Oxidative Cell Damage Research Articles

Zinc Oxide Nanoparticle Loaded L-Carnosine Biofunctionalized Polyacrylonitrile Nanofibrous Wound Dressing for Post-Surgical Treatment of Melanoma

Nanofibrous dressing materials with an antitumor function can potentially inhibit recurrence of melanoma following the surgical excision of skin tumors. In this study, hydrolyzed polyacrylonitrile (hPAN) nanofibers biofunctionalized with L-carnosine (CAR) and loaded with bio (CAR)-synthesized zinc oxide (ZnO) nanoparticles, ZnO/CAR-hPAN (hereafter called ZCPAN), were employed to develop an antimelanoma wound dressing. Inspired by the formulation of the commercial wound healing Zn-CAR complex, i.e., polaprezinc (PLZ), for the first time, we benefitted from the synergy of zinc and CAR to create an antimelanoma nanofibrous wound dressing. According to scanning electron microscopy (SEM) images, ultrafine ZnO nanoparticles were homogenously distributed throughout the nanofibrous dressing. The ZCPAN nanofiber mat showed a significantly higher toughness (18.7 MJ.m−3 vs. 1.4 MJ.m−3) and an enhanced elongation at break (stretchability) compared to the neat PAN nanofiber mat (12% vs. 9.5%). Additionally, optical coherence elastography (OCE) measurements indicated that the ZCPAN nanofibrous dressing was as stiff as 50.57 ± 8.17 kPa which is notably larger than that of the PAN nanofibrous dressing, i.e., 24.49 ± 6.83 kPa. The optimum mechanical performance of the ZCPAN nanofibers originates from physicochemical interaction of CAR ligands, hPAN nanofibers, and ZnO nanoparticles through hydrogen bonding, electrostatic bonding, and esterification, as verified using ATR-FTIR. An in vitro cell viability assay using human skin melanoma cells implied that the cells are notably killed in the presence of the ZCPAN nanofibers compared to the PAN nanofibers. Thanks to ROS generating ZnO nanoparticles, this behavior originates from the high reactive oxygen species (ROS)-induced oxidative damage of melanoma cells, as verified through a CellROX assay. In this regard, an apoptotic cell response to the ZCPAN nanofibers was recorded through an apoptosis assay. Taken together, the ZCPAN nanofibers induce an antimelanoma effect through oxidative stress and thus are a high potential wound dressing material to suppress melanoma regrowth after surgical excision of skin tumors.

The total extract of Abelmoschus manihot (L.) medic flowers (TEA) mediated Nrf2-TFAM signalling to regulate mitochondrial antioxidant mechanism

Skin, as the first line of defence of the human body, is exposed to dangers such as overheating substances, ultraviolet rays, and environmental pollutants, and the incidence of skin diseases is increasing annually. Oxidative stress plays a dominant role in most skin diseases. Abelmoschus manihot (L.) medic flower (TEA) is a traditional Chinese medicine widely used to treat injuries to the skin such as water and fire scalds. It has been reported that TEA has excellent antioxidant effects. In this study, we aimed to explore the antioxidant and mitochondrial protection effects of TEA in H2O2-mediated HaCaT cell damage. HaCaT cells were incubated with H2O2 to simulate oxidative stress in the skin. The effect of TEA on HaCaT cells was also evaluated. Cell morphology was observed via inverted microscopy, and cell viability was measured via the MTT reagent. The cells were stained with Hoechst 33,324 solution. Reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA) and ATP detection kits were used to detect the corresponding indicators. The mitochondrial membrane potential was detected by JC-1. RT-PCR was used to detect mRNA and mtDNA expression. The expression of the target protein was detected by Western blotting and immunofluorescence. H2O2 triggered oxidative damage in HaCaT cells, which manifested as apoptosis, increased ROS and MDA contents, and decreased SOD activity. H2O2 activates the KEAP1/Nrf2/NQO1 signalling pathway, which decreases the expression of the intracellular KEAP1 protein and slightly increases the expression of the Nrf2 and NQO1 proteins, further causing mitochondrial oxidative stress, resulting in changes in the mitochondrial membrane potential, a reduction in the mtDNA copy number, and decreased expression of the PGC-1α and TFAM proteins. In addition the expression of mitochondrial respiratory chain genes and proteins decreased. TEA promoted the expression of Nrf2 in HaCaT cells, activated the downstream antioxidant response, and alleviated the oxidative stress and mitochondrial damage caused by H2O2. ML385 is an Nrf2 inhibitor, under which the antioxidant and mitochondrial protective effects of TEA are inhibited. When TFAM was knocked down, the protective effect of TEA on mitochondria was also inhibited. TEA protects HaCaT cells from H2O2-induced oxidative damage and mitochondrial oxidative damage through the KEAP1/Nrf2/NQO1/PGC-1α/TFAM pathway.

