Oxidative Cell Damage Research Articles

The role of nitric oxide in the development of diseases of the male reproductive system and its potential applications in clinical practice

Nitric oxide (NO), a reactive nitrogen species, is a molecule of high physiological and pathological importance. Physiological mechanisms mediated by NO mainly include angiogenesis, growth, puberty, and senescence. NO has vital roles in normal reproduction, including steroidogenesis, gametogenesis, and the regulation of germ-cell apoptosis. In males, NO is a key player in steroidogenesis, erectile functions, sperm capacitation, and acrosome reaction. Moreover, NO is also a regulator of Sertoli cell-germ cell interaction and maintenance of the blood-testis barrier. In pathological conditions such as infections, increased nitric oxide synthase activities stimulate the excessive synthesis of NO which acts as a proinflammatory mediator inducing oxidative stress, detrimental to reproductive functions in males. Excessive NO synthesis disrupts gonadal functions and induces germ cell apoptosis and oxidative damage to the germ cells. This review elucidates how the differences in NO expression levels account for its beneficial and adverse impacts on male fertility.

Starving cancer cells to enhances DNA damage and immunotherapy response.

Prostate cancer (PCa) poses significant challenges in treatment, particularly when it progresses to a metastatic, castrate-resistant state. Conventional therapies, including chemotherapy, radiotherapy, and hormonal treatments, often fail due to toxicities, off-target effects, and acquired resistance. This research perspective defines an alternative therapeutic strategy focusing on the metabolic vulnerabilities of PCa cells, specifically their reliance on non-essential amino acids such as cysteine. Using an engineered enzyme cyst(e)inase to deplete the cysteine/cystine can induce oxidative stress and DNA damage in cancer cells. This depletion elevates reactive oxygen species (ROS) levels, disrupts glutathione synthesis, and enhances DNA damage, leading to cancer cell death. The combinatorial use of cyst(e)inase with agents targeting antioxidant defenses, such as thioredoxins, further amplifies ROS accumulation and cytotoxicity in PCa cells. Overall, in this perspective provides a compressive overview of the previous work on manipulating amino acid metabolism and redox balance modulate the efficacy of DNA repair-targeted and immune checkpoint blockade therapies in prostate cancer.

Fumaria vaillantii extract protects PC12 cells against neurotoxicity induced by 6-OHDA.

Parkinson's disease is a neurological disorder caused by the loss of dopaminergic neurons in the midbrain. Various mechanisms are involved in the incidence of the disease including oxidative stress. Several herbs and natural products may interfere with the oxidative-stress pathway due to their antioxidant effects. Herein, we aimed to investigate the neuroprotective role of F. vaillantii extract on Parkinson's in vitro and in vivo model owing to the presence of the bioactive agents with antioxidant properties. In vitro experments showed that 6-hydroxydopamine could induce toxicity in PC12 cells. The impact of F. vaillantii extract on cell viability was measured by using MTT assay. Nuclear morphological changes were qualitatively evaluated employing Hoechst staining. The antioxidant activity of the extract was determined by ROS and lipid peroxidation assays. Tyrosine hydroxylase protein expression was measured by western blotting in PC12 cells. For in vivo study, movement parameters were evaluated. The results indicated that 75 µΜ of 6-OHDA induced 50% toxicity in PC12 cells for 24h. Following post-treatment with F. vaillantii extract (0.1mg/ml) for 72h, we observed that the extract effectively prevented cell toxicity induced by 6-OHDA and reduced the apoptotic cell population. Furthermore, the extract attenuated the ROS level, lipid peroxidation and increased protein expression of TH after 72h of treatment. In addition, oral administration of 300mg/kg of F. vaillantii extract for 14 days improved locomotor activity, catalepsy, bradykinesia, motor coordination and reduced the apomorphine-caused rotation in 6-OHDA- induced Parkinson's disease-like symptoms in male rats. The present study suggests a protective role for the extract of F. vaillantii against oxidative stress-induced cell damage in the PC12 cells exposed to neurotoxin 6-OHDA which was verified in in vivo model by reducing the motor defects induced by 6-OHDA. This extract could be a promising therapeutic agent for the prevention of PD progression.

