Search Results (105)

Background/Objectives: Chemotherapy-induced neuropathic pain (CINP) represents a critical challenge in oncology, emerging as a common and debilitating side effect of widely used chemotherapeutic agents, such as paclitaxel (PTX). Current therapeutic interventions and preventive strategies for CINP are largely insufficient, as they fail to address the underlying peripheral nerve damage, highlighting an urgent need for the development of new drugs. This study aimed to investigate the dual-function effects on normal cell protection and tumor suppression of BMX-001, a redox-active manganese metalloporphyrin that has demonstrated antioxidant and anti-inflammatory properties, which offers potential in protecting central nervous system tissues and treating CINP. Methods: This study assessed BMX-001’s different roles in protecting normal cells while acting as a pro-oxidant and pro-inflammatory molecule in cancer cells in vitro. We also evaluated its neuroprotective effect in preclinical PTX-induced CINP models in vivo. Results: Our results showed significant reductions in mechanical and cold allodynia, decreased pro-inflammatory cytokine levels, and restored antioxidant capacity in peripheral nerves and dorsal root ganglia (DRGs) following BMX-001 treatment. Conclusions: Overall, our study highlights the therapeutic potential of BMX-001 to mitigate CINP and enhance anticancer efficiency. Its dual-selective mechanism supports the future clinical investigation of BMX-001 as a novel adjunct to chemotherapeutic regimens. Full article

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Its sustained proliferative signaling poses a major challenge for effective therapeutic intervention. Since CRC originates from aberrantly proliferating crypt cells, limiting proliferation or inducing senescence may offer a promising treatment approach. Lycium barbarum glycopeptide (LbGP), a traditional Chinese medicine component, is known for its immunomodulatory and other beneficial effects. This study aims to examine the anti-tumor effects of LbGP in CRC as well as its underlying mechanisms of action. We used CT26 CRC cells to investigate the effects of LbGP on tumor proliferation both in vitro and in an allograft mouse model. LbGP treatment significantly inhibited CT26 cell proliferation in vitro and suppressed tumor growth in CT26-implanted mice. Furthermore, LbGP treatment significantly upregulated p53/p21 levels both in vitro and in vivo, leading to CT26 cell cycle arrest in the S phase and the induction of tumor cell senescence. These findings demonstrate that LbGP effectively induces CRC cell cycle arrest and senescence via the p53/p21 pathway and may serve as a promising candidate for CRC adjuvant therapy. Full article

Background: Percutaneous electrolysis (PE) is an emerging therapeutic approach for tendinopathies, applying a galvanic current through a dry-needling needle to induce regenerative tissue responses. However, current dosing strategies are often empirical and lack objective physiological feedback. Objective: This study aimed to evaluate the echogenic effects of different galvanic current intensities on cadaveric tendon tissue using quantitative ultrasound. Methods: An ex vivo study was conducted on 29 cadaveric patellar tendon samples, each exposed to a single intensity (0–10 mA for 1 s). Quantitative ultrasound analysis was performed post-intervention, and echogenic variables were extracted using UZ eDosifier software. A composite variable, Electrolysis_UZ_Dose, was created via multiple regression to capture the overall ultrasound-visible changes. Data were analyzed using correlation, regression models, and dose–range comparisons. Results: An intensity-dependent response was observed in key echogenic parameters. Minimal changes occurred at low intensities (0–2 mA), whereas a progressive response emerged between 2 and 6 mA. Beyond 6 mA, a plateau effect suggested either tissue saturation or imaging limitations due to gas-induced acoustic shadowing. The Electrolysis_UZ_Dose variable strongly correlated with applied intensity (R² = 0.732). Conclusions: This study suggests an intensity-dependent echogenic effect of PE on tendon tissue in key ultrasound-derived parameters (A_Number, A_Area, A_Perimeter, A_Homogeneity, and A_ASM). However, as this study was conducted under experimental conditions with a single 1 s application per sample, the results should not be extrapolated to clinical practice without further validation. Full article