Hybridization Design and High-Throughput Screening of Peptides with Immunomodulatory and Antioxidant Activities

With the increasing recognition of the role of immunomodulation and oxidative stress in various diseases, designing peptides with both immunomodulatory and antioxidant activities has emerged as a promising therapeutic strategy. In this study, a hybridization design was applied as a powerful method to obtain multifunctional peptides. A total of 40 peptides with potential immunomodulatory and antioxidant activities were designed and screened. First, molecular docking was employed to screen peptides with a high binding affinity to MD2, a key receptor protein in the NFκB immune pathway. For the in vitro high-throughput screening, we constructed a reporter gene-based stable cell line, IPEC-J2-Lucia ARE cells, which was subsequently used to screen peptides with antioxidant activity. Furthermore, the biocompatibility, immunomodulatory, and antioxidant activities of these peptides were assessed. Among the candidates, the hybrid peptide VA exhibited the strongest immune-enhancing activity through the activation of the NF-κB pathway and significant antioxidant activity via the Nrf2-ARE pathway. Additionally, VA demonstrated protective effects against H2O2-induced oxidative damage in HepG2 cells. This study not only demonstrates the potential of peptide hybridization, but also develops a screening platform for multifunctional peptides. It provides a new tool for the treatment of autoimmune diseases and oxidative stress-related diseases.

Protective Effects of Hydrogen Treatment Against High Glucose-Induced Oxidative Stress and Apoptosis via Inhibition of the AGEs/RAGE/NF-κB Signaling Pathway in Skin Cells.

Diabetic wounds are major clinical challenges, often complicated by oxidative stress and free radical generation. Hydrogen (H2), a selective antioxidant, offers potential as a therapeutic agent for chronic diabetic wounds. However, its precise mechanisms remain underexplored. This study aimed to investigate the protective effects of H2 on high glucose-induced oxidative damage and apoptosis in human skin cells. HaCaT keratinocytes and HSF fibroblasts were treated with high glucose or AGEs. Cell viability, oxidative stress markers, inflammatory cytokines, and apoptosis were analyzed. AGEs/RAGE/NF-κB signaling was evaluated via Western blot. H2 treatment significantly reduced ROS, MDA, IL-1β, and TNF-α levels, while enhancing SOD and GSH activity. It also inhibited AGEs/RAGE/NF-κB signaling and apoptosis. Hydrogen therapy protects against oxidative stress and inflammation induced by high glucose or AGEs, offering potential as an adjunctive treatment for diabetic wound healing.

Structural characteristics of a polysaccharide isolated from Potentilla anserina L. and its mitigating effect on Zearalenone-induced oxidative damage in Sertoli cells.

The present study aims to characterize the structural features of a natural polysaccharide called PAP-1b extracted from the roots of Potentilla anserina L. and to evaluate its antioxidant activity. Structural characterization indicated that PAP-1b with a molecular weight of 1.22 × 104 Da was primarily composed of glucose and galactose. Methylation and NMR analyses showed that PAP-1b mainly consisted of →4)-α-D-Glcp-(1→, →4,6)-β-D-Glcp-(1→, →3,4)-α-Glcp-(1→ and α-D-Glcp-(1→). Subsequently, we evaluated the antioxidant activity of PAP-1b using zearalenone (ZEA)-induced oxidative damage in porcine Sertoli cells (SCs) as a model. Cellular experiments revealed that PAP-1b significantly attenuated ZEA-induced oxidative damage in SCs via the mitochondrial pathway, as evidenced by the increase in cell viability, the enhancement of antioxidant enzyme activities, and the reduction of reactive oxygen species (ROS), lactate dehydrogenase (LDH) and malondialdehyde (MDA) levels, as well as stabilization of the mitochondrial membrane potential and the reduction of apoptosis rate. These results suggest that Potentilla anserina L. polysaccharides can serve as a promising natural antioxidant for applications in the field of functional foods.

