Signaling lipids regulate key physiological and pathological processes, providing insights into disease mechanisms and therapeutic targets. While plasma is the standard biofluid for their analysis, its collection and handling pose challenges, including the need for venous access, immediate processing, and stringent cold-chain transportation to prevent lipid degradation. Volumetric absorptive microsampling (VAMS) has emerged as an alternative to conventional whole blood (WB) and dried blood spot (DBS), yet its suitability for comprehensive signaling lipid profiling, including low-abundance species, remains unexplored. This study evaluated the feasibility of VAMS for profiling diverse signaling lipid classes using a single liquid-liquid extraction(LLE) protocol. Analytical performance was assessed by evaluating precision, LLE recovery, matrix effects, and endogenous metabolite levels across WB, DBS, and VAMS. Short-term stability of VAMS at room temperature was examined over 24h, 48h, and 1week storage. VAMS demonstrated superior precision compared to DBS while achieving moderate but comparable recoveries. The metabolic profile of VAMS aligned closely to WB, while DBS deviated substantially, demonstrating improved lipid stability in VAMS in the initial 24h period at room temperature. However, extended storage for 1week introduced significant artifacts, altering metabolome composition and emphasizing the need for stabilization strategies, such as desiccant-assisted storage or antioxidant pretreatment to minimize hydrolytic and oxidative degradation. These findings provide initial evidence supporting VAMS as a feasible and promising alternative to DBS for signaling lipid profiling. Further studies are needed to assess extraction efficiency from the VAMS tip, optimize LLE recovery, and evaluate long-term stability, advancing theapplicability of VAMS in lipidomics research.

Imiquimod-induced colitis: A novel ROS/ERK-driven model of intestinal inflammation and barrier dysfunction.

Background: Overcoming therapeutic resistance and tumor microenvironment-mediated survival remains a major challenge in ovarian cancer treatment. This study investigated the individual and combined antitumor effects of etoposide and curcumin in human ovarian cancer models, with emphasis on synergistic interactions, apoptosis induction, tumor microenvironment modulation, and oxidative stress-associated mechanisms. We hypothesized that the combination of etoposide and curcumin exerts enhanced antitumor activity through an integrated mechanism involving DNA damage-associated apoptotic signaling, tumor microenvironment modulation, and ROS-associated cellular stress, rather than through a single dominant pathway. Methods: Cell viability was assessed using the MTT assay, and drug-drug interactions were quantitatively evaluated using the Chou-Talalay and Bliss independence models. Apoptosis was analyzed by Annexin V/propidium iodide flow cytometry, caspase-8/9 activity assays, and cell cycle analysis. Transcriptional regulation of apoptosis- and microenvironment-related genes was examined by quantitative real-time PCR. Inflammatory and angiogenic cytokines were measured by ELISA. Therapeutic efficacy was further validated in three-dimensional (3D) tumor spheroid models using morphological assessment and adenosine triphosphate (ATP)-based viability assays. The contribution of reactive oxygen species (ROS) was evaluated using antioxidant pretreatment. Results: The etoposide-curcumin combination demonstrated significantly enhanced antiproliferative and pro-apoptotic effects compared with either agent alone, with consistent synergism observed across quantitative interaction models. Combination treatment increased apoptotic cell death, activated both intrinsic and extrinsic apoptotic pathways, and induced G2/M cell cycle arrest. In parallel, inflammatory and angiogenic signaling was markedly suppressed at both transcriptional and protein levels. These effects were preserved and amplified in 3D tumor spheroid models, where combination therapy induced pronounced spheroid shrinkage and reduced viability. Antioxidant pretreatment partially attenuated ROS generation and cytotoxicity, indicating that oxidative stress contributes to, but does not fully account for, the observed antitumor effects. Conclusions: The combination of etoposide and curcumin exerts synergistic and multi-layered antitumor effects in ovarian cancer models by integrating apoptosis induction, tumor microenvironment modulation, and ROS-associated mechanisms. These findings support further preclinical evaluation of this combination as a rational therapeutic strategy for ovarian cancer.