Porcine epidemic diarrhea (PED), a highly contagious enteric disease caused by the porcine epidemic diarrhea virus (PEDV), is characterized by vomiting, diarrhea, and dehydration, leading to high mortality in newborn piglets and significant economic losses in the swine industry. The shortage of effective PED vaccines emphasizes the need to explore potent natural compounds for therapeutic intervention. It has been shown that glycerol monolaurate (GML) effectively inhibits PEDV replication in vivo and in vitro. Further investigation is needed to assess whether complex medium-chain triglycerides (CMCTs), composed of glyceryl tricaprylate/caprate (GTCC) and GML, offer an efficient anti-PEDV activity. In this study, piglets were orally infected with PEDV and exhibited typical clinical signs, including diarrhea and vomiting, accompanied by intestinal inflammation, oxidative stress, and tissue damage. CMCTs were administered orally twice daily for one week. In vivo findings indicate that CMCT treatment alleviated clinical signs and prevented weight loss. It significantly increased serum immunoglobulins (IgG, IgM, and IgA) and intestinal mucosal sIgA and MUC-2 levels, while reducing pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, and IL-17) and increasing antiviral interferons (IFN-α and IFN-γ), anti-inflammatory cytokines (IL-4 and IL-10), and IL-22. Antioxidant enzyme activities (T-AOC, SOD, GSH-Px, and CAT) were elevated, whereas oxidative stress markers (iNOS, NO, and MDA) were decreased. Expression of intestinal tight junction proteins claudin-1 and ZO-1 was restored. Moreover, CD4⁺ and CD8⁺ T cell populations increased, and the functions of regulatory T cells (Tregs) were restored. Gut microbiota analysis showed increased beneficial genera (Streptococcus and Ligilactobacillus) and decreased pathogenic Escherichia-Shigella. These results demonstrate that CMCTs mitigate PEDV infection by enhancing anti-inflammation, antioxidation, and intestinal barrier function, as well as modulating gut microbiota composition. This study improves the understanding of the pathogenesis of PEDV and highlights CMCTs as a promising therapeutic candidate for PED. Full article

Alkylating agents, historically employed as chemical warfare agents and currently used as chemotherapeutic drugs, are known to induce significant pulmonary toxicity. Current clinical interventions often fail to fully prevent or reverse these pathological changes, highlighting the urgent need for safe, broad-spectrum therapeutic agents that are effective across diverse exposure scenarios. Melatonin has emerged as a promising protective agent due to its antioxidant, anti-inflammatory, and immunomodulatory properties, along with a well-established safety profile. This systematic review evaluates the potential of melatonin in mitigating vesicant-induced pulmonary damage, synthesizing and critically analyzing preclinical evidence in accordance with the PRISMA guidelines. Three in vivo rodent studies met the inclusion criteria and were analyzed. In all cases, melatonin demonstrated protective effects against alkylating agents such as mechlorethamine (HN2) and cyclophosphamide (CP). These effects were dose-dependent and observed across various animal models, administration protocols, and dosages (ranging from 2.5 to 100 mg/kg), highlighting the importance of context-specific considerations. The human equivalent doses (HEDs) ranged from 12 to 973 mg per day, suggesting that the effective doses may exceed those typically used in clinical trials for other conditions. Melatonin’s pleiotropic mechanisms, including a reduction in oxidative stress, the modulation of inflammatory pathways, and support for tissue repair, reinforce its therapeutic potential in both prophylactic and treatment settings for alkylating agent exposure. Nonetheless, this review underscores the critical need for further randomized clinical trials to establish the optimal dosing strategies, refine treatment protocols, and fully elucidate melatonin’s role in managing alkylating-agent-induced pulmonary toxicity. Full article

Malignant mesothelioma (MM) is a highly aggressive cancer strongly associated with asbestos exposure, and accumulating evidence suggests that high mobility group box 1 (HMGB1) plays a central role in its pathogenesis. Our in vitro and in vivo experiments revealed that HMGB1 was highly expressed in MM. Both genetic and pharmacological inhibition of HMGB1 markedly suppressed MM cell viability, migration, and invasion, while inducing G1-phase cell cycle arrest and enhancing apoptosis. Interestingly, the inhibition of Toll-like receptor 4 (TLR4), achieved through both siRNA and TAK-242 treatment, not only suppressed tumor-promoting signals but also reduced HMGB1 expression, suggesting a self-amplifying HMGB1-TLR4 loop. Mechanistically, in vitro experiments indicated that suppression of HMGB1 and TLR4 was associated with decreased activation of NF-κB, AKT, and ERK pathways, which are involved in regulating MM cell survival and motility. In xenograft models, treatment with ethyl pyruvate (EP) and TAK-242 significantly suppressed tumor growth and HMGB1 expression, reinforcing their therapeutic potential. Given HMGB1’s influence on both tumor cell behavior and the immune microenvironment, targeting the HMGB1-TLR4 axis may not only provide a novel therapeutic strategy for MM but also offer insights into the mechanisms underlying asbestos-induced tumorigenesis, potentially guiding future prevention and intervention strategies in asbestos-exposed populations. Full article

