Biology subjects

Wang, L. P.

Publications and source records attributed to Wang, L. P..

7 recordsLinked to original sources

bioRxiv2025

Adoptive Transfer of ILC2s into the Brain Reveals Tumor Homing in Glioblastoma: A Proof-of-Concept for Cellular Therapy

Glioblastoma (GBM) is an aggressive brain tumor with limited treatment options and poor immune cell infiltration. Cellular immunotherapies have transformed cancer treatment but remain largely ineffective against GBM due to the restrictive blood-brain barrier (BBB) and its profoundly immunosuppressive microenvironment. Innate lymphoid cells type 2 (ILC2s) have recently emerged as potential candidates for cellular immunotherapy because of their regenerative and immunomodulatory functions. Here, we provide the first in vivo evidence that systemically administered ILC2s can cross the BBB and home to glioblastoma. Bone marrow-derived ILC2s from C57BL/6 mice were labeled with CFSE and intravenously transferred into hosts bearing orthotopic, luciferase-expressing GL261 tumors. Fluorescence imaging and flow cytometry analyses indicated that transferred ILC2s successfully entered the brain, localized within tumor tissue, and were also detected in meninges and peripheral organs. Although no measurable reduction in tumor growth was observed, these findings support a proof-of-concept for adoptive ILC2 transfer as a feasible approach for targeting CNS tumors and exploring their immunomodulatory potential in GBM.

immunology↗

bioRxiv2025

Cannabidiol as a Prophylactic Agent Against Glioblastoma Growth: A Preclinical Investigation

PurposeGlioblastoma (GBM) is one of the most aggressive brain tumors, with limited treatment options and poor outcomes due to frequent relapse after surgery. This study aims to investigate whether pretreatment with inhaled cannabidiol (CBD) can inhibit GBM growth in a preclinical murine model. Specifically, we hypothesize that CBD pretreatment may reduce tumor progression and modulate the tumor microenvironment. MethodsC57BL/6 mice were pretreated with inhaled CBD for either 3 or 14 days, or a placebo, followed by intracranial implantation of glioblastoma cells. Tumor growth, immune checkpoint expression (IDO, PD-L1), and key biomarkers (MGMT, Ki67) were assessed to determine the impact of CBD pretreatment on tumor progression and the immune microenvironment. ResultsThe 14-day CBD pretreatment significantly reduced tumor growth compared to both the placebo and 3-day CBD groups. Additionally, this group showed lower expression of immune checkpoints (IDO, PD-L1) and reduced levels of MGMT and Ki67, suggesting enhanced tumor suppression. These results indicate that prolonged CBD pretreatment modulates the tumor microenvironment and may improve tumor control and reduce relapse risk. ConclusionThis study demonstrates that inhaled CBD pretreatment significantly inhibits GBM growth in a preclinical model. CBDs ability to reduce immune checkpoint expression and key biomarkers associated with tumor progression suggests that it could be an effective strategy for enhancing the efficacy of GBM therapies and potentially improving post-surgical outcomes. Further research is required to investigate its clinical potential and mechanisms of action.

cancer biology↗

bioRxiv2025

Protective role of Cannabidiol against nicotine pouch-induced seizure aggravation and alterations in brain glymphatic biomarkers.

