Reactive Oxygen Species Research Articles

Reactive oxygen species and oxidative stress in acute pancreatitis: Pathogenesis and new therapeutic interventions

Acute pancreatitis (AP) is a common acute gastrointestinal disorder affecting approximately 20% of patients with systemic inflammatory responses that may cause pancreatic and peripancreatic fat necrosis. This condition often progresses to multiple organ failure, significantly increasing morbidity and mortality. Oxidative stress, characterized by an imbalance between the body’s reactive oxygen species (ROS) and antioxidants, activates the inflammatory signaling pathways. Although the pathogenesis of AP is not fully understood, ROS are increasingly recognized as critical in the disease's progression and development. Modulating the oxidative stress pathway has shown efficacy in mitigating the progression of AP. Despite numerous basic studies examining this pathway, comprehensive reviews of recent research remain sparse. This systematic review offers an in-depth examination of the critical role of oxidative stress in the pathogenesis and progression of AP and evaluates the therapeutic potential of antioxidant interventions in its management.

Glutathione's Role in Liver Metabolism and Hangover Symptom Relief: Dysregulation of Protein S-Glutathionylation and Antioxidant Enzymes.

Hangovers from alcohol consumption cause symptoms like headaches, nausea, and fatigue, disrupting daily activities and overall well-being. Over time, they can also lead to inflammation and oxidative stress. Effective hangover relief alleviates symptoms, prevents dehydration, and replenishes energy needed for daily tasks. Natural foods considered high in antioxidants and antiinflammatory properties may aid in the hepatic breakdown of alcohol. The study aims to investigate the impact of glutathione or its enriched yeast extract, which is recognized for its antioxidant characteristics, on alcohol metabolism and alleviating hangovers in a rat model exposed to binge drinking. In this study, glutathione and its enriched yeast extract controlled hangover behaviour patterns, including locomotor activity. Additionally, it enhanced the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) following ethanol ingestion (3 g/kg). Further, the incorporation of glutathione led to an increase in the expression of antioxidant enzymes, such as SOD and catalase, by activating the nuclear erythroid 2-related factor 2 (Nrf2) signaling pathway. This activation reduced the excessive production of reactive oxygen species (ROS) and malondialdehyde. Next, glutathione modulated the activity of cytochrome P450 2E1 (CYP2E1) and the protein expressions of Bax and Bcl2. Besides, in vitro and in vivo investigations with glutathione demonstrated a regulating effect on the pan-s-glutathionylation and its associated protein expression, glutaredoxin 1 (Grx1), glutathione-S-transferase Pi (GST-π), and glutathione reductase (GR). Together, these findings suggest that glutathione or its enriched yeast extract as a beneficial dietary supplement for alleviating hangover symptoms by enhancing alcohol metabolism and its associated Nrf2/Keap1 signalings.

6-Gingerol Induced Apoptosis and Cell Cycle Arrest in Glioma Cells via MnSOD and ERK Phosphorylation Modulation.

6-gingerol, a bioactive compound from ginger, has demonstrated promising anticancer properties across various cancer models by inducing apoptosis and inhibiting cell proliferation and invasion. In this study, we explore its mechanisms against glioblastoma multiforme (GBM), a notably aggressive and treatment-resistant brain tumor. We found that 6-gingerol crosses the blood-brain barrier more effectively than curcumin, enhancing its potential as a therapeutic agent for brain tumors. Our experiments show that 6-gingerol reduces cell proliferation and triggers apoptosis in GBM cell lines by disrupting cellular energy homeostasis. This process involves an increase in mitochondrial reactive oxygen species (mtROS) and a decrease in mitochondrial membrane potential, primarily due to the downregulation of manganese superoxide dismutase (MnSOD). Additionally, 6-gingerol reduces ERK phosphorylation by inhibiting EGFR and RAF, leading to G1 phase cell cycle arrest. These findings indicate that 6-gingerol promotes cell death in GBM cells by modulating MnSOD and ROS levels and arresting the cell cycle through the ERFR-RAF-1/MEK/ ERK signaling pathway, highlighting its potential as a therapeutic agent for GBM and setting the stage for future clinical research.