Gengnianchun Against H2O2-Induced Oxidative Damage in KGN Cells via miR-548m/FOXO3 Signaling.

Gengnianchun (GNC) is a traditional remedy used for diminished ovarian reserve, but its underlying mechanisms remain unclear. This study aimed to explore these mechanisms in human granulosa-like cancer (KGN) cells pretreated with medicated rat serum (MRS) before H2O2 exposure. MRS pretreatment significantly alleviated H2O2-induced cell damage, including improvements in cell viability, superoxide dismutase and GSH-Px activities, and Bcl-2 expression. Conversely, H2O2 treatment increased apoptosis, autophagosomes, IL-1β, TNF-α, reactive oxygen species, malondialdehyde levels, and the expression of LC-II/LC3-I, Bax, and Beclin-1. GEO database analysis revealed significant differential expression of several miRNAs, including miR-548m. qPCR confirmed that MRS upregulated miR-548m expression, which was downregulated by H2O2 in a dose-dependent manner. Preincubation with MRS prevented the decline in miR-548m expression and mitigated H2O2-induced damage, including improvements in cell viability, apoptosis, autophagy, and oxidative stress. miR-548m suppressed FOXO3 3'-UTR luciferase activity, and anti-miR-548m enhanced it. Transfection with miR-548m reduced FOXO3 mRNA and protein levels, while anti-miR-548m increased them. These findings suggest that GNC protects against H2O2-induced ovarian damage by modulating the miR-548m/FOXO3 axis, triggering autophagy and apoptosis.

Local delivery of mesenchymal stem cell-extruded nanovesicles through a bio-responsive scaffold for acute spinal cord injury treatment.

Intense inflammatory responses and elevated levels of reactive oxygen species (ROS) extremely exacerbate the pathological process of spinal cord injury (SCI). Mesenchymal stem cell (MSC)-derived extracellular vesicles (EV) can mitigate SCI-related inflammation but their production yield remains limited. Alternatively, MSC-extruded nanovesicles (NV) inherit the therapeutic potential from MSCs and have a markedly higher yield than EV. In the present study, a bio-responsive scaffold system (RS + NV) was created for SCI treatment. NV was generated from human MSCs by physical extrusion and encapsulated in a ROS-responsive scaffold (RS). RS + NV efficiently scavenged environmental ROS and underwent degradation, thus facilitating the responsive release of NV. NV inhibited the pro-inflammatory phenotypic transformation, and reduced the secretion of TNF-α and IL-6 from lipopolysaccharide-stimulated BV2 cells, exhibiting comparable anti-inflammatory properties to EV. Additionally, NV posed a superior antioxidative effect than EV and could effectively alleviate the oxidative stress damage of H2O2-stimulated PC12 cells. Furthermore, in SCI rats, the uptake of NV was primarily attributed to microglia and neurons. RS + NV exhibited synergistic effects in regulating the hostile microenvironment in vivo during the acute phase, thereby establishing a conducive environment for long-term locomotor, tissue repair, and recovery of neuropathic pain. Overall, RS + NV shows promising potential for use as an anti-inflammatory and antioxidative therapeutic approach for treating SCI.

Chlorinated Phenolic, Benzenoid, and Phenylethanoid Glucosides From the Mangrove Endophytic Fungus Fuscoporia sp. A2A6.

