Search Results (425)

Osteoclasts are the primary bone-resorbing cells responsible for maintaining skeletal homeostasis through balanced bone remodeling. Accumulating evidence suggests that oxidative stress is an emerging regulator of osteoclast differentiation, metabolic reprogramming, and bone resorption, arising from excessive reactive oxygen species (ROS) and insufficient antioxidant defenses. Dysregulated redox signaling contributes to osteoporosis, rheumatoid arthritis, periodontitis, periapical lesions, and other osteolytic disorders. This review summarizes recent advances in the molecular mechanisms linking oxidative stress to osteoclast metabolism, focusing on ROS sources, mitochondrial dysfunction, redox-sensitive signaling pathways, endogenous antioxidant systems, and emerging antioxidant-based therapies. Oxidative stress regulates osteoclastogenesis through interconnected signaling networks, including NF-κB, MAPKs, PI3K/Akt, AMPK, mTOR, NFATc1, and Keap1/Nrf2. Under both physiological and pathological conditions, osteoclast function is regulated by mitochondrial dynamics, mitophagy, and epigenetic mechanisms. Although both synthetic and natural antioxidants have been shown to reduce pathological osteoclast activity in preclinical studies, limitations in bioavailability, target specificity, and long-term efficacy hinder clinical translation. Advances in multi-omics technologies, single-cell analyses, biomarker discovery, precision medicine, and targeted antioxidant delivery may facilitate the development of effective therapies for oxidative stress-related bone disorders. Full article

Panax ginseng Meyer has been commonly used as a traditional herbal medicine in East Asia for millennia. Ginsenosides Rg1 and Rb1 are the primary pharmacologically active ingredients and exhibit broad therapeutic efficacy against immunometabolic disorders, including inflammatory bowel disease (IBD), metabolic dysfunction-associated steatotic liver disease (MASLD), and rheumatoid arthritis (RA). To summarize the protective roles of these ginsenosides and investigate their underlying mechanisms, we integrated literature evidence with network pharmacology and gut microbiota–host gene association analyses. Published experimental studies have identified multiple mechanisms by which Rg1 and Rb1 ameliorate IBD, MASLD, and RA, including modulation of the phosphoinositide 3-kinase (PI3K)/Akt, AMP-activated protein kinase (AMPK), and peroxisome proliferator-activated receptor γ (PPARγ)/nuclear factor kappa-B (NF-κB) pathways, as well as direct toll-like receptor 4 (TLR4) binding and aryl hydrocarbon receptor (AHR)-mediated transcriptional regulation. Our network pharmacology analysis predicted target overlap among IBD, MASLD, and RA, prioritizing TNF, NFKB1, PPARG, and MAPK1 as putative hubs. Our gut microbiota–host gene association analysis identified conserved microbial taxa sharing host gene targets with Rg1 and Rb1, such as Akkermansia and Faecalibacterium. Integrating these computational findings with published evidence, we propose that ginsenoside-associated shifts in these taxa may be linked to modulation of host signaling pathways, though causal relationships require experimental validation. This review summarizes the convergent mechanisms of Rg1 and Rb1 in ameliorating barrier-immunity-metabolism dysfunction across the gut-liver-joint axis. We also highlight the translational gap between preclinical research and clinical practice. This integrated analysis provides a novel research paradigm for understanding Rg1 and Rb1 as multi-target therapeutics for complex immunometabolic diseases. Full article

This study evaluated the effects of replacing soybean meal with fermented dried tomato pomace (FDTP) on biochemical, immune, and antioxidant responses, meat quality, and hepatic transcriptomic profiles in Boer goats. Twenty-four male goats were assigned to a control diet or diets in which FDTP replaced 33.33% (T1), 66.66% (T2), or 100% (T3) of soybean meal for 60 days (n = 6). Serum biochemical parameters, total immunoglobulin, and alternative complement hemolytic activity were unaffected, whereas lysozyme activity increased linearly with FDTP replacement. FDTP increased muscular SOD1 expression and altered cytokine expression in a tissue-specific manner, including increased IL10 and reduced IL1B and TNFα expression in selected tissues. In gastrocnemius muscle (n = 3), T2 had higher collagen content and lower cooking loss than the control and T3, whereas T3 had higher drip loss than T2; selected textural properties were also altered. During refrigerated storage, lipid oxidation was affected by storage day but not by treatment or the treatment × day interaction. T2 was selected post hoc for exploratory hepatic transcriptomic comparison with the control (n = 5). Among 587 DEGs, significantly enriched KEGG pathways involved metabolism and biotransformation, including steroid hormone biosynthesis, retinol metabolism, bile secretion, xenobiotic metabolism, and pentose and glucuronate interconversions. In addition to the enriched pathways, PI3K–Akt, MAPK, NF-κB, and cytokine–cytokine receptor pathways contained DEGs related to metabolic, stress, and immune responses. Overall, FDTP replacement was associated with changes in selected immune and meat-quality traits and with hepatic transcriptional responses predominantly related to metabolic and biotransformation processes. Full article