Herein, we adopted a dual approach combining molecular modeling and biological studies, in order to assess the interaction between four selected natural antioxidants (NAs; berberine, curcumin, astaxanthin, indicaxanthin) and tissue transglutaminase (TG2) levels both in the absence and in the presence of full native peptide of amyloid-β (Aβ). Docking studies were performed to ascertain the binding affinity of NAs against the TG2 closed, Ca2+-bound closed, and open forms. In the biological investigation, the effect of berberine and curcumin treatment on TG2 in Olfactory Ensheathing Cells (OECs) exposed to Aβ(1-42) or to Aβ(25-35), a Aβ toxic fragment, or to reverse-sequence fragment Aβ(35-25), an Aβ not toxic fragment, was tested. In addition, their effect on the percentage of cell viability and cytoskeleton marker (GFAP, vimentin and nestin) levels were evaluated. The role of berberine and curcumin on both endocellular levels of reactive oxygen species (ROS) and apoptotic pathway activation were also assessed. Our findings demonstrate that pretreatment of OECs with these NAs counteracted the Aβ-induced upregulation of TG2, restoring its expression to control levels and preserving its predominant cytosolic localization. Furthermore, antioxidant pretreatment reinstated cell viability, normalized the expression of GFAP, vimentin, and nestin, reduced intracellular ROS accumulation, and prevented activation of the apoptotic cascade. Our findings demonstrate that integrating computational and biological approaches, enhances the identification of potent therapeutic agents and also highlights berberine and curcumin as promising candidates for the development of novel neuroprotective drugs against neurodegenerative disorders, including Alzheimer's disease.

Temozolomide (TMZ) is the first-line drug for the treatment of glioblastoma multiforme (GBM). Unfortunately, most patients with GBM eventually develop drug resistance. Camptothecin (CPT) and honokiol (HNK) are bioactive ingredients of Camptotheca acuminata and Magnolia officinalis, respectively. Our previous studies showed the benefits of CPT and CPT-containing nanoparticles on suppressing GBM tumorigenesis. However, CPT can have side effects. This study evaluated the synergistic effects of HNK and CPT at low and non-toxic concentrations on the killing of TMZ-resistant glioblastoma cells, as well as the underlying mechanisms. Cytotoxicity of HNK and CPT toward normal human astrocytes and mouse cerebral endothelial cells (CECs) was assessed using colorimetric and flow cytometric assays. Synergistic apoptotic effects in human and mouse TMZ-resistant GBM cells were evaluated by viability assays, trypan blue exclusion, DNA fragmentation, flow cytometry, and caspase activity analyses. CDK1 involvement was examined using siRNA knockdown. The roles of intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and caspase-9 activation were investigated using fluorogenic assays and antioxidant pretreatment. Under low and non-toxic concentrations, HNK enhanced CPT-triggered apoptosis of human TMZ-resistant glioblastomas cells. Cotreatment of TMZ-resistant glioblastoma cells with HNK and CPT stimulated production of CDK1 and subsequent G2/M arrest. CDK1 knockdown alleviated these effects. Moreover, HNK sequentially enhanced CPT-triggered production of intracellular ROS, reduced the mitochondrial membrane potential, and activated caspase-9 and cell apoptosis. Suppressing the levels of intracellular ROS attenuated the HNK-induced enhanced effects. The effects of HNK on CPT-induced apoptotic insults were further confirmed in mouse TMZ-resistant glioblastoma cells. HNK synergistically enhances CPT-induced apoptosis in TMZ-resistant glioblastoma cells through CDK1-mediated G2/M arrest and ROS-dependent mitochondrial activation of caspases-9, -3, and -6. Co-administration of HNK may enable effective CPT-based therapy at reduced doses, potentially minimizing CPT-related toxicity and offering a promising strategy for treating drug-resistant GBM.

