Cutaneous wounds, both acute and chronic, begin with loss of the integrity, and thus barrier function, of the skin. Surgery and trauma produce acute wounds. There are 22 million surgical procedures per year in the United States alone, based on data from the American College of Surgeons, resulting in a prevalence of 6.67%. Acute traumatic wounds requiring repair total 8 million per year, 2.42% or 24.2 per 1000. The cost of wound care is increasing; it approached USD 100 billion for just Medicare in 2018. This burden for wound care will continue to rise with population aging, the increase in metabolic syndrome, and more elective surgeries. To heal a wound, an orchestrated, evolutionarily conserved, and complex series of events involving cellular and molecular agents at the local and systemic levels are necessary. The principal factors of this important function include elements from the neurological, cardiovascular, immune, nutritional, and endocrine systems. The objectives of this review are to provide clinicians engaged in wound care and basic science researchers interested in wound healing with an updated synopsis from recent publications. We also present data from our primary investigations, testing the hypothesis that cannabidiol can alter cutaneous wound healing and documenting their effects in wild type (C57/BL6) and db/db mice (Type 2 Diabetes Mellitus, T2DM). The focus is on the potential roles of the endocannabinoid system, cannabidiol, and the important immune-regulatory wound cytokine IL-33, a member of the IL-1 family, and connective tissue growth factor, CTGF, due to their roles in both normal and abnormal wound healing. We found an initial delay in the rate of wound closure in B6 mice with CBD, but this difference disappeared with time. CBD decreased IL-33 + cells in B6 by 70% while nearly increasing CTGF + cells in db/db mice by two folds from 18.6% to 38.8% (p < 0.05) using a dorsal wound model. We review the current literature on normal and abnormal wound healing, and document effects of CBD in B6 and db/db dorsal cutaneous wounds. CBD may have some beneficial effects in diabetic wounds. We applied 6–mm circular punch to create standard size full-thickness dorsal wounds in B6 and db/db mice. The experimental group received CBD while the control group got only vehicle. The outcome measures were rate of wound closure, wound cells expressing IL-33 and CTGF, and ILC profiles. In B6, the initial rate of wound closure was slower but there was no delay in the time to final closure, and cells expressing IL-33 was significantly reduced. CTGF + cells were higher in db/bd wounds treated with CBD. These data support the potential use of CBD to improve diabetic cutaneous wound healing.

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.

Glomerular endothelial injury and effectiveness of glomerular endothelial repair play a crucial role in the progression of glomerulonephritis. Although the potent immune suppressive everolimus is increasingly used in renal transplant patients, adverse effects of its chronic use have been reported clinically in human glomerulonephritis and experimental renal disease. Recent studies suggest that progenitor stem cells could enhance glomerular endothelial repair with minimal adverse effects. Increasing evidence supports the notion that stem cell therapy and regenerative medicine can be effectively used in pathological conditions within the predictive, preventive and personalized medicine (PPPM) paradigm. In this study, using an experimental model of glomerulonephritis, we tested whether bone marrow-derived stem cells (BMDSCs) could provide better effect over everolimus in attenuating glomerular injury and improving the repair process in a rat model of glomerulonephritis. Anti-Thy1 glomerulonephritis was induced in male Sprague Dawley rats by injection of an antibody against Thy1, which is mainly expressed on glomerular mesangial cells. Additional groups of rats were treated with the immunosuppressant everolimus daily after the injection of anti-Thy1 or injected with single bolus dose of BMDSCs after one week of injection of anti-Thy1 (n = 6–8). Nine days after injection of anti-Thy1, glomerular albumin permeability and albuminuria were significantly increased when compared to control group (p < 0.05). Compared to BMDSCs, everolimus was significantly effective in attenuating glomerular injury, nephrinuria and podocalyxin excretion levels as well as in reducing inflammatory responses and apoptosis. Our findings suggest that bolus injection of BMDSCs fails to improve glomerular injury whereas everolimus slows the progression of glomerular injury in Anti-Thy-1 induced glomerulonephritis. Thus, everolimus could be used at the early stage of glomerulonephritis, suggesting potential implications of PPPM in the treatment of progressive renal injury.

Emerging evidence suggests that aberrant expression levels of Sigma1 (SIGMAR1, also known as sigma-1 receptor) have been implicated in the progression of various diseases, including cancer. However, its significance in oral cancer (OC) has not been thoroughly explored. To advance in this field, the present study aimed to investigate the impact of SIGMAR1 knockdown in oral cancer cells. To do so, we included in this study our cohort of human OC samples and OC cell lines, which were utilized for experimental verification through several in vitro assays. Our findings revealed that SIGMAR1 overexpression was associated with poor survival rates and positively correlated with PD-L1 overexpression in human oral cancer samples. Furthermore, SIGMAR1 inhibition led to a decrease in PD-L1 expression and sensitized oral cancer cells to cisplatin treatment by enhancing apoptosis. These results suggest that SIGMAR1 knockdown may present a promising strategy worthy of further exploration in the management of oral cancer.

