Search Results (446)

Tumor mutational burden (TMB) and tumor-infiltrating lymphocytes (TILs) are key biomarkers for predicting immunotherapy responses in cutaneous melanoma. The discordance between brisk TIL morphology and absent cytokine signals complicates immune profiling. We examined the interactions between TMB, TIL patterns, cytokine expression, and genomic alterations to uncover immune escape mechanisms and refine prognostic tools. A structure-based BRAF druggability analysis was performed to anchor the genomic findings in a therapeutic context. Primary cutaneous melanoma cases (N = 205) were classified as brisk (n = 65), non-brisk (n = 60), or absent TILs (n = 80) according to the American association for cancer research (AACR) guidelines. Inter-observer concordance was measured using intraclass correlation. Tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) levels were graded using immunohistochemistry. Eleven brisk TIL cases lacking TNF-α expression were analyzed using the (Illumina TruSight Oncology 500, Illumina-San Diego, CA, USA). Dabrafenib docking to the BRAF ATP site was performed with Glide SP/XP and rescored with Prime MM-GBSA. Brisk TILs lacking cytokine signals suggested post-translational silencing of TNF-α/IFN-γ. Among the 11 profiled cases, eight exhibited high TMB and copy number alterations, with enrichment of nine metastasis/immune regulation genes. Inter-observer concordance was high (absent TILs, 95%; brisk TILs, 90.7%). BRAF docking yielded a canonical type-I pose and strong ATP pocket engagement (ΔG_bind −84.93 kcal·mol⁻¹). Single biomarkers are insufficient for diagnosis. A multiparametric framework combining histology, cytokine immunohistochemistry (IHC), and genomic profiling enhances stratification and reveals immune escape pathways, with BRAF modeling providing a mechanistic anchor for the targeted therapy. Full article

Background: Treatment with androgen receptor (AR) signaling inhibitors, such as enzalutamide, can induce neural lineage plasticity in prostate cancer, potentially progressing to t-NEPC. However, the molecular mechanisms underlying this enzalutamide-driven plasticity, particularly the contribution of immune signaling pathways, remain poorly understood. Methods: We analyzed transcriptomic profiles of patient samples and prostate cancer cell lines to investigate changes in immune signaling pathways. Interferon gamma (IFNγ), interferon alpha (IFNα), and interleukin 6 (IL6)-Janus kinase (JAK)-signal transducer and activator of transcription 3 (STAT3) signaling were assessed in enzalutamide-sensitive and -resistant prostate cancer cells. Functional assays were conducted to examine cell responsiveness to cytokine stimulation and susceptibility to STAT1 inhibition using fludarabine. Results: Immune-related pathways, including IFNγ, IFNα, IL6-JAK-STAT3, and inflammatory responses, were significantly suppressed in NEPC patient samples compared to those with castration-resistant prostate cancer (CRPC). Enzalutamide-resistant and NEPC cells exhibited markedly impaired IFNγ and IL6 signaling. In contrast, early-stage enzalutamide treatment paradoxically enhanced IFNγ and IL6 responsiveness. Transcriptomic profiling revealed coordinated upregulation of E2F target genes and activation of IFNα/IFNγ and JAK/STAT signaling pathways during early treatment. Importantly, these early-stage cells remained highly sensitive to IFNγ and IL6 stimulation and showed increased susceptibility to STAT1 inhibition by fludarabine, a sensitivity that was lost in resistant cells. Conclusions: Early enzalutamide treatment enhances immune responsiveness, while the development of resistance is associated with suppressed immune signaling and increased lineage plasticity. These results suggest a therapeutic window where combining enzalutamide with STAT inhibitors may delay or prevent lineage plasticity and resistance. Full article

Chronic hepatitis B virus (HBV) infection remains a major global health burden, affecting millions and contributing significantly to liver-related morbidity and mortality. While substantial progress has been made in elucidating the virology and natural history of HBV, the management of chronic hepatitis B (CHB) continues to present clinical challenges. The development of potent nucleos(t)ide analogs and pegylated interferon has improved viral suppression and delayed disease progression, yet a definitive cure remains elusive due to the persistence of covalently closed circular DNA (cccDNA). Recent research has focused on novel antiviral agents, immunomodulatory therapies, and combination strategies aimed at achieving a functional cure. This review summarizes current therapeutic approaches, recent advancements, and emerging directions in CHB management. Full article

