Biology subjects

Baglole, C. J.

Publications and source records attributed to Baglole, C. J..

4 recordsLinked to original sources

bioRxiv2025

The AhR is a Critical Regulator of the Pulmonary Response to Cannabis Smoke

Cannabis use is prevalent worldwide, with smoking being the most common method of consumption. When smoking cannabis, users are exposed to both harmful combustion products as well as cannabinoids such as tetrahydrocannabinol (THC) and cannabidiol (CBD). THC and CBD have purported anti-inflammatory effects through activation of cannabinoid receptors; however, the minimal expression of these receptors in lung tissue suggests that respiratory effects of cannabis may be mediated through alternative pathways. One potential mediator of these effects is the aryl hydrocarbon receptor (AhR), a transcription factor involved in xenobiotic metabolism. Notably, the AhR is activated by both combustion products and cannabinoids. This receptor is also known to dampen lung inflammation induced by tobacco smoke or air pollution. Therefore, we hypothesized that AhR activation would reduce susceptibility to the harmful effects of inhaled cannabis smoke. To investigate this hypothesis, Ahr+/- and Ahr-/- mice were exposed to air or cannabis smoke using a controlled puff regimen over a three-day period. In the first study to characterize the effects of cannabis smoke on lung tissue and the pulmonary secretome, including extracellular vesicles and secreted proteins, we found that acute exposure induced neutrophilia, vascular leakage, and activation of tissue remodeling pathways, all of which were regulated by AhR. These findings highlight not only the detrimental effects of cannabis smoke on lung health but also the pivotal role of the AhR as a key regulator of the pulmonary response to cannabis smoke exposure.

pharmacology and toxicology↗

bioRxiv2024

AB-free kava enhances resilience against the adverse health effects of tobacco smoke in mice

Tobacco smoke remains a serious global issue, resulting in serious health complications, contributing to the onsets of numerous preventive diseases, and imposing significant financial burdens. Despite regulatory policies and cessation measures aimed at curbing its usage, novel interventions are urgently needed for effective damage reduction. Our preclinical and pilot clinical studies showed that AB-free kava has the potential to reduce tobacco smoke-induced lung cancer risk, mitigate tobacco dependence, and reduce tobacco use. To understand the scope of its benefits in damage reduction and potential limitations, this study evaluated the effects of AB-free kava on a panel of health indicators in mice exposed to 2 - 4 weeks of daily tobacco smoke exposure. Our comprehensive assessments included global transcriptional profiling of the lung and liver tissues, analysis of lung inflammation, evaluation of lung function, exploration of tobacco nicotine withdrawal, and characterization of the causal PKA signaling pathway. As expected, Tobacco smoke exposure perturbed a wide range of biological processes and compromised multiple functions in mice. Remarkably, AB-free kava demonstrated the ability to globally mitigate tobacco smoke-induced deficits at the molecular and functional levels with promising safety profiles, offering a unique promise to mitigate tobacco smoke-related health damages. Further pre-clinical evaluation and clinical translation are warranted to fully harness the potential of AB-free kava in combating tobacco smoke-related harms. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=105 SRC="FIGDIR/small/599576v1_ufig1.gif" ALT="Figure 1"> View larger version (26K): org.highwire.dtl.DTLVardef@1f6ee4corg.highwire.dtl.DTLVardef@96e062org.highwire.dtl.DTLVardef@16579a0org.highwire.dtl.DTLVardef@1140a8e_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

bioRxiv2023

DENetwork: Unveiling Regulatory and Signaling Networks Behind Differentially-Expressed Genes

Differential gene expression analysis from RNA-sequencing (RNA-seq) data offers crucial insights into biological differences between sample groups. However, the conventional focus on differentially-expressed (DE) genes often omits non-DE regulators, which are an integral part of such differences. Moreover, DE genes frequently serve as passive indicators of transcriptomic variations rather than active influencers, limiting their utility as intervention targets. To address these shortcomings, we have developed DENetwork. This innovative approach deciphers the intricate regulatory and signaling networks driving transcriptomic variations between conditions with distinct phenotypes. Unique in its integration of both DE and critical non-DE genes in a graphical model, DENetwork enhances the capabilities of traditional differential gene analysis tools, such as DESeq2. Our application of DENetwork to an array of simulated and real datasets showcases its potential to encapsulate biological differences, as demonstrated by the relevance and statistical significance of enriched gene functional terms. DENetwork offers a robust platform for systematically characterizing the biological mechanisms that underpin phenotypic differences, thereby augmenting our understanding of biological variations and facilitating the formulation of effective intervention strategies.

bioinformatics↗

bioRxiv2018

Endocrine aryl hydrocarbon receptor signaling is induced by moderate cutaneous exposure to ultraviolet light

Links between solar UV exposure and immunity date back to the ancient Greeks with the development of heliotherapy. Skin contains several UV-sensitive chromophores and exposure to sunlight can produce molecules, such as vitamin D3, that act in an endocrine manner. We investigated whether the aryl hydrocarbon receptor (AHR), an environmental sensor and ligand-regulated transcription factor activated by numerous planar compounds of dietary or environmental origin, could be the target of endocrine photoproducts produced by cutaneous UV exposure. 15-to 30-minute exposure of cells to a minimal erythemal dose of UVB irradiation in vitro induced translocation of the AHR to the nucleus, rapidly inducing site-specific DNA binding and target gene regulation. Importantly, ex vivo studies with Ahr wild-type or null fibroblasts showed that serum from mice whose skin was exposed to a 15 min UVB dose, but not control serum, contained agonist activity within 30 min of UV irradiation, inducing AHR-dependent gene expression. Moreover, a 15-min cutaneous UVB exposure induced AHR site-specific DNA binding and target gene regulation in vivo within 3-6 hr post-irradiation in blood and in peripheral tissues, including intestine. These results show that cutaneous exposure of mice to a single minimal erythemic dose of UVB induces rapid AHR signaling in multiple peripheral organs, providing compelling evidence that moderate sun exposure can exert endocrine control of immunity through the AHR.

molecular biology↗