Background: The hominoid loss of urate oxidase (uricase) represents a classic evolutionary trade-off, shifting uric acid (UA) from a metabolic waste product to a potent physiological modulator. In modern metabolic environments, however, this adaptation drives hyperuricemia and gout, transforming UA into a primary pathological substrate. Objective: This review aims to dissect the molecular architecture and biophysical networks of the renal and intestinal urate transportosome, delineate the dual intracellular/extracellular “urate paradox,” and synthesize genotype-based pharmacogenetic strategies to achieve personalized clinical management. Mechanistic Insights: During the Miocene epoch, inactivating pseudogenization of the UOX gene fixed a novel metabolic phenotype characterized by fructose-driven lipid deposition and enhanced antioxidant protection. Structurally, systemic urate homeostasis is strictly governed by a macromolecular interactome assembled by the four-domain scaffold protein PDZK1 on the epithelial apical membrane. Pathogenic gain-of-function variants in reabsorption facilitators (SLC22A12/URAT1, SLC2A9/GLUT9) or loss-of-function mutations in the efflux pump (ABCG2/BCRP) disrupt this delicate vector kinetics. Within the extracellular space, soluble urate acts as a critical hydrophilic radical scavenger. Paradoxically, upon URAT1/GLUT9-mediated internalization or intracellular supersaturation, intracellular urate triggers a pro-oxidant cascade mediated by NADPH oxidase (NOX4) activation and mitochondrial electron transport chain decoupling. This chronic cellular stress activates downstream p38 MAPK and NF-κB signaling pathways, driving localized endothelial injury and macrovascular inflammation, while crystalline monosodium urate (MSU) orchestrates NLRP3 inflammasome assembly in macrophages. Pharmacogenetic Implications: Striking ethno-geographic heterogeneity dictates immediate clinical stratification. The HLA-B*58:01 allele, an absolute molecular contraindication for allopurinol due to life-threatening severe cutaneous adverse reactions (SCARs), exhibits a critical genetic gradient in northern and eastern Eurasian populations, surging from under 1% in ethnic Caucasians to over 10% in indigenous populations of East/North Asian ancestry. Furthermore, structural defects in ABCG2 (such as the p.Q141K variant) alter the ATP-binding cassette domain, inducing standard allopurinol resistance and elevated statin exposure, which mandates a therapeutic pivot toward selective xanthine oxidase inhibitors (febuxostat) or precision uricosurics (benzbromarone, dotinurad) matched to the patient’s interactive network profile. Conclusions: Transitioning from generalized epidemiological guidelines to a comprehensive “transportosome genetic passport” is a fundamental prerequisite for predicting single-nucleotide polymorphism (SNP)-driven therapeutic responses and mitigating visceral complications. Full article

Formerly recognized as an opioid receptor, the sigma-1 receptor (σ1R) is a multifunctional chaperone protein that plays a crucial role in regulating neuronal signaling, neuroprotection, and synaptic plasticity. Increasing evidence highlights a tight functional association between the σ1R and the N-methyl-D-aspartate receptor (NMDAR), a central mediator of excitatory neurotransmission and calcium-dependent neuronal processes. This review summarizes the shared signaling pathways underlying σ1R and NMDAR activity, including calcium homeostasis, calcium/calmodulin-dependent protein kinases (CaMKs), protein kinase C (PKC), phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), and mitogen-activated protein kinase (MAPK) cascades, as well as transcriptional regulators such as cAMP response element-binding protein (CREB), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and B-cell lymphoma 2 (Bcl-2). Experimental data demonstrate that pharmacological agents initially characterized as NMDAR antagonists—such as ketamine, dextromethorphan, and memantine—also interact with σ1R, suggesting that their therapeutic efficacy may arise from coordinated modulation of both receptor systems. These findings collectively indicate that the σ1R is a key regulatory element enabling proper NMDAR function and that disruption of this interaction may contribute to excitatory imbalance implicated in the pathophysiology of neuropsychiatric disorders. Recognizing the σ1R–NMDAR crosstalk as an integrated signaling axis may thus inform the development of dual-target therapeutic strategies aimed at improving neuronal resilience and clinical outcomes in psychiatric and neurodegenerative diseases. Full article