Heterojunction Nanozyme Hydrogels Containing Cu-O-Zn Bonds with Strong Charge Transfer for Accelerated Diabetic Wound Healing.

The complex microenvironment of persistent inflammation and bacterial infection is a major challenge in chronic diabetic wounds. The development of nanozymes capable of efficiently scavenging reactive oxygen species (ROS) is a promising method to promote diabetic wound healing. However, many nanozymes show rather limited antioxidant activity and ROS-dependent antibacterial effects under certain circumstances, further weakening their ability to scavenge ROS. To meet these challenges, electronically regulated bioheterojunction (E-bio-HJ) nanozyme hydrogels derived from metal-organic frameworks (MOFs) were designed and prepared via an interface engineering strategy. Owing to the electron transfer and redistribution effects of the abundant and highly dispersed Cu-O-Zn sites at the heterogeneous interface, the E-bio-HJ nanozymes exhibited catalase (CAT)-like activity with ultrahigh hydrogen peroxide affinity (Km = 25.76 mM) and sustained ROS consumption. In addition, owing to the enhanced interfacial effect of E-bio-HJ and the good biocompatibility and cell adhesion of the methacryloylated gelatin (Gel) hydrogel, the E-bio-HJ gelatin hydrogel (E-bio-HJ/Gel) further reduced inflammation by inducing macrophage transformation to the M2 phenotype, accompanied by excellent antimicrobial properties and enhanced cell migration, angiogenesis, and collagen deposition, which synergistically promoted diabetic wound healing. This highly effective and comprehensive strategy offers a new approach for the rapid healing of diabetic wounds.

PACS2/CPT1A/DHODH signaling promotes cardiomyocyte ferroptosis in diabetic cardiomyopathy

ObjectivesThe pathophysiology of diabetic cardiomyopathy (DCM) is a phenomenon of great interest, but its clinical problems have not yet been effectively addressed. Recently, the mechanism of ferroptosis in the pathophysiology of various diseases, including DCM, has attracted widespread attention. Here, we explored the role of PACS2 in ferroptosis in DCM through its downregulation of PACS2 expression.Methods and resultsCardiomyocytes were treated with high glucose and palmitic acid (HGPA), and the detection of cardiomyocyte iron ions, lipid peroxides, and reactive oxygen species (ROS) revealed clear ferroptosis during these treatments. Silencing PACS2 downregulated CPT1A expression and upregulated DHODH expression significantly, reversing HGPA-induced ferroptosis. Further silencing of PACS2 with a CPT1A agonist exacerbated cardiomyocyte ferroptosis while promoting mitochondrial damage in cardiomyocytes. Using a mouse model of type 2 diabetes induced by streptozotocin (STZ) and a high-fat diet (HFD), we found that PACS2 deletion reversed these treatment-induced increases in cellular iron ions, impaired cardiac function, mitochondrial damage and ferroptosis in cardiac muscle tissues.ConclusionsThe PACS2/CPT1A/DHODH signalling pathway may be involved in ferroptosis in DCM by regulating cardiomyocyte mitochondrial function.

Light-activated channelrhodopsins: a revolutionary toolkit for the remote control of plant signalling.

Channelrhodopsins (CHRs), originating within algae and protists, are membrane-spanning ion channel proteins that are directly activated and/or deactivated by specific wavelengths of light. Since 2005, CHRs have been deployed as genetically encoded optogenetic tools to rapidly advance understanding of neuronal networks. CHRs provide the opportunity to finely tune ion transport across membranes and regulate membrane potential. These are fundamental biochemical signals, which in plants can be translated into physiological and developmental responses such as changes in photosynthesis, growth, turgor, vascular hydraulics, phosphorylation or reactive oxygen species (ROS) status, gene expression, or even cell death. Exploration of CHR family diversity and structure-function engineering has led to the expansion of the CHR optogenetic toolbox, offering unparalleled opportunities to precisely control and understand electrical and secondary messenger signalling in higher plants. In this Tansley Insight, we provide an overview of the recent progress in the application of CHR optogenetics in higher plants and discuss their possible uses in the remote control of plant biology, illuminating a new future domain for plant research enabled through synthetic biology.

