Intestinal epithelial barrier dysfunction is a hallmark feature of inflammatory bowel disease and closely associated with tight junction (TJ) disruption and increased epithelial permeability. Cinnamon contains bioactive compounds with antioxidant and anti-inflammatory properties; however, its protective effects on intestinal barrier integrity remain unclear. This study investigated whether Cinnamomum cassia ethanol extract (CNCE) protects against interleukin-6 (IL-6)-induced epithelial barrier dysfunction in Caco-2 cells by regulating TJ-associated proteins. An IL-6-induced inflammatory barrier dysfunction model was established using Caco-2 cells. The antioxidant activity of CNCE was assessed using 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azino-bis(3-ethylbenzothiazoline−6-sulfonic acid) assays, and noncytotoxic concentrations were determined using cell viability analysis. Barrier function was evaluated using transepithelial electrical resistance (TEER) and 4-kDa fluorescein isothiocyanate (FITC)-dextran permeability assays. TJ protein localization and expression were examined by immunofluorescence staining and western blotting. LC–MS/MS and molecular docking analyses were performed to identify major CNCE-derived compounds and assess their potential interaction with zonula occludens-1 (ZO-1). CNCE exhibited concentration-dependent antioxidant activity and was noncytotoxic up to 100 μg/mL. IL-6 reduced TEER and increased epithelial permeability, whereas CNCE pretreatment restored TEER values and reduced FITC-dextran permeability. Moreover, CNCE preserved the junctional localization of ZO-1 and occludin, restored their protein expression, and suppressed IL-6-induced claudin-2 upregulation. LC–MS/MS tentatively identified five major compounds in CNCE, including coniferaldehyde, coumarin, syringaldehyde, cinnamaldehyde, and 2-methoxycinnamaldehyde, and docking analysis suggested their potential interaction with ZO-1. CNCE protects against IL-6-induced epithelial barrier dysfunction by preserving TJ structure and regulating TJ-associated protein expression, suggesting its potential as a natural barrier-protective agent for inflammatory intestinal disorders.
Diatoms are important primary producers in aquatic ecosystems and are continuously affected by pollutants that disturb cellular redox homeostasis. Glutathione S-transferases (GSTs) are involved in glutathione-dependent detoxification and redox regulation; however, information regarding GSTs class specific characteristics and pollutant-responsive expression patterns in diatoms remains limited. We identified a novel Nu class GST, designated as FsGSTNu, from the freshwater diatom Fragilaria saxoplanctonica and examined its transcriptional responses under exposures of six metals (NaAsO2, CdSO4, K2Cr2O7, CuSO4, NiSO4 and ZnSO4) and three pesticides (atrazine, chlorpyrifos, and S-metolachlor). The open reading frame (ORF) of FsGSTNu was 885 bp, encoding 295 amino acids, without an intron in the genomic coding region. The protein was predicted to localize in the cytoplasm and contain conserved structural features related to glutathione (GSH) binding and substrate interaction. Phylogenetic analysis showed that FsGSTNu was clustered within the Nu class GST clade, clearly separated from other GST class. FsGSTNu gene expression was differentially induced by specific metals and pesticides depending on exposure time. In particular, FsGSTNu was significantly up-regulated in response to ZnSO4, NaAsO2, NiSO4, chlorpyrifos, and S-metolachlor exposure. Chlorophyll autofluorescence (CAF) decreased in NiSO4, CdSO4, and S-metolachlor treatments, whereas reactive oxygen species (ROS) production increased except in CdSO4. These results suggest that FsGSTNu may participate in responses to specific pollutants that induce oxidative stress in F. saxoplanctonica. In addition, the gene can be used as a potential biomarker for assessing the molecular toxicity of specific metal and pesticide contamination in freshwater ecosystems.