To evaluate the effect of antioxidant pretreatment on the shear bond strength and failure modes of total-etch and self-etch adhesive systems applied to sodium hypochlorite (NaOCl)-treated dentin. Eighty extracted human premolars were prepared and irrigated with NaOCl. The specimens were allocated into two groups based on the adhesive strategy employed: total-etch and self-etch. Each group was further subdivided according to antioxidant pretreatment: control (no antioxidant), sodium ascorbate, alpha-tocopherol, and nanocurcumin. Composite resin was bonded, and shear bond strength was tested using a universal testing machine. Failure modes were evaluated microscopically. Data were analyzed using one-way ANOVA with post-hoc tests, two-way ANOVA to assess the effects of antioxidant type and adhesive system, and chi-square analysis for failure modes (P < 0.05). NaOCl-treated dentin without antioxidant pretreatment showed the lowest bond strength values in both adhesive systems. Sodium ascorbate and nanocurcumin significantly improved bond strength compared with control and alpha-tocopherol, with no significant difference between them. Self-etch adhesives demonstrated lower baseline bond strength but greater recovery following antioxidant pretreatment. Two-way ANOVA revealed significant effects of antioxidant type, adhesive system, and their interaction. Control groups predominantly exhibited adhesive failures, while antioxidant-treated groups showed increased mixed and cohesive failures. Antioxidant pretreatment effectively restores bonding to NaOCl-treated dentin. Sodium ascorbate and nanocurcumin demonstrated comparable efficacy, with greater benefit observed for self-etch adhesives.

Human exposure to Di(2-ethylhexyl) Phthalate (DEHP) occurs through ingestion of contaminated food. Yet, the effects of DEHP on gastrointestinal toxicity at the cellular level are poorly understood and studies conducted to date have used malignant cell lines, limiting our understanding of molecular signaling in intestinal epithelia of otherwise healthy individuals. The objective of our study was to use a non-transformed, colonic epithelial cell line (Young Adult Mouse Colonocytes; YAMCs) to characterize the in vitro effects of DEHP on non-malignant colonic epithelia. A 72 h DEHP exposure significantly reduced cell number and proliferation while short-term exposure increased: cellular apoptosis, BAX expression, Reactive Oxygen Species (ROS) production, gene expression linked to oxidative stress (NRF2, GCLC, HO-1, CHOP). Antioxidant pretreatment prior to DEHP exposure attenuated the phthalate’s apoptotic effect, suggesting a link between oxidative stress and apoptosis. Using YAMCs with a CRISPR-deleted Aryl Hydrocarbon Receptor (AhR) we further showed that the apoptotic and pro-oxidative effects of the phthalate are partially mediated through AhR. In conclusion, we have demonstrated that DEHP-induced toxicity in non-malignant colonocytes is due to ROS-induced oxidative stress and subsequently, apoptosis. We have further demonstrated that these effects are partly mediated by the AhR, a mechanism that deserves further investigation. Future studies should build on these findings by (a) characterizing the specific mechanisms linking ROS production to apoptosis demonstrated in our model of exposure, (b) measuring the dynamics of the receptor following DEHP exposure and (c) examining these effects over a longer exposure period.

Atrial fibrillation (AF) is a growing cardiovascular epidemic lacking effective treatment. Reactive oxygen species are believed to contribute to AF pathophysiology, yet general antioxidants have limited effectiveness. Since mitochondria are abundant in the heart and a major ROS producer, mitochondrial oxidative stress (MitoOxS) could be a therapeutic target. To determine this, rat inducible immortalized atrial myocytes (iAMs) were tachypaced to mimic AF, followed by assessment of calcium transients, contractility, mitochondrial respiration and morphology, and ROS damage. Cells were pretreated with MitoTEMPO or Sul-238 to assess their protective effects. In Drosophila, heart wall contractions were analyzed to assess arrhythmogenesis after mitochondrial antioxidant pretreatment. Using the GAL4-UAS system, mitochondrial ROS levels and the effect of SOD1 or SOD2 knockdown or overexpression on arrhythmogenesis were evaluated. Tachypacing induced contractile dysfunction and arrhythmogenesis, mitochondrial impairment, and ROS damage in iAMs and increased mitochondrial ROS and arrhythmogenesis in Drosophila. Both MitoTEMPO and Sul-238 treatments prevented mitochondrial dysfunction and arrhythmogenesis in iAMs and rescued arrhythmia in Drosophila. Underscoring the potential to target MitoOxS specifically, SOD2 knockdown promoted arrhythmogenesis in iAMs and Drosophila, whereas SOD2 overexpression rescued tachypacing-induced arrhythmia. MitoOxS is thus a key driver of tachypacing-induced contractile dysfunction and arrhythmia. Mitochondria-targeted antioxidants, such as MitoTEMPO or Sul-238, represent promising therapeutic strategies for AF.