Biomimetic Nanovesicles Synergize with Short-Term Fasting for Enhanced Chemotherapy of Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is the most aggressive and lethal subtype of breast cancer among women. Chemotherapy acts as the standard regimen for TNBC treatment but suffers from limited drug accumulation in tumor regions and undesired side effects. Herein, we developed a synergistic strategy by combining a red blood cell (RBC) membrane-liposome hybrid nanovesicle with short-term fasting (STF) for improved chemotherapy of TNBC. The biomimetic nanovesicles exhibited reduced phagocytosis by macrophages while displaying a significant increase in tumor cell uptake through caveolae/raft-mediated endocytosis under nutrient-deprivation conditions. Importantly, drug-loaded nanovesicles and STF treatment synergistically increased the cytotoxicity of tumor cells by inhibiting their cell cycles and aerobic glycolysis as well as amplifying the reactive oxygen species (ROS) and autophagosomes generation. In the STF-treated mice, biomimetic nanovesicles greatly improved the antitumor efficacy at a lower drug dosage and inhibited the undesired metastasis of TNBC. Overall, we demonstrated that biomimetic nanovesicles synergizing with STF therapy serve as a promising therapeutic strategy for enhanced chemotherapy of malignant TNBC.

Dual Porphyrin-Loaded Scintillating Nanoparticles Enhanced Photodynamic Therapy in Hypoxic Cancer Cells under X-ray Irradiation.

Tumor hypoxia represents a major challenge to achieving successful therapy outcomes with photodynamic therapy (PDT). We hypothesized that systemic loading of dual porphyrins, protoporphyrin IX (PPIX) as a photosensitizer (PS) and hemin (Fe3+-PPIX) as an oxygen generator, onto Eu-doped NaYF4 scintillator (Sc), collectively terms as Eu-PPIX@Hemin, could enhance the activity of X-ray mediated PDT. Catalase-like property of hemin in the presence of H2O2 facilitated the production of oxygen molecules (3O2) in hypoxic cancer cells. The produced 3O2 reacts with nearby excited PPIX molecules (PPIX*) in the Sc-PS pairs to produce singlet oxygen (1O2), as cytotoxic reactive oxygen species (ROS) under X-ray irradiation. Eu-PPIX@Hemin nanoparticles (NPs) with a diameter of ~60 nm efficiently produced oxygen in the presence of H2O2, which its concentration in tumor cells is higher than that in normal cells. Eu-PPIX@Hemin generated similar amounts of ROS in hypoxic cultured cancer cells under low dose X-ray irradiation (0.5 Gy), compared to those in normoxic cancer cells. Notably, Eu-PPIX@Hemin exhibited similar cytotoxic effects in both hypoxic and normoxic cancer cells under X-ray irradiation. Overall, the mutual Sc-PS performance between PPIX and Eu was synergistically enhanced by hemin in Eu-PPIX@Hemin, which relieved hypoxia in the cancer cells under X-ray irradiation.

Thermoelectric Nanoheterojunction-Mediated Multiple Energy Conversion for Enhanced Cancer Therapy.

Electron-hole recombination and exogenous local hypoxia both impede the effectiveness of thermoelectric tumor catalytic therapy. Here, a thermoelectric heterojunction (Pt-TiO2-x/Ti3C2Tx-PEG) was developed to enhance charge carrier separation and alleviate tumor hypoxia. By incorporating titanium oxide with oxygen vacancies and platinum single atoms onto Ti3C2Tx MXene, we not only improve the charge separation efficiency but also prevent the recombination of positive and negative charges generated by the thermoelectric effect, leading to an increased production of reactive oxygen species (ROS). Furthermore, the Pt SAs exhibited excellent catalase-mimicking (CAT-mimicking) activity, catalyzing hydrogen peroxide to generate oxygen and alleviating the hypoxic tumor microenvironment. Titanium oxide with oxygen vacancies also serves as a sonosensitizer for sonodynamic therapy (SDT), enhancing ROS generation in collaboration with thermoelectric catalytic therapy. Moreover, the photothermal conversion efficiency of Pt-TiO2-x/Ti3C2Tx-PEG is augmented by Pt SAs with a surface plasmon resonance effect, further boosting CAT-mimicking activity and thermoelectric catalytic therapy efficacy. This tumor-specific thermoelectric heterojunction integrates thermoelectric therapy, SDT, and photothermal therapy, demonstrating excellent tumor suppression efficacy both in vitro and in vivo. Therefore, this study offers highly valuable and promising insights into utilizing photothermoelectric/ultrasound-mediated methods for cancer treatment.

