Oxidative Stress Damage Research Articles

Exogenous allyl isothiocyanate mitigates the drought stress by regulating the stomatal characteristic, antioxidant capacity, and glucosinolate metabolism in pakchoi

Drought is a global issue that has increasingly garnered worldwide attention. Glucosinolates (GSLs) are significant sulfur-containing compounds in cruciferous plants such as pakchoi (Brassica rapa L. ssp. chinensis), and their primary biological functions are exerted through their hydrolysis products. Allyl isothiocyanate (AITC), which is one of the degradation products of GSL, plays a crucial role in plants’ response to environmental stresses. To date, the drought-resistant mechanism of AITC has not been fully explored. This study investigated the effects of spraying different concentrations of AITC solutions (1 mM and 10 mM) on the growth parameters, stomatal characteristics, antioxidant indices, and glucosinolate metabolism of pakchoi under drought stress, compared to a control group treated with distilled water. The results shown that under drought stress, AITC spraying enhanced the plant's water retention capacity and restored their growth by promoting stomatal closure and improving photosynthetic capacity in pakchoi; mitigated oxidative stress damage and augmenting the plant's water absorption by increasing the activities of antioxidant enzymes and the concentrations of osmoregulatory substances in pakchoi; the application of AITC restored the glucosinolate metabolism in pakchoi, inhibiting the downregulation of genes associated with GSL synthesis and the upregulation of genes related to degradation that is induced by drought stress, thereby maintaining the balance between GSLs and ITCs.. In conclusion, AITC application alleviated the inhibition of pakchoi growth under drought stress by fostering stomatal closure, bolstering antioxidant defenses, and modulating glucosinolate metabolism.

Quercetin regulating oxidative stress damage repair in periodontal OMSCs

Quercetin regulating oxidative stress damage repair in periodontal OMSCs

Boosting Tumor Apoptosis and Ferroptosis with Multienzyme Mimetic Au Single‐Atom Nanozymes Engaged in Cascade Catalysis

AbstractNanozyme‐based catalytic therapy has garnered much attention in cancer treatment for converting endogenous substrates into reactive oxygen species (ROS), which induce oxidative stress damage in tumors. However, the effectiveness of nanozymes is hindered by the limited availability of these endogenous substrates in the tumor microenvironment. To address this, a novel gold‐based single‐atom nanozyme (AuSAN), glucose oxidase (GOx, G), and lactate oxidase (LOx, L) are meticulously engineered into a highly ordered biomimetic composite nanozyme M/GLB@AuSAN, forming an interconnected cascade catalysis that catalyzes the carbon sources of tumor into ROS as a sustained antitumor strategy. The loaded GOx and LOx aerobically catalyze glucose and lactate to produce H2O2, which is then rapidly converted into ·OH, O2•−, and O2 by AuSAN. The generated O2 serves as a positive feedback substrate for further GOx‐ and LOx‐mediated aerobic catalysis, significantly amplifying cascade catalysis, and thereby enhancing ROS accumulation. The abundant intracellular ROS and scarce carbon sources effectively exacerbate protein phosphorylation, lipid peroxidation, and mitochondrial damage, ultimately provoking tumor apoptosis and ferroptosis in vitro and in vivo. Therefore, the integrated design of GOx/LOx/AuSAN provides a promising strategy to combine multiple enzymatic activities, deplete carbon sources, and enhance ROS production, resulting in the suppression of melanoma progression.