Baicalein attenuates oxidative damage in mice haematopoietic cells through regulation of PDGFRβ

Platelet-derived growth factor receptor β (PDGFRβ) plays a crucial role in murine haematopoiesis. Baicalein (BAI), a naturally occurring flavonoid, can alleviate disease damage through anti-oxidative, anti-apoptotic, and anti-inflammatory mechanisms. However, whether BAI attenuates oxidative damage in murine haematopoietic cells by PDGFRβ remains unexplored. In this study, we utilized a tert-butyl hydroperoxide (TBHP)-induced BaF3 cell injury model and an ionising radiation (IR)-induced mice injury model to investigate the impact of the presence or absence of PDGFRβ on the pharmacological effects of BAI. In addition, the BAI-PDGFRβ interaction was characterized by molecular docking and dynamics simulations. The results show that a specific concentration of BAI led to increased cell viability, reduced reactive oxygen species (ROS) content, upregulated nuclear factor erythroid 2-related factor 2 (NRF2) expression, and its downstream target genes heme oxygenase 1 (HO-1) and NAD(P)H Quinone Dehydrogenase 1 (NQO1), and activated protein kinase B (AKT) pathway in cells expressing PDGFRβ plasmid and experiencing damage. Similarly, BAI elevated lineage−Sca1+cKIT+ (LSK) cell proportion, promoted haematopoietic restoration, enhanced NRF2-mediated antioxidant response in PDGFRβ+/+ mice. However, despite BAI usage, PDGFRβ knockout mice (PDGFRβ−/−) showed lower LSK proportion and less antioxidant capacity than the total body irradiation (TBI) group. Furthermore, we demonstrated an interaction between BAI and PDGFRβ at the molecular level. Collectively, our results indicate that BAI attenuates oxidative stress injury and helps promote haematopoietic cell recovery through regulation of PDGFRβ.

Notoginsenoside R1 (NGR1) regulates the AGE-RAGE signaling pathway by inhibiting RUNX2 expression to accelerate ferroptosis in breast cancer cells.

Ferroptosis is a new way of cell death, and stimulating the process of cell ferroptosis is a new strategy to treat breast cancer. NGR1 has good anti-cancer activity and is able to slow the progression of breast cancer. However, NGR1 has not been reported in the field related to ferroptosis. By searching the online database for potential targets of NGR1 and the breast cancer disease database, among 11 intersecting genes we focused on Runt-related transcription factor 2 (RUNX2), which is highly expressed in breast cancer, and KEGG pathway enrichment showed that the intersecting genes were mainly enriched in the AGE (advanced glycosylation end products)-RAGE (receptor of AGEs) signaling pathway. After that, we constructed overexpression and down-regulation breast cancer cell lines of RUNX2 in vitro, and tested whether NGR1 treatment induced ferroptosis in breast cancer cells by regulating RUNX2 to inhibit the AGE-RAGE signaling pathway through phenotyping experiments of ferroptosis, Western blot experiments, QPCR experiments, and electron microscopy observation. The results showed that NGR1 was able to inhibit the expression level of RUNX2 and suppress the AGE/PAGE signaling pathway in breast cancer cells. NGR1 was also able to promote the accumulation of Fe2+ and oxidative damage in breast cancer cells by regulating RUNX2 and then down-regulating the expression level of GPX4, FIH1 and up-regulating the expression level of ferroptosis-related proteins such as COX2, ACSL4, PTGS2 and NOX1, which eventually led to the ferroptosis of breast cancer cells.

Circ_002033 Regulates Proliferation, Apoptosis, and Oxidative Damage of Bovine Mammary Epithelial Cells via the miR-199a-5p-MAP3K11 Axis in Heat Stress.