Background: Chronic atrophic gastritis precancerous lesions (PL-CAG) are characterized by the atrophy of gastric mucosal glands, often accompanied by intestinal metaplasia or dysplasia. Timely intervention and treatment can effectively reverse its malignant progression and prevent the onset of gastric cancer. Bombyx Batryticatus (BB) exhibits a range of pharmacological effects, including anticoagulation, antiepileptic properties, anticancer activity, and antibacterial effects. However, the pharmacological basis and mechanisms underlying BB’s efficacy in treating PL-CAG remain unclear. Methods: A three-factor modeling approach was implemented to develop a rat PL-CAG model, while the MNNG-induced PLGC (precancerous lesions of gastric cancer) cell model was served as a cell PL-CAG model. UPLC-QE-Orbitrap-MS/MS (Ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry) was utilized to perform an in-depth analysis of the components in the plasma extract of BB. Leveraging network pharmacology, molecular docking analyses, and experimental validation, we initially elucidated the potential mechanisms through which BB mediates its therapeutic effects on PL-CAG at both in vivo and in vitro levels. Results: Prototype compounds of 42 blood-entering components were identified by UPLC-QE-Orbitrap-MS/MS analysis. Network pharmacology analysis and molecular docking studies indicate that the core targets are primarily enriched in the PI3K-Akt signaling pathway, and the key components, including Nepitrin, Quercetin 3-O-neohesperidoside, Rutin, and others, exhibited stable docking conformations with the first eleven pivotal targets. Both in vivo and in vitro experiments validated that BB may effectively treat PL-CAG via modulation of the PI3K-Akt signaling pathway. Conclusions: The therapeutic efficacy of BB in the management of PL-CAG may be achieved through the synergistic interaction of multiple components and targets, which may be more closely related to the inhibition of the PI3K/AKT signaling pathway. This approach will establish a solid experimental foundation and provide essential data for the clinical application of BB in treating PL-CAG, while also facilitating further research initiatives. Full article

Iron deficiency is highly prevalent in patients with idiopathic pulmonary hypertension; nevertheless, its role and clinical significance in hypoxic pulmonary hypertension (HPH) remain elusive. Therefore, this study aims to clarify the role and molecular mechanisms of iron in HPH. By means of a retrospective analysis of clinical data from HPH patients and examinations of HPH animal models, we discovered that both HPH patients and animal models exhibit significant iron deficiency, characterized by reduced hepatic iron storage and elevated hepcidin expression. To further explore iron’s role in HPH, we modulated iron metabolism through pharmacological and dietary interventions in chronic hypoxic animal models. The results showed that iron deficiency exacerbated chronic hypoxia-induced pulmonary hypertension and right ventricular hypertrophy, while iron supplementation alleviated these conditions. Further investigations revealed that iron regulates HIF2α expression in pulmonary arterial endothelial cells (PAECs) under chronic hypoxia. Therefore, through in vivo and in vitro experiments, we demonstrated that HIF2α inhibition attenuates chronic hypoxia-induced pulmonary hypertension and right ventricular hypertrophy. Mechanistically, chronic hypoxia-mediated iron deficiency enhances HIF2α activation, subsequently suppressing iron/sulfur cluster assembly enzyme (ISCU) expression. This leads to decreased mitochondrial complexes I and III activity, increased reactive oxygen species (ROS) production, and inhibited oxidative phosphorylation. Consequently, metabolic reprogramming in PAECs results in a proliferation/apoptosis imbalance, ultimately exacerbating hypoxia-induced pulmonary hypertension and right ventricular hypertrophy. Collectively, our findings demonstrate that iron supplementation mitigates HPH progression by modulating HIF2α-mediated metabolic reprogramming in PAECs, revealing multiple therapeutic targets for HPH. Full article