Antioxidative properties of baicalin on methylparaben-induced testicular oxidative stress and oxidative DNA damage in a rat experimental model

Antioxidative properties of baicalin on methylparaben-induced testicular oxidative stress and oxidative DNA damage in a rat experimental model

Pre-treatment with notoginsenoside R1 from Panax notoginseng protects against high-altitude-induced pulmonary edema by inhibiting pyroptosis through the NLRP3/caspase-1/GSDMD pathway

High-altitude pulmonary edema (HAPE) is a potentially fatal condition that occurs when exposed to high-altitude hypoxia environments. Currently, there is no effective treatment for HAPE, and available interventions focus on providing relief. Notoginsenoside R1 (NGR1), a major active constituent of Panax notoginseng (Burkill) F.H.Chen (sānqī), has demonstrated heart and lung-protective effects under hypobaric hypoxia. However, there is a lack of clarity regarding the precise mechanisms that underlie the protective effects of NGR1 against inflammation.In this study, a rat model of HAPE was developed to assess the effect of NGR1 on this pathology. High-altitude hypoxia corresponding to 6000m altitude was simulated with a hypobaric chamber. We found that NGR1 dose-dependently alleviated pulmonary oxidative stress damage and inflammatory response, and prevented acid-base balance disruption. In addition, NGR1 restored the expression levels of hypoxia-inducible factor-1 alpha, vascular endothelial growth factor, and aquaporin protein-5, correlated with the development of pulmonary edema induced by hypobaric hypoxia. Furthermore, NGR1 pre-treatment remarkably mitigated NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-induced pyroptosis, and this effect was partially counteracted by the use of an NLRP3 agonist. Thus, NGR1 may exert a lung-protective effect against HAPE by ameliorating hypoxia-induced lung edema, oxidative damage, and inflammation through inhibition of the NLRP3/Caspase-1/ GSDMD signaling pathway.

Potentiated Calcium Carbonate with Enhanced Calcium Overload Induction and Acid Neutralization Capabilities to Boost Chemoimmunotherapy against Liver Cancer.

Unfavorable phenotypes characterized by low immunogenicity and acidity within the tumor microenvironment (TME) contribute to immunosuppression and therapeutic resistance. Herein, we rationally synthesized a multifunctional nanoregulator by encapsulating DOX and erianin into calcium carbonate (CaCO3)-based nanoparticles using a modified double emulsion method. The DOX and erianin-loaded CaCO3-based nanoparticles, termed DECaNPs, could effectively induce the calcium overload by triggering calcium influx and absorbing CaCO3 nanoparticles. Additionally, DECaNPs also neutralize the acidic TME by interacting with extracellular protons and limiting lactic acid production, a result of metabolic remodeling in cancer cells. As a result, DECaNPs elicit cellular oxidative stress damage, which mediates the activation of ferroptosis/apoptosis hybrid pathways, and profound immunogenic cell death. Treatment with DECaNPs could inhibit the growth of tumors by promoting oxidative stress, acid neutralization, metabolic remodeling, and protective antitumor immunity in vivo. In addition, DECaNPs could synergistically amplify the antitumor effects of αPD-L1 in a bilateral tumor model by eliciting systemic immune responses. In all, our work presents the preparation of CaCO3-based nanoregulators designed to reverse the unfavorable TME and enhance αPD-L1 immunotherapy through multiple mechanisms.

Trimethylamine N-oxide promotes PERK-mediated endothelial-mesenchymal transition and apoptosis thereby aggravates atherosclerosis

The endothelial-mesenchymal transition (EndMT) is involved in the development of atherosclerosis (AS) and is a key process in vascular endothelial injury. Oxidative stress, inflammation, and apoptosis are common causes of EndMT, and EndMT progression can further accelerate the development of AS. The metabolite trimethylamine N-oxide (TMAO) is produced by the gut microbiome and is implicated in the development of several diseases, including diabetes and chronic kidney disease. However, the impact of TMAO on transforming growth factor β1(TGF-β1)-induced EndMT remains unclear. We hypothesize that TMAO exacerbates plaque formation and cardiac function impairment by promoting EndMT. Herein, we showed that high serum TMAO levels caused plaque formation, cardiac function damage and haemodynamic changes in ApoE−/− mice. In vitro, TMAO upregulated mesenchymal markers and downregulated endothelial markers in HAECs. Furthermore, TMAO increased the migratory capacity of EndMT cells. Mechanistically, we found that PERK downregulation could alleviate TMAO-induced oxidative stress, EndMT, plaque formation and cardiac function damage. Further study showed that activated transcription factor 3 (ATF3), the downstream molecule of protein kinase RNA-like endoplasmic reticulum kinase (PERK), could bind with TGF-β1/2 and affect EndMT. Overall, TMAO promotes EndMT, possibly through the PERK-eIF2α-ATF4-CHOP or the PERk-eIF2α-ATF3-TGF-β signalling pathways.