Bioactive Nanoparticle-Embedded Micro/Nanofibrous Dressing with Improved Angiogenesis and Immunoregulation for Facilitating Burn Wound Healing.

In the context of severe burn injuries, the presence of excessive reactive oxygen species (ROS), prolonged microbial infection, and compromised angiogenesis can contribute to the metabolic reprogramming of macrophages, resulting in a dysregulated inflammatory response that hinders the healing process. In this study, cerium oxide nanoparticles (CeNPs) are encapsulated within a silk fibroin-poly(e-caprolactone) polymer to create an electrospun PSF/CeNPs nanofiber membrane (PSF/membrane). This membrane is further modified through the addition of an angiopoietin-1 mimetic peptide, QHREDGS, resulting in the formation of QPSF/CeNPs (QHREDGS modified PSF/CeNPs membrane). In vitro assessments revealed that the QPSF/CeNPs displayed the intended ability to regulate ROS levels, favorable biocompatibility with cells, promoted endothelial cell attachment and growth, exhibited anti-inflammatory properties through the modulation of macrophage phenotypes from M1 to M2, as well as pro-angiogenetic and antibacterial effects. In vivo, the membrane dressing demonstrated an acceleration of burn wound healing, promotion of angiogenesis, downregulation of inflammatory factors, and enhancement of collagen deposition. This bioactive membrane dressing shows potential as a clinical therapy for promoting the regeneration of both acute and chronically damaged skin tissue.

Metal Doping Enabling Defective CoMo-Layered Double Hydroxide Nanosheets as Highly Efficient Photosensitizers for NIR-II Photodynamic Cancer Therapy.

Photodynamic therapy (PDT) is attracting widespread attention as a promising strategy for tumor treatment. However, the efficacy of PDT is severely limited by the insufficient tissue penetration depth of the light source and low reactive oxygen species (ROS) generation efficiency. Herein, the metal doping strategy is reported to construct a series of defect-rich M-doped amorphous CoMo-layered double hydroxide (a-M-CoMo-LDH, M = Mn, Cu, Al, Ni, Mg, Zn) photosensitizers (PSs) for NIR-II PDT. Especially, M-doped CoMo-LDH nanosheets are synthesized through a simple hydrothermal method and then etched by acid treatment to prepare defect-rich a-M-CoMo-LDH nanosheets. Under NIR-II 1270 nm laser irradiation, the defect-rich a-Zn-CoMo-LDH nanosheets exhibit the optimal PDT performance compared with other a-M-CoMo-LDH nanosheets, and also possess much higher ROS production activity (3.9 times) than that of the pristine a-CoMo-LDH, with a singlet oxygen quantum yield up to 1.86, which is the highest among all the reported PSs. After polyethylene glycol (PEG) modification, the a-Zn-CoMo-LDH-PEG nanosheets can function as an effective inorganic PS for PDT, effectively inducing cell apoptosis in vitro and eradicating tumors in vivo. Notably, transcriptome sequencing analysis and further molecular validation highlight the critical role of the apoptotic/p53/AMPK/oxidative phosphorylation signaling pathways in a-Zn-CoMo-LDH-PEG-induced cancer cell apoptosis.

Apoc1 Knockdown Alleviates High Glucose-induced Oxidative Stress and Apoptosis of Renal Tubular Cells by Binding to Clusterin.