Heat stress is becoming the major factor regarding dairy cow health and milk quality because of global warming. Circular RNAs (circRNAs) represent a special type of noncoding RNAs, which are related to regulating many biological processes. Nonetheless, little is known concerning their effects on heat-stressed bovine mammary epithelial cells (BMECs). Here, this study found a novel circRNA, circ_002033, using RNA sequencing (RNA-seq) and explored the role and underlying regulatory mechanism in proliferation, apoptosis, and oxidative damage in a heat-stressed bovine mammary epithelial cell line (MAC-T). According to the previous RNA-seq analysis, the abundance of circ_002033 in mammary gland tissue of heat-stressed cows increased relative to nonheat-stressed counterparts. This study found that the knockdown of circ_002033 promoted proliferation and alleviated apoptosis and oxidative damage in heat-stressed MAC-T. Mechanistically, circ_002033 localizes to miR-199a-5p in the cytoplasm of MAC-T to regulate mitogen-activated protein kinase kinase 11 (MAP3K11) expression. Meanwhile, miR-199a-5p and MAP3K11 are also involved in regulating the proliferation and apoptosis of heat-stressed MAC-T. Importantly, circ_002033 knockdown promoted the expression of miR-199a-5p while decreasing that of MAP3K11, thereby enhancing proliferation while alleviating apoptosis and oxidative damage in heat-stressed MAC-T. In summary, we found that circ_002033 regulates the proliferation, apoptosis, and oxidative damage of heat-stressed BMECs through the miR-199a-5p/MAP3K11 axis, providing the theoretical molecular foundation for mitigating heat stress of dairy cows.

Delivery of neurotrophin-3 by RVG-Lamp2b-modified mesenchymal stem cell-derived exosomes alleviates facial nerve injury.

We aim to investigate the effect of RVG-Lamp2b-modified exosomes (exos) loaded with neurotrophin-3 (NT-3) on facial nerve injury. Exos were collected from control cells (Ctrl Exo) or bone marrow mesenchymal stem cells co-transfected with RVG-Lamp2b and NT-3 plasmids (RVG-NT-3 Exo) by gradient centrifugation and identified by western blotting, transmission electron microscopy, and nanoparticle tracking analysis. Effect of RVG-NT-3 Exo on oxidative stress damage was determined by analysis of the morphology, viability, and ROS production of neurons. Effect of RVG-NT-3 Exo on facial nerve axotomy (FNA) was determined by detecting ROS production, neuroinflammatory reaction, microglia activation, facial motor neuron (FMN) death, and myelin sheath repair. Loading NT-3 and modifying with RVG-Lamp2b did not alter the properties of the exos. Moreover, RVG-NT-3 Exo could effectively target neurons to deliver NT-3. Treatment with RVG-NT-3 Exo lowered H2O2-induced oxidative stress damage in primary neurons and Nsc-34 cells. RVG-NT-3 Exo treatment significantly decreased ROS production, neuroinflammatory response, FMN death, and elevated microglia activation and myelin sheath repair in FNA rat models. Our findings suggested that RVG-NT-3 Exo-mediated delivery of NT-3 is effective for the treatment of facial nerve injury.

Protective effect of the total alkaloid extract from Bulbus Fritillariae Pallidiflorae on cigarette smoke-induced Beas-2B cell injury model and transcriptomic analysis.