Targeting Nrf2/HO-1 signaling by crocin: Role in attenuation of arsenic trioxide-induced neurotoxicity in mice

Ethnopharmacology relevanceSaffron is a valued herb, obtained from the stigmas of the C.sativus Linn (Iridaceae). Pharmacopoeias have described it as having a variety of actions, such as stimulant, anti-carcinogen, and anti-depressant. As a folk medicine, crocin has been reported to have anti-cardiotoxicity and anti-hepatotoxicity effects. This paper focuses on crocin, one of the bioactive molecules found in saffron that are known to have therapeutic effects. Crocin has been shown in numerous experimental studies to be beneficial in treating depression, however, there aren't many studies on its neurotoxicity. Aim of the studyApplications of arsenic trioxide (ATO) in medical settings is limited by its side effects. This study aims to examine crocin's protective effect against ATO-induced neurotoxicity and understand its potential molecular mechanism. Materialandmethods: A neurotoxicity model was created by administering ATO (4 mg/L/d). To counteract this, mice were intraperitoneally injected with crocin (100, 200 mg/kg/d). After 60 days, biochemical, histopathological, transmission electron microscopy, ELISA, and western blotting analyses were then performed. ResultsOur results indicated that crocin decreased neuronal death and loss caused by ATO, countered oxidative stress damage, and mitigated pro-inflammatory cytokines. Mice treated with crocin also displayed positive signs of brain tissue recovery. Additionally, crocin reduced the protein expressions of NLRP1, apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, GRP78, CHOP, and ATF4. ConclusionsThis study attests that crocin can reduce ATO-induced neurotoxicity by safeguarding nerves from oxidative stress, inflammation, and apoptosis, possibly through the activation of the Nrf2/HO-1 signaling pathway.

Study on the mechanism of ROS-induced oxidative stress injury and the broad-spectrum antimicrobial performance of nickel ion-doped V6O13 powder

In this study, pure V6O13 and nickel ion-doped V6O13 powders were synthesized by a simple hydrothermal-calcination method, and their broad-spectrum antimicrobial properties and mechanisms were investigated. The crystal structure, morphology, and chemical state of the powders were thoroughly analyzed by XRD, SEM, TEM, XPS, and UV–Vis. Their antimicrobial properties and mechanisms were evaluated by the ring of inhibition, bio-SEM, live-dead cell staining, ROS detection, and protein leakage experiments. The results showed that nickel ion doping modulated the oxygen defects of V6O13, generating more reactive oxygen species and leading to more severe oxidative stress, resulting in a broad-spectrum and highly efficient antimicrobial effect. This study also revealed the antimicrobial mechanism based on oxygen defect -induced ROS production, which caused cellular oxidative stress damage, leading to leakage of intracellular substances and cell death. This study not only demonstrates the potential of V6O13 as an efficient antimicrobial agent but also provides a strong experimental basis and theoretical support for the engineering design and optimization of novel antimicrobial materials by modulating material defects through ion doping.

Possible mechanisms for adverse effects on zebrafish sperm and testes associated with low-level chronic PFOA exposure

