocellular pathophysiology remains ill-understood. Human livers are a long-term accumulative site for many toxic heavy metals (e.g., cadmium and arsenic) whose effects are unknown. In the current study, we studied effects of chronic, low-dose exposures of cadmium (CLEC) modulated by normoglycemic (5.6 mM) and hyperglycemic (15 mM) exposures, focusing on hepatocellular mitochondrial function. HepG2 and HUH7 cell lines were exposed to CLEC and glucose for 24 weeks, mimicking a chronic heavy metal exposure paradigm seen in normal and type II diabetic individuals. We observe that CLEC exposures significantly affect the long-term health of mitochondria, including decreased mitochondrial mass, increased superoxide production, and loss of mitochondrial membrane potential (MMP) in a CLEC and glucose-dependent manner. Furthermore, the Seahorse MitoStress assay revealed CLEC induced significant chronic oxidative stress. In particular, CLEC cells showed altered levels of basal and non-mitochondrial respiration, causing dysregulation in mitochondrial oxygen consumption rates (OCRs). Lastly, we identified significant impacts of CLEC and glucose exposures on the mitochondrial dynamics (fission/fusion) of the CLEC cells, which showed enhanced mitochondrial fragmentation and turnover rates. We also identified novel cell compensatory mechanisms that may mask the true extent of chronic Cd exposure induced damage in liver cells. CLEC and glucose work additively to damage hepatocellular mitochondrial function. New approach methodologies (NAMs), such as the current vitro toxicology study, establish the insidious effects of chronic heavy metal pollutant exposures on human hepatocellular function.

pharmacology and toxicology↗

bioRxiv2024

White matter hyperintensities and microplastics

SynopsisWhite matter hyperintensities are abnormalities that appear in MRI scans of living patients but are not apparent in MRI post-mortem. GoalOur goal is to understand the cellular/biological basis of white matter hyperintensities (WMH). ApproachWe aligned post-mortem MR scans with those collected ante-mortem and performed histopathology and pyrGC/MS for plastics on regions with WMH. ResultPyrGC/MS detected large amounts of plastics and we determined their cellular locations with a novel optical imaging approach in regions with small vessel disease and Abeta plaques. ImpactMicroplastics in the brains of people with cognitive impairment may be due to pre-existing vascular injury or contribute to it. Many questions remain: Where do they come from, do they impair function? Can they be diagnosed by MRI ante-mortem?

neuroscience↗

bioRxiv2023

Uranium-bearing dust induces differentiation and expansion of enteroendocrine cells in human colonoids

Chronic exposure to environmental toxins and heavy metals has been associated with intestinal inflammation, increased susceptibility to pathogen-induced diseases, and higher incidences of colorectal cancer, all of which have been steadily increasing in prevalence for the past 40 years. The negative effects of heavy metals on barrier permeability and inhibition of intestinal epithelial healing have been described; however, transcriptomic changes within the intestinal epithelial cells and impacts on lineage differentiation are largely unknown. Uranium exposure remains an important environmental legacy and physiological health concern, with hundreds of abandoned uranium mines located in the Southwestern United States largely impacting underserved indigenous communities. Herein, using human colonoids, we defined the molecular and cellular changes that occur in response to uranium bearing dust (UBD) exposure. We used single cell RNA sequencing to define the molecular changes that occur to specific identities of colonic epithelial cells. We demonstrate that this environmental toxicant disrupts proliferation and induces hyperplastic differentiation of secretory lineage cells, particularly enteroendocrine cells (EEC). EECs respond to UBD exposure with increased differentiation into de novo EEC sub-types not found in control colonoids. This UBD-induced EEC differentiation does not occur via canonical transcription factors NEUROG3 or NEUROD1. These findings highlight the significance of crypts-based proliferative cells and secretory cell differentiation as major colonic responses to heavy metal-induced injury.

cell biology↗

bioRxiv2023

In Vivo Tissue Distribution of Microplastics and Systemic Metabolomic Alterations After Gastrointestinal Exposure

Global plastic use has consistently increased over the past century with several different types of plastics now being produced. Much of these plastics end up in oceans or landfills leading to a substantial accumulation of plastics in the environment. Plastic debris slowly degrades into microplastics (MPs) that can ultimately be inhaled or ingested by both animals and humans. A growing body of evidence indicates that MPs can cross the gut barrier and enter into the lymphatic and systemic circulation leading to accumulation in tissues such as the lungs, liver, kidney, and brain. The impacts of mixed MPs exposure on tissue function through metabolism remains largely unexplored. To investigate the impact of ingested MPs on target metabolomic pathways, mice were subjected to either polystyrene microspheres or a mixed plastics (5 {micro}m) exposure consisting of polystyrene, polyethylene and the biodegradability and biocompatible plastic, poly-(lactic-co-glycolic acid). Exposures were performed twice a week for four weeks at a dose of either 0, 2, or 4 mg/week via oral gastric gavage. Our findings demonstrate that, in mice, ingested MPs can pass through the gut barrier, be translocated through the systemic circulation, and accumulate in distant tissues including the brain, liver, and kidney. Additionally, we report on the metabolomic changes that occur in the colon, liver and brain which show differential responses that are dependent on dose and type of MPs exposure. Lastly, our study provides proof of concept for identifying metabolomic alterations associated with MPs exposure and adds insight into the potential health risks that mixed MPs contamination may pose to humans.

pharmacology and toxicology↗