Background: Oxeiptosis is a ROS-induced, caspase-independent form of regulated cell death, but its role in osteoarthritis (OA) remains largely unexplored. This study aimed to identify oxeiptosis-associated molecular markers in OA synovium and establish an oxeiptosis-based molecular classification system. Methods: This study integrated five publicly available GEO datasets for comprehensive analysis. GSE55235 and GSE55457 were used as discovery cohorts to identify DEGs between OA and normal synovial tissues. The GSE206848 dataset was utilized to perform correlation analysis with the key oxeiptosis regulators, including KEAP1, PGAM5, AIFM1, and CUL3, thereby establishing an oxeiptosis-associated gene set. These genes were intersected with OA-related DEGs to obtain ORDEGs. Subsequently, LASSO regression, SVM-RFE, and RF algorithms were jointly applied to identify hub differential genes. Based on the identified oxeiptosis-related feature genes, molecular subtypes of OA were constructed, with the GSE46750 dataset used for machine learning-based feature selection. Consensus clustering was then performed based on the selected features to identify distinct OA molecular subtypes. The immune microenvironment characteristics and potential regulatory networks of different subtypes were further investigated using CIBERSORT, ESTIMATE, and WGCNA. Finally, an independent GSE89408 cohort was employed for external validation. Results: A total of 159 common differentially expressed genes were identified from the two OA synovial cohorts, which were mainly enriched in cellular response to hydrogen peroxide, the MAPK signaling pathway, the PI3K-Akt signaling pathway, and NF-κB-related inflammatory processes. Further screening identified seven ORDEGs, including OTUD4, GATM, KTN1, FGGY, ACACB, RERE, and APLP2. Machine learning analysis ultimately identified ACACB and FGGY as potential molecular features of OA. Molecular clustering based on oxeiptosis-related features demonstrated that OA samples could be stably classified into two subtypes, C1 and C2. The C2 subtype exhibited higher ORDEG scores, increased ACACB expression levels, greater M1 macrophage infiltration, and higher ESTIMATE scores, indicating oxidative stress-related transcriptional characteristics and enhanced inflammatory features, whereas FGGY was mainly highly expressed in the C1 subtype. WGCNA further revealed that the salmon module closely associated with the C2 subtype was mainly enriched in calcium signaling, focal adhesion, cytoskeletal remodeling, and cell adhesion-related pathways. In the independent GSE89408 validation cohort, exploratory clustering analysis again identified two potential molecular subtypes, and FGGY remained significantly differentially expressed between the two subtypes. In addition, ACACB and FGGY showed AUC values of 0.735 and 0.647, respectively, for distinguishing OA from normal synovial tissues. Conclusion: This study establishes an oxeiptosis-associated molecular subtyping framework for OA synovium and identifies ACACB and FGGY as candidate oxeiptosis-associated genes. Further analyses revealed distinct immune microenvironment characteristics and transcriptional regulatory patterns associated with different oxeiptosis states. External validation provided partial support for the reproducibility of these molecular patterns, particularly the FGGY-related features. These findings provide transcriptomic evidence for exploring molecular heterogeneity in OA and generate hypotheses for future mechanistic and clinical validation studies. Full article