Perfluorooctanoic acid (PFOA), which is widely used during the manufacturing of fluoropolymer coatings and polytetrafluoroethylene, is now a widespread pollutant in the environment and within the human body. This study used zebrafish, an aquatic model species, to investigate how low levels of chronic PFOA exposure affect the reproductive system. The results of the experiments in which zebrafish were exposed to 414 ng/L or 4140 ng/L for 60 days showed a variety of adverse effects on testicular tissue and sperm, including dose-dependent changes in plasma estradiol and testosterone levels, various sperm malformations, decreased sperm motility and concentration, and PFOA-induced oxidative stress and testicular damage with increased rates of apoptosis. In addition, offspring of the zebrafish that had been exposed to PFOA were characterized by increased malformation and mortality. Subsequent transcriptional analyses of the male gonads revealed the significant activation of oxidative stress bioprocesses and immuno-inflammatory signaling pathways, along with the dysregulation of reproductive bioprocesses. In conclusion, low-level chronic exposure to PFOA affects both the reproductive performance of adults and the development of offspring; the mechanisms for these adverse effects involve alterations in several molecular pathways that may be involved in PFOA-induced oxidative stress and reproductive abnormalities. The presented data can be used to assess the ecotoxicity of PFOA to the male reproductive system at environmentally-relevant concentrations.

A Comparative Analysis of Two Agonist Muscle Superset Training Variations on Muscle Damage and Oxidative Stress Markers in Resistance-Trained Men

Background: Evidence suggests that heavy resistance activities can damage muscle cell membranes by increasing free radical production. However, the specific type of resistance activity and the adaptations made by resistance-trained men can influence oxidative stress indicators and muscle damage. Objectives: This study aimed to evaluate the acute impact of two agonist muscle superset resistance training protocols on malondialdehyde (MDA), creatine kinase (CK), lactate dehydrogenase (LDH), total antioxidant capacity (TAC), and catalase (CAT) in resistance-trained men. Methods: A quasi-experimental study with a pretest-posttest design was conducted. Ten resistance-trained men (age: 24.25 ± 4.92 years; height: 175.12 ± 19.6 cm; weight: 74.75 ± 8.44 kg) participated in one of two superset agonist muscle resistance training protocols (post-exhaustion supersets and pre-exhaustion supersets). Subjects performed three sets of ten repetitions at an intensity of 80% of their 1-repetition maximum (1RM). Blood samples were taken immediately before and 24 hours after each session, and serum levels of MDA, CK, LDH, TAC, and CAT were evaluated. Results: Both types of superset resistance training significantly increased MDA, CK, LDH, TAC, and CAT levels, with no significant difference in the effects on MDA, CK, and LDH. However, a significant difference was observed between the two training protocols in terms of TAC and CAT, with post-exhaustion supersets showing a greater increase in these antioxidant indices. Conclusions: A single session of both protocols can induce oxidative stress and muscle damage in resistance-trained men. Additionally, post-exhaustion superset training of agonist muscles may have a greater impact on enhancing antioxidant capacity.

Prospects of phycoerythrin: Structural features, antioxidation and applications in food

Phycoerythrin (PE) is a naturally occurring plant protein of algal origin. The colour, bioactivity and stability of PE are inextricably linked to its structure. PE has powerful antioxidant properties that effectively prevent oxidative stress and cellular damage, for which the chromophore structure plays a key role. However, the relationship between the chromophore and thermal stability is unclear in PE. The environmental factors affecting the thermal stability of PE are mainly light, high temperature and extreme pH. PE stability can be enhanced through various techniques, including the incorporation of additives, cross-linking processes, and the formation of complexes. Improving the stability of PE is of significant importance for its applications within the food industry. This paper outlines the structural characteristics of PE, discusses the relationship between its structure and antioxidant activity, and focuses on the application of PE in the food industry, as well as the factors affecting its stability and strategies for its improvement.

Metabolic perturbations associated with hIAPP-induced insulin resistance in skeletal muscles: Implications to the development of type 2 diabetes