Climate-driven environmental changes are reshaping the distribution of marine harmful algal blooms, with several subtropical benthic harmful algal bloom (BHAB) dinoflagellates increasingly reported from warm-temperate coastal ecosystems. Among them, ciguatera-causing dinoflagellates have attracted increasing attention because of their potential impacts on seafood safety, fisheries, and public health. Their occurrence beyond traditionally recognized tropical and subtropical ranges presents an emerging challenge for coastal ecosystem management. This review synthesizes current knowledge on the ecology, distribution, toxicological significance, and environmental factors associated with subtropical ciguatera-causing dinoflagellates, with particular emphasis on their occurrence in Korean coastal waters. We further identify current knowledge gaps and discuss future monitoring and management strategies to support ecological and toxicological risk assessment. Recent studies indicate that ocean warming, marine heatwaves, changing ocean circulation, and local habitat conditions may contribute to distributional changes in subtropical benthic dinoflagellates, including Gambierdiscus, Fukuyoa, Ostreopsis, Prorocentrum, Coolia, and Amphidinium. Monitoring surveys conducted by the authors between 2020 and 2025 repeatedly detected several of these genera around Jeju Island and along the southern and eastern coasts of Korea. Their occurrence in regions influenced by the Tsushima Warm Current is consistent with a potential contribution of warm-water transport, although a direct causal relationship has not been established. In addition, toxin characterization of Korean isolates remains limited, emphasizing the need for species- and strain-specific toxin analyses to better assess their potential toxicological risks. The increasing occurrence of subtropical BHAB dinoflagellates in temperate coastal waters highlights the need for integrated long-term monitoring, species-level molecular identification, toxin characterization, and climate-based distribution modeling. Strengthening these approaches will improve early detection, ecological forecasting, and evidence-based management while supporting seafood safety under ongoing climate change.
Butyrylcholinesterase (BChE) is a serine hydrolase enzyme involved in various physiological processes and may act as a biomarker of environmental exposure effects. However, the biochemical and genetic factors influencing its activity remain unclear. To identify biochemical, hematological, and transcriptomic gene expression factors associated with BChE activity. Our study analyzed 199 pesticide-exposed agricultural workers in Cajamarca, Peru, assessing biochemical and hematological parameters to predict BChE activity using regression and Random Forest models, complemented by transcriptomic correlation analyses. Data from 199 individuals with occupational pesticide exposure were analyzed. Multiple linear regression models using Box-Cox, logarithmic, and square root transformations, along with a Random Forest algorithm, were evaluated. The logarithmic model showed the best performance. Urea, cholesterol, and triglycerides were identified as the main biochemical predictors of BChE activity. Transcriptomic analysis using data from the Human Protein Atlas revealed that the expression of the genes LIPG and PLTP was positively correlated with BCHE expression, while LIPC, NOS1, and PADI4 showed negative correlations. These findings support the involvement of BChE in lipid and nitrogen metabolism and reinforce its potential use as a biomarker of metabolic disturbances linked to chronic environmental exposure in agricultural populations.
Radioresistance is a major problem in non-small cell lung carcinoma (NSCLC) treatment. Osthole is a natural coumarin with antitumor effects. This research sought to clarify if Osthole enhances the sensitivity of NSCLC to radiotherapy and to uncover the underlying mechanisms involved. Cell Counting Kit-8 (CCK-8) assay evaluated the impact of Osthole on the viability of BEAS-2B as well as NSCLC cells, and evaluated the combined effect of different Ionizing radiation (IR) doses with Osthole in order to screen for the appropriate treatment concentration. The malignant biology of NSCLC cells was determined using Scratch-wound assay, clone formation, transwell assay and flow cytometry. To evaluate cellular senescence, SA-β-Gal staining was utilized, and the concentrations of senescence-related cytokines were analyzed using ELISA kits. A model of subcutaneous tumors was developed using nude mice, followed by pathological staining to assess cell growth, apoptosis and changes in indicator protein expression. Western blot evaluated the expression levels of Sirt1/NF-κB pathway, apoptosis, cell cycle and cellular senescence related proteins. Osthole at 40 μM showed no notable influence on BEAS-2B cell viability, but could reduce the viability and clone formation ability of NSCLC cells, hindered their migration and invasion, and triggered apoptosis. Co-treatment of Osthole with IR increased the suppressive effect of IR on the malignant biology of NSCLC cells, and also blocked cells in G1 phase and induced senescence-related marker changes. Furthermore, Osthole modulated the Sirt1/NF-κB pathway, and the Sirt1 agonist SRT1720 alleviated Osthole-induced cell senescence-like phenotype and apoptosis. Osthole treatment reduced the volume and mass of tumor tissue, inhibited cell proliferation and promoted apoptosis. Notably, Osthole also modulated Sirt1/NF-κB pathway and induced cell senescence-like phenotype in vivo. Osthole increases the radiosensitivity of NSCLC cells and promotes cell senescence-like phenotype and G1-phase blockade possibly through modulating Sirt1/NF-κB pathway. Osthole enhances the responsiveness of NSCLC cells to radiotherapy, promotes cell senescence-like phenotype and apoptosis possibly via modulating Sirt1/NF-κB pathway, thus effectively inhibits the malignant progression of NSCLC.