Undergraduate researchis a method to enhance student engagementin science courses as well as expand scientific curiosity. One methodin doing so is performing course undergraduate research experiences.This project started as an undergraduate research project and expandedinto a six-week in-class honor’s research experience. The fieldof traumatic brain injury (TBI) evokes instant name recognition andinterest among undergraduate students based on their previous knowledgeof sports and related concussion consequences in the news and on socialmedia platforms. Currently, there is no clear treatment for traumaticbrain injury. The rise of TBI-related deaths and debilitation hasdriven research efforts. Secondary effects of TBI are a current focusfor research efforts including the regulation of oxidative stresswithin mitochondrial pathways. This work aims to investigate antioxidanttherapies in preventing oxidative stress, a consequence of traumaticbrain injury. Oxidative stress was stimulated by hydrogen peroxide(H2O2) and tert-butyl hydrogenperoxide (t-BHP) in primary cortical rat astrocytes. Astrocytes receivedan antioxidant pretreatment or post-treatment by administering gamma-glutamylcysteineethyl ester (GCEE), a glutathione precursor, in an effort to combatoxidative stress that triggers apoptosis. The results showed thatGCEE had a statistically significant therapeutic effect as both apost-treatment and a pretreatment, but to a lesser extent. “Afterthese positive initial results with GCEE, this project was expandedinto an undergraduate honors course, where students selected additionalantioxidant molecules to test. Although results varied from this studentexperience, it should be noted that this was the first research endeavorfor 100% of the students involved, broadening their participationin research and bridging the gap between basic classroom conceptsand translational research that could potentially add to our knowledgebase of TBI therapeutic strategies.

BackgroundOral squamous cell carcinoma (OSCC) remains a major clinical challenge with limited effective treatment options. In this context, several natural compounds (NC), such as curcumin, have shown promising effects in OSCC. However, there is still limited evidence about curcumin’s effects on cell death in metastatic OSCC cells and its cytotoxicity in preclinical models. To address this gap, this study aimed to evaluate the effects of curcumin on mitochondrial stress–induced apoptotic cell death and its cytotoxicity in preclinical models.MethodsCurcumin’s cytotoxicity was assessed in both 2D (monolayer) and 3D (spheroid model) cell cultures using a luminescent assay. Additionally, morphological parameters (FSC and SSC), apoptosis, and reactive oxygen species (ROS) production were analyzed in 2D cell cultures by flow cytometry, while morphological changes were evaluated in 3D cultures through microscopy. The in vivo assay was performed using a xenograft model in mice (C.B-17 SCID).ResultsCurcumin demonstrated cytotoxicity in 2D cell cultures, induced apoptosis, and increased ROS production, effects that were confirmed with antioxidant pretreatment (N-acetyl-L-cysteine). In the 3D cell culture, curcumin caused loss of spheroid integrity, suppressed tumor growth, and reduced tumor emboli and metastatic nodules in mice.ConclusionOur findings suggest that curcumin induces cell death via apoptosis mediated by oxidative stress and exhibits promising cytotoxic activity in the spheroid model, while also inhibiting OSCC growth in mice.

Oxidative stress mediates cardiac electrophysiological injury in inhalation exposure to flavored vaping products.