Skin cancer is the most common cancer worldwide. The incidence of skin cancer has been increasing worldwide. Nearly 75% of all skin cancers are basal cell carcinomas (BCC), cutaneous squamous cell carcinoma (cSCC) represents approximately 20%, and those remaining are melanomas (4%) or other rare tumors (1%). Given the high cure rates and the ability to histologically confirm tumor clearance, surgical therapy is the gold standard for the treatment of skin cancer. Conventional surgery is the most employed technique for the removal of non-melanoma skin cancer (NMSCs). Mohs Micrographic Surgery (MMS) is the most precise surgical method for the treatment of non-melanoma skin cancer, allowing for 100% margin evaluation, being the gold-standard method for surgical treatment of non-melanoma skin cancer. Whenever it is possible to obtain wide margins (4 to 6 mm), cure rates vary from 70% to 99%. Imiquimod, a synthetic imidazoquinolinone amine, is a topical immune response modifier approved by the U.S. Food and Drug Administration (FDA) for the treatment of external anogenital warts, actinic keratosis (AK), and superficial basal cell carcinoma (sBCC). The efficacy of imiquimod is primarily attributed to its ability to modulate both innate and adaptive immune responses, as well as its direct effects on cancer cells. Imiquimod exerts its immunomodulatory effects by activating Toll-like receptors 7 and 8 (TLR7/8) on various immune cells, including dendritic cells, macrophages, and natural killer (NK) cells. Upon binding to these receptors, imiquimod triggers the MyD88-dependent signaling pathway, leading to the activation of nuclear factor kappa B (NF-κB) and interferon regulatory factors (IRFs). This cascade leads to the production of pro-inflammatory cytokines, including interferon-alpha (IFN-α), tumor necrosis factor-alpha (TNF-α), interleukin-12 (IL-12), and interleukin-6 (IL-6). These cytokines enhance local inflammation, recruit additional immune cells to the tumor site, and stimulate antigen presentation, thereby promoting an anti-tumor immune response. Radiation therapy (RTh) may be employed as a primary treatment to BCC. It may also be employed as an adjuvant treatment to surgery for SCC and aggressive subtypes of BCC. RTh triggers both direct and indirect DNA damage on cancer cells and generates reactive oxygen species (ROS) within cells. ROS trigger oxidative damage to DNA, proteins, and lipids, exacerbating the cellular stress and contributing to tumor cell death. Recently, immunotherapy emerged as a revolutionary treatment for all stages of SCC. Cemiplimab is a human programmed cell death 1 (PD-1)-blocking antibody that triggers a response to over 50% of patients with locally advanced and metastatic SCC. A randomized clinical trial (RCT) published in 2022 revealed that cemiplimab was highly effective in the neoadjuvant treatment of large SCCs. The drug promoted a significant tumor size decrease, enabling organ-sparing operations and a much better cosmetic effect. A few months ago, a RCT of cemiplimab on adjuvant therapy for locally aggressive SCC was published. Interestingly, cemiplimab was administered to patients with local or regional cutaneous squamous cell carcinoma after surgical resection and postoperative radiotherapy, at high risk for recurrence owing to nodal features, revealed that cemiplimab led to much lower risks both of locoregional recurrence and distant recurrence. Full article

Fracture healing failure affects millions globally, yet early molecular mechanisms remain poorly understood. This study aimed to characterize initial fracture response through analyzing peripheral blood hematology, multiplex cytokine profiles, and microRNA (miRNA) expression in fracture hematoma within the first 5 days post-injury. In a prospective cohort of 64 patients with acute clavicle fractures, we assessed hematological parameters, cytokine levels via multiplex immunoassays, and miRNA expression through RNA sequencing, and quantitative PCR (qPCR) validation. Fracture severity and time elapsed post-injury were key drivers of molecular response variability. Severe fractures (type C) were associated with older patient age and impaired hematological parameters, including reduced hemoglobin, erythrocyte counts, and hematocrit. Leukocyte counts declined over time, reflecting evolving systemic inflammation. Severity-dependent cytokines included eotaxin, interferon alpha-2 (IFNα2), interleukin-1 alpha (IL-1α), macrophage inflammatory protein-1 (MIP-1α), whereas interferon gamma-induced protein 10 (IP-10) and MIP-1α distinguished temporal healing phases. MiRNA profiling revealed 55 miRNAs with significant time-dependent expression changes (27 downregulated, 28 upregulated). Five key miRNAs (miR-140-5p, miR-181a-5p, miR-214-3p, miR-23a-3p, miR-98-5p) showed robust temporal patterns and enrichment in cytokine signaling pathways critical for bone repair. This work presents the first detailed molecular portrait of early human fracture healing, highlighting hematological, immune cytokine, and miRNA networks orchestrating repair. These insights provide a foundation for biomarkers development to predict healing outcomes and support precision-targeted interventions in fracture management. Full article