Gamisoyo-san (GSS) is a traditional polyherbal formula derived from Soyo-san, a classic prescription used to treat liver disorders and metabolic imbalances, supplemented with Gardenia jasminoides Ellis and Paeonia × suffruticosa Andrews to enhance antioxidant and lipid-lowering effects. Although GSS is primarily prescribed in East Asia for gynecological conditions, its direct therapeutic efficacy in metabolic dysfunction-associated steatotic liver disease (MASLD) and underlying mechanisms remain to be fully elucidated. This study aimed to investigate the hepatoprotective effects of GSS in a high-fat diet (HFD)-induced MASLD model and to elucidate the mechanisms of action. Following oral administration of GSS for eight weeks, body weight gain was significantly inhibited, with a concomitant reduction in the weights of liver and adipose tissues. GSS treatment also improved serum markers for liver function (ALT, AST, and albumin), lipid profiles (triglycerides and total/LDL cholesterol), and glucose levels. Furthermore, it enhanced hepatic antioxidant defenses (glutathione, SOD, and catalase) while suppressing lipid peroxidation (MDA), pro-inflammatory cytokine production (TNF-α and IL-1β), and apoptosis (caspase-3). Mechanistically, GSS regulated hepatic lipid homeostasis by inhibiting lipogenesis and promoting β-oxidation, potentially through modulation of the SIRT1/AMPK/NRF2 signaling pathway. Histopathology and immunohistochemistry confirmed that GSS effectively ameliorated MASLD by regulating lipid metabolism and inhibiting oxidative stress, inflammation, and apoptosis. These findings provide scientific evidence validating the traditional use of GSS in metabolic liver disorders and suggest its potential as a natural, multi-target therapeutic candidate for MASLD management.
Our research team’s series on nanoparticle safety in 2014 revealed a significant public knowledge gap in nanotechnology despite its growing industrial use. Over a decade later, with nanotechnology deeply integrated into various sectors and the onset of COVID-19, reassessment is essential. This study investigated patterns in nanotechnology product registration and nanotechnology-related media coverage in South Korea across the periods preceding, during, and following the COVID-19 pandemic. The aim was to describe temporal trends and identify factors that may have contributed to the observed changes. The data from nanoproduct databases, publications, and news articles were analyzed to track changes in nanotechnology use and public awareness across the three pandemic phases. A marked increase in product registrations was observed in 2016, followed by substantially lower annual registration activity in subsequent years, including the COVID-19 period. These findings suggested that the decline in registrations preceded the pandemic and should not be interpreted as a direct consequence of COVID-19. Despite decreased consumer product registration, nanotechnology played a crucial role in diagnostics, vaccines, and protective equipment. The need for increased public awareness and better regulatory enforcement remains critical for future growth and safety.