The human islet amyloid polypeptide (hIAPP) tends to misfold and self-assemble to form amyloid fibrils, which has been associated with the loss of function and viability of pancreatic β-cells in type 2 diabetes mellitus (T2DM). The role of hIAPP in the development of insulin resistance (a hallmark of T2DM) in skeletal muscles – the major sites for glucose utilization – needs further investigation. Even though, insulin-resistant conditions have been known to stimulate hIAPP aggregation, the events that lead to the development of insulin resistance due to hIAPP aggregation in skeletal muscles remain unidentified. Here, we have attempted to identify metabolic perturbations in L6 myotubes that were exposed to increasing concentrations of recombinant hIAPP for different time durations. It was observed that hIAPP exposure was associated with increased mitochondrial and cellular ROS levels, loss in mitochondrial membrane potential and viability of the myotubes. Metabolomic investigations of hIAPP-treated myotubes revealed significant perturbations in o-phosphocholine, sn-glycero-3-phosphocholine and dimethylamine levels (p < 0.05). Therefore, we anticipate that defects in glycerophospholipid metabolism and the associated oxidative stress and membrane damage may play key roles in the development of insulin resistance due to protein misfolding in skeletal muscles. In summary, the perturbed metabolites and their pathways have not only the potential to be used as early biomarkers to predict the onset of insulin resistance and T2DM but also as therapeutic targets for the effective management of the same.

Novel tris-bipyridine based Ru(II) complexes as type-I/-II photosensitizers for antitumor photodynamic therapy through ferroptosis and immunogenic cell death

Ru(II) complexes have attracted attention as photosensitizers for their promising photodynamic properties. Herein, novel tris-bipyridine based Ru(II) complexes (6a-e) were synthesized by introducing saturated heterocycles to improve photodynamic properties and lipid-water partition coefficients. Among them, 6d demonstrated significant phototoxicity towards three cancer cells, with IC50 values of 5.66–7.17 μM, exceeding values in dark (IC50s > 100 μM). Under hypoxic conditions, 6d maintained excellent photodynamic activity in A549 cells, with PI values exceeding 24, highlighting its potential for highly effective type-I/-II photodynamic therapy by inducing ROS generation, oxidative stress, and mitochondrial damage. Additionally, it induced ferroptosis and immunogenic cell death of A549 cells by regulating the expression of relevant markers. Finally, 6d remarkably inhibited the growth of A549 transplanted tumor growth by 95.4 %. This Ru(II) complex shows great potential for cancer treatment with its potent photodynamic activity and diverse mechanisms of tumor cell death.

Administration of Lacticaseibacillus casei CSL3 in Swiss Mice with Immunosuppression Induced by Cyclophosphamide: Effects on Immunological, Biochemical, Oxidative Stress, and Histological Parameters.

The study aimed to evaluate the effects of supplementation with Lacticaseibacillus casei CSL3 in Swiss mice immunosuppressed with cyclophosphamide on immunological, biochemical, oxidative stress, and histological parameters. The animals were distributed into four groups (control, CSL3, cyclophosphamide, and CSL3 + cyclophosphamide), where two groups were treated with L. casei CSL3 (10 log CFU mL-1) for 30days, and two groups received chemotherapy (days 27 and 30-total dose of 250mgkg-1). Counts of lactic acid bacteria (LAB) and bile-resistant LAB in stool samples; blood count (erythrogram, leukogram, and platelets); serum total cholesterol levels; catalase enzyme activity; and thiobarbituric acid reactive substances (TBARS) levels in liver, kidney, and brain; IL-4 expression; IL-23, TNF-α, NF-κβ in the spleen; and histological changes in the liver, kidneys, and intestine were evaluated. The CSL3 + cyclophosphamide group showed a significant increase in bile-resistant LAB counts in feces (p = 0.0001), leukocyte counts, and expression of IL-23, TNF-α, and NF-κβ (p < 0.05) significantly reduced total cholesterol levels (p = 0.001) and protected liver damage of supplemented animals. For oxidative stress damage, the bacterium did not influence the results. It is concluded that the bacterium is safe at a concentration of 10 log CFU mL-1 and has probiotic potential due to its positive influence on the immune response and lipid metabolism.