Neuroinflammatory responses are central to the pathogenesis of neurodegenerative diseases, affecting cells of both neuronal and glial origin that respond to immune-driven inflammatory stimuli. The PI3K/mTOR signaling pathway is essential for the regulation of these neuroinflammatory processes and is therefore a promising target for therapeutic intervention. Here, we investigated the consequences of PI3K/mTOR pathway inhibition on neuroinflammation employing PF-04691502, an agent with combined PI3K and mTOR inhibitory activity. We treated SH-SY5Y, C6, BV-2, and Mo3.13 cell lines with PF-04691502 at concentrations of 0.1, 0.5, and 1 µM to assess the modulation of neuroinflammatory responses. To induce inflammation, cells were stimulated with lipopolysaccharide (LPS, 1 μg/mL) and interferon-gamma (IFN-γ, 100 U/mL). The results from the MTT assays demonstrated that PI3K/mTOR inhibition preserved cell viability at 0.5 and 1 µM across all of the cell lines, indicating its potential to mitigate inflammation-driven cytotoxicity. Subsequent ELISA assays revealed a marked decrease in the NF-κB and pro-inflammatory cytokine levels, confirming the effective suppression of inflammation through PI3K/mTOR inhibition. In addition, the SH-SY5Y cell line was exposed to MPP+ to simulate Parkinson’s disease (PD)-like toxicity; then, cell viability, PD-associated markers, and apoptotic indicators were assessed. Our results indicate that inhibition of the PI3K/mTOR signaling axis may alleviate neurodegenerative processes by modulating both neuroinflammatory responses and apoptotic pathways. These findings highlight the therapeutic promise of targeting PI3K/mTOR in the context of neurodegenerative disorders and support the need for further validation through in vivo and clinical investigations. Full article

Background: Oropouche virus (OROV), part of the Peribunyaviridae family, is an emerging pathogen causing Oropouche fever, a febrile illness endemic in South and Central America. Transmitted primarily through midge bites (Culicoides paraensis), OROV has no specific antiviral treatment or vaccine. This study aims to identify host-targeted therapeutics against OROV using computational approaches, offering a potential strategy for sustainable antiviral drug discovery. Methods: Virus-associated host targets were identified using the OMIM and GeneCards databases. The Enrichr and DSigDB platforms were used for drug prediction, filtering compounds based on Lipinski’s rule for drug likeness. A protein–protein interaction (PPI) network analysis was conducted using the STRING database and Cytoscape 3.10.3 software. Four key host targets—IL10, FASLG, PTPRC, and FCGR3A—were prioritized based on their roles in immune modulation and OROV pathogenesis. Molecular docking simulations were performed using the PyRx software to evaluate the binding affinities of selected small-molecule inhibitors—Acetohexamide, Deptropine, Methotrexate, Retinoic Acid, and 3-Azido-3-deoxythymidine—against the identified targets. Results: The PPI network analysis highlighted immune-mediated pathways such as Fc-gamma receptor signaling, cytokine control, and T-cell receptor signaling as critical intervention points. Molecular docking revealed strong binding affinities between the selected compounds and the prioritized targets, suggesting their potential efficacy as host-targeting antiviral candidates. Acetohexamide and Deptropine showed strong binding to multiple targets, indicating broad-spectrum antiviral potential. Further in vitro and in vivo validations are needed to confirm these findings and translate them into clinically relevant treatments. Conclusions: This study highlights the potential of using computational approaches to identify host-targeted therapeutics for Oropouche virus (OROV). By targeting key host proteins involved in immune modulation—IL10, FASLG, PTPRC, and FCGR3A—the selected compounds, Acetohexamide and Deptropine, demonstrate strong binding affinities, suggesting their potential as broad-spectrum antiviral candidates. Further experimental validation is needed to confirm their efficacy and potential for clinical application, offering a promising strategy for sustainable antiviral drug discovery. Full article

