Journal of Biochemical and Molecular Toxicology最新文献

{"title":"A Comparative Study of Quercetin/Rutin Loaded PEG Polymeric Nanoparticles: Controlled Drug Release and Its Biological Activity","authors":"Renuka Mani,&nbsp;Swethaa Viswaresh Babu,&nbsp;Nishanth Murugesan,&nbsp;Ramachandhiran Duraisamy,&nbsp;Palvannan Thayumanavan","doi":"10.1002/jbt.70269","DOIUrl":"https://doi.org/10.1002/jbt.70269","url":null,"abstract":"<div>\u0000 \u0000 <p>Flavonoids are natural polyphenolic compounds that primarily possess antioxidant properties and play a significant role in opposing various diseases. Current chemotherapeutic approaches are largely ineffective, thus calling for the development of alternative strategies to combat this disease. In this regard, numerous studies have reported the anticancer effect of flavonoids in different types of cancer. To enhance its therapeutic value, polymeric nanoparticles (PEG NPs) represent an ideal delivery system. Further, surface modification of NPs with PEG holds tremendous potential for improving the bioavailability and circulation time of native drugs in the blood. The present study aimed to develop Quercetin/Rutin-loaded PEG polymeric NPs (Qu-PEG/Ru-PEG NPs) with enhanced encapsulation efficiency and sustained drug release. The synthesized Qu-PEG NPs &amp; Ru-PEG NPs were characterized by UV-Vis Spectroscopy, FTIR spectrum, NMR, and XRD and SEM analysis. In-vitro drug release study exhibited a cumulative release of Quercetin &amp; rutin for 24 h at pH 7.4. Further, the polymeric nano-formulations of Quercetin &amp; Rutin showed enhanced antioxidant activity, leading to defense against oxidative stress. In-vitro cellular studies demonstrated that Qu-PEG NPs and Ru-PEG NPs significantly inhibit KB cell proliferation compared to free drugs alone. The current study also showed that Qu-PEG NPs &amp; Ru-PEG NPs enhance intracellular ROS generation compared to the drug alone. Hence, our research findings revealed that successful encapsulation of Quercetin &amp; Rutin in PEG NPs targets the tumor microenvironment and enhances the efficacy of drugs. Based on these preliminary results, flavonoid-loaded polymeric-based NPs might be potential therapeutic molecules against cancer in the future.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Auraptene Mitigates Cigarette Smoke and Lipopolysaccharide-Induced Chronic Obstructive Pulmonary Disease in Mice and BEAS-2B Cells via Regulating Keap1/Nrf2/HO-1 Pathway","authors":"Rui Qi,&nbsp;Yuwen Fei","doi":"10.1002/jbt.70253","DOIUrl":"https://doi.org/10.1002/jbt.70253","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Chronic obstructive pulmonary disease (COPD) is a most common respiratory condition characterized by airflow limitation, airway inflammation, and lung injury. The present study was undertaken to unveil the therapeutic potentials of the auroptene against lipopolysaccharide (LPS) and cigarette smoke (CS)-induced COPD in mice. The CS along with LPS was exposed to healthy C57BL/6 mice through the intranasal route to induce COPD. The exposure to CS was continued for 12 weeks. The LPS challenge was occurred on weeks 2, 4, 6, and 8. The auraptene was treated orally by gavage route 1 h before to CS exposure for last 4 weeks. After the completion of treatment, the respiratory function was assessed using a pulmonary function test equipment. The levels of mucin proteins, extracellular matrix (ECM) proteins, proliferative cytokine markers, epithelial marker protein E-cadherin, oxidative stress-related biomarkers, and inflammation-associated markers were assessed using respective commercial assay kits. An analysis of histopathology and histo-morphology was conducted on the pulmonary tissues. An in vitro assays were conducted on the CS condensate (CSC) and LPS-challenged BEAS-2B cells. The expressions of Keap1/Nrf2/HO-1 pathway associated proteins were assessed using assay kits. The findings of the current work has clearly proved that auraptene at 25 mg/kg concentrations significantly increased the pulmonary functions in the mice with COPD. The treatment of auraptene effectively reduced the ECM protein levels, proliferative cytokine marker levels, and inflammation-related cytokine levels in the COPD mice. In addition, the auraptene treatment effectively increased the antioxidants and mitigated the lung tissue injuries in the COPD mice. The Keap1/Nrf2/HO-1 signaling pathway expressions successfully regulated by the auraptene treatment in the CSC and LPS-induced BEAS-2B cells. Therefore, the current findings has highlighted that auraptene has the capability to be a beneficial intervention to treat COPD.