Investigation of erythrocyte membrane lipid profile, oxidative stress and dna damage parameters in patients with chronic lymphoid leukemia

Purpose: Chronic lymphocytic leukemia (CLL) is the most seen type of leukemia in adults. There are few biomarkes that are used for better understanding how oxidative stress is involved in the pathophysiology of hematologic malignency.We aimed to oxidative stress, DNA damage and erythrocyte membrane lipid profile in CLL patients in this study. The study is included 38 CLL patients and 38 age-sex matched controls. Materials and method: Total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), DNA damage examination with Comet assay, serum 8-OHdG measurement and gas chromatographic analysis were performed between the case and control groups. Results: It was observed that TOS and OSI values were higher in the case group than in the control group (p=0.014 and p=0.022, respectively). DNA damage measured by Comet method was found to be increased in the case group (p0.05). Conclusion: It has been shown that CLL patients had higher oxidant capasity as consequence. Oxidative stress and DNA damage are increased in CLL patients in this study. It is early to evaulate on erythrocyte membrane lipid profile in CLL patients. However, the study can be ligthed the way future studies on the subject.

Overexpression of the EuSIP5 Gene to Improve Drought Resistance in Tobacco

Soluble inorganic pyrophosphatase (s-PPase), a pyrophosphate hydrolase, is crucial for various physiological processes including plant growth and development, metabolic functions, and responses to abiotic stresses. However, research on s-PPase in woody plants is limited. To investigate the potential role of soluble inorganic pyrophosphatase in Eucommia ulmoides Oliver (E. ulmoides) in drought stress, the E. ulmoides soluble inorganic pyrophosphatase 5 (EuSIP5) cDNA sequence was amplified via RT-PCR. A bioinformatic analysis suggested that EuSIP5 may be an unstable amphipathic protein predominantly localized in the cytoplasm. In E. ulmoides, the highest expression of the EuSIP5 gene was detected in the leaves and pericarp of male plants from April to October, and in the leaves in July and September. Under drought conditions, the expression of EuSIP5 in E. ulmoides leaves was significantly greater than that in the control. An overexpression vector containing EuSIP5 was constructed and introduced into Nicotiana tabacum L. cv. Xanthi (N. tabacum L.). Compared with that in wild-type (WT) plants, wilting in N. tabacum L. EuSIP5-overexpressing (OE) plants was delayed by 4 days under drought stress. Additionally, the expression levels of the drought-related genes DET2, CYP85A1, P5CS, ERF1, F-box, and NCED1 were elevated in the leaves of transgenic N. tabacum L. Moreover, the activities of the protective enzymes peroxidase, superoxide dismutase, and catalase were significantly greater, whereas the malondialdehyde content was lower in the transgenic plants than in the WT plants. These findings suggest that the introduction of the EuSIP5 gene into N. tabacum L. enhances drought-related gene expression, increases antioxidant capacity, and reduces oxidative stress damage, thereby improving drought resistance.

Crocin Protects the 661W Murine Photoreceptor Cell Line against the Toxic Effects of All-Trans-Retinal.

Age-related macular degeneration (AMD) is a common disease contributing to vision loss in the elderly. All-trans-retinal (atRAL) is a retinoid in the retina, and its abnormal accumulation exhibits toxicity to the retina and promotes oxidative stress-induced photoreceptor degeneration, which plays a crucial role in AMD progression. Crocin is a natural product extracted from saffron, which displays significant antioxidant and anti-inflammatory effects. The present study elucidates the protective effects of crocin on photoreceptor cell damage by atRAL and its potential mechanisms. The results revealed that crocin significantly attenuated cytotoxicity by repressing oxidative stress, mitochondrial injury, and DNA damage in atRAL-loaded photoreceptor cells. Moreover, crocin visibly inhibited DNA damage-induced apoptosis and gasdermin E (GSDME)-mediated pyroptosis in photoreceptor cells after exposure to atRAL. It was also observed that crocin distinctly prevented an increase in Fe2+ levels and lipid peroxidation caused by atRAL via suppressing the Kelch-like ECH-associated protein 1 (KEAP1)/nuclear factor-erythroid 2-related factor 2 (NRF2)/heme oxygenase-1 (HO-1) signaling pathway, thereby ameliorating photoreceptor cell ferroptosis. In short, these findings provide new insights that crocin mitigates atRAL-induced toxicity to photoreceptor cells by inhibiting oxidative stress, apoptosis, pyroptosis, and ferroptosis.