Nicotine pouches are increasingly popular as a smokeless alternative to tobacco, yet their long-term neurological effects remain poorly understood. In this preclinical study, we investigated the time-dependent impact of oral nicotine pouch exposure on seizure susceptibility, glymphatic function, and neuroinflammation in mice, and evaluated the therapeutic potential of inhaled cannabidiol (CBD). Using the Racine scale, we found that acute nicotine exposure transiently reduced seizure severity, while chronic exposure significantly exacerbated seizures and impaired glymphatic integrity, as evidenced by downregulation of aquaporin-4 (AQP4). Chronic nicotine also elevated circulating levels of HMGB1 and IL-6, indicating sustained systemic inflammation. Notably, inhaled CBD reversed these pathological changes, reducing seizure severity, restoring AQP4 expression, and normalizing inflammatory markers. Molecular analyses further revealed upregulation of BDNF and c-FOS with chronic nicotine exposure, which was also mitigated by CBD. In conclusion, these findings suggest that while nicotine pouches may confer short-term neurophysiological modulation, chronic use poses significant risks for seizure vulnerability and glymphatic dysfunction. Inhaled CBD demonstrates strong neuroprotective potential and may serve as a promising therapeutic approach for individuals exposed to prolonged nicotine use. HighlightsO_LIChronic exposure to oral nicotine pouches exacerbates seizure severity in a preclinical model. C_LIO_LINicotine-induced seizures are associated with elevated neuroinflammation and impaired glymphatic function. C_LIO_LIInhaled cannabidiol (CBD) reverses nicotine-induced increases in HMGB1, IL-6, and seizure activity. C_LIO_LICBD restores Aquaporin-4 expression and reestablishes glymphatic integrity disrupted by nicotine. C_LIO_LISystems biology analysis reveals an IL-6-centered protein network targeted by CBD, offering mechanistic insight into its neuroprotective effects. C_LI

neuroscience↗

bioRxiv2025

Rethinking Alzheimer's: Harnessing Cannabidiol to Modulate IDO and cGAS Pathways for Neuroinflammation Control

Alzheimers disease has traditionally been associated with amyloid-{beta} plaques, but growing evidence underscores the role of neuroinflammation in disease progression. The autoimmune hypothesis of Alzheimers disease suggests chronic inflammation and immune dysfunction contribute to neuronal damage, making modulation of immune responses a promising therapeutic strategy for the disease. Cannabidiol, a phytocannabinoid with anti-inflammatory properties, may offer therapeutic potential. This study explores how cannabidiol influences the Indoleamine 2,3-dioxygenase (IDO) and cyclic GMP-AMP synthase (cGAS) pathway, a key regulator of neuroinflammation in Alzheimers disease. Using the 5XFAD transgenic mouse model of Alzheimers disease, we administered cannabidiol via inhalation. We assessed immune markers, including Indoleamine 2,3-dioxygenase and cyclic GMP-AMP synthase, through flow cytometry, immunofluorescence staining, and gene expression analysis. Cytokine levels and neuroinflammatory responses were evaluated, and protein-protein interactions within the Indoleamine 2,3-dioxygenase/cyclic GMP-AMP synthase pathway were analyzed using the STRING database. Cannabidiol treatment significantly reduced Indoleamine 2,3-dioxygenase and cyclic GMP-AMP synthase expression, correlating with lower levels of pro-inflammatory cytokines, including Tumor Necrosis Factor-alpha, Interleukin-1 beta, and Interferon-gamma. Bioinformatics analysis identified potential interactions between cannabidiol and immune targets such as Protein Kinase B (AKT1), Transient Receptor Potential Vanilloid 1, and G-protein coupled receptor 55, suggesting a multi-targeted therapeutic effect. These findings support cannabidiol as a potential monotherapy or adjunctive treatment for Alzheimers disease, targeting neuroinflammatory pathways, particularly the Indoleamine 2,3-dioxygenase/cyclic GMP-AMP synthase axis. Further studies are needed to explore its full therapeutic potential.

immunology↗

bioRxiv2024

Optimization of Seizure Prevention by Cannabidiol (CBD)

ObjectiveCannabidiol (CBD) is one of the most prominent non-psychotropic cannabinoids with known therapeutic potentials. Based on its anti-seizure efficacy, the first cannabis derived, pharmaceutical grade CBD-based medication was approved in the USA in 2018 for the treatment of seizures in patients 2 years and older. Despite the effectiveness in reducing seizures, there remain several major questions on the optimization of CBD therapy for epilepsy such as the optimal dosage, composition, and route of delivery, which are the main objective of this current study. MethodsWe evaluated the antiseizure effects of CBD through different compositions, routes of delivery, and dosages in a pre-clinical model. We used a kainic acid-induced epilepsy model in C57BL/6 mice, treated them with placebo and/or CBD through inhalation, oral and injection routes. We used CBD broad spectrum (inhaled and injection) versus CBD isolate formulations. We employed the Racine scaling system to evaluate the severity of the seizures, flow cytometry for measuring Immune biomarkers and neurotrophic factors, and histologic analysis to examine and compare the groups. ResultsOur findings showed that all forms of CBD reduced seizures severity. Among the combination of CBD tested. CBD broad spectrum via inhalation was the most effective in the treatment of epileptic seizures (p<0.05) compared to other forms of CBD treatments. ConclusionOur data suggest that route and CBD formulations affect its efficacy in the prevention of epileptic seizures. Inhaled broad spectrum CBD showed a potential superior effect compared to other delivery routes and CBD formulations in the prevention of epileptic seizures, warrants further research.