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"N-Acety-L-Cysteine Alleviates Isoflurane-Triggered Neuronal Cell Parthanatos by Suppressing Reactive Oxygen Species Accumulation Through the Induction of c-Jun N-Terminal Kinase Signaling Pathway Inhibition","authors":"Nan Liu,&nbsp;Ya Liu,&nbsp;Xuedong Wang,&nbsp;Ming Liu,&nbsp;Yingying Wang,&nbsp;Chunsheng Feng,&nbsp;Meihua Piao","doi":"10.1002/jbt.70268","DOIUrl":"https://doi.org/10.1002/jbt.70268","url":null,"abstract":"<p>In recent years, the potential neurotoxicity of inhaled anesthetics on the developing brain has increasingly garnered attention, yet its mechanism remains unclear. Parthanatos is a newly discovered form of programmed cell death dependent on PARP-1, and it is believed to be closely associated with cellular oxidative stress response. However, it is still to be proven whether isoflurane, a commonly used clinical anesthetic, can induce parthanatos in developing brain neurons and whether it activates the oxidative stress signaling pathway in neuronal cells. In this study, we treated SH-SY5Y cells and rat hippocampus neuron cells (RN-h) with isoflurane, measured cell viability using the MTT assay, examined the activation of the parthanatos-related PARP-1/AIF/PAR signaling pathway using western blot analysis, detected the accumulation of ROS using DCFH-DA, detected mitochondrial membrane potential (Δψm) by a JC-1 assay, and assessed the activation of the oxidative stress-related JNK signaling pathway using western blot. In vivo, we examined the damaging effects of inhaled isoflurane on neonatal rat hippocampal neurons using HE staining. The results showed that 2% and 4% concentrations of isoflurane significantly inhibited cell survival and upregulated the expression levels of PARP-1, AIF, and PAR in both types of neuronal cells. Moreover, isoflurane significantly enhanced ROS levels and decreased Δψm, and activated the JNK signaling pathway in both cell types. Importantly, we found that pretreatment with N-Acetylcysteine (NAC) could inhibit isoflurane-induced parthanatos and the accumulation of ROS in cells, as well as the activation of the JNK pathway. The experimental results in neonatal rats also demonstrated that isoflurane led to significant neuronal death in the hippocampal CA1 region. However, pretreatment with NAC significantly increased the survival rate of pyramidal neurons in this region. In summary, through our experiments, we confirmed that isoflurane can induce parthanatos in neuronal cells, and NAC can decrease ROS accumulation in neuronal cells and thus mitigate the damage isoflurane causes to neuronal cells.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70268","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Indole-3-Carbinol Mechanisms Combating Chemicals and Drug Toxicities","authors":"Marian N. Gerges,&nbsp;Thoria Donia,&nbsp;Tarek M. Mohamed","doi":"10.1002/jbt.70280","DOIUrl":"https://doi.org/10.1002/jbt.70280","url":null,"abstract":"<div>\u0000 \u0000 <p>The toxicity of chemicals and drugs is a common crisis worldwide. Therefore, the search for protective compounds is growing. Natural compounds such as indole-3-carbinol (I3C) derived from cruciferous vegetables are preferred since they are safe for humans and the environment. This review focuses on I3C potential role in preventing and repairing damage caused by chemicals and drugs. Interestingly, I3C ameliorates hepatotoxicity induced by carbon tetrachloride (CCl₄), diethylnitrosamine (DENA), alcohol, gold nanoparticles, and microbial toxins. Additionally, it inhibits carcinogenesis induced by different chemicals and prevents the deleterious effects of different antineoplastic drugs including cisplatin, doxorubicin (DOX), and trabectidin on normal tissues. Moreover, it reduces fetal malformation and protects against micronuclei formation and calstogenecity induced by cyclophosphamide (CP) in bone marrow cells. It also attenuates methotrexate (MTX)-induced hepatotoxicity, mitigates neurotoxicity caused by thioacetamide and clonidine, and protects against aspirin side effects in gastric mucosa. Furthermore, its nanoparticles inhibit neuronal damage caused by glutamate and rotenone. Thus, I3C prevents the toxicities caused by chemicals in the surrounding environment as well as those of consumed drugs.