Natural products have extensive attractiveness as therapeutic agents due to their low toxicity and high efficiency. Our previous study has identified a depside-type Aspergillusidone G (Asp G) derived from Aspergillus unguis DLEP2008001, which shows excellent neuroprotective activity for 1-methyl-4-phenylpyridinium (MPP⁺)-induced primary cortical neurons and anti-neuroinflammatory property, promising to be a potential therapeutic agent for Parkinson’s disease (PD). To further explore the anti-PD potential and mechanisms of Asp G, we employed network pharmacology, cellular experiments, and various biological techniques for analysis and validation. The analysis of network pharmacology suggested that Asp G’s anti-PD potential might be attributed to its modulation of inflammation. The data from nitric oxide (NO) detection, qRT-PCR, and Western blot confirmed that Asp G dose-dependently inhibited lipopolysaccharide (LPS)-stimulated NO production, with 40 μM Asp G suppressing 90.54% of the NO burst compared to the LPS group, and suppressed the overproduction of inflammatory-related factors in LPS-induced BV2 cells. Further protein–protein interaction analysis indicated that matrix metalloproteinase 9 (MMP9), a promising target for PD intervention, was the most likely anti-PD target of Asp G, and the results of gelatin zymography, qRT-PCR, and Western blot validated that Asp G could inhibit the active and inactive forms of MMP9 directly and indirectly, respectively. Notably, the inhibition of 67 kDa-MMP9 by Asp G is expected to compensate for the inability of TIMP-1 to inhibit this form. Furthermore, a selective inhibitor of MMP9 (20 μM SB-3CT) further potentiated the anti-inflammatory effects of Asp G (20 μM), with inhibition rate on NO increasing from 27.57% to 63.50% compared to LPS group. In summary, our study revealed that Asp G exerts anti-neuroinflammatory effects by inhibiting MMP9, which provides a valuable lead compound for the development of anti-neuroinflammatory drugs and offers insights into the intervention of PD-associated neuroinflammation. Future studies will further investigate the upstream regulatory mechanisms of Asp G-mediated MMP9 inhibition and its effects in in vivo PD models. Full article

Liver injury poses major health risks in livestock, necessitating effective therapeutic interventions. This study elucidates the hepatoprotective mechanisms of Euphorbia humifusa Willd. ex Schltdl. (EHW) by integrating network pharmacology, molecular docking, and experimental validation. Using a CCl₄-induced liver injury model mimicking veterinary clinical scenarios, EHW markedly alleviated hepatic damage, demonstrated by reduced liver index, serum ALT and AST levels, histopathological lesions, iron accumulation, inflammatory cytokines, and ferroptosis-associated gene expression. Network pharmacology identified EHW’s core bioactive components (quercetin, kaempferol, and β-sitosterol) and critical targets (IL-6, STAT3, HIF-1α, PTGS2, NFE2L2, and KEAP1) which were linked to ferroptosis and oxidative stress. Molecular docking revealed robust binding affinities between these compounds and ferroptosis-related proteins. In vivo validation confirmed that EHW inhibited KEAP1, activated NFE2L2-mediated antioxidant defenses (upregulating SOD1 and NQO1), restored iron homeostasis (lowering TFR1, elevating FTH1), and attenuated phospholipid peroxidation by suppressing ACSL4 and ALOX12. These results indicate that EHW mitigates ferroptosis-driven liver injury via KEAP1-NFE2L2 signaling to restore iron homeostasis and reduce oxidative stress, offering a mechanistic foundation for its clinical application in veterinary hepatoprotection. Full article

Background: Over thirty years of basic research has demonstrated that the deuterium-to-hydrogen ratio plays a pivotal role in regulating metabolism and cell growth via a sub-molecular regulatory system that orchestrates the intricate complexity of life in eukaryotic organisms. Deuterium depletion, achieved through deuterium-depleted water (DDW), has shown anticancer effects in vitro, in vivo, and in Phase 2 prospective and retrospective clinical studies. Methods: In this population-based observational study, 2649 cancer patients undergoing conventional therapy and consuming DDW were included between October 1992 and October 2024. With various cancer types and stages and conventional therapies received, they are representing a broad spectrum of the Hungarian cancer population. Survival was selected as the primary endpoint, and the median survival time (MST) of these patients and various subgroups was calculated and compared to the overall Hungarian cancer population’s MST of 2.4 years. Results: For the entire study population, MST from diagnosis was 12.4 years (95% CI: 9.8–14.9), and from the initiation of DDW treatment, 7.6 years (95% CI: 5.9–9.3). Conclusions: Utilizing DDW enables targeted intervention in the sub-molecular regulatory system, paving the way for innovative therapeutic applications and a more profound understanding of cellular processes. Integrating deuterium depletion into conventional cancer therapies has the potential to significantly enhance survival rates and reduce cancer-related mortality by 75–80%. Full article