Background: Various studies have demonstrated fucoidan’s immunomodulatory effects. A previous study reported the anticancer effects of Durvillaea antarctica fucoidan (DAF) via immune activation in mice. Methods: In this study, we confirmed the DAF’s pulmonary immune activation ability by nasal administration of the dendritic cells (DCs) and T cells. Furthermore, we examined its ability to enhance the efficacy of lung cancer treatment by combining it with anti-PD-L1 antibodies to activate the lung immune response. Results: Nasal DAF administration increased C-C chemokine receptor type 7 expression in DCs and promoted DC migration to the mediastinal lymph nodes (mLN). Specifically, DAF increased conventional DC type 1 (cDC1) and cDC2 numbers in mLN and potently activated cDC1. Furthermore, the nasal administration of DAF increased the production of inflammatory cytokines in the lungs and peripheral blood. Repeated intranasal administration of DAF induced T-cell activation, resulting in the enhanced production of interferon-gamma and tumor necrosis factor-alpha in CD4 T and CD8 T cells. CD8 T cells also showed increased secretion of cytotoxic mediators after DAF treatment, and the proportion of Tregs expressing FoxP3 decreased in the mLN. DAF inhibited lung cancer growth in Lewis lung carcinoma 2 cells, which was enhanced by combining it with an anti-programmed death-ligand 1 antibody. Finally, the anticancer effects of DAF were not observed in mice with depleted CD4-positive and CD8-positive cells. Conclusions: Nasal administration of DAF may inhibit lung cancer growth by inducing lung immune activation and is expected to be helpful as an immune activator for nasal administration. Full article

Background/Objectives: Hepatitis B virus (HBV) infection poses a major global health challenge, with current therapies like nucleos(t)ide analogs and pegylated interferon alpha offering limited functional cure rates due to persistent HBsAg-driven immune tolerance. This study aimed to develop a targeted immunoadsorption system using a high-affinity humanized anti-HBsAg monoclonal antibody for efficient HBsAg and viral particle clearance, providing a novel approach to overcome therapeutic bottlenecks in chronic hepatitis B (CHB). Methods: A murine anti-HBsAg monoclonal antibody was humanized via complementarity-determining region grafting, resulting in HmAb-12 (equilibrium dissociation constant, K_D = 0.36 nM). A stable Chinese Hamster Ovary K1 (CHO-K1) cell line was established for high-yield expression (fed-batch yield: 8.31 g/L). The antibody was covalently coupled to agarose microspheres (coupling efficiency > 95%) to prepare the immunoadsorbent. Efficacy was evaluated through in vitro dynamic circulation assays with artificial sera and preclinical trials using an integrated blood purification system in two CHB participants. Clearance rates for HBsAg and HBV DNA were quantified, with safety assessed via blood component monitoring. Results: In vitro, a single treatment cycle achieved HBsAg clearance rates of 70.14% (high antigen load, >10⁵ IU/mL) and 92.10% (low antigen load, ~3000 IU/mL). Preclinically, one treatment session resulted in acute HBsAg reductions of 78.30% and 74.31% in participants with high and moderate antigen loads, respectively, alongside HBV DNA decreases of 65.66% and 73.55%. Minimal fluctuations in total protein and albumin levels (<15%) confirmed favorable safety profiles, with no serious adverse events observed. Conclusions: Preliminary findings from this study indicate that the HBsAg-specific immunoadsorption system can achieve efficient HBV antigen clearance with an initial favorable safety profile in a small cohort. These results support its further investigation as a potential therapeutic strategy for functional cure in CHB. Future work will focus on validating these findings in larger studies and exploring the system’s combinatory potential with existing blood purification platforms. Full article