Diabetic nephropathy (DN) is a serious diabetic complication. Renal tubular damage is an important aspect of DN. Increased apolipoprotein C1 (Apoc1) has been confirmed in serum of patients with DN. The exact mechanism of Apoc1 in DN is unclear as yet. We aimed to elaborate the molecular mechanism underlying high glucose (HG)-induced renal tubular epithelial damage. In this content, a DN mouse model was established to assess renal damage. Apoc1 and Clusterin expression in renal tissue was detected using immunoblotting and immunofluorescence staining. In vitro, human kidney proximal tubular epithelial cells (HK-2 cells) were exposed to HG to simulate the DN model. After Apoc1 and/or Clusterin knockdown, HK-2 cell viability under HG conditions was detected using CCK-8 assay. DCFH-DA staining was used to examine the production of intracellular reactive oxygen species (ROS). MDA and SOD levels were tested by kits. Moreover, cell apoptosis was measured using TUNEL staining. Immunoblotting was employed to evaluate the expression of proteins. Additionally, the binding between Apoc1 and Clusterin was analyzed using co-immunoprecipitation experiments. Our data revealed that Apoc1 expression was upregulated while Clusterin expression was downregulated in renal tissue of DN mice and HG-treated HK-2 cells. Apoc1 knockdown alleviated oxidative stress and apoptosis in HG-treated HK-2 cells. Importantly, Apoc1 could bind to Clusterin and regulate Clusterin expression in HK-2 cells. Finally, Clusterin silencing blocked the influences of Apoc1 knockdown on the oxidative stress and apoptosis in HK-2 cells under HG conditions. Collectively, Apoc1 knockdown exerts potential anti-DN effects by binding to Clusterin to alleviate HG-induced renal tubular damage, suggesting that Apoc1/Clusterin can be used as a valuable therapeutic target for DN.

Protective effect of Apelin-13 on oxygen and glucose deprivation induced-damage in retinal ganglion cells cultured in vitro.

Ischemic-anoxic injury plays an important role in the pathophysiology of diabetes retinopathy, optic neuropathy, even glaucoma and other ocular diseases. It may ultimately cause damage to neuronal death like retinal ganglion cells (RGCs) and subsequent visual loss. RGCs are essential elements of the retina and optic nerve that are crucial to visual formation. Ischemic-anoxic injury, inflammation, and oxidative stress are vital causes of RGC death. Thus, neuroprotection is essential for the treatment of these ocular diseases. Recent studies have shown the neuroprotective property of apelin-13 in many disease models. In this study, we isolated RGCs and found that apelin-13 promoted the viability of RGCs and increased the phosphorylation of Protein kinase B (PKB, Akt) in an in vitro oxygen-glucose deprivation model. Moreover, apelin-13 increased the expressions of glucose-6-phosphate dehydrogenase (G6PD) and nicotinamide adenine dinucleotide phosphate (NADPH) and reduced the level of reactive oxygen species (ROS). And, we also found that apelin-13 could promote the expressions of glucose transporter-1 (GLUT1) and adenosine triphosphate (ATP). These results indicated that apelin-13 could delay or stop RGC death, which might be as potential therapeutic targets for treatment of diseases mediated by ischemic-anoxic damage like diabetes retinopathy, optic neuropathy, even glaucoma.

Loss of PTPN21 disrupted mitochondrial metabolic homeostasis and aggravated experimental pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a high-mortality lung disease with unclear pathogenesis. Convincing evidence suggests that an imbalance in mitochondrial homeostasis resulting from repeated injury to alveolar epithelial type 2 cells (AEC2) underlies IPF. Non-receptor protein tyrosine phosphatase 21 (PTPN21) performs various functions in cancer; however, its role in IPF has not been studied. This study aimed to investigate the role of PTPN21 in lung fibrosis. The experimental results showed that loss of PTPN21 exacerbated lung fibrosis by increasing cell numbers in bronchoalveolar lavage fluid, lung hydroxyproline content, and extracellular matrix protein expression of fibronectin and α-smooth muscle actin (α-SMA) in bleomycin-challenged mouse lungs. In A549 cells (AEC2), knockdown of PTPN21 suppressed focal adhesion and migration, reduced mitochondrial fission and increased fusion, increased the level of mitochondrial superoxide, decreased mitochondrial membrane potential and ATP levels. Simultaneously, knockdown of PTPN21 impaired autophagy, and increased intracellular reactive oxygen species levels. Treatment of fibroblasts (MRC-5) and primary human lung fibroblasts (PHLF)) with the supernatant from PTPN21-knockdown A549 cells increased the expression of fibronectin, collagen 1 and α-SMA. Conversely, overexpression of PTPN21 in A549 cells produced opposite effects. However, treatment of MRC-5 and PHLF with the supernatant from PTPN21-overexpressing A549 cells only slightly reduced the expression of fibronectin, collagen 1 in MRC-5 cells, but did not change the expression of α-SMA. In summary, this study revealed that the loss of PTPN21 in epithelial cells disrupted mitochondrial metabolic homeostasis, leading to epithelial cell inactivation and increased the deposition of extracellular matrix proteins in fibroblasts, thereby exacerbating experimental pulmonary fibrosis.