Oxidative stress caused by excessive reactive oxygen species (ROS) contributes to numerous chronic diseases. Marine green algae of the Caulerpa genus are rich in bioactive compounds with potential antioxidant activity. Objective: This study aimed to evaluate the intracellular antioxidant effects of caulerpin (CAU) and its derivative caulerpinic acid (CA) using Saccharomyces cerevisiae as a eukaryotic model. Methods: Yeast cells were pretreated with 1 μM of CAU or CA, or with 1 μM of resveratrol (RESV) as a positive control, then exposed to 2 mM of H2O2. Growth, ROS levels, oxidative damage markers, and antioxidant defenses were assessed. Results: Both CAU and CA significantly improved cell survival under oxidative stress, restoring growth rates (CAU: 0.129 h−1, CA: 0.137 h−1) and doubling times (CAU: 5.38 h, CA: 5.07 h) close to control values. Intracellular ROS accumulation, protein carbonylation, and lipid peroxidation were reduced to near-baseline levels. While catalase (Cat) and superoxide dismutase (Sod) activity remained unchanged, CAU and CA elevated intracellular glutathione (GSH) levels (1.6–1.8 fold) and preserved glutathione peroxidase (GPx) activity, compared to stressed cells without antioxidant pretreatment. Conclusions: CAU and CA act as effective intracellular antioxidants, primarily via ROS scavenging and GSH-dependent pathways. These findings support their potential as natural candidates for developing antioxidant-based therapies against ROS-related disorders.

Malania oleifera Chun & S.K. Lee, an endemic monotypic species that belongs to the family Olacaceae, is under continuous pressure of decline owing to several ecological and physiological factors. The present study aimed to establish an efficient in vitro protocol for callus-mediated indirect somatic embryogenesis in M. oleifera by alleviating tissue browning. Internodes and leaves obtained from seedlings were used as explants. Antioxidant pre-treatment (ascorbic acid, AA) followed by different carbon sources (sucrose, maltose, glucose, and fructose) and plant growth regulators in various concentrations and combinations were employed in Woody Plant Medium (WPM) to alleviate explant browning and induce callus formation from the explants. AA pre-treatment and subsequent culture on maltose at a concentration of 116.8 mM were optimal for controlling phenolic exudation on >90% of both explants. The highest responses of 53.77% and 57.43% for embryogenic calli were induced from internode and leaf explants, respectively. The highest responses, 85.22% and 93.80%, were observed for somatic embryos that matured into the globular, heart-shaped and torpedo stages at different percentages on NAA 2.5 mg/L in combination with BA 1.0 mg/L for both explants. The matured somatic embryos were finally germinated at a maximum concentration of GA3, 2.0 mg/L. All plantlets were successfully hardened and acclimatized under culture room conditions and then transferred to the greenhouse. The current study suggests an efficient protocol for indirect somatic embryogenesis by alleviating phenolic exudation from the explants of M. oleifera. This first successful report of in vitro culture establishment in M. oleifera may offer an effective alternative measure to conserve this species and provide a system for analyzing bioactive chemicals and for use in the oil industry.

BackgroundThis study aimed to assess the influence of different pretreatment protocols and antioxidants application on the shear bond strength (SBS) of universal adhesive to sound (SoD) and caries-induced dentin (CID).MethodsOne hundred and twenty posterior teeth had their occlusal enamel removed, then the specimens were divided into two main groups according to dentin substrates; SoD and CID, three subgroups according to pretreatments protocols control (no pretreatment), NaOCl-treated, and Er, Cr:YSGG-treated and two divisions according to antioxidant application (with and without sodium ascorbate (SA) application). All-Bond Universal (ABU) universal adhesives was applied in self-etch (SE) mode then resin composite discs were built. The specimens were stored in distilled water for 24-hr at 37°C before SBS testing. Three-way ANOVA and Tukey HSD tests were used for data analysis (a = 0.05).Results6% NaOCl resulted in a significant reduction in SBS in SoD without antioxidant application. 10% SA application showed significant increase in SBS for 6% NaOCl group only in SoD. Laser application recorded a significantly higher SBS compared to 6% NaOCl group without or with antioxidant application, while 10% SA application revealed a significant increase in SBS for control group only.ConclusionsEr, Cr:YSGG laser irradiation followed by antioxidant application has the potential to enhance the bonding quality of both tested dentin substrates. NaOCl application has significantly compromised the bonding to SoD and CID substrates.