Long COVID is characterized by persistent symptoms associated with chronic inflammation and oxidative stress. While high-intensity interval training (HIIT) and supplementation with antioxidants such as Triphala have demonstrated individual therapeutic benefits, their combined effects remain unclear. This study aimed primarily to evaluate the effects of an 8-week HIIT program on markers of inflammation, oxidative stress, and exercise-related symptoms in individuals with long COVID, and secondarily to explore whether Triphala supplementation provided additional benefits. A total of 104 participants (aged 18–59 years) were randomized into three groups—control (placebo), HIIT (cycling for 28 min/day, 3 days/week), and combined (HIIT + Triphala, 1000 mg/day)—for 8 weeks. The biomarkers assessed included interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), protein carbonyls, and superoxide dismutase (SOD) activity. Following the intervention, significant reductions in IFN-γ, TNF-α, MDA, protein carbonyls, and rating of perceived exertion were observed in both the HIIT and combined groups (p < 0.05), with no significant differences between the two. SOD activity significantly increased in all groups, including the control group (p < 0.05), with no between-group differences. An 8-week HIIT program appears to be effective in reducing inflammation, oxidative stress, and dyspnea in individuals with long COVID. Triphala supplementation did not provide any additional statistically significant benefit but was safe and well tolerated. Full article

Authorized SARS-CoV-2 vaccines elicit both antibody and T-cell responses; however, benchmark correlates and update decisions have largely emphasized neutralizing antibodies. Motivated by the complementary role of cellular immunity, we designed a prototype polyepitope DNA vaccine encoding conserved human and mouse T-cell epitopes from non-structural proteins of the original strain SARS-CoV-2 lineage. Epitope selection was guided by in silico predictions for common HLA class I alleles in the Brazilian population and the mouse H-2Kb haplotype. To enhance immunogenicity, the polyepitope sequences were fused to glycoprotein D (gD) from Herpes Simplex Virus 1 (HSV-1), an immune activator of dendritic cells (DCs), leading to enhanced activation of antigen-specific T-cell responses. Mice were immunized with two doses of the electroporated DNA vaccine encoding the gD-fused polyepitope, which induced robust interferon-gamma– and tumor necrosis factor-alpha–producing T cell responses compared to control mice. In addition, K18-hACE2 transgenic mice showed protection against intranasal challenge with the original SARS-CoV-2 strain, with reduced clinical symptoms, less weight loss, and decreased viral burden in both lung and brain tissues. The results experimentally confirm the protective role of T cells in vaccine-induced protection against SARS-CoV-2 and open perspectives for the development of universal anti-coronavirus vaccines. Full article

Protocadherin-7 (Pcdh7) is a member of the protocadherin family, a subgroup of the cadherin superfamily. We previously demonstrated that Pcdh7 functions as a signaling receptor in osteoclast differentiation. In this study, we investigated the potential gene regulatory role of Pcdh7 in this process and identified Pyrin domain-containing protein 3 (Pydc3) as a key mediator of Pcdh7-mediated regulation of osteoclast differentiation. Differential gene expression analysis comparing wild-type (Pcdh7^+/+) and Pcdh7-deficient (Pcdh7^−/−) cells revealed a significant upregulation of Pydc3 in Pcdh7^−/− cells. RNAi-mediated knockdown of Pydc3 rescued the impaired osteoclast differentiation in Pcdh7^−/− cells, whereas overexpression of Pydc3 suppressed osteoclast differentiation in Pcdh7^+/+ cells, suggesting that Pydc3 negatively regulates osteoclast differentiation. Additionally, Pcdh7^−/− cells showed elevated expression of interferon response genes and increased production of interferon-β (IFN-β). Neutralization of IFN-β signaling using anti-IFN-β and/or anti-interferon alpha and beta receptor 1 (IFNAR1) antibodies significantly restored osteoclast differentiation in Pcdh7^−/− cells. Collectively, these findings uncover a novel role for Pcdh7 in osteoclast differentiation through regulation of Pydc3 expression and IFN-β production. Full article