A total of 12 new compounds, named fuscoposides A-L (1-12), including 2 phenolic, 9 benzenoid, and 1 phenylethanoid glucosides, were isolated from the mangrove endophytic fungus Fuscoporia sp. A2A6. The structures of these compounds were established by HRESIMS, NMR spectroscopic data, single-crystal x-ray diffraction analysis, and chemical methods. Most notably, 10 compounds, namely, fuscoposides A-I (1-9) and fuscoposide L (12), are mono- or di-chlorinated. Fuscoposide C (3) exhibited moderate neuroprotective effects against H2O2-induced oxidative damage in mouse hippocampal neuron HT-22 cells in a dose-dependent manner at the concentration range of 2.0-6.0µM, whereas fuscoposide G (7) decreased the expression of COX2 in lipopolysaccharide-stimulated mouse microglia BV2 cells at the concentration of 5.0µM, thereby displaying anti-inflammatory activity.

Role of PCBP2 in regulating nanovesicles loaded with curcumin to mitigate neuroferroptosis in neural damage caused by heat stroke

ObjectiveThis study aims to elucidate the mechanisms by which nanovesicles (NVs) transport curcumin(CUR) across the blood–brain barrier to treat hypothalamic neural damage induced by heat stroke by regulating the expression of poly(c)-binding protein 2 (PCBP2).MethodsInitially, NVs were prepared from macrophages using a continuous extrusion method. Subsequently, CUR was loaded into NVs using sonication, yielding engineered cell membrane Nanovesicles loaded with curcumin (NVs-CUR), which were characterized and subjected to in vitro and in vivo tracking analysis. Evaluations included assessing the toxicity of NVs-CUR using the MTT assay, evaluating neuroprotection of NVs-CUR against H2O2-induced oxidative stress damage in PC12 cells, examining effects on cell morphology and quantity, and detecting ferroptosis-related markers through Western blot and transmission electron microscopy (TEM). Proteomic analysis was conducted on PC12 cells treated with NVs (n = 3) and NVs-CUR (n = 3) to identify downstream key factors. Subsequently, the expression of key factors was modulated, and rescue experiments were performed to validate the impact of NVs-CUR through the regulation of key factor expression. Furthermore, a mouse model of hypothalamic neural damage induced by heat stroke was established, where CUR, NVs-CUR, and ferroptosis inducer Erastin were administered to observe mouse survival rates, conduct nerve function deficit scoring, perform histological staining, and measure levels of inflammation and oxidative stress factors in hypothalamic tissue.ResultsNVs-CUR was successfully prepared with excellent stability, serving as an advantageous drug delivery system that effectively targets brain injury sites or neurons both in vitro and in vivo. Subsequent in vitro cell experiments demonstrated the biocompatibility of NVs-CUR, showing superior protective effects against H2O2-induced PC12 cell damage and reduced ferroptosis compared to CUR. Moreover, in the mouse model of hypothalamic neural damage induced by heat stroke, NVs-CUR exhibited enhanced therapeutic effects. Proteomic analysis revealed that NVs-CUR exerted its effects through the regulation of key protein PCBP2; silencing PCBP2 reversed the protective effect of NVs-CUR on neural damage and its inhibition of ferroptosis. Additionally, NVs-CUR regulated solute carrier family 7 member 11 (SLC7A11) expression by PCBP2; overexpression of SLC7A11 reversed the promotion of neural damage and ferroptosis by silencing PCBP2. Animal experiments indicated that ferroptosis inducers reversed the improved survival and nerve function observed with NVs-CUR, silencing PCBP2 reversed the ameliorative effects of NVs-CUR on hypothalamic neural injury induced by heat stroke, and overexpression of SLC7A11 further reversed the adverse effects of silencing PCBP2 on hypothalamic neural injury induced by heat stroke. This suggests that NVs-CUR alleviates hypothalamic neural damage induced by heat stroke by targeting the PCBP2/SLC7A11 axis to reduce neuronal ferroptosis.ConclusionThis study successfully developed engineered cell membrane NVs-CUR with neuron-targeting properties. NVs-CUR increased the expression of PCBP2, maintained the stability of SLC7A11 mRNA, reduced ferroptosis, and ultimately alleviated hypothalamic neuroinflammation induced by heatstroke.Graphical

One-Pot Synthesis of Oxygen Vacancy-Rich Amorphous/Crystalline Heterophase CaWO4 Nanoparticles for Enhanced Radiodynamic-Immunotherapy.