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.

Dated about 12000 years ago in two domestication centers situated in Europe and Central Asia.Through the years cannabis spread to the Middle East and Africa (2000-500 yr BP) and then to the Americas from Europe (1545-1800 CE) and Asia (1800Asia ( -1945) ) (Warf, 2014;Crocq, 2020;Rull, 2022). Through these years cannabis varied uses and was associated with alleviating illnesses (Mirzaei et al., 2020), rituals and recreational practices (Kovalchuk et al., 2020;Mirzaei et al., 2020), and as a source of fiber for textiles, food, and oil (van Bakel et al., 2011;Salami et al., 2020).In its recent history, stigma, and prohibition, particularly during the 20th century, have complicated cannabis research and use, despite its importance (Russo, 2007;Maida and Daeninck, 2016). The identification of cannabinoids, especially delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), represented a pivotal moment in cannabinoid research. This was particularly significant following the discovery of the endocannabinoid system in the 1990s, which established a biological foundation for comprehending the effects of these compounds (Zuardi, 2006;Appendino, 2020).Many countries' recent legalization movement has sparked interest in its therapeutic uses, which has revived scientific research and public acceptance. Research on the active elements of cannabis has strengthened the present view of marijuana as a medicinal tool. In the past decades, the therapeutic potential of cannabinoids has been explored in several research areas.In the present research topic "Therapeutic Potential of Cannabinoids: From Health to Disease", the journal aimed to shed light on the local and systemic effects of cannabis and cannabinoids on cognitive function, and their implications in neurodegenerative and age-related diseases. In the manuscript "The effects of standardized cannabis products in healthy volunteers and patients: a systematic literature review", Leen and colleagues review the effects of standardized cannabis products, especially those made by Bedrocan, on patients and healthy volunteers (Leen et al., 2024). The authors emphasize how crucial consistent cannabis formulations are for successful therapy, pointing to dose-dependent acute effects in healthy volunteers, like anxiety and impaired cognition. With few minor adverse effects, medicinal cannabis has been shown to help individuals with chronic pain. In order to evaluate cannabis dosage, composition, and other variables including age and gender to determine safety and efficacy, the review recommends additional randomized clinical trials.Yndart et al., also discuss the importance of standardized formulations and consistent dosing to ensure reliability (Yndart Arias et al., 2024). The authors discuss the need for more thorough research to determine the best dosage, formulations, and therapeutic efficacy for neurocognitive disorders while reviewing randomized trials assessing cannabidiol (CBD) as a possible treatment for cognitive impairments. By demonstrating the advantages of CBD for anxiety and cognition and emphasizing the need for more carefully planned research to confirm its use in treating neurocognitive impairments like Alzheimer's disease, this manuscript has the potential to further our understanding of CBD as a therapeutic option for cognitive disorders. Also focusing on clinical research, in their review "Implications for blinding in clinical trials with THC-containing cannabinoids based on the CANNA-TICS trial", Müller-Vahl and colleagues discuss the issue of unblinding clinical trials using THC-containing cannabinoids, specifically examining the unblinding rates in the CANNA-TICS trial (Muller-Vahl et al., 2022).It states that 17% of individuals unblinded themselves on purpose or by mistake, and that some participants were not aware that they could do so. Due to the potential impact of growing public awareness of THC testing on trial integrity, the study emphasizes the significance of addressing unblinding concerns in subsequent randomized controlled trials utilizing THC-containing cannabinoids.Using an animal model, Melkumyan et al. investigated how mice's anxiety-like behaviors and neuroimmune function were affected by cannabidiol (CBD) and a CBD: THC (3:1) mixture during alcohol withdrawal (Melkumyan et al., 2024). It reveals that whereas CBD and CBD: THC enhanced anxiety during the first four hours of withdrawal, CBD by itself decreased anxiety throughout the next twenty-four hours. According to the study, using cannabis during alcohol withdrawal may have different impacts on anxiety depending on when it is used. These effects may be related to modifications in the central amygdala's neuroimmune function. This manuscript contributes to understanding the potential therapeutic effects of cannabinoids, specifically CBD and CBD: THC, on neuroimmune function modulation in the central amygdala. These results may help guide future studies and therapeutic strategies for treating alcohol withdrawal and related anxiety.The present research topic offers a comprehensive perspective on cannabis research and highlights that effectiveness of medicinal cannabis treatments and patient results are largely dependent on the dosage and formulation evaluation of cannabinoids. Accurate dosage reduces the possibility of side effects while guaranteeing that patients get the right quantity of cannabinoids to produce therapeutic benefits. Inhalants, oils, and foods are examples of formulations that alter the bioavailability and commencement of action, which can have a substantial impact on clinical results (Bhandari et al., 2024). Moreover, personalized dosing based on factors like patient age, weight, metabolism, and the specific condition being treated can enhance treatment efficacy.Without proper assessment and standardization, variations in dosing and formulation can lead to inconsistent results and undermine the potential benefits of medical cannabis for...