Bulbus Fritillariae Pallidiflorae (BFP) is a traditional Chinese medicine that has long been used to treat lung diseases, but the active components and mechanism are still unclear. This study aimed to investigate the effect and mechanism of the total alkaloid extract from BFP (BFP-TA) on cigarette smoke extract (CSE)-induced Beas-2B cells injury. The Beas-2B cells injury model was induced by 2% CSE, then the effect of BFP-TA on the levels of total antioxidant capacity (T-AOC), superoxide dismutase (SOD) and malondialdehyde (MDA) was detected according to the instructions of the T-AOC assay kit, the SOD detection kit and the MDA detection kit, and the production of ROS was detected by fluorescence microscopy. The effect of BFP-TA on Beas-2B cells apoptosis was detected by flow cytometry, and the effect of BFP-TA on related protein expression was detected by western blot. Subsequently, the effect of BFP-TA on differentially expressed genes (DEGs) in CSE-induced Beas-2B cells was studied by transcriptomic sequencing, and the expression of DEGs was verified by quantitative real-time polymerase chain reaction (qPCR). The results showed that BFP-TA could attenuate CSE-induced oxidative damage in Beas-2B cells by elevating T-AOC and SOD levels while inhibiting ROS and MDA levels, and the mechanism was potentially related to the SIRT1/Nrf2/Keap1 signaling pathway. Furthermore, BFP-TA could inhibit CSE-induced apoptosis by inhibiting the protein expression of Bax, MST1 and FOXO3a, and exert anti-inflammatory effect by inhibiting the activation of MAPK signaling pathway. Subsequently, transcriptome analysis and qPCR validation showed that BFP-TA could alleviate inflammation, oxidative stress, apoptosis and lipid metabolism disorders by regulating the expression of DEGs in PPAR and PI3K-Akt signaling pathways, thereby exerting a protective effect against CSE-induced Beas-2B cell injury. This study is the first to demonstrate that BFP-TA could exert a protective effect on CSE-induced Beas-2B cell injury by exerting anti-inflammatory, antioxidant, anti-apoptotic and regulate lipid metabolism disorders.

Zinc Doping Engineering in ZnxFe3-xO4 Heterostructures for Enhancing Photodynamic Therapy in the Near-Infrared-II Region.

Currently, photodynamic therapy (PDT) is restricted by the laser penetration depth. Except for PDT at 1064 nm wavelength excitation, the development of other NIR-II-activated nanomaterials with a higher response depth is still hindered and rarely reported in the literature. To overcome these problems, we fabricated a nanoplatform with heterostructures that generate reactive oxygen species (ROS) and ferrite nanoparticles under a high concentration of zinc doping (ZnxFe3-xO4 NPs), which can achieve oxidative damage of tumor cells under near-infrared (NIR) illumination. The recombination of photoelectrons and holes has been markedly inhibited due to the formation of heterostructures in the interfaces, thus greatly enhancing the capability for ROS and oxygen production by modulating the single-component doping content. The efficiency of PDT was verified by in vivo and in vitro assays under NIR light. Our results revealed that NIR-II (1208 nm) light irradiation of ZnxFe3-xO4 NPs exerted a remarkable antitumor activity, superior to NIR-I light (808 nm). More importantly, the reported ZnxFe3-xO4 NPs strategy provides an opportunity for the success of comparison with light in the first and second near-infrared regions.

Relationship between jejunum ATPase activity and antioxidant function on the growth performance, feed conversion efficiency, and jejunum microbiota in Hu sheep (Ovis aries)