Cadmium (Cd) has been identified as a neurotoxic agent, leading to various adverse neurological effects, including neurodegeneration, oxidative stress, and inflammation in the brain. This study aimed to investigate the protective effects of Nigella sativa oil (NSO) against Cd-induced alterations in body weight, hematological and biochemical parameters, and the nervous system in mice. A total of 60 male Swiss Albino mice, aged 4 weeks, were assigned to treatment groups receiving Cd, NSO, or a combination of Cd and NSO. The results demonstrated that Cd significantly reduced body weight and blood parameters, such as TEC, Hb, PCV. However, Cd significantly increased the lipid parameters, such as TC, TG, and LDL, but decreased HDL levels. Whereas, supplementation of mice with NSO reduced the effect of Cd on these parameters. In Cd-exposed mice, a significantly decreased locomotor activity combined with increased anxiety-like behavior was observed by performing behavioral tests, such as open field, the elevated plus maze, light/dark transition test, and force swimming test. The mice treated with NSO showed marked improvements in these neurobehavioral parameters, suggesting a neuroprotective effect. Histological analysis of brain tissue revealed that Cd exposure induced gliosis, perivascular cuffing, and vacuolation of the neuropil. Treatment with NSO significantly reduced the extent of cortical damage. The study demonstrates that NSO exhibited significant neuroprotective effects against Cd-induced neurotoxicity in mice. However, further studies investigating oxidative stress, inflammatory responses, and molecular signaling pathways are required to clarify the mechanisms underlying these beneficial effects.
Exposure to electric fields has been associated with oxidative stress, inflammation and apoptosis in various tissues. However, the duration-dependent effects of electric field exposure on renal tissue and the balance between adaptive cytoprotective responses and tissue injury remain unclear. This study aimed to investigate the histopathological, immunohistochemical and molecular effects of different durations of 10 kV/m electric field exposure on rat kidney tissue, with particular emphasis on oxidative stress, apoptosis and inflammatory pathways. Forty Wistar rats were randomly assigned to five groups: control, 1 min, 5 min, 15 min and 30 min exposure. Histological analysis (hematoxylin–eosin staining) revealed that the 30 min exposure group exhibited severe hyperemia, hemorrhage, inflammatory cell infiltration and tubular degeneration. Immunohistochemical findings demonstrated markedly increased expression of caspase-3 (Cas-3), nuclear factor kappa B (NF-κB) and tumor suppressor protein p53 (p53) in the 30 min group, indicating activation of apoptotic and inflammatory pathways. Gene expression analysis by quantitative real-time PCR showed significant upregulation of sirtuin-1 (SIRT1), nuclear factor erythroid 2-related factor 2 (NRF2) and heme oxygenase-1 (HO-1) in the 1, 5 and 15 min groups, suggesting adaptive cytoprotective activation. In contrast, these protective markers were sharply downregulated in the 30 min group, coinciding with extensive tissue damage. Short-term electric field exposure induces adaptive cytoprotective responses in renal tissue, whereas prolonged exposure (30 min) overwhelms these mechanisms, leading to increased oxidative stress, inflammation, apoptosis and significant histopathological damage.
Amygdalin (Amy) exhibits multiple pharmacological properties, including anti-fibrotic and anti-inflammatory effects, but its protective role against Hyperuricemia (HUA)-related kidney injury remains unclear. To investigate whether Amy improves HUA by regulating the reactive oxygen species (ROS)/NLRP3 axis. Amy lowered serum LDH levels in HUA mice, improved renal function indicators, and alleviated renal tissue pathological damage and fibrosis. Amy effectively reduced ROS and inflammatory factor levels in the kidney tissue of HUA mice, alleviating macrophage infiltration and oxidative stress. Concurrently, Amy enhanced the viability of NRK-52E cells after UA induction while reducing LDH activity and cell death rates, thereby alleviating inflammatory and oxidative stress. Mechanistically, Amy hindered NLRP3 inflammasome activation and down-regulated pyroptosis-associated proteins. The ROS-inducing activator 3-NPA/rotenone reversed the aforementioned protective effect, elevating ROS levels and pyroptosis-related protein expression. Amy mitigates UA-induced damage to NRK-52E cells and renal injury in mice by hindering ROS production and blocking NLRP3 inflammasome-mediated pyroptosis.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global health concern characterized by hepatic steatosis and metabolic dysregulation. Metyrapone (MTR), an 11β-hydroxylase inhibitor, is widely used clinically to modulate cortisol levels; however, its potential hepatotoxicity during early zebrafish development remains poorly understood. This study investigated the hepatotoxic effects and underlying mechanisms of MTR exposure in the early developmental stages of zebrafish. Survival rates and morphology, including body length, were largely unaffected at the tested concentrations. However, MTR treatment induced fatty liver, as evidenced by Oil Red O staining and dose-dependent increases in total triglyceride and cholesterol levels. This lipid accumulation was accompanied by the upregulation of key lipid metabolism-related genes, including pparγ, acsl1b, srebp1, and fasn. Although biochemical changes were observed, no significant alterations in liver area were observed in Tg[fabp10a:DsRed] larvae. MTR exposure triggered oxidative stress, characterized by the increased production of reactive oxygen species, upregulation of gpx1a, and downregulation of cat. MTR exposure increased the expression of endoplasmic reticulum (ER) stress markers (ern1, atf4, atf6, and ddit3). MTR induces hepatic steatosis and cellular stress in zebrafish larvae, reflecting key features associated with early hepatic lipid dysregulation, oxidative stress, and ER stress that are relevant to MASLD.