Targeting Caveolin-1 in Multiple Myeloma Cells Enhances Chemotherapy and Natural Killer Cell-Mediated Immunotherapy.

The cell membrane transport capacity and surface targets of multiple myeloma (MM) cells heavily influence chemotherapy and immunotherapy. Here, it is found that caveolin-1 (CAV1), a primary component of membrane lipid rafts and caveolae, is highly expressed in MM cells and is associated with MM progression and drug resistance. CAV1 knockdown decreases MM cell adhesion to stromal cells and attenuates cell adhesion-mediated drug resistance to bortezomib. CAV1 inhibition in MM cells enhances natural killer cell-mediated cytotoxicity through increasing CXCL10, SLAMF7, and CD112. CAV1 suppression reduces mitochondrial membrane potential, increases reactive oxygen species, and inhibits autophagosome-lysosome fusion, resulting in the disruption of redox homeostasis. Additionally, CAV1 knockdown enhances glutamine addiction by increasing ASCT2 and LAT1 and dysregulates glutathione metabolism. As a result of CAV1 inhibition, MM cells are more sensitive to starvation, glutamine depletion, and glutamine transporter inhibition, and grow more slowly in vivo in a mouse model treated with bortezomib. The observation that CAV1 inhibition modulated by 6-mercaptopurine, daidzin, and statins enhances the efficacy of bortezomib in vitro and in vivo highlights the translational significance of these FDA-approved drugs in improving MM outcomes. These data demonstrate that CAV1 serves as a potent therapeutic target for enhancing chemotherapy and immunotherapy for MM.

Synergistic Strategy toward Enhancing Photosynthesizing Reactive Oxygen Species of Covalent Organic Frameworks

Synergistic Strategy toward Enhancing Photosynthesizing Reactive Oxygen Species of Covalent Organic Frameworks

Caspase-8-dependent autophagy regulates neutrophil infiltration in oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is a subtype of head and neck cancer that arises in the multilayered epithelia of the mouth and lips. Although inactivating mutations in CASP8 are frequently found in human OSCC their role in the disease is unknown. To investigate this, we deleted Casp8 in the oral epithelium of adult mice. Loss of Caspase-8 resulted in defects in the tongue epithelial barrier and triggered a neutrophil-rich immune infiltrate distinct from that observed on epidermal Casp8 deletion. Oral Casp8 deletion led to activation of autophagy. Inhibition of autophagy partially rescued epithelial integrity in Casp8-/- mice, while induction of autophagy in wild type mice resulted in oral barrier defects and excessive neutrophil infiltration. On treatment with the carcinogen 4-nitroquinoline-1-oxide Casp8-/- mice showed increased susceptibility to developing oral tumors. Depletion of neutrophils reduced tumor incidence, which correlated with a reduction in reactive oxygen species and decreased epithelial DNA damage. Our findings establish a functional link between epithelial integrity, autophagy, and the tumor immune microenvironment, placing Caspase-8 at the center of these processes.

Insights into the Removal of Organic Contaminants by Co-CeO2 Nanocatalysts via CaCO3 Activation: Performance, Kinetic, and Mechanism.