BackgroundATPase activity and the antioxidant function of intestinal tissue can reflect intestinal cell metabolic activity and oxidative damage, which might be related to intestinal function. However, the specific influence of intestinal ATPase activity and antioxidant function on growth performance, feed conversion efficiency, and the intestinal microbiota in sheep remains unclear.ResultsThis study analyzed the correlation between ATPase activity and antioxidant function in the jejunum of 92 Hu sheep and their growth performance and feed conversion efficiency. Additionally, individuals with the highest (H group) and lowest (L group) jejunum MDA content and Na+ K+-ATPase activity were further screened, and the effects of jejunum ATPase activity and MDA content on the morphology and microbial community of sheep intestines were analyzed. There was a significant correlation between jejunum ATPase and SOD activity and the initial weight of Hu sheep (P < 0.01). The H-MDA group exhibited significantly higher average daily gain (ADG) from 0 to 80 days old and higher body weight (BW) after 80 days. ATPase and SOD activities, and MDA levels correlated significantly and positively with heart weight. The jejunum crypt depth and circular muscle thickness in the H-ATP group were significantly higher than in the L-ATP group, and the villus length, crypt depth, and longitudinal muscle thickness in the H-MDA group were significantly higher than in the L-MDA group (P < 0.01). High ATPase activity and MDA content significantly reduced the jejunum microbial diversity, as indicated by the Chao1 index and observed species, and affected the relative abundance of specific taxa. Among species, the relative abundance of Olsenella umbonata was significantly higher in the H-MDA group than in the L-MDA group (P < 0.05), while Methanobrevibacter ruminantium abundance was significantly lower than in the L-MDA group (P < 0.05). In vitro culture experiments confirmed that MDA promoted the proliferation of Olsenella umbonata. Thus, ATPase and SOD activities in the jejunum tissues of Hu sheep are predominantly influenced by congenital factors, and lambs with higher birth weights exhibit lower Na+ K+-ATPase, Ca2+ Mg2+-ATPase, and SOD activities.ConclusionsThe ATPase activity and antioxidant performance of intestinal tissue are closely related to growth performance, heart development, and intestinal tissue morphology. High ATPase activity and MDA content reduced the microbial diversity of intestinal tissue and affect the relative abundance of specific taxa, representing a potential interaction between the host and its intestinal microbiota.

The Mechanism of Catalpol to Improve Oxidative Damage of Dermal Fibroblasts Based on Nrf2/HO-1 Signaling Pathway.

Catalpol, as a natural medicine small-molecule drug, has been proven to have anti-inflammatory and antioxidant pharmacological effects. The effect of catalpol on oxidative damage of mouse epidermal fibroblast L929 model and its mechanism were investigated by using hydrogen peroxide model, CCK8 method, flow cytometry, and Western blot. The effect of catalpol on Nrf2/HO-1 signaling pathway was further studied to improve oxidative stress in cell models. The results showed that catalpol had no cytotoxicity to L929 cells, and inhibited the apoptosis of L929 cells after oxidative damage in a concentration-dependent manner, thus playing a role in cell protection. The oxidative damage of cells was inhibited by up-regulating the expression of the signature protein of Nrf2/HO-1 signaling pathway and inhibiting the interstitial formation of cells. This study is a preliminary study on the protective function of catalpol against oxidation and apoptosis in dermal fibroblasts, which can provide a theoretical basis and drug guidance for promoting skin wound healing in the later stage.

Antioxidant and Anti-Inflammatory Activities of the Extract and Bioaccessible Fraction of Mango Peel in Muffins.

Mango peel is a production waste and can cause environmental problems, but its nutritional value consists of bioactive compounds that could be beneficial for human health. The aim of this study is to determine the bioactive compounds, antioxidant and anti-inflammatory activities of mango peels and their use in muffins. The content of polyphenols, carotenoids and total phenols as well as the antioxidant activity of mango peel extract were evaluated. The anti-inflammatory activity of the extract was investigated using Caco-2 cell assay. The mango peel powder was then incorporated into muffin formulations. The sensory properties of these fortified muffins were evaluated. The total phenolic content, antioxidant activity and anti-inflammatory properties of the muffin extracts and their bioaccessible fractions were also analysed. The mango peel contained quercetin, phenolic compounds, α-carotene, β-carotene and lutein, which have antioxidant potential. In Caco-2 cells exposed to induced inflammation, the mango peel powder extract (γ=10, 50 and 100 µg/mL) attenuated the production of reactive oxygen species (ROS), tumour necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8), while maintaining cell viability. Muffins supplemented with 5 % mango peel powder showed good sensory properties, but not as good as those of plain muffins without mango peel powder. The total phenolic content and antioxidant activities in both the extract and the bioaccessible fraction of the supplemented muffins were higher than those observed in the standard muffins. Moreover, the extract and bioaccessible fraction of the supplemented muffins resulted in a higher reduction of ROS, IL-8 and TNF-α production in Caco-2 cells than those obtained from the standard muffins. This study is the first to investigate the protective effects of mango peel and muffins supplemented with mango peel powder against IL-1β-induced oxidative damage in Caco-2 cells. The results confirm that both mango peel and the supplemented muffins inhibited the production of inflammatory markers, including ROS and cytokines. These findings suggest that mango peel could be a valuable component of functional food formulations including dietary supplements.