In Traditional East Asian Medicine, the concept of ‘static blood’ has long served as a framework for understanding health problems associated with impaired blood circulation or blood stagnation. Although it has guided therapeutic practices for centuries, its definition and clinical relevance remain insufficiently clarified in modern biomedical science. This review aims to bridge traditional and contemporary perspectives by examining the definition, causes, clinical manifestations, and diagnostic criteria of static blood, alongside its modern interpretations, current research approaches, disease associations, and treatment strategies. Traditionally, static blood is identified through characteristic signs and symptoms frequently observed in chronic conditions, including cardiovascular disease, stroke, organ dysfunction, and gynecological disorders. From a biomedical standpoint, static blood is increasingly interpreted in relation to impaired circulation, increased blood viscosity, vascular inflammation, endothelial dysfunction, and an elevated risk of thrombosis. Recent studies have identified potential biomarkers, such as d-dimer, gelsolin, and inflammatory cytokines, as well as omics-derived candidates, offering insight into its physiological basis and enabling measurable links between traditional diagnosis and modern evidence. However, the current evidence remains limited by insufficient biomarker specificity, heterogeneity in diagnostic criteria, incomplete mechanistic validation, and poor reproducibility across experimental systems. Overall, static blood is re-emerging as a meaningful integrative concept that connects traditional medical theory with observable biological mechanisms, supporting a more comprehensive and personalized approach to managing complex chronic diseases. We propose that static blood may be interpreted as a systemic vascular-inflammatory-metabolic network disorder characterized by endothelial dysfunction, hypercoagulability, impaired microcirculation, and immune dysregulation. Further standardization of diagnostic criteria, validation of multidimensional biomarkers, and translational studies are required to enhance the scientific rigor and clinical applicability of the approach.
Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) is marked by Th2-type inflammation and defective regulatory T (Treg) cell function, with unclear upstream regulatory mechanisms. Nemo-like kinase (NLK), a conserved serine/threonine kinase involved in immune regulation, has an uncharacterized role in ECRSwNP. This study aimed to investigate the involvement of NLK in the pathogenesis of ECRSwNP, particularly its association with Treg/Th2 imbalance. Clinical sample analyses (immunohistochemistry, RT-qPCR, Western blot) showed that NLK was specifically downregulated in ECRSwNP tissues, with expression negatively correlated with Th2 cytokines (IL-4, IL-5, IL-13), eosinophil marker ECP, and disease severity, but positively correlated with Treg cell quantity and function. Co-immunoprecipitation and in vitro kinase assays revealed that NLK directly phosphorylated Foxp3 at 7 conserved sites (such as S19, T341), inhibiting STUB1-mediated K48-type ubiquitination via steric hindrance to stabilize Foxp3. NLK knockdown impaired Treg suppression of PBMC proliferation, increased Th2 cell proportion, and upregulated Th2 cytokines, forming a pathological cascade of reduced NLK, destabilized Foxp3, defective Treg function, and excessive Th2 inflammation. NLK acts as a critical hub regulating Treg/Th2 balance in ECRSwNP by stabilizing Foxp3 through phosphorylation-dependent inhibition of STUB1-mediated ubiquitination.