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Anti-Hyperlipidemic and Anti-Atherogenic Activity of Asiatic Acid and Its Effect on Lipid Peroxidation in Hyperlipidemic Rats","authors":"Aarti Tiwari,&nbsp;Amit Shukla,&nbsp;Pradeep Kumar Samal","doi":"10.1002/jbt.70255","DOIUrl":"https://doi.org/10.1002/jbt.70255","url":null,"abstract":"<div>\u0000 \u0000 <p>Atherosclerosis is associated with several illnesses, such as coronary heart disease (CHD), peripheral vascular disease, and ischemic cerebrovascular disease. Atherosclerosis development and accompanying complications are predominantly influenced by Hyperlipidemia, which plays a crucial role. These illnesses are the primary cause of most sickness and death among those who are in their middle age or older. The incidence of dyslipidemia among Chinese adults aged 18 and older is 18.6%, indicating that there are around 160 million individuals affected by this condition. This represents the smallest number of patients globally. This analysis was derived from research undertaken in the field of epidemiology. Hence, developing a comprehensive approach for early prevention and treatment of Hyperlipidemia is imperative. The reason for this is that Hyperlipidemia has the potential to deteriorate progressively. Despite the notable progress made in treating Hyperlipidemia with synthetic drugs, there has been a renewed interest in medicinal plants and phytoconstituents known for their therapeutic capabilities. Asiatic acid, primarily present in <i>Centella asiatica</i> (L.), is classified as one of the phytocompounds that can decrease plasma lipids and lipid peroxidation. This plant may include asiaticoside, asiatic acid, and other components. Asiatic acid has the potential to prevent Hyperlipidemia. The aim of our research is to explore the anti-Hyperlipidemic and anti-atherosclerosis potential of Asiatic acid, which will help to explore its potential mechanism of action and a possibility of its usefulness in this regard.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143861583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of Nano-Microplastics Exposure-Induced Myocardial Fibrosis: DKK3-Mediated Mitophagy Dysfunction and Pyroptosis","authors":"Liang Xiong,&nbsp;Ziyi Xiong,&nbsp;Juan Hua,&nbsp;Qi Chen,&nbsp;Dandan Wang","doi":"10.1002/jbt.70245","DOIUrl":"https://doi.org/10.1002/jbt.70245","url":null,"abstract":"<div>\u0000 \u0000 <p>Nano-microplastics (NMPs), as environmental pollutants, are widely present in nature and pose potential threats to biological health. This study aims to investigate the mechanisms by which NMPs inhibit mitophagy through the suppression of dickkopf-related protein 3 (DKK3) expression, leading to NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome-mediated cardiomyocyte pyroptosis and promoting myocardial fibrosis. Healthy adult male C57BL/6 mice were administered NMP solution via gavage, and their cardiac function was monitored. The results showed that NMP exposure significantly reduced left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) and increased the extent of myocardial fibrosis. Transcriptome sequencing identified 14 differentially expressed genes (DEGs), including MYL7. Using the random forest algorithm and functional enrichment analysis, DKK3 was identified as a key gene. In Vitro experiments further confirmed that NMPs downregulate DKK3 expression, thereby inhibiting mitophagy and promoting cardiomyocyte pyroptosis. This study elucidates the molecular mechanisms by which NMPs induce myocardial fibrosis and provides new theoretical bases and molecular targets for the diagnosis and treatment of heart diseases.