The advanced oxidation process based on S(IV) has garnered increasing attention, owing to its efficiency in degrading contaminants. Here, a cobalt-doped cerium oxide catalyst (Co-CeO2) was employed to activate calcium sulfite (CaSO3) for imidacloprid degradation. The Co-CeO2 catalyst was characterized by using SEM, BET, XRD, and XPS techniques to analyze its structural and chemical properties. XPS analysis revealed the presence of Co0, Co2+, and Co3+ species in the Co-CeO2 catalyst. Compared to the CeO2/CaSO3 system, the Co-CeO2/CaSO3 system significantly enhanced the degradation rate of imidacloprid from 5.00% to 94.01%. Scavenging experiments, in conjunction with electron paramagnetic resonance spectroscopy, identified hydroxyl radicals (•OH), sulfate radicals (SO4•-), superoxide radicals (O2•-), sulfite radicals (SO3•-), and singlet oxygen (1O2) as the primary reactive species responsible for the degradation of imidacloprid within the Co-CeO2/CaSO3 system. Density functional theory calculation analysis was employed to investigate the specific sites of imidacloprid attacked by reactive oxygen species, proposing four potential degradation pathways. Furthermore, the Ecological Structure Activity Relationships (ECOSAR) program predicted a significant diminution in the toxicity of intermediate products compared to imidacloprid. Even after five cycles, Co-CeO2 maintained an excellent removal efficiency of 86.35%.

Targeting acetylated high mobility group box 1 protein (HMGB1) and toll-like receptor (TLR4) interaction to alleviate hypertension and neuroinflammation in fructose-fed rats.

Our previous study reported that fructose intake increased systemic blood pressure and reduced nitric oxide (NO) in the nucleus tractus solitarius (NTS) due to oxidative stress and neuroinflammation. However, it remains unclear how reactive oxygen species (ROS) reduce NO and how this process impacts neuroinflammation in the NTS. This study aimed at investigating the effect of ROS on acetylation of high mobility group box 1 protein (HMGB1) in the NTS of fructose-induced hypertensive rats. Male Wistar-Kyoto (WKY) rats were fed with 10% fructose water to elevate blood pressure. Thereafter, CLI-095 and glycyrrhizic acid (GA) treatments were delivered for up to 2weeks (1mg·12 μL-1·day-1, by intracerebroventricular injection) to reduce the negative effects of toll-like receptor 4 (TLR4) and HMGB1 activation. Two weeks of CLI-095 and GA treatment reduced systemic blood pressure and significantly preserved neuronal and endothelial nitric oxide synthase (nNOS and eNOS) availability against the inflammatory insults of fructose consumption. Both CLI-095 and GA halted the interaction of acetylated HMGB1 and TLR4. Two weeks of CLI-095 and GA treatment markedly reduced NTS inflammation (pro-inflammatory cytokines and microglial activation) and lowered serum norepinephrine levels. Our data reveal novel pharmacological properties for CLI-095 and GA, which improved blood pressure and inflammatory conditions by decreasing the interaction of acetylated HMGB1 with TLR4. These findings challenge the commonly accepted dogma that essential hypertension is specifically mediated by neuroinflammation due to acetylated HMGB1 coupling to TLR4.

Caviar extract inhibitsskin photoaging by activating skin stem cells through NF-κB/MMPs/COL17A1 axis.

Ultraviolet radiations (UVR) produce harmful entities and reactive oxygen species (ROS) in skin cells, leading to skin photoaging. Caviar extract(CE) showed outstanding effects in delaying skin aging, but the underlying mechanism remains largely unknown. In this study, we prepared CE with acid protease and examined the anti-skin photoaging effects. The results showed that CE performed no cytotoxicity to HaCaT cells. For antioxidant properties, the EC50 values of DPPH and ABTS radical scavenging activity for CE were 1.27 and 5.20 mg/mL, respectively. It significantly reduced NF-κB, MMP-3 and MMP-9 protein expression levels, and increased IκB and TIMP-1 expression level in UVA-irradiated HaCaT cells. In the skin aging mice model, CE reduced the degree of UV-induced skin photoaging. Histological study confirmed that CE can ameliorate the adverse effects of UV exposure on the skin. Moreover, we found that CE could enhance the activities of Superoxide dismutase (SOD), and increased the contents of hydroxyproline (HYP) in photoaged mice skin. And CE elevated the protein expression level of COL17A1, KRT10, and KRT14 in mice skin. Taken together, our results bright systemic and new insights of CE into preventing UV-induced skin photoaging.