Biology subjects

Orozco, J.

Publications and source records attributed to Orozco, J..

3 recordsLinked to original sources

bioRxiv2026

Preclinical evaluation of a natural extract-based oral nanoformulation from Eucalyptus tereticornis for potential use in treating type 2 diabetes mellitus.

The acute, subacute, and subchronic oral toxicities, as well as the combined chronic toxicity and carcinogenicity, of a nanotechnology-based formulation derived from a natural extract of Eucalyptus tereticornis leaves were investigated. This nanoformulation demonstrates anti-obesogenic and potentially anti-diabetic properties. Our study aims to conduct preclinical tests to evaluate the chemical formulation. To assess acute toxicity, rats received a single oral dose of 2000 mg/kg of the nanoformulation. In the subacute trial, mice were treated with approximately 1180 mg/kg of the nanoformulation for 28 days. In the combined chronic toxicity and carcinogenicity study, the nanoformulation was administered daily at approximately 590 mg/kg for 10 months. At the end of the experiment, hematological, biochemical, and histopathological assessments were conducted. Throughout the acute, subacute, subchronic, and chronic/carcinogenicity studies, animals showed no toxic effects from the treatment or the vehicle. No histopathological lesions, such as degeneration or cell death in the liver, kidney, or gastrointestinal tract, were observed. Treatments did not cause any clinical changes, and there were no significant differences in weight, hematological, or biochemical parameters. Therefore, the nanoformulation did not produce toxic effects in the animals.

pharmacology and toxicology↗

bioRxiv2026

Dietary Microplastics Engage Gut Mechanosensory-Endocrine Signaling to Disrupt Bone Homeostasis

Background and AimsMicroplastics are pervasive environmental contaminants increasingly detected in food and water supplies; however, their effects on gastrointestinal physiology and systemic health remain poorly understood. We investigated whether chronic dietary microplastic exposure alters colonic neuroendocrine signaling and skeletal health. MethodsFemale and male C57BL/6J mice were fed purified basal, high-fat/high-cholesterol, or high-fiber diets with or without a physiological relevant polystyrene microplastic mixture ([~]1.7 mg/kg; particle sizes 0.49 - 5.0 {micro}m) for 12 weeks. Colonic cellular responses were evaluated using ELISA, histology, immunofluorescence, and single-nuclei RNA sequencing. Fecal microbiota transplantation was performed to assess microbial contributions to microplastic-induced phenotypes. Bone microarchitecture was assessed by micro-computed tomography. Human bone specimens were analyzed for microplastic content, and primary osteoblast mineralization assays were performed. ResultsDietary microplastic exposure increased chromogranin A-positive enteroendocrine cells and enhanced serotonergic signaling in the colon without evidence of intestinal inflammation or lineage reprogramming. Single-nuclei transcriptomic analysis identified compartment-specific serotonergic and mechanosensory adaptations in epithelial and enteric neuronal populations. Transfer of microbiota from microplastic-exposed donors to control recipients recapitulated increased enteroendocrine cell abundance. Chronic microplastic ingestion induced sex- and diet-dependent reductions in trabecular bone loss and architecture without systemic inflammatory activation. Microplastics were detected in human mineralized bone, and microplastic exposure impaired osteoblast mineralization in a donor-dependent manner. ConclusionsChronic ingestion of microplastics remodels gut neuroendocrine signaling through microbiota-dependent mechanisms and impairs skeletal homeostasis in the absence of overt inflammation. These findings identify a previously unrecognized gut-bone pathway through which dietary microplastic exposure may influence host physiology.

physiology↗

bioRxiv2025

Clostridioides difficile major toxins remodel the intestinal epithelia, affecting spore adherence/internalization into intestinal tissue and their association with gut vitronectin.

The most common cause of healthcare-associated diarrhea and colitis in the U.S., is Clostridioides difficile, a spore-forming pathogen. Two toxins, TcdA and TcdB, are major virulence factors essential for disease manifestations, while C. difficile spores are essential for disease transmission and recurrence. Both toxins cause major damage to the epithelial barrier, trigger massive inflammation, and reshape the microbiome and metabolic composition, facilitating C. difficile colonization. C. difficile spores, essential for transmission and recurrence of the disease, persist adhered and internalized in the intestinal epithelia. Studies have suggested that toxin-neutralization in combination with antibiotic during CDI treatment in humans significantly reduces disease recurrence, suggesting a link between toxin-mediated damage and spore persistence. Here, we show that TcdA/TcdB-intoxication of intestinal epithelial Caco-2 cells leads to remodeling of accessible levels of fibronectin (Fn) and vitronectin (Vn) and their cognate alpha-integrin subunits. While TcdB-intoxication of intestinal tissue had no impact in accessible levels of Fn and Vn, but significantly increased levels of intracellular Vn. We observed that Fn and Vn released to the supernatant readily bind to C. difficile spores in vitro, while TcdB-intoxication of intestinal tissue led to increased association of C. difficile spores with gut Vn. Toxin-intoxication of the intestinal tissue also contributes to increased adherence and internalization of C. difficile spores. However, TcdB-intoxicated ligated loops infected of mice treated with Bezlotoxumanb (monoclonal anti- TcdB antibodies) did not prevent TcdB-mediated increased spore adherence and internalization into intestinal tissue. This study highlights the importance of studying the impact of C. difficile toxins of host tissues has in C. difficile interaction with host surfaces that may contribute to increased persistence and disease recurrence.

microbiology↗