As a result of the increasing use of quantum dots (QDs) and increased exposure of human beings to quantum dots, the study of the toxicity of the particles has become an important issue. In this study, the protective activity of silymarin and mitoquinone (MitoQ), which are known to have antioxidant properties, on the histopathological and biochemical changes observed in the liver of mice treated with CdTe QDs was investigated. 26 male Swiss mice were randomly divided into four groups: Control (G1), CdTe QDs (G2), silymarin + CdTe QDs (G3), mitoquinone + CdTe QDs (G4) application groups. Animals were sacrificed 24 hours (h) after injections and hyperspectral microscopy images were obtained. According to the ICP–MS results, the CdTe QDs injected through the tail vein accumulated in the liver at the end of 24 h and caused tissue damage according to the hematoxylin &amp; eosin examination, and better preservation was observed with the antioxidant pre–treatment. The immunofluorescence results showed increased inflammation and apoptosis in the QDs group. It was observed that silymarin and mitoquinone decreased anti–MMP–9, anti–IL–10, anti–IL–1b, anti–TNF–α, and anti–caspase–9, TUNEL–positive cell ratio, liver MDA levels. There was no significant difference in serum TAS (P=0.509), TOS (P=0.588) levels, but antioxidants also increased tissue SOD and CAT levels. Antioxidants had no significant effect on anti–MT–MMP2 and anti–caspase–8 levels (P&lt;0.001). In conclusion, it was shown that pretreatment of CdTe QD–administered mice with silymarin and mitoquinone can reduce oxidative stress in liver tissue and may have a protective effect through reduction of apoptosis and inflammation.

Protective effects of olive oil antioxidant phenols on mercury-induced phosphatidylserine externalization in erythrocyte membrane: Insights into scramblase and flippase activity

This systematic review aims to evaluate whether the application of antioxidant solutions can enhance the bond strength of resin-based materials to sodium hypochlorite (NaOCl)-treated dentin. This study follows the PICOT strategy: population (sodium hypochlorite-treated dentin), intervention (application of antioxidants), control (distilled water), outcome (bond strength), and type of studies (in vitro studies). The systematic review and meta-analysis were conducted following PRISMA guidelines. Electronic databases were searched for in vitro studies evaluating the effects of antioxidants on bond strength to sodium hypochlorite-treated dentin. Two independent reviewers screened articles, extracted data, and assessed risk of bias. Meta-analyses were performed using a random-effects model to compare standardized mean differences in bond strength between antioxidant pretreatment and control groups. Inclusion criteria consisted of in vitro studies that examined the bond strength of resin-based materials to NaOCl-treated dentin with antioxidant application, while exclusion criteria included studies with incomplete data, those not using a control group, or those that did not directly measure bond strength. From 3041 initial records, 29 studies were included in the qualitative analysis and 25 in the meta-analysis. Ascorbic acid, sodium ascorbate, grape seed extract, green tea, and rosmarinic acid significantly improved bond strength to sodium hypochlorite-treated dentin (p < 0.05). The effectiveness of grape seed extract varied with adhesive system type. Hesperidin, p-toluene sulfonic acid, and sodium thiosulfate did not significantly improve bond strength. Most studies had a high risk of bias. This suggests that the conclusions drawn from these studies should be interpreted with caution, and further research with more robust methodologies may be needed to confirm the findings. In conclusion, this systematic review implies that certain antioxidants can improve bond strength to sodium hypochlorite-treated dentin, with efficacy depending on the specific agent and adhesive system used. Further standardized studies are needed to optimize protocols and confirm these findings.