Investigating the Hepatoprotective Properties of Mulberry Leaf Flavonoids against Oxidative Stress in HepG2 Cells.

Oxidative stress significantly contributes to ageing and disease, with antioxidants holding promise in mitigating its effects. Functional foods rich in flavonoids offer a potential strategy to mitigate oxidative damage by free radicals. We investigated the protective effects of mulberry leaf flavonoids (MLF) against H2O2-induced oxidative damage in HepG2 cells. It assessed the inhibitory effect of MLF (62.5-500 μg/mL) on H2O2-induced oxidative damage by analyzing cellular morphology and oxidative stress markers, including ROS production, mitochondrial membrane potential, antioxidant enzyme levels, MDA, and apoptosis-related proteins. The results demonstrated that MLF prevented spiny cell formation triggered by 750 μM H2O2 and significantly reduced ROS levels, restored mitochondrial membrane potential, decreased lactate dehydrogenase and alanine transaminase leakage, and reduced MDA content induced by H2O2. MLF also modulated antioxidant enzymes and attenuated oxidative damage to HepG2 cell DNA, as confirmed by staining techniques. These findings indicate the potential of MLF as a hepatoprotective agent against oxidative damage in HepG2 cells.

Ginseng total saponin improves red blood cell oxidative stress injury by regulating tyrosine phosphorylation and glycolysis in red blood cells

BackgroundOxidative stress is the main cause of many diseases, but because of its complex pathogenic factors, there is no clear method for treating it. Ginseng total saponin (GTS) an important active ingredients in Panax ginseng C.A. Mey (PG) and has potential therapeutic ability for oxidative stress due to various causes. However, the molecular mechanism of GTS in the treating oxidative stress damage in red blood cells (RBCs) is still unclear. PurposeThis study aimed to examine the protective effect of GTS on RBCs under oxidative stress damage and to determine its potential mechanism. MethodsThe oxidative stress models of rat RBCs induced by hydrogen peroxide (H2O2) and exhaustive swimming in vivo and in vitro was used. We determined the cell morphology, oxygen carrying capacity, apoptosis, antioxidant capacity, and energy metabolism of RBCs. The effect of tyrosine phosphorylation (pTyr) of Band 3 protein on RBCs glycolysis was also examined. ResultsGTS reduced the hemolysis of RBCs induced by H2O2 at the lowest concentration. Moreover, GTS effectively improved the morphology, enhanced the oxygen carrying capacity, and increased antioxidant enzyme activity, adenosine triphosphate (ATP) levels, and adenosine triphosphatase (ATPase) activity in RBCs. GTS also promoted the expression of membrane proteins in RBCs, inhibited pTyr of Band 3 protein, and further improved glycolysis, restoring the morphological structure and physiological function of RBCs. ConclusionsThis study shows, that GTS can protect RBCs from oxidative stress damage by improving RBCs morphology and physiological function. Changes in pTyr expression and its related pTyr regulatory enzymes before and after GTS treatment suggest that Band 3 protein is the main target of GTS in the treating endogenous and exogenous oxidative stress. Moreover, GTS can enhance the glycolytic ability of RBCs by inhibiting pTyr of Band 3 protein, thereby restoring the function of RBCs.