Background: Atherosclerotic diseases, including coronary heart disease and cerebrovascular disease, are leading causes of morbidity and mortality worldwide. Atherosclerosis is a chronic vascular condition marked by the accumulation of lipid plaque within arterial walls. These plaques can become unstable and rupture, leading to thrombosis and subsequent cardiovascular events. Therefore, early identification of vulnerable plaque is critical for preventing such events. Objectives: This study aims to develop a novel imaging platform for atherosclerotic plaque by designing a molecular imaging probe based on fluorescent molecules that target lipid necrotic cores. The goal is to specifically detect high-risk plaque, enabling early diagnosis and intervention. Methods: Bioinformatic analysis and immunofluorescence were used to detect CD36 expression in human carotid plaque. CD36pep-ICG was synthesized using the Fmoc solid-phase peptide method. A series of experiments was conducted to characterize the probe’s properties. To assess imaging performance, probe concentration gradients were tested using FLI equipment. Ex vivo imaging was performed on atherosclerotic mice and treatment models to evaluate the probe’s targeting ability and effectiveness in monitoring disease progression. Results: The CD36 expression was significantly elevated in the core of plaque compared to distal regions. The CD36pep-ICG probe, specifically designed to target lipids, was successfully synthesized and exhibited excellent fluorescence properties. In animal models, FLI imaging demonstrated that the CD36pep-ICG probe selectively accumulated in atherosclerotic plaque, enabling precise plaque detection. Moreover, the probe was used to monitor the therapeutic efficacy of anti-atherosclerotic drugs. Conclusions: The CD36pep-ICG probe developed in this study is an effective molecular imaging tool for the specific identification of vulnerable atherosclerotic plaque, offering a novel approach for early diagnosis and treatment. Additionally, the probe shows promise in tracking the therapeutic effects of the drug, potentially advancing the precision treatment of cardiovascular diseases. Full article

Colorectal cancer (CRC) remains a principal contributor to oncological mortality worldwide, with chronic inflammation serving as a fundamental driver of its pathogenesis. Protease-activated receptor-2 (PAR-2), a G-protein-coupled receptor, orchestrates inflammation-driven tumorigenesis by potentiating NF-κB and Wnt/β-catenin signaling, thereby fostering epithelial–mesenchymal transition (EMT), immune evasion, and therapeutic resistance. Despite its pathological significance, targeted modulation of PAR-2 remains an underexplored avenue in CRC therapeutics. Oleocanthal (OC), a phenolic constituent of extra virgin olive oil, is recognized for its potent anti-inflammatory and anti-cancer properties; however, its regulatory influence on PAR-2 signaling in CRC is yet to be elucidated. This study interrogates the impact of OC on PAR-2-mediated inflammatory cascades using HT-29 and Caco-2 CRC cell lines subjected to lipopolysaccharide (LPS)-induced activation of PAR-2. Expression levels of PAR-2 and TNF-α were quantified through Western blotting and RT-PCR, while ELISA assessed TNF-α secretion. Intracellular calcium flux, a pivotal modulator of PAR-2-driven oncogenic inflammation, was evaluated via Fluo-4 calcium assays. LPS markedly elevated PAR-2 expression at both mRNA and protein levels in CRC cells (p < 0.01, one-way ANOVA). OC administration (20–150 μg/mL) elicited a dose-dependent suppression of PAR-2, with maximal inhibition at 100–150 μg/mL (p < 0.001, Tukey’s post hoc test). Concomitant reductions in TNF-α transcription (p < 0.01) and secretion (p < 0.001) were observed, corroborating the anti-inflammatory efficacy of OC. Additionally, OC ameliorated LPS-induced calcium dysregulation, restoring intracellular calcium homeostasis in a concentration-dependent manner (p < 0.01). Crucially, OC exhibited selectivity for PAR-2, leaving PAR-1 expression unaltered (p > 0.05), underscoring its precision as a therapeutic agent. These findings position OC as a selective modulator of PAR-2-driven inflammation in CRC, disrupting the pro-tumorigenic microenvironment through attenuation of TNF-α secretion, calcium dysregulation, and oncogenic signaling pathways. This study furnishes mechanistic insights into OC’s potential as a nutraceutical intervention in inflammation-associated CRC. Given the variability in OC bioavailability and content in commercial olive oil, future investigations should delineate optimal dosing strategies and in vivo efficacy to advance its translational potential in CRC therapy. Full article