Secondary lymphedema is caused by damage to the lymphatic system from surgery, cancer treatment, infection, trauma, or obesity. This damage induces stresses such as oxidative stress and hypoxia in lymphatic tissue, impairing the lymphatic system. In response to damage, vascular endothelial growth factor C (VEGF-C) levels increase to induce lymphangiogenesis. Unfortunately, VEGF-C often fails to repair the lymphatic damage in lymphedema. The underlying mechanism contributing to lymphedema is not well understood. In this study, we found that surgery-induced tail lymphedema in a mouse model increased oxidative damage and cell death over 16 days. This corresponded with increased VEGF-C levels in mouse tail lymphedema tissue associated with macrophage infiltration. Similarly, in the plasma of patients with secondary lymphedema, we found a positive correlation between VEGF-C levels and redox imbalance. To determine the effect of oxidative stress in the presence or absence of VEGF-C, we found that hydrogen peroxide (H2O2) induced cell death in human dermal lymphatic endothelial cells (HDLECs), which was potentiated by VEGF-C. The cell death induced by VEGF-C and H2O2 in HDLECs was accompanied by increased reactive oxygen species (ROS) levels and a loss of mitochondrial membrane potential. Antioxidant pre-treatment rescued HDLECs from VEGF-C-induced cell death and decreased ROS under oxidative stress. As expected, VEGF-C increased the number of viable and proliferating HDLECs. However, upon H2O2 treatment, VEGF-C failed to increase either viable or proliferating cells. Since oxidative stress leads to DNA damage, we also determined whether VEGF-C treatment induces DNA damage in HDLECs undergoing oxidative stress. Indeed, DNA damage, detected in the form of gamma H2AX (γH2AX), was increased by VEGF-C under oxidative stress. The potentiation of oxidative stress damage induced by VEFG-C in HDLECs was associated with p53 activation. Finally, the inhibition of vascular endothelial growth factor receptor-3 (VEGFR-3) activation blocked VEGF-C-induced cell death following H2O2 treatment. These results indicate that VEGF-C further sensitizes lymphatic endothelial cells to oxidative stress by increasing ROS and DNA damage, potentially compromising lymphangiogenesis.

This study aimed to evaluate the effect of antioxidant solutions on fracture strength and bonding performance in non-vital and bleached (38% hydrogen peroxide) teeth. One hundred and eighty dentin specimens were obtained, 60 for each test: fracture strength, hybrid layer thickness, and bond strength. The groups (n=10) were randomly composed according to post-bleaching protocol: REST - restoration, without bleaching; BL - bleaching + restoration; SA - bleaching, 10% sodium ascorbate solution, and restoration; AT - bleaching, 10% α-tocopherol solution, and restoration; CRAN - bleaching, 5% cranberry solution, and restoration; CAP - bleaching, 0.0025% capsaicin solution, and restoration. Data were analyzed with ANOVA, Kruskal-Wallis, Dunn, and Qui-Square tests (α=0.05). The highest fracture strength values were observed in REST (1508.96 ±148.15 N), without significant difference for the bleached groups (p>0.05), regardless of the antioxidant use. The hybrid layer thickness in the group that was not subjected to bleaching (REST) was significantly higher than in any other group. The bond strength in the bleached and antioxidants-treated groups (SA, AT, CRAN, CAP) has no differences with the bleached group without antioxidants (BL). Adhesive failures were predominant in the groups that did not receive the antioxidant application. In conclusion, the evaluated antioxidants did not show an effect on the fracture strength, hybrid layer thickness, or bond strength of dentin bleached after endodontic treatment. The application of 10% sodium ascorbate, 10% alpha-tocopherol, 5% cranberry, or 0.0025% capsaicin solutions is not an effective step and should not be considered for the restorative protocols after non-vital bleaching.

BS-454195-4 MITOCHONDRIAL REMODELING MEDIATES CARDIAC ELECTROPHYSIOLOGICAL INJURY IN INHALATION EXPOSURE TO FLAVORED ELECTRONIC NICOTINE DELIVERY SYSTEMS.