Radiodynamic therapy that employs X-rays to trigger localized reactive oxygen species (ROS) generation can tackle the tissue penetration issue of phototherapy. Although calcium tungstate (CaWO4) shows great potential as a radiodynamic agent benefiting from its strong X-ray absorption and the ability to generate electron-hole (e--h+) pairs, slow charge carrier transfer and fast e--h+ recombination greatly limit its ROS-generating performance. Herein, via a one-pot wet-chemical method, oxygen vacancy-rich amorphous/crystalline heterophase CaWO4 nanoparticles (Ov-a/c-CaWO4 NPs) with enhanced radiodynamic effect are synthesized for radiodynamic-immunotherapy of cancer. The phase composition and oxygen vacancy content of CaWO4 can be easily tuned by adjusting the solvothermal temperature. More intriguingly, the amorphous/crystalline interfaces and abundant oxygen vacancies accelerate charge carrier transfer and suppress e--h+ recombination, respectively, enabling synergistically improved ROS production from X-ray-irradiated Ov-a/c-CaWO4 NPs. In addition to directly inducing oxidative damage of cancer cells, radiodynamic generation of ROS also boosts immunogenic cell death to provoke a systemic antitumor immune response, thereby allowing the inhibition of both primary and distant tumors as well as cancer metastasis. This study establishes a synergistic enhancement strategy involving the integration of phase and defect engineering to improve the ROS generation capacity of radiodynamic-immunotherapeutic anticancer nanoagents.

Furan impairs cell function by inducing oxidative stress, DNA damage and apoptosis in mouse Sertoli cells in vitro.

Research on heat-induced food contaminants, such as furan, has shown its harmful effects on various systems. However, the impact of furan on Sertoli cells, a crucial male reproductive system cell, has not been studied. The investigation involved the treatment of furan to TM4 Sertoli cells at various concentrations (750, 1500, and 3000 µM) over a period of 24 h. This in vitro study determined that furan causes a decrease in Sertoli cell viability and an increase in lactate dehydrogenase activity, leading to cytotoxicity. Additionally, we observed an increase in MDA, one of the oxidative stress markers, in Sertoli cells, indicating that furan exposure leads to lipid peroxidation. It was determined that enzyme activities in the antioxidant defense system in Sertoli cells decreased after furan exposure. The findings indicate that furan induces oxidative damage in Sertoli cells by impairing the activity of antioxidant enzymes and promoting the production of ROS. This study discovered that furan triggers apoptosis in Sertoli cells by damaging DNA and altering the expression levels of apoptotic genes. Moreover, results suggest that furan causes cellular toxicity and apoptosis, leading to damage to Sertoli cells and thus causing male infertility.

S32, a Novel 3-Acetylaminocoumarin Compound, Exerts Neuroprotective Effects through the Inhibition of Neuroinflammation and Oxidative Stress In Vitro and In Vivo.

Neuroinflammation and oxidative stress are key factors leading to neuronal injury. In this study, we investigated the role of S32, a novel 3-acetylaminocoumarin compound, in ameliorating neuronal injury induced by neuroinflammation and oxidative stress in vitro and in vivo. First, we found that S32 reduced the expression levels of p-P65 and p-P38, inhibited the nuclear translocation of P65, and lowered the levels of pro-inflammatory factors in LPS-induced BV2 cells, which indicated that S32 had an antineuroinflammatory effect. Second, BV2 cell culture medium was used as the conditioned medium to establish a model of oxidative damage in PC12 cells. It was found that S32 reduced the level of ROS and increased mitochondrial membrane potential of PC12 cells, which indicated that S32 can protect PC12 cells against conditioned medium-induced injury. Next, we found that S32 inhibited the decrease of cell viability of PC12 cells caused by H2O2, inhibited nuclear damage, decreased the level of ROS, increased MMP, activated the AKT and ERK pathways, increased Bcl-2 levels, and decreased Bax and Cleaved-Caspase3 expression levels, indicating that S32 ameliorated the damaging effects of H2O2-induced PC12 cells. Finally, we found that S32 exerted the antineuroinflammatory and apoptosis-inhibiting effects in LPS-induced mice. In conclusion, this study first demonstrated that S32, a novel 3-acetylaminocoumarin compound, can reduce neuroinflammation and neuroinflammation-induced neuronal injury, exerting an indirect protective effect on neurons, and also exert a direct protective effect on neurons by reducing oxidative stress.