With the growing interest in natural strategies for preventing skin aging, plant-derived compounds are being actively investigated for their potential protective effects against skin inflammation and extracellular matrix (ECM) degradation. In this study, we explored the anti-aging and anti-inflammatory effects of harringtonine, an alkaloid isolated from Cephalotaxus harringtonia, in normal human epidermal keratinocytes (NHEKs) under inflammatory stress induced by tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ). Harringtonine significantly suppressed the expression of matrix metalloproteinases (MMP)-1, MMP-2, and MMP-9 and restored the expression of collagen synthesis-related genes [collagen type I alpha 1 chain (COL1A1), collagen type I alpha 2 chain (COL1A2), and collagen type IV alpha 1 chain COL4A1)], indicating its protective role in ECM degradation. Additionally, harringtonine improved the expression of skin barrier-related genes, such as serine peptidase inhibitor kazal type 5 (SPINK5), loricrin (LOR), quaporin-3 (AQP3), filaggrin (FLG), and keratin 1 (KRT1) although it had no significant effect on involucrin (IVL). Harringtonine also markedly reduced the production of pro-inflammatory cytokines [interleukin (IL)-1β, IL-6, and IL-8] and inflammatory mediators, including prostaglandin E₂ (PGE₂), cyclooxygenase-2 (COX-2), and nitric oxide (NO). Our findings suggest that harringtonine may serve as a promising natural compound for mitigating skin aging and inflammation through multi-targeted modulation of ECM remodeling, skin barrier function, and inflammatory response. Full article

Cell culture-based influenza vaccines exhibit comparable safety and immunogenicity to traditional egg-based vaccines. However, improving viral yield remains a key challenge in optimizing cell culture-based production systems. Madin–Darby canine kidney (MDCK) cells, the predominant cell line for influenza vaccine production, inherently activate interferon (IFN)-mediated antiviral defenses that restrict viral replication. To overcome this limitation, we employed CRISPR/Cas9 gene-editing technology to generate an IFN alpha/beta receptor subunit 1 (IFNAR1)-knockout (KO) adherent MDCK cell line. Viral titer analysis demonstrated significant enhancements in the yield of multiple vaccine strains (H1N1, H3N2, and type B) in IFNAR1-KO cells compared to wild-type (WT) cells. Transcriptomic profiling revealed marked downregulation of key interferon-stimulated genes (ISGs)—including OAS, MX2, and ISG15—within the IFNAR1-KO cells, indicating a persistent suppression of antiviral responses that established a more permissive microenvironment for influenza virus replication. Collectively, the engineered IFNAR1-KO cell line provides a valuable tool for influenza virus research and a promising strategy for optimizing large-scale MDCK cell cultures to enhance vaccine production efficiency. Full article

Human leukocyte antigen class I (HLA-I) molecules present intracellular peptides on the cell surface to enable CD8+ T cells to effectively control viral infections. Many viruses disrupt this antigen presentation pathway to evade immune detection. In this study, we demonstrate that SARS-CoV-2 Nsp1 impairs both the constitutive and interferon-γ (IFN-γ)-induced upregulation of HLA-I. Moreover, Nsp1 also blocks IFN-γ-induced expression of HLA-II. We found that, contrary to previously published work, the early SARS-CoV-2 B 1.1.7 Alpha variant lacking the accessory protein ORF8 retained full capacity to downregulate HLA-I, comparable to an ORF8-expressing wild-type isolate. While ectopic overexpression of ORF8 could reduce HLA-I surface levels, this effect was only observed at high expression levels. In contrast, moderate expression of the viral protein Nsp1 was sufficient to potently suppress both basal and IFN-γ-induced HLA-I, as well as HLA-II expression. To probe the underlying mechanism, we analyzed HLA-I-associated genes in previously published RNA-sequencing datasets and confirmed that Nsp1 reduces expression of components required for HLA-I biosynthesis and antigen processing. These findings identify Nsp1 as a key factor that impairs antigen presentation pathways, potentially contributing to the ability of SARS-CoV-2 to modulate immune recognition. Full article