Pelvic irradiation is widely used in cancer therapy but frequently damages non-cancerous tissues, particularly the highly proliferative spermatogenic cells of the testes, leading to infertility. Endoplasmic reticulum (ER) stress and apoptosis are key mechanisms underlying radiation-induced germ cell loss. Tauroursodeoxycholic acid (TUDCA), an endogenous bile acid, has been reported to exert cytoprotective effects in testicular injury models by suppressing ER stress. This study aimed to evaluate the protective role of TUDCA against radiation-induced testicular dysfunction in mice, with a specific focus on its ability to inhibit germ cell apoptosis and modulate ER stress–related pathways. At 12 h after irradiation, TUDCA administration significantly reduced germ cell apoptosis. By 30 days post-irradiation, TUDCA-treated mice exhibited increased testis weight compared with irradiated controls. Histological analyses revealed improvements in seminiferous tubule diameter and epithelial height, alongside higher seminiferous tubule repopulation and stem cell survival indices. In the epididymis, TUDCA prevented the radiation-induced decline in sperm count and motility. Molecular analysis showed that irradiation elevated Ddit3 (CHOP) and Atf6 expression, whereas TUDCA markedly suppressed these ER stress markers. TUDCA effectively protects the testes from radiation-induced injury by reducing germ cell apoptosis, maintaining testicular architecture, preserving sperm function, and attenuating ER stress signaling. These findings suggest that TUDCA has potential as a therapeutic agent to prevent male infertility following pelvic irradiation.
Aging-associated muscle decline is closely associated with oxidative stress-induced apoptosis and chronic inflammatory signaling. Excessive accumulation of reactive oxygen species disrupts cellular redox homeostasis and promotes mitochondrial dysfunction, ultimately leading to myocyte apoptosis and muscle degeneration. In addition, inflammatory mediators and cytokine signaling pathways further amplify oxidative damage and contribute to progressive muscle deterioration. This study evaluated the biological effects of the mycelial culture filtrate of Trametes suaveolens KMRB 17121435 (Ts_MY) on oxidative stress-associated cytotoxicity in C2C12 myoblasts and inflammatory responses in lipopolysaccharide-stimulated RAW 264.7 macrophages. Under H2O2 exposure, Ts_MY treatment increased C2C12 cell viability in a concentration-dependent manner and modulated apoptosis-related regulators, including decreased Bax expression, increased Bcl-2 levels, reduced caspase-9 and caspase-3 cleavage, and attenuated PARP cleavage. In RAW 264.7 macrophages, Ts_MY exhibited no cytotoxicity within the tested concentration range and significantly suppressed nitric oxide and prostaglandin E2 production. Ts_MY also reduced the expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), accompanied by decreased inducible nitric oxide synthase and cyclooxygenase-2 expression and inhibition of NF-κB signaling. Radical scavenging activity was confirmed using ABTS and DPPH assays. LC–MS/MS profiling tentatively indicated the presence of phenolic and aromatic metabolites, including protocatechuic acid-related signals based on accurate mass and database matching. These findings demonstrate that Ts_MY modulates oxidative stress- and inflammation-associated cellular responses in vitro through regulation of apoptosis-related signaling and NF-κB-mediated inflammatory pathways. Because all experiments were conducted in cell-based systems, further studies are required to identify active constituents and validate their biological effects in more complex models.
Climate change-driven heat stress is an emerging toxicological stressor that disrupts thermoregulation and endocrine function, impairing livestock fertility across the reproductive lifespan. This review aims to synthesize mechanistic evidence linking heat stress to female reproductive dysfunction in cattle, pigs, and poultry. Growing evidence indicates that climate change-associated heat stress compromises female reproduction in cattle, pigs, and poultry. In cattle, chronic heat stress perturbs the hypothalamic–pituitary–gonadal and stress axes, induces oxidative and mitochondrial damage in gametes and embryos, and disrupts uterine signaling, thereby impairing implantation and maternal recognition of pregnancy. In pigs, impaired heat dissipation, negative energy balance, and uterine and placental injury converge to reduce fertility and compromise pregnancy maintenance. In poultry, heat stress alters neuroendocrine and intestinal functions and diverts energy away from reproduction, leading to sustained declines in laying performance and egg quality. These findings highlight heat stress as a multidimensional reproductive toxicant in livestock and the need to evaluate its cumulative impact on fertility under climate warming.