Xuebijing Exerts Protective Effects on Myocardial Cells by Upregulating TRIM16 and Inhibiting Oxidative Stress and Apoptosis.

This study utilized transcriptomic sequencing combined with cellular and animal models to explore the potential mechanisms of Xuebijing in treating sepsis-induced myocardial dysfunction, also known as sepsis-induced myocardial injury. We investigated potential targets and regulatory mechanisms of XBJ injection using network pharmacology and RNA sequencing. The effects of XBJ on oxidative stress and apoptosis levels in human cardiac myocytes (AC16) and C57BL/6 mice exposed to lipopolysaccharide (LPS) were evaluated by Enzyme-Linked Immunosorbent Assay (ELISA), fluorescent probe, Fluorescent Quantitative Polymerase Chain Reaction (qPCR), Western Blot, Transmission Electron Microscopy, oxidative stress-related indicators detection kit, flow cytometry, and Immunohistochemistry (IHC). First, it was verified that XBJ can reduce the deformation of AC16 cardiomyocytes induced by LPS and the production and secretion of ROS (P <0.01). The transcriptome sequencing results showed that the TRIM16 gene was significantly increased after XBJ treatment, and the data of KEGG and GO analyses demonstrated that XBJ could inhibit the pathway expression of oxidative stress damage in AC16 cells, and PCR verified that XBJ could indeed increase the expression level of TRIM16 gene in AC16 cells (P <0.01). Basic animal and cell experiments showed that LPS could inhibit the expression of TRIM16 and NRF2 in cardiomyocytes (P <0.05) and promote the expression of Keap1 (P <0.01), while XBJ could significantly upregulate the expression levels of TRIM16 and NRF2 (P <0.01) and inhibit the expression of Keap1 (P <0.01), thereby affecting the expression levels of downstream proinflammatory cytokines and alleviating LPS-induced oxidative stress damage. In addition, XBJ also inhibited the expression of the pro-apoptotic proteins Bax and c-caspase3 (P <0.01), promoted the expression of the anti-apoptotic protein Bcl2 (P <0.01), and reduced LPS-induced apoptosis by upregulating TRIM16. Our comprehensive data demonstrated that TRIM16 is a key gene in the therapeutic action of Xuebijing in sepsis-induced myocardial dysfunction, protecting myocardial cells from injury through antioxidative stress and anti-apoptotic mechanisms.

Ebeiedinone and peimisine inhibit cigarette smoke extract-induced oxidative stress injury and apoptosis in BEAS-2B cells.

Ebeiedinone and peimisine are the major active ingredients of Fritillariae Cirrhosae Bulbus. In this study, we looked at how these two forms of isosteroidal alkaloids protect human bronchial epithelial BEAS-2B cells from oxidative stress and apoptosis caused by cigarette smoke extract (CSE). First, the cytotoxicity was determined using the CCK8 assay, and an oxidative stress model was established. Then the antioxidative stress activity and mechanism were investigated by ELISA, flow cytometry, and Western blotting. By the CCK-8 assay, exposure to CSE (20%, 40%, and 100%) reduced the viability of BEAB-2S cells. The flow cytometry findings indicated that CSE-induced production of ROS (0.5% to maximum) and treatments with 10μM ebeiedinone and 20μM peimisine attenuated the production of ROS. The western blot assay results indicate that ebeiedinone and peimisine reduce CSE-induced oxidative stress, DNA damage, apoptosis, and autophagy dysregulation by inhibiting ROS, upregulating SOD and GSH/GSSG, and downregulating MDA, 4-HNE, and 8-OHdG through the NRF2/KEAP1 and JNK/MAPK-dependent pathways, thereby delaying the pathological progression of COPD caused by CS.Our data suggest that CSE causes oxidative stress, DNA damage, and apoptosis in BEAS-2B cells, as well as the progression of COPD. Ebeiedinone and peimisine fight CS-induced COPD by suppressing autophagy deregulation and apoptosis.