Oligomeric Tau-induced oxidative damage and functional alterations in cerebral endothelial cells: Role of RhoA/ROCK signaling pathway

Despite of yet unknown mechanism, microvascular deposition of oligomeric Tau (oTau) has been implicated in alteration of the Blood-Brain Barrier (BBB) function in Alzheimer's disease (AD) brains. In this study, we employed an in vitro BBB model using primary mouse cerebral endothelial cells (CECs) to investigate the mechanism underlying the effects of oTau on BBB function. We found that exposing CECs to oTau induced oxidative stress through NADPH oxidase, increased oxidative damage to proteins, decreased proteasome activity, and expressions of tight junction (TJ) proteins including occludin, zonula occludens-1 (ZO-1) and claudin-5. These effects were suppressed by the pretreatment with Fasudil, a RhoA/ROCK signaling inhibitor. Consistent with the biochemical alterations, we found that exposing the basolateral side of CECs to oTau in the BBB model disrupted the integrity of the BBB, as indicated by an increase in FITC-dextran transport across the model, and a decrease in trans endothelial electrical resistance (TEER). oTau also increased the transmigration of peripheral blood mononuclear cells (PBMCs) in the BBB model. These functional alterations in the BBB induced by oTau were also suppressed by Fasudil. Taken together, our findings suggest that targeting the RhoA/ROCK pathway can be a potential therapeutic strategy to maintain BBB function in AD.

Protective Effects of the Postbiotic Levilactobacillus brevis BK3 against H2O2-Induced Oxidative Damage in Skin Cells.

Postbiotics have various functional effects, such as antioxidant, anti-inflammatory, and anti-obesity. Levilactobacillus brevis BK3, the subject of this study, was derived from lactic acid bacteria isolated from Kimchi, a traditional Korean fermented food. The antioxidant activity of BK3 was confirmed through the measurements of 2,2-diphenyl-1-picryl-hydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and total antioxidant capacity (TAC). The wrinkle improvement effect was validated by assessing elastase inhibitory activity and collagenase inhibitory activity. The intracellular activity was confirmed using human keratinocytes (HaCaT) and human fibroblasts (HFF-1). BK3 protects skin cells from oxidative stress induced by H2O2 and reduces intracellular reactive oxygen species (ROS) production. In addition, the expressions of the antioxidant genes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were upregulated. Meanwhile, matrix metalloproteinase-1 (MMP-1) and collagen type I alpha 1 (COL1A1), involved in collagen degradation and synthesis, were significantly regulated. These results suggest the possibility of utilizing BK3 as a functional ingredient with antioxidant and wrinkle-improving effects.

Quantifying the Level of 8-oxo-dG Using ELISA Assay to Evaluate Oxidative DNA Damage in MCF-7 Cells

Quantifying the Level of 8-oxo-dG Using ELISA Assay to Evaluate Oxidative DNA Damage in MCF-7 Cells

Comparison of Protective Effects of Antidepressants Mediated by Serotonin Receptor in Aβ-Oligomer-Induced Neurotoxicity.

Amyloid β-peptide (Aβ) synthesis and deposition are the primary factors underlying the pathophysiology of Alzheimer's disease (AD). Aβ oligomer (Aβo) exerts its neurotoxic effects by inducing oxidative stress and lesions by adhering to cellular membranes. Though several antidepressants have been investigated as neuroprotective agents in AD, a detailed comparison of their neuroprotection against Aβo-induced neurotoxicity is lacking. Here, we aimed to elucidate the neuroprotective effects of clinically prescribed selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, and noradrenergic and specific serotonergic antidepressants at the cellular level and establish the underlying mechanisms for their potential clinical applications. Therefore, we compared the neuroprotective effects of three antidepressants, fluoxetine (Flx), duloxetine (Dlx), and mirtazapine (Mir), by their ability to prevent oxidative stress-induced cell damage, using SH-SY5Y cells, by evaluating cell viability, generation of reactive oxygen species (ROS) and mitochondrial ROS, and peroxidation of cell membrane phospholipids. These antidepressants exhibited potent antioxidant activity (Dlx > Mir > Flx) and improved cell viability. Furthermore, pretreatment with a 5-hydroxytryptamine 1A (5-HT1A) antagonist suppressed their effects, suggesting that the 5-HT1A receptor is involved in the antioxidant mechanism of the antidepressants' neuroprotection. These findings suggest the beneficial effects of antidepressant treatment in AD through the prevention of Aβ-induced oxidative stress.