This study aimed to analyze the principal chemical constituents of Salicornia europaea (S. europaea) extract and to evaluate its antioxidant and anti-inflammatory effects using HaCaT cells. S. europaea was prepared via 70
Despite being a prevalent benign vascular tumor, infantile hemangioma (IH) is still not well understood concerning its pathogenesis. This study was to investigate the effects of M1 macrophage-derived exosomes (M1-Exos) on hemangioma endothelial cells (HemECs) and their mechanism. Proliferative IH tissues were collected from our hospital and HemECs were isolated. M1 macrophages were obtained from THP-1 cells (M0 macrophages) induced by phorbol myristate acetate using interferon-γ (IFN-γ) and lipopolysaccharide (LPS). M1 macrophage markers (CD80 and CD86) were analyzed by flow cytometry. M1-Exos were extracted and characterized. Following co-culture with M1-Exos, the proliferation of HemECs was evaluated using Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU), and colony formation assays. Western blot analysis was performed to detect cell proliferation-related proteins, components of the AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α) pathway, and endothelial-mesenchymal transition (EndMT)-related proteins. Adipogenesis was detected by Oil Red O staining. M1 macrophages were successfully induced and M1-Exos were successfully isolated. M1-Exos inhibited the proliferation of HemECs and inhibited the protein expression of cell proliferation markers (Ki-67 and PCNA). M1-Exos activated the AMPK/SIRT1/PGC1α signaling pathway, as indicated by the increased expression of phospho (p)-AMPK, SIRT1, and PGC1α proteins. The inhibitory effects of M1-Exos on HemEC proliferation and on the protein expression of cell proliferation markers [Ki-67 and proliferating cell nuclear antigen (PCNA)] were attenuated by Compound C (an AMPK inhibitor) or SR-18292 (a PGC1α inhibitor). M1-Exos induced EndMT in HemECs, as evidenced by a decrease in the protein expression of the endothelial markers and an increase in the protein expression of the mesenchymal markers. Moreover, M1-Exos-treated HemECs could differentiate into adipocytes after adipogenic induction. M1-Exos promote IH regression by activating the AMPK/SIRT1/PGC1α pathway and inducing EndMT.
Amyloid-β (Aβ) is a major toxic molecule linked to the pathogenesis of Alzheimer’s disease (AD). Astrocytes, the major homeostatic non-neuronal cells in the brain, contribute to extracellular Aβ clearance through phagocytosis; however, the underlying mechanism has been elusive. Acetate serves as an alternative energy substrate to glucose for reactive astrocytes in AD, yet its role in modulating astrocytic Aβ uptake has not been fully explored. This study investigated whether acetate induces astrocyte reactivity and subsequently enhances Aβ uptake. Primary cortical astrocytes treated with acetate (1, 3, and 5 mM) to assess changes in reactive astrocyte-related gene expression, including GFAP, MAOB, C3, and Serpina3n. Astrocytic uptake of Aβ oligomer was evaluated by immunohistochemistry following acetate treatment. To examine the involvement of astrocytic phagocytic pathways, the expression levels of MEGF10 and MERTK were analyzed using quantitative real-time PCR. Acetate treatment dose-dependently increased the expression of reactive astrocyte markers (GFAP, MAOB, C3, and Serpina3n), indicating enhanced astrocytic reactivity. Acetate at 5 mM significantly promoted astrocytic uptake of Aβ. In parallel, acetate treatment led to a dose-dependent upregulation of MEGF10 and MERTK, genes associated with astrocytic phagocytosis. These findings suggest that elevated acetate levels induce reactive astrocyte phenotypes and enhance Aβ uptake, potentially through activation of the MEGF10/MERTK-mediated phagocytic pathway. Acetate-dependent modulation of astrocyte function may represent a previously underappreciated mechanism influencing Aβ clearance in AD.