N6-methyladenosine mediated-NRF2 signaling pathway attenuates cadmium cytotoxicity by inhibiting oxidative damage in bronchial epithelial cells.

Although N6-methyladenosine (m6A) and its regulatory proteins were involved in multiple cellular damage processes, the roles of m6A and its regulatory proteins in cadmium-induced pulmonary cell damage remain largely unknown. Our present data indicated that cadmium exposure caused serious damage in bronchial epithelial cells, as evidenced by reduction of cell viability and elevation of oxidative damage and apoptosis. These processes were accompanied by alterations of m6A modification and its regulatory proteins (FTO, ALKBH5, YTHDC2). It is noteworthy that pretreatment with the m6A agonist entacapone (ENT) markedly attenuated the detrimental effects of cadmium, including cell death, oxidative damage, and the activation of the nuclear factor erythroid 2-related factor 2(NRF2）signalling pathway. Conversely, the detrimental effects of CdSO4 were significantly exacerbated when m6A levels were inhibited by 3-deazidyladenosine (DAA). Further prediction result revealed that multiple m6A-modified sites occur on NRF2 mRNA with high confidence level, implicating that m6A modification on NRF2 mRNA may affect the protein expression of NRF2. In conclusion, our data together suggest that m6A modification play critical roles in cadmium-induced bronchial epithelial cell damage, during which NRF2 signaling pathway may act as an important bridge for m6A modification to regulate cellular damage. This study offer a promising avenue for further investigation into the mechanisms underlying cadmium-induced bronchial epithelial cell damage from the perspective of RNA epigenetics.

Protective Effects of Polysaccharides From Sargassum hemiphyllum (Turner) C. Agardh Against Alcohol-Induced LO2 Cell Damage.

The study aimed to explore the protective impact of polysaccharide derived from Sargassum hemiphyllum (Turner) C. Agardh (SHP) against ethanol-induced injury in LO2 hepatocytes, along with its potential mechanism of action. A model of alcoholic injury in LO2 cells was established to assess the shielding effect of SHP against liver injury induced by alcohol. Treatment with 800 mmol/L ethanol for 6 h was selected for the construction of the hepatocyte injury model. Compared with those in the alcohol model group, the survival rate of LO2 cells in the SHP treatment group was significantly greater. When the concentration of SHP reached 60 μg/mL, the cell viability increased to 89.17% ± 3.58%. Moreover, SHP treatment significantly reduced the level of intracellular reactive oxygen species (ROS), increased the levels of intracellular glutathione (GSH), lactate dehydrogenase (LDH), and catalase (CAT), reduced the level of malondialdehyde (MDA), and prevented the leakage of intrahepatic enzymes (aspartate aminotransferase (AST) and alanine transaminase (ALT)) to protect LO2 cells from alcohol-induced injury. Moreover, at a concentration of 60 μg/mL, SHP inhibited the ethanol-induced reduction in the protein expressions of Nrf2, HO-2, and GCLC, indicating its potential to modulate the antioxidant system to restore the homeostatic state, consequently shielding the liver from peroxidative damage induced by alcohol. These results propose that SHP exhibits a protective role against oxidative damage in LO2 cells and holds promise as a novel natural hepatoprotective agent for averting liver injury.

ROS-responsive quercetin-based polydopamine nanoparticles for targeting ischemic stroke by attenuating oxidative stress and neuroinflammation.