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) represent a promising cell-free therapeutic strategy for cartilage regeneration and inflammation modulation in degenerative and inflammatory musculoskeletal disorders, including osteoarthritis (OA), rheumatoid arthritis (RA) and intervertebral disc degeneration (IVDD). MSC-EVs enhance cartilage repair by promoting chondrocyte proliferation, migration, survival and extracellular matrix (ECM) synthesis to maintain cartilage homeostasis. In parallel, they exert anti-inflammatory and anti-catabolic effects by suppressing inflammatory cytokines, matrix-degrading enzymes, oxidative stress and inflammasome activation. In OA, MSC-EVs regulate chondrocyte function, ECM remodelling, immune responses and tissue regeneration by modulating multiple signalling pathways, including NF-κB, PI3K/AKT, MAPK, Wnt/β-catenin and YAP signalling. In RA, MSC-EVs orchestrate innate and adaptive immune regulation, metabolic reprogramming and tissue repair pathways. In IVDD, MSC-EVs suppress chronic inflammation, reduce nucleus pulposus cell apoptosis, enhance cell proliferation and promote ECM synthesis, facilitating disc regeneration and functional restoration. Despite their therapeutic potential, several challenges hinder clinical translation. This review summarises current understanding of MSC-EV-mediated mechanisms in OA, RA and IVDD, and proposes strategies to enhance therapeutic efficacy and accelerate clinical application in musculoskeletal regenerative medicine. Full article

Oxidative stress is caused by the imbalance between the generation of free reactive oxygen species (ROS)/reactive nitrogen species (RNS) and the antioxidant defense systems, which participate in animal growth, development, disease pathogenesis, and aging. This review summarizes endogenous and exogenous triggers of ROS/RNS overproduction, as well as model animals and cell models together with oxidative stress biomarkers and detection methods. We further dissect the three-layered redox regulatory network, focusing on crosstalk among four core pathways (Nrf2-ARE, NF-κB, MAPK, PI3K/Akt) that govern cell fate via oxidative eustress or distress. Excessive ROS/RNS trigger irreversible DNA damage and metabolic disorders, leading to inflammation and apoptosis. Finally, we prospect integrating non-model animals and multi-omics to advance oxidative stress research. This work provides a comprehensive theoretical framework for animal redox biology studies. Full article

Background/Objectives: Reflux esophagitis (RE) is a chronic inflammatory disorder caused by reflux of gastric contents into the esophagus, leading to mucosal injury and epithelial barrier dysfunction. Although proton pump inhibitors are widely used, persistent inflammation and oxidative stress remain important therapeutic challenges. Yeokwisan (YWS) is prescribed for gastroesophageal reflux disease and functional dyspepsia; however, its protective mechanisms against RE remain unclear. This study investigated the protective and anti-inflammatory effects of YWS. Methods: We integrated network pharmacology analysis, mechanistic studies in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, and efficacy evaluation in a rat model of acute RE induced by pyloric and forestomach ligation. Results: Network pharmacology identified 174 common targets between YWS and RE and 23 hub genes through protein–protein interaction network and topological analyses, implicating PI3K/Akt, MAPK, Ras, HIF-1, chemokine, and other inflammation-related signaling pathways. In LPS-stimulated RAW264.7 macrophages, YWS significantly reduced intracellular reactive oxygen species, nitric oxide, TNF-α, and IL-6 production without inducing cytotoxicity and suppressed MAPK, PI3K/Akt, and NF-κB activation. In vivo, YWS attenuated acute reflux-induced esophageal mucosal injury and histopathological alterations, restored esophageal superoxide dismutase activity, reduced malondialdehyde levels, and lowered serum TNF-α, IL-6, and IL-1β levels. YWS also suppressed NF-κB/IκB activation and COX-2 expression in esophageal tissue. Conclusions: YWS exerted protective effects against acute reflux-induced esophageal injury and anti-inflammatory effects in activated macrophages, accompanied by attenuation of oxidative stress and inflammation-associated signaling. These findings support further investigation of YWS for reflux-associated esophageal inflammation. Full article