neuroscience↗

bioRxiv2024

Cannabidiol reverses fentanyl-induced addiction and modulates neuroinflammation

IntroductionFentanyl and non-pharmaceutical fentanyl use have been the leading causes of opioid-induced death worldwide. Being 50 times stronger than heroin and 100 times stronger than morphine, fentanyl is a potent opioid with overdoses causing over 250,000 deaths since 2018 in the US alone. The treatment of fentanyl addiction is a complex process and a clinical challenge. There is a dire need to find other innovative and alternative modalities in the fight against fentanyl crisis. Increasing evidence suggests a correlation between neuroinflammation and symptoms of drug abuse, opening up the possibility of immunoregulatory agents as therapy for fentanyl addiction as well as a other opioid-induced addiction. Cannabidiol (CBD) is a non-opioid, relatively safe, non-psychoactive phyto-cannabinoid produced by cannabis plants. Importantly, recent reports have documented benefits of CBD in the treatment and management of complications related to opioid withdrawal. We investigated if inhaled CBD could reverse the fentanyl addiction and whether the CBD treatment could ameliorate the addiction symptoms by regulating neuroinflammatory signals and re-establishing the homeostasis in CNS. MethodWe used a fentanyl-induced conditioned place preference (CPP) model in mouse to test whether inhaled CBD could reverse the fentanyl addiction and ameliorate the adversarial symptoms. By employing a combination of flow cytometry as well as behavioral tests, we further assessed the impact of fentanyl addiction on cells and neuroinflammatory signals in CNS and we measured the effects of CBD in the treatment of addiction symptoms and inflammatory signals. ResultsOur findings suggest that CBD inhalation could be used effectively in the treatment of fentanyl addiction. CBD mitigated the excessive fentanyl-induced neuroinflammatory responses and decreased cellular stress and senescence. Conclusioninhaled CBD could alleviate the fentanyl addiction and regulate neuroinflammatory responses. This novel approach is non-invasive, accessible, effective, and warrants further, translational and research.

animal behavior and cognition↗

bioRxiv2024

The synergy between cannabidiol and probiotics curtails the glycemic indicators, enhances insulin production, and alleviates the symptoms of type 2 diabetes.

Diabetes continues to challenge healthcare system as one of the most growing epidemics with staggering economic burden. It is estimated that 783 million by 2045 will live with diabetes worldwide, 90% of those cases are type 2 diabetes (T2D). T2D is a multifaceted disease, its treatment requires a holistic approach, beyond single target medications with high efficacy. There is a dire need to explore and invent new and effective therapeutic modalities for T2D. In this study we tested whether a combined formulation of cannabidiol (CBD) and probiotics could control glycemic indices and alleviate symptoms of T2D. We used a mouse model of T2D, replaced their drinking water with a combination of CBD and probiotics formulated as a commercially available beverage. Our findings demonstrated that combination of CBD and probiotics not only reduced the glycemic indices (HbA1c & FBG), but also altered the microbiome profile, promoted beneficial bacteria. Further, the CBD/probiotic combination reduced peripheral inflammatory cytokines and enhanced insulin production in pancreatic islets. In conclusion, our results suggest that consumption of combined CBD and probiotics could be used as a natural, practical, affordable, and safe alternative and complementary therapeutic modality to treat T2D.

molecular biology↗