Reactive Oxygen Species Triggered Cleavage of Thioketal‐Containing Supramolecular Nanoparticles for Inflammation‐Targeted Oral Therapy in Ulcerative Colitis

AbstractCombating reactive oxygen species (ROS) and targeted drug delivery to inflammatory sites are considered effective therapeutic strategies for ulcerative colitis (UC), a refractory chronic inflammatory disease. Herein, a ROS‐responsive thioketal (TK) crosslinked cyclodextrin metal‐organic framework (TCOF) is fabricated, to which a non‐ROS‐sensitive vector, sulfur substituted by carbon chain‐crosslinked cyclodextrin metal‐organic framework (CCOF) is parallelly designed as ROS negative reference. Dexamethasone (DEX) loaded in TCOF (TCD) and CCOF (CCD) are investigated to demonstrate the advantages of precision medicine for UC. After the ROS‐induced collapse of nanoparticles, TCD selectively triggered the release of DEX. Moreover, TCD effectively protected cells from oxidative stress damage and reduced inflammation levels in vitro. Remarkably, the TK group of TCD is oxidatively broken by consuming ROS at the inflammatory site, exposing the thiol group to mucosal adhesion, which enhances the retention of TCD at colons. In vivo studies of UC treatment reveals that oral administration of TCD demonstrated excellent inflammation‐targeting properties, remarkably attenuated oxidative stress, and ameliorated both acute and chronic colitis compared to CCD. Furthermore, TCD exhibits an excellent safety profile in mice. These results instill confidence in advancing targeted drug delivery and precision therapy for UC.

Dynamic changes in Beclin-1, LC3B, and p62 in aldose reductase-knockout mice at different time points after ischemic stroke

Ischemic stroke is a brain injury caused by cerebral blood circulation disorders and is closely related to oxidative stress. Aldose reductase (AR) is a critical enzyme involved in oxidative stress. Autophagy has previously been found to play a key role in cerebral ischemia‒reperfusion injury. However, it is still unclear how autophagy molecules change after cerebral ischemia‒reperfusion injury in AR knockout mice (AR−/−). A transient middle cerebral artery occlusion (tMCAO) model was generated in AR−/− mice, and the neurological deficit scores of the mice were observed and recorded on Days 1, 3 and 5 after tMCAO. Neuronal damage in the ischemic penumbra was observed by TTC, HE, and Nissl staining. The expression of the autophagy-related molecules Beclin-1, LC3II/I, and P62 as well as that of molecules related to inflammation, oxidative stress, and neurological damage was detected by RT‒qPCR, western blotting, and immunofluorescence. Autophagosomes were observed using a transmission electron microscope. Cerebral ischemia‒reperfusion injury caused neurological deficits and ischemic infarction in tMCAO mice (P < 0.01). Beclin-1, Bcl2/Bax, SOD, GSH-px, P62, PSD95, and TOM20 levels decreased (P < 0.05), while IL-6, LC3II/I, and GFAP levels increased (P < 0.01) in the AR−/− tMCAO-1d group and the AR−/− tMCAO-3d group, compared to those in the sham group. Beclin-1, Bcl2/Bax, NOX4, GSH-px, P62, and PSD95 levels increased (P < 0.01), while IL-6, LC3II/I, and GFAP levels decreased (P < 0.01) in the AR−/− tMCAO-5d group compared to those in the AR−/− tMCAO-1d group. Autophagosome formation was observed in tMCAO mice. In summary, the changes in autophagy proteins in the brain tissue of the AR−/− mice after tMCAO were more obvious on Days 1 and 3 after tMCAO. The expression of Beclin-1 and P62 decreased, and the expression of LC3B increased after cerebral ischemia‒reperfusion injury in AR−/− mouse brain tissue.