Camel milk has long been used as a traditional health-promoting food, and growing biomedical evidence now supports its modulatory effects across multiple age-related conditions. This narrative review evaluates current experimental and clinical findings on the effects of camel milk across major categories of age-related disease, spanning metabolic dysregulation, cardiovascular pathology, neurological dysfunction, and immune-inflammatory conditions. Across these conditions, camel milk has been reported to modulate oxidative stress, chronic inflammation, and metabolic homeostasis through shared molecular pathways, including NF-κB, MAPK, PI3K/AKT, and PPAR-α/γ signaling. Mapping these effects against the twelve hallmarks of aging reveals particular engagement with chronic inflammation, deregulated nutrient sensing, and dysbiosis. Collectively, the available evidence supports a biologically plausible role for camel milk in modulating key pathological processes associated with age-related disease. However, the clinical evidence remains limited across most disease areas, and future research should prioritize standardized clinical trials and systematic mechanistic validation, with particular attention paid to the bioavailability and dose–response characterization of key bioactive components. This review provides an integrative synthesis of camel milk research within the hallmarks of the aging framework, offering a cross-disease mechanistic perspective that extends beyond single-disease or compositional approaches. Full article

Acute lung injury (ALI) is a common clinical acute respiratory disorder driven primarily by a diffuse pulmonary inflammatory response. Cordycepin (COR) is a bioactive metabolite extracted from the fungus Cordyceps militaris, which possesses antioxidant and anti-inflammatory properties. However, its underlying molecular mechanism remains to be elucidated. This study evaluated the therapeutic effect of COR on ALI and the underlying molecular mechanisms. MH-S cells were primed with lipopolysaccharide (LPS) at 1 µg/mL for 24 h and then treated with varying doses of COR for an additional 24 h. WB and RT-qPCR analyses showed that COR inhibited the phosphorylation of TGF-β-activated kinase 1 (TAK1) as well as the key kinases in the MAPK and NF-κB pathways in LPS-induced MH-S cells, as evidenced by decreased TAK1, p38, JNK, IκB-α and P65 expression levels, as well as decreased TNF-α, IL-6, IL-1β, MAP3K7, MAPK8 and MAPK14 relative expression. Six-week-old BALB/c mice were intranasally instilled with LPS at 3 mg/kg, followed 24 h later by oral gavage administration of various concentrations of COR. The results showed that COR can effectively suppress the progression of pulmonary tissue injury; similarly, the expression levels of key proteins and inflammatory factors in the TAK1-MAPK and NF-κB signaling pathways were downregulated. In summary, COR exerts a therapeutic effect on ALI by directly targeting TAK1 to inhibit the activation of the MAPK and NF-κB signaling pathways and concurrently suppressing key inflammatory cytokines. Full article

Uveitis comprises a heterogeneous group of intraocular inflammatory diseases that differ in anatomical location, etiology, clinical course, and immune mechanisms. Despite this diversity, evidence derived predominantly from experimental autoimmune uveitis (EAU) suggests that oxidative stress may act as a context-dependent amplifier linking immune activation, ocular barrier dysfunction, and tissue injury. Excess reactive oxygen species (ROS) disrupt redox homeostasis and activate redox-sensitive inflammatory signaling, thereby amplifying cytokine production, mitochondrial dysfunction, leukocyte recruitment, and retinal damage. This review summarizes current evidence on oxidative stress in uveitis, focusing on major ROS-generating systems, NF-κB-driven inflammation, Nrf2/HO-1-mediated antioxidant responses, MAPK and PI3K-Akt signaling, and immune–metabolic pathways involved in autoimmune ocular inflammation. Cell-specific responses in retinal and immune cells further illustrate how redox imbalance may contribute to local tissue injury and immune-mediated disease progression. The role of oxidative stress in blood–ocular barrier dysfunction, particularly blood–retinal barrier disruption during posterior segment inflammation, is also discussed. Overall, preclinical studies support an active role for oxidative stress in inflammatory amplification and ocular tissue injury, whereas evidence from patients with defined uveitic entities remains limited, heterogeneous, and largely associative. Redox-directed treatments should therefore currently be regarded as investigational adjunctive strategies rather than established therapies for uveitis. Full article

