Alzheimer’s disease (AD) is a challenging medical issue that requires efficacious treatment options to improve long-term quality of life. Cannabidiol (CBD) is a cannabis-derived phytocannabinoid with potential health benefits, including reports from our laboratory and others showing a therapeutic role in the pre-clinical treatment of AD; however, the mechanisms whereby CBD affects AD progression remain undefined. Innate lymphoid cells (ILCs) are recently discovered immune cells that initiate and orchestrate inflammatory responses. ILC2, a sub-class of ILCs, is proposed to have a role in cognitive function via unknown mechanisms. In this present study, we explored whether CBD ameliorates AD symptoms via the enhancement of acetylcholine (ACh), a cholinergic neurotransmitter involved in cognition that may regulate ILC2. 5xFAD mice were chronically treated by inhalation of a formulation of broad-spectrum CBD for seven months. ACh production, ILC2s profile, brain histopathology, and long-term behavior were assessed. Together, our studies showed that long-term inhalation of CBD improved cognitive function and reduced senile plaques in a murine AD model, effects that were associated with enhanced ACh production and altered ILC2s distribution within the CNS. These findings indicate that inhaled CBD could offer a cost-effective, non-invasive, and effective treatment for managing AD. The beneficial effects of CBD inhalation may be linked to increased ACh production and an altered distribution of ILC2s, highlighting the need for further research in this area.

Glioblastoma (GBM) remains one of the most lethal brain tumors, with current therapies offering limited benefits and high relapse rates. This study presents the first preclinical evidence that pretreatment with inhaled cannabidiol (CBD) before tumor establishment can markedly inhibit GBM progression. We hypothesized that early CBD exposure could prime the immune and molecular landscape to resist tumor growth. C57BL/6 mice were pretreated with inhaled CBD for 3 or 14 days, or with placebo, prior to intracranial implantation of glioblastoma cells. Tumor growth, immune checkpoint expressions (IDO, PD-L1), and key biomarkers (MGMT, Ki67) were analyzed to evaluate tumor dynamics and immune modulation. Fourteen-day CBD pretreatment significantly reduced tumor burden compared with both placebo and 3-day CBD groups, accompanied by decreased IDO, PD-L1, MGMT, and Ki67 expression, which are signatures of a less aggressive tumor phenotype. These findings suggest that prolonged CBD exposure can precondition the tumor microenvironment toward an anti-tumor state, improving disease control and potentially lowering relapse risk. This study introduces a novel concept of CBD pretreatment as an immune-modulatory strategy with high translational potential for glioblastoma management.

Elabela is a component of the apelinergic system and may exert a cardioprotective role by regulating the innate immune responses. Innate lymphoid cells (ILCs) have a significant role in initiating and progressing immune-inflammatory responses. While ILCs have been intensively investigated during the last decade, little is known about their relationship with the apelinergic system and their cardiac diversity in a gender-based paradigm. In this study, we investigated the polarization of cardiac ILCs by Elabela in males versus females in a mouse model. Using flow cytometry and immunohistochemistry analyses, we showed a potential interplay between Elabela and cardiac ILCs and whether such interactions depend on sexual dimorphism. Our findings showed, for the first time, that Elabela is expressed by cardiac ILCs, and its expression is higher in females’ ILC class 3 (ILC3s) compared to males. Females had higher frequencies of ILC1s, and Elabela was able to suppress T-cell activation and the expression of co-stimulatory CD28 in a mixed lymphocyte reaction assay (MLR). In conclusion, our results suggest, for the first time, a protective role for Elabela through its interplay with ILCs and that it can be used as an immunotherapeutic target in the treatment of cardiovascular disorders in a gender-based fashion.

Background: Gastrostomy tube placement is sometimes necessary during chemoradiation for head and neck cancer (HNC), but it is associated with worse swallowing outcomes. Despite best efforts, the need for gastrostomy cannot be perfectly predicted, and some patients develop the need for gastrostomy while undergoing chemotherapy. To date, the impact of cisplatin on gastrostomy site healing has not been investigated. The aim of this study is to compare the levels of procollagen, connective tissue growth factor (CTGF), and CD26 in the gastrostomy sites of mice at varying timepoints after cisplatin versus saline. Methods: For this study we used 32 C57BL/6 mice. Cisplatin (1 mg/kg) was injected intraperitoneally into the mice from treatment groups. Control groups received the same volume of normal saline intraperitoneally. Mice underwent gastrostomy tube placement at 7, 10, 14, and 17 days post cisplatin or saline therapy. Ten days after gastrostomy placement, mice were sacrificed, and the gastrostomy site tissue was examined. We measured the levels of procollagen type 1, CTGF, and CD26 by flow cytometry. Massons trichrome stain was used for qualitative comparison of collagen formation in surgical site tissue. Results: Massons trichrome staining showed more collagen formation in surgical site tissue at 17 versus 7 days post-cisplatin. Levels of procollagen type 1 by flow cytometry were significantly higher in the control group compared to the treatment group (P < 0.0001) for each time point. There was a statistically significant difference in procollagen type 1 between the 7 days post-chemotherapy group and the 17 days post-chemotherapy group (P = 0.0024). The percentage of cells with procollagen, CTGF, and CD26 in the 7 days post-saline control group were similar to the percentage in the 14 days post-cisplatin treatment group. Conclusions: CTGF, CD26, and procollagen were decreased by cisplatin in gastrostomy site tissue at each time point, but levels 14 days after a cisplatin treatment approximate the levels 7 days after saline. These results suggest that it is safe to proceed with gastrostomy tube placement 14 - 17 days after cisplatin because the CTGF, CD26, and procollagen levels approximate the levels 7 days after saline. Additional studies are needed to extrapolate to humans. J Curr Surg. 2023;13(1):6-11 doi: https://doi.org/10.14740/jcs468