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143861586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resveratrol—A Herbal Immunomodulator, Ameliorates Experimental Autoimmune Myasthenia Gravis by Regulating the Foxo1-Foxp3 Pathway","authors":"Heyun Cheng,&nbsp;Yunan Shan,&nbsp;Xiaoyue Shen,&nbsp;Yanbin Li","doi":"10.1002/jbt.70265","DOIUrl":"https://doi.org/10.1002/jbt.70265","url":null,"abstract":"<div>\u0000 \u0000 <p>Resveratrol (RES), extracted from traditional Chinese medicinal plants, demonstrates notable potential in managing autoimmune diseases by modulating multiple pathways and targeting various immune cell subsets with minimal adverse effects. Current treatments for a novel form of myasthenia gravis (MG) face challenges such as inconsistent efficacy and numerous side effects. The exact mechanisms by which RES affects MG progression remain unclear. To investigate RES's impact on MG, an experimental model was created using <i>Lewis female mice</i> immunized with an antigenic emulsion from the 97–116 region of the <i>rat AChR alpha subunit</i> (R97-116 peptide). RES was administered orally in varying doses. Following treatment, the experimental autoimmune myasthenia gravis (EAMG) model was assessed through several metrics, including EAMG score, autoantibody levels, and antibody affinity via ELISA. Network pharmacology was employed to construct the RES action pathway. Validation of RES effects on immune cell pathways in immune organs was performed using Western blot, real-time PCR, immunofluorescence, and immunohistochemistry, with dendritic cells (DCs) in vitro confirming the pathway. Flow cytometry was used for immunophenotyping. RES mitigated EAMG clinical symptoms and reduced both autoantibody content and affinity in serum. Network pharmacology identified the Foxo1/Foxp3 pathway as integral to RES's therapeutic effects on MG. In the RES-treated group, Foxo1 and Foxp3 expression levels were elevated in the spleen, lymph nodes, and thymus. In vitro experiments indicated decreased Foxp3 expression following Foxo1 inhibition in DCs. Flow cytometry revealed an increase in regulatory DCs, reduced DC activation, and diminished lymphocyte proliferation stimulation. Concurrently, Treg levels increased while germinal center B cells decreased. RES can serve as a potential drug for the treatment of MG, as it can regulate DC cells and other immune cells by affecting the Foxo1/Foxp3 pathway.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143861584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HHLA3 Silencing Suppresses KRAS-Mutant Non-Small-Cell Lung Cancer Cell Progression Through Triggering MYEOV-Mediated Ferroptosis","authors":"Zhimiao Tang,&nbsp;Jia Ye,&nbsp;Dong Chen","doi":"10.1002/jbt.70271","DOIUrl":"https://doi.org/10.1002/jbt.70271","url":null,"abstract":"<div>\u0000 \u0000 <p>KRAS mutation is one of the most common mutational events in non-small-cell lung cancer (NSCLC). However, due to the complex signaling pathways and high biological heterogeneity of KRAS-mutant NSCLC, the current clinical treatment for patients with KRAS mutations still faces many difficulties. The oncogenic effector in KRAS-mutant NSCLC was screened using GEO data sets. CCK-8, colony formation, transwell, and flow cytometry were conducted to assess the malignant phenotype of KRAS-mutant NSCLC cells. The indicators intracellular Fe²⁺, ROS, GSH, and MDA levels were employed to reflect the ferroptosis of cells. The mechanism of myeloma overexpressed (MYEOV) in KRAS-mutant NSCLC was explored from the perspective of noncoding RNA (ncRNA) and validated by rescue experiments. MYEOV presented a high expression trend in KRAS-mutant NSCLC specimens. MYEOV silencing effectively repressed the malignant phenotype and promoted ferroptosis of NSCLC cells carrying KRAS mutations. Based on bioinformation analysis and a series of rescue experiments, we established the HHLA3/miR-139-5p/MYEOV regulatory network in KRAS-mutant NSCLC cells and disclosed that HHLA3 served as a molecular sponge for miR-139-5p to regulate MYEOV expression. The mechanism of MYEOV and its ncRNA network affecting the progression of KRAS-mutant NSCLC revealed in this study intends to provide a theoretical basis for KRAS-mutant NSCLC treatment.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143861585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Newly Synthesized PW06 Induced Cell Apoptosis in Human Glioblastoma Multiforme GBM 8401 Cells Through Caspase- and Mitochondria-Dependent Pathways","authors":"Jin-Cherng Lien,&nbsp;Sheng-Yao Hsu,&nbsp;Fu-Shin Chueh,&nbsp;Yi-Shih Ma,&nbsp;Yung-Lin Chu,&nbsp;Yu-Cheng Chou,&nbsp;Kuang-Chi Lai,&nbsp;Jaw-Chyun Chen,&nbsp;Yi-Ping Huang,&nbsp;Rick Sai-Chuen Wu","doi":"10.1002/jbt.70264","DOIUrl":"https://doi.org/10.1002/jbt.70264","url":null,"abstract":"<div>\u0000 \u0000 <p>Glioblastoma multiforme (GBM) is the most common, aggressive, and dangerous lethal tumor in the brain, which develops in adults. Currently, the efficiency of chemotherapy treatment for GBM patients is still unsatisfactory. PW06 was