Bioactive polyphenols have emerged as multi-target regulators of cellular processes involved in the pathogenesis of skin diseases. Skin disorders, including inflammatory conditions, photoaging, and skin cancers, are characterized by complex pathogenic mechanisms associated with oxidative stress, mitochondrial dysfunction, dysregulated signaling pathways, and metabolic imbalance. Excessive production of reactive oxygen species (ROS) and persistent inflammatory signaling contribute to disease progression and cellular adaptation under stress conditions. Unlike conventional agents that typically target a single pathway, polyphenols act on interconnected signaling and metabolic networks. These compounds regulate key signaling pathways, including phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), AMP-activated protein kinase (AMPK), nuclear factor-κB (NF-κB), and nuclear factor erythroid 2-related factor 2 (Nrf2), thereby regulating cell survival, proliferation, inflammatory responses, antioxidant defense, and metabolic adaptation. Polyphenols also influence mitochondrial function by maintaining redox homeostasis, regulating energy metabolism, and affecting apoptosis-related signaling pathways. This review provides a mechanistic overview of the effects of polyphenols on oxidative stress, mitochondrial function, and cell survival signaling in skin diseases. In addition, the therapeutic implications and current limitations of polyphenol-based approaches are discussed, with particular emphasis on the translational gap between experimental findings and physiological relevance. Factors such as concentration, bioavailability, and cellular microenvironment are highlighted as major determinants of polyphenol activity and key challenges for clinical translation. Finally, the need for further in vivo and clinical investigations is emphasized to support the development of effective polyphenol-based therapeutic strategies for skin diseases. Full article

Glaesserella parasuis (G. parasuis, GPS) is a known causative agent of meningitis. A growing body of research indicates that non-coding RNAs (ncRNAs) are deeply involved in modulating inflammatory responses. In our study, we profiled the expression changes in circRNAs, lncRNAs, miRNAs, and mRNAs using a G. parasuis-induced mouse meningitis model and constructed the ceRNA networks by integrated analysis of the expression data. A total of 674 circRNAs, 376 lncRNAs, 57 miRNAs, and 373 mRNAs were differentially expressed. Functional GO and KEGG analysis showed enrichment of the source genes of differentially expressed (DE) circRNAs in protein binding, tight junction, and inflammatory pathways such as NF-kappaB, PI3K–Akt, and MAPK. The target genes of DEmiRNAs were enriched in phospholipase D, calcium, Rap1, and mTOR signaling pathways, whereas those of DElncRNAs were largely connected to tight junction, cytokine–cytokine receptor interaction, inflammatory response, and immune system processes. Subsequently, the DEcircRNAs–DEmiRNAs–DEmRNAs ceRNA network consisted of 177 DEcircRNAs, 20 DEmiRNAs, and 134 DEmRNAs, and the DElncRNAs–DEmiRNAs–DEmRNAs ceRNA network consisted of 152 DElncRNAs, 36 DEmiRNAs, and 177 DEmRNAs. Furthermore, the differential expression of randomly selected DEcircRNAs, DElncRNAs, DEmiRNAs, and DEmRNAs was confirmed by qRT-PCR, and the results were consistent with transcriptome sequencing. As far as we know, this study is the first integrative analysis for the ceRNA regulatory networks in G. parasuis-induced mouse meningitis, providing a theoretical basis for elucidating the pathogenic mechanisms of G. parasuis infection. Full article

Cannabinoids are terpenophenolic compounds derived from Cannabis sativa L. that exert a broad range of biological and pharmacological activities. Increasing evidence highlights their potential as modulators of cancer progression specifically through the suppression of tumor cell growth, angiogenesis, and metastasis across multiple tumor models. This review provides a comprehensive overview of the molecular mechanisms by which natural and synthetic cannabinoids induce regulated cancer cell death. Current evidence demonstrates that cannabinoids regulate multiple forms of cancer cell death, including apoptosis, autophagy-dependent cell death, necroptosis, ferroptosis, and parthanatos. These effects are mediated through complex and interconnected signaling pathways such as TRIB3/AKT/mTORC1, PI3K/AKT/mTOR, MAPK/ERK, NF-κB, ERK/JNK/p38-MAPK, and ceramide/Raf1/ERK/ROS. In addition to their direct antitumor effects, cannabinoids can enhance the efficacy of conventional anticancer therapies through the coordinated regulation of complementary cell death pathways. They also provide clinically relevant supportive benefits in palliative care, alleviating chemotherapy-induced nausea, cachexia, and mood or sleep disturbances. Collectively, these findings identify cannabinoids as promising anticancer agents and therapeutic adjuvants, predominantly in the preclinical setting. However, significant challenges remain regarding their safety, optimal dosing, formulation, and clinical efficacy. Further mechanistic studies, rigorous preclinical research, and well-designed clinical trials are required to establish the translation of cannabinoid-based therapies into precision oncology. Full article