Ischemic stroke (IS), a prevalent cerebrovascular disorder, is characterized by high morbidity rates and significant disability. However, relevant drug therapy for IS still suffers from limitations such as limited blood-brain barrier (BBB) penetration efficiency, single therapeutic target, short half-life, and strong side effects. The development of multi-target neuroprotective agents using natural drug molecules with low toxicity and combining them with nanotechnology to improve BBB permeability and drug utilization is an important direction in the development of IS therapeutic strategies. Based on the anti-inflammatory and antioxidant properties of quercetin (Que), as well as the ROS-responsive degradation properties of polydopamine (PDA), an IS therapeutic strategy (Que@DAR NPs) was developed in this study. Que@DAR NPs were formed by dopamine wrapping Que by oxidative self-assembly and wrapping the rabies virus glycoprotein (RVG29) on the surface. The results showed that Que@DAR NPs greatly improved the dispersion stability of Que and exhibited ROS-responsive degradation properties. Cellular internalization assay in human neuroblastoma cells (SH-SY5Y) showed that RVG29 peptide substantially augmented the cellular uptake of Que@DAR NPs. Moreover, Que@DAR NPs can effectively reduce the oxidative damage of SH-SY5Y cells and induce the polarization of microglia to anti-inflammatory (M2) phenotype. In vivo studies further demonstrated that Que@DAR NPs inhibited neuroinflammation, reduced neuronal apoptosis, and significantly ameliorated neurological dysfunction in a rat model of middle cerebral artery occlusion (MCAO). In conclusion, Que@DAR NPs provide a safe and effective new strategy for the precision treatment of IS.

Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Play a Role in PM2.5 and Hypoxia-Induced Simultaneously Oxidative Damage in Human Bronchial Epithelial Cells

Peroxisome Proliferator-Activated Receptor Gamma Coactivator-1 Alpha Play a Role in PM2.5 and Hypoxia-Induced Simultaneously Oxidative Damage in Human Bronchial Epithelial Cells

Afamin Ameliorates Testosterone Propionate (TP)-Induced Oxidative Stress and Mitochondrial Damage in Human Ovarian Granulosa Tumor Cells (KGN) by Upregulating the Expression of SIRT1

Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting women of reproductive age. Considerable research has confirmed that afamin is associated with the prevalence and development of metabolic syndrome. Thus, this study investigated the mechanism of action of afamin in PCOS and its potential therapeutic value. We found that PCOS patients had higher levels of afamin than normal control subjects. Afamin significantly enhanced the overall antioxidant ability and activity of antioxidant enzymes and reduced the levels of 8-hydroxydeoxyguanosine (8-OHdG), malondialdehyde (MDA), reactive oxygen species (ROS) and superoxide anion () in human ovarian granulosa tumor cells (KGN cells). In addition, afamin was also found to protect KGN cells against testosterone propionate (TP)-induced mitochondrial damage and apoptosis. Additionally, silencing of SIRT1 revealed that SIRT1 protected KGN cells against TP-induced oxidative stress (OS) injury, mitochondrial damage and apoptosis. Furthermore, this study showed that besides restoring the estrous cycle in PCOS mice, afamin might also reduce the increased cycling testosterone (T) and luteinizing hormone (LH) levels and LH/Follicle-stimulating hormone (FSH) ratio, as well as decrease the number of cystic follicles, indicating the significance of afamin in the treatment of PCOS. Moreover, afamin reduced oxidative damage in PCOS mice by enhancing their antioxidant capacity. Also, afamin may protect KGN cells against TP-induced OS by enhancing their antioxidant ability, restoring mitochondrial function, and inhibiting cell apoptosis by upregulating the expression of SIRT1. Thus, afamin may play a protective role in PCOS mice.

Molecular weight distribution and structure analysis of phlorotannins in Sanhai kelp (Saccharina japonica) and evaluation of their antioxidant activities.

In this paper, the structures and composition of phlorotannins with different molecular weights in juvenile and mature kelp (Saccharina japonica), as well as their relationship with antioxidant activity were comprehensively analyzed. Macroporous resin and ultrafiltration were used to obtain phlorotannins with different molecular weights. The structures of low molecular weight and high molecular weight phlorotannins in Sanhai kelp were analyzed using UHPLC-Q-Orbitrap-MS/MS and NMR techniques, respectively. In addition, the antioxidant capacity of phlorotannins with different molecular weights was determined by chemical and HepG2 cell oxidative damage models methods assays. Results showed that the content and molecular weight distribution of phlorotannins in Sanhai kelp were related to its growth stage. Seventeen low molecular weight phlorotannins were identified, and the composition types of the high molecular weight phlorotannins were fucols, phlorethols, fucophlorethols, fuhalols and eckols. In addition, high molecular weight phlorotannins exhibit higher antioxidant activity than low molecular weight phlorotannins.