synthesized by Dr. Lien's laboratory (China Medical University, Taichung, Taiwan), and it was demonstrated to induce cancer cell apoptosis in human pancreatic carcinoma MIA PaCa-2 cells. However, the anti-cancer activities of PW06 on human GBM cancer cells are not reported. Thus, herein, PW06 was investigated on the anticancer activity on human glioblastoma multiforme GBM 8401 cells. Both PI exclusion and Annexin V/PI double staining methods were conducted for investing cell viability and apoptosis in GBM 8401 cells, respectively; they were analyzed with flow cytometer assay. Results showed that PW06 decreased total viable cell number with the process of cell apoptosis in GBM 8401 cells. Both productions of reactive oxygen species (ROS) and Ca²⁺, affect mitochondria membrane potential (ΔΨm) levels, and activities of caspase-3, -8, and -9 in GBM 8401 cells after exposure with PW06 were assayed by flow cytometer. Results showed that PW06 promoted ROS production and Ca²⁺ release from ER but lowered the levels of ΔΨm, and it also induced higher activities in caspase-3, -8, and -9 in GBM 8401 cells. Evaluation of protein expressions associated with apoptosis in GBM 8401 cells after being incubated with PW06 were conducted by Western blot analysis. Results show that PW06 increased GADD153, BiP, ATF-6α, ATF-6β, eIF2α, eIF2α^pSer51, CHOP, and caspase-4, and they are associated with ER stress-associated protein expression. However, it induced higher pro-apoptotic proteins (Bax and Bad) expression and inhibited anti-apoptotic proteins (Bcl-2, Bcl-xl, and Mcl-1) expression, even promoting higher cleaved caspase-8, -9, and -3 protein expression and increased EndoG and AIF in GBM 8401 cells. Collectively, it may suggest PW06 exits anti-GBM activity to process cell apoptosis in the human GBM 8401 cells in vitro.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143856990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin-Stimulated Mesenchymal Stem Cells-Derived Exosomes Carrying LINC00052 Alleviate Hyperoxic Lung Injury by Promoting miR-152-3p-KLF4-Nrf2 Pathway","authors":"Nan Li,&nbsp;DeYu Fang,&nbsp;Feng Ge,&nbsp;Lin Zhang,&nbsp;Ying Liu,&nbsp;Yan Gao,&nbsp;HongXu Jin","doi":"10.1002/jbt.70241","DOIUrl":"https://doi.org/10.1002/jbt.70241","url":null,"abstract":"<div>\u0000 \u0000 <p>Exposure of the lungs to high O2 levels, can lead to a noninfectious lung damage known as hyperoxia-induced lung injury (HILI). Melatonin stimulation can enhance the efficacy of stem cells in some diseases. This study aims to investigate the mechanism of exosomes secreted by mesenchymal stem cells (MSCs) stimulated by melatonin in HILI. The MSCs-derived exosomes were isolated and identified after stimulation with melatonin, and the neonatal rat model of HILI was constructed. After injection of exosomes and related lentiviruses, the ratio of wet lung to dry lung was calculated to evaluate pulmonary edema. Inflammatory factors in medium or serum were measured by ELISA. HE staining was used to evaluate the pathological status of lung tissue. Masson staining was used to evaluate collagen deposition in lung tissue. Lung cell apoptosis was detected by Tunel staining. In vitro model of HILI was established, CCK-8 and EDU staining were used to detect cell viability and proliferation, and flow cytometry was used to detect cell apoptosis. The binding relationship between LINC00052, miR-152-3p, and KLF4 was verified through bioinformatics websites, dual luciferase reporter experiments, RIP experiments, and RNA pull down experiments. Melatonin-stimulated MSCs-derived exosomes could alleviate HILI. Exosomes had a therapeutic effect on HILI neonatal rats by carrying LINC00052. Inhibition of LINC00052 reversed the therapeutic effect of exosomes on HILI, while low expression of miR-152-3p or inducing KLF4 negated the effect of sh-LINC00052. LINC00052 bound to miR-152-3p. miR-152-3p targeted KLF4. In vitro, melatonin-stimulated MSC-derived exosomes alleviated the cytotoxicity and cell viability inhibition of AEC-II cells induced by hyperoxia. KLF4 overexpression activated NRF2 signaling in AEC-II cells. LINC00052 in MSCs-derived exosomes stimulated by melatonin activates the Nrf2 pathway through the miR-152-3p/KLF4 axis to alleviate HILI, which may be a potential therapeutic approach for HILI.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143857149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}