Sanshentongmai Mixture Improves Oxidative Damage in Rat Cardiomyocytes H9C2 via Upregulation of microRNA-146a

To investigate the effect of Sanshentongmai (SSTM) mixture on the regulation of oxidative damage to rat cardiomyocytes (H9C2) through microRNA-146a and its mechanism. H9C2 were cultured in vitro, H2O2 was used as an oxidant to create an oxidative damage model in H9C2 cells. SSTM intervention was administered to the H9C2 cells. Then, the changes in H2O2-induced oxidative damage in H9C2 cells and the expression of microRNA-146a were observed to explore the protective effect of SSTM on H9C2 and its mechanism. H9C2 cells cultured i n vitro were divided into 3 groups, including a control group, a model group of H2O2-induced oxidative damage (referred to hereafter as the model group), and a group given H2O2 modeling plus SSTM intervention at 500 μg/L for 72 h (referred to hereafter as the treatment group). The cell viability was measured by CCK8 assay. In addition, the levels of N-terminal pro-brain natriuretic peptide (Nt-proBNP), nitric oxide (NO), high-sensitivity C-reactive protein (Hs-CRP), and angiotensin were determined by enzyme-linked immunosorbent assay (ELISA). The expression level of microRNA-146a was determined by real-time PCR (RT-PCR). H9C2 cells were pretreated with SSTM at mass concentrations ranging from 200 to 1500 μg/L. Then, CCK8 assay was performed to measure cell viability and the findings showed that the improvement in cell proliferation reached its peak when the mass concentration of SSTM was 500 μg/L, which was subsequently used as the intervention concentration. ELISA was performed to measure the indicators related to heart failure, including Nt-proBNP, NO, Hs-CRP, and angiotensin Ⅱ. Compared with those of the control group, the expressions of Nt-proBNP and angiotensin Ⅱ in the treatment group were up-regulated (P<0.05), while the expression of NO was down-regulated (P<0.05). There was no significant difference in the expression of Hs-CRP between the treatment group and the control group. These findings indicate that SSTM could effectively ameliorate oxidative damage in H9C2 rat cardiomyocytes. Finally, according to the RT-PCR findings for the expression of microRNA-146a in each group, H2O2 treatment at 15 μmol/L could significantly reduce the expression of microRNA-146a, and the expression of microRNA-146a in the treatment group was nearly doubled compared with that in the model group. There was no significant difference between the treatment group and the control group. SSTM can significantly resist the H2O2-induced oxidative damage of H9C2 cells and may play a myocardial protective role by upregulating microRNA-146a.

The Mitochondrial-Derived Peptide MOTS-c Alleviates Radiation Pneumonitis via an Nrf2-Dependent Mechanism.

Radiation pneumonitis (RP) is a prevalent and fatal complication of thoracic radiotherapy due to the lack of effective treatment options. RP primarily arises from mitochondrial injury in lung epithelial cells. The mitochondrial-derived peptide MOTS-c has demonstrated protective effects against various diseases by mitigating mitochondrial injury. C57BL/6 mice were exposed to 20 Gy of lung irradiation (IR) and received daily intraperitoneal injections of MOTS-c for 2 weeks. MOTS-c significantly ameliorated lung tissue damage, inflammation, and oxidative stress caused by radiation. Meanwhile, MOTS-c reversed the apoptosis and mitochondrial damage of alveolar epithelial cells in RP mice. Furthermore, MOTS-c significantly inhibited oxidative stress and mitochondrial damage in MLE-12 cells and primary mouse lung epithelial cells. Mechanistically, MOTS-c increased the nuclear factor erythroid 2-related factor (Nrf2) level and promoted its nuclear translocation. Notably, Nrf2 deficiency abolished the protective function of MOTS-c in mice with RP. In conclusion, MOTS-c alleviates RP by protecting mitochondrial function through an Nrf2-dependent mechanism, indicating that MOTS-c may be a novel potential protective agent against RP.