Fecal microbiota transplantation (FMT) promotes growth performance and intestinal development in yellow-feathered broilers, but whether the virome and metabolites contribute to its growth-promoting effect remains unclear. This study removed the microbiota from FMT filtrate using a 0.45 μm filter membrane, retaining the virome and metabolites to perform fecal virome transplantation (FVT), aiming to investigate its regulatory role in broiler growth. Healthy yellow-feathered broilers with high body weights (top 10% of the population) were used as FVT donors. Ninety-six 8-day-old healthy male yellow-feathered broilers (95.67 ± 3.31 g) served as FVT recipients. Recipient chickens were randomly assigned to a control group and an FVT group. The control group was gavaged with 0.5 mL of normal saline daily, while the FVT group was gavaged with 0.5 mL of FVT solution daily. Growth performance, immune and antioxidant capacity, intestinal development and related gene expression, and microbial diversity were measured. The results showed that FVT improved the feed utilization rate of broilers (the feed conversion ratio decreased by 3%; p < 0.05), significantly increased jejunal length (21%), villus height (69%), and crypt depth (84%) (p < 0.05), and regulated the jejunal barrier: insulin-like growth factor-1 (IGF-1) (2.5 times) and Mucin 2 (MUC2) (63 times) were significantly upregulated (p < 0.05). FVT increased the abundance of beneficial bacteria Lactobacillales. However, negative effects were also observed: Immunoglobulin A (IgA), Immunoglobulin G (IgG), Immunoglobulin M (IgM), Interleukin-1 beta (IL-1β), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), and Interferon-gamma (IFN-γ) in broilers were significantly upregulated (p < 0.05), indicating immune system overactivation. Duodenal barrier-related genes Mucin 2 (MUC2), Occludin (OCLN), Claudin (CLDN1), and metabolism-related genes solute carrier family 5 member 1 (SLC5A1) and solute carrier family 7 member 9 (SLC7A9) were significantly downregulated (p < 0.05). The results of this trial demonstrate that, besides the microbiota, the gut virome and metabolites are also functional components contributing to the growth-promoting effect of FMT. The differential responses in the duodenum and jejunum reveal spatial heterogeneity and dual effects of FVT on the intestine. The negative effects limit the application of FMT/FVT. Identifying the primary functional components of FMT/FVT to develop safe and targeted microbial preparations is one potential solution. Full article

Background: Cerebral aneurysm (CA) is a focal or diffuse pathological dilation of the cerebral arterial wall that arises due to various etiological factors. It represents a serious vascular condition, particularly affecting the elderly, and carries a high risk of rupture and neurological morbidity. Clonidine (CL), an α2-adrenergic receptor agonist, has been reported to suppress aneurysm progression; however, its underlying molecular mechanisms, especially in relation to cerebral endothelial dysfunction, remain unclear. This study aimed to investigate the potential of CL to mitigate CA development by modulating apoptosis, inflammation, and oxidative stress in an Angiotensin II (Ang II)-induced endothelial injury model. Methods: Human brain microvascular endothelial cells (HBMECs) were used to establish an in vitro model of endothelial dysfunction by treating cells with 1 µM Ang II for 48 h. CL was administered 2 h prior to Ang II exposure at concentrations of 0.1, 1, and 10 µM. Cell viability was assessed using the MTT assay. Oxidative stress markers, including reactive oxygen species (ROS) and Nitric Oxide (NO), were measured using 2′,7′–dichlorofluorescin diacetate (DCFDA). Gene expression levels of vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMP-2 and MMP-9), high mobility group box 1 (HMGB1), and nuclear factor kappa B (NF-κB) were quantified using RT-qPCR. Levels of proinflammatory cytokines; tumor necrosis factor-alpha (TNF-α), Interleukin-6 (IL-6), and interferon-gamma (IFN-γ); were measured using commercial ELISA kits. Results: Ang II significantly increased ROS production and reduced NO levels, accompanied by heightened proinflammatory cytokine release and endothelial dysfunction. MTT assay revealed a marked decrease in cell viability following Ang II treatment (34.18%), whereas CL preserved cell viability in a concentration-dependent manner: 44.24% at 0.1 µM, 66.56% at 1 µM, and 81.74% at 10 µM. CL treatment also significantly attenuated ROS generation and inflammatory cytokine levels (p < 0.05). Furthermore, the expression of VEGF, HMGB1, NF-κB, MMP-2, and MMP-9 was significantly downregulated in response to CL. Conclusions: CL exerts a protective effect on endothelial cells by reducing oxidative stress and suppressing proinflammatory signaling pathways in Ang II-induced injury. These results support the potential of CL to mitigate endothelial injury in vitro, though further in vivo studies are required to confirm its translational relevance. Full article