Journal of Biochemical and Molecular Toxicology最新文献

{"title":"LncRNA PVT1 Promotes Intracranial Aneurysm Development via USP10/KLF4/NLRP3 Axis-Mediated Pyroptosis in Human Cerebral Smooth Muscle Cells","authors":"Min Chen,&nbsp;Zhihong Li,&nbsp;Longbiao Da,&nbsp;Jie Liu,&nbsp;Chun Huang,&nbsp;Zhengjiang Zha","doi":"10.1002/jbt.70102","DOIUrl":"10.1002/jbt.70102","url":null,"abstract":"<div>\u0000 \u0000 <p>Our previous research identified that lncRNA PVT1 is upregulated in patients with IA. However, the precise functions of PVT1 in IA remain unclear. We compared the levels of PVT1, caspase-3, caspase-1, and NLRP3 in normal and IA patients. The GEO database was utilized to evaluate the expression of KLF4 and NLRP3 in IA. In vitro, we constructed transfected plasmids for silencing (si) and overexpression (oe) of PVT1 and USP10. We assessed cell apoptosis and measured the levels of IL-18, IL-1β, NLRP3, ASC, GSDMD-N, cleaved-caspase-3, and cleaved-caspase-1. CHX chase, immunoprecipitation assays, and bioinformatics tools were employed to evaluate the interactions among PVT1, USP10, and KLF4. Significant differences were observed in the levels of PVT1, KLF4, NLRP3, caspase-3, caspase-1, and histological examinations between normal and IA patients. Compared to the oe-NC group, the levels of IL-18, IL-1β, NLRP3, ASC, GSDMD-N, cleaved-caspase-3, and cleaved-caspase-1 were significantly increased in the oe-PVT1 and oe-USP10 groups. The effect of oe-USP10 was completely inhibited in the oe-USP10+si-PVT1 group. The RIPseq database demonstrated that PVT1 interacts with both USP10 and KLF4. The CHX chase assay showed that KLF4 interacts with both USP10 and PVT1. The RIP assay confirmed the interaction between PVT1 and USP10. The Co-IP assay and UbiBrowser indicated that KLF4 interacts with USP10. The ChIP assay demonstrated that KLF4 interacts with NLRP3. PVT1 may play a role in the pathophysiology of IA by regulating the USP10/KLF4/NLRP3 axis-mediated pyroptosis of HCSMCs.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881906","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":"Anti-Hyperlipidemic, Antioxidant, Anti-Inflammatory and Antidiabetic Effect of Brucine Against Streptozotocin-Induced Diabetic Nephropathy in Rats","authors":"Ling Feng,&nbsp;Lei Gao","doi":"10.1002/jbt.70098","DOIUrl":"10.1002/jbt.70098","url":null,"abstract":"<div>\u0000 \u0000 <p>Among the diabetes-related complications, diabetic nephropathy is the major complication and it leads to end-stage renal failure. In the current investigation, we examined the protection of brucine, an alkaloid extracted from the seeds of Strychnos nux vomica plant widely used in traditional Chinese and Indian medicines against diabetic-induced nephropathy. Male Wistar rats were divided into four groups: control, diabetic rats, diabetic-induced + 40 mg/kg brucine-treated rats, and diabetic-induced + 25 mg/kg metformin-treated rats. The 35 mg/kg streptozotocin (STZ) was injected into (i.p.) rats to induce diabetes, and then rats were post-treated with brucine and metformin for 45 days. The food intake, weight gain, fasting blood glucose, HbA1C, insulin, and HOMA-IR values were measured on initial and after completion of treatment to confirm the induction of diabetes by STZ and the antidiabetic effect of brucine. The rats were euthanized on 45th day, and kidney tissue was isolated to assess the nephroprotective effect of brucine. The antioxidant property of brucine was analyzed by measuring the oxidative stress and antioxidant biomarkers. The lipid profiles in the control and treated rats were measured. To assess the nephroprotective effect of brucine KIM-1 protein was measured. The anti-inflammatory property of brucine was assessed by quantifying the levels of pro-inflammatory cytokines i.e., NF-κB, TNF-α, IL-1β, IL-6, TGF-β and to confirm the nephroprotective effect. The histopathological analysis was also performed with H&amp;E staining. Our results suggested that brucine showed potent antidiabetic, antioxidant, antilipidemic, anti-inflammatory, and nephroprotective properties.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881959","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":"Overexpression of lncRNA LINC00294 Induces Cell Cycle Arrest and Apoptosis in Colorectal Cancer by Regulating the miR-499a-5p/LARP4B Axis","authors":"Ke Wang,&nbsp;Yuanhua Nie,&nbsp;Shilong Wang,&nbsp;Dongmin Chang","doi":"10.1002/jbt.70104","DOIUrl":"10.1002/jbt.70104","url":null,"abstract":"<div>\u0000 \u0000 <p>Increasing long noncoding RNAs (lncRNAs) have been found to participate in regulating the progression of colorectal cancer (CRC), which is a common gastrointestinal malignancy. Here, the specific role and mechanisms of lncRNA LINC00294 were investigated in CRC. The expression levels of LINC00294, miR-499a-5p, and La-related protein 4B (LARP4B) in CRC cells (HCT116 and SW620) and tissues were assessed by RT-qPCR. The viability, proliferation, cell cycle, and apoptosis of HCT116 and SW620 cells were determined by CCK-8, EdU, and flow cytometry assays. Protein levels of cell cycle and cell apoptosis markers were measured by western blot analysis. FISH assay was performed to evaluate the subcellular localization of LINC00294 in CRC cells. Luciferase reporter assay, RNA pull-down assay, as well as RIP assay verified the interactions between miR-499a-5p and LINC00294 (or LARP4B). The xenograft model was established in mice to investigate the function of LINC00294 in vivo. LINC00294 presented a decreased expression level in CRC cells and tissues. LINC00294 overexpression suppressed the cell proliferative capacity, promoted cell cycle arrest, and induced cell apoptosis in CRC HCT116 and SW620 cells. LINC00294 interacted with miR-499a-5p, and miR-499a-5p targeted LARP4B. MiR-499a-5p was upregulated while LARP4B was downregulated in CRC cells. In rescue assays, LARP4B knockdown reversed the inhibition of LINC00294 overexpression on malignant phenotypes of HCT116 and SW620 cells. In the xenograft model, LINC00294 overexpression inhibited tumor growth in vivo. LINC00294 exerted an antitumor function in CRC by forming a LINC00294/miR-499a-5p/LARP4B regulatory network.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882030","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":"miR-105-5p/PTEN Axis Modulates the Immune Response and Epithelial-Mesenchymal Transition of Colon Cancer via NF-κB Activation","authors":"Fei Yao,&nbsp;Biwen Hu,&nbsp;SenJuan Li,&nbsp;Chenxi Cao,&nbsp;Yiting Ling","doi":"10.1002/jbt.70103","DOIUrl":"10.1002/jbt.70103","url":null,"abstract":"<div>\u0000 \u0000 <p>The underlying regulating mechanisms of miR-105-5p/PTEN in colon cancer (CC) progression are still unknown. MiR-105-5p and PTEN expressions were determined using RT-PCR. PTEN protein levels were examined by western blot. Also, the contents of inflammatory cytokines (IL–1β, TNF–α, and IL-6) were measured via ELISA. An inflammation model was constructed via LPS. NF–κB p65 expression was assessed via immunofluorescence assay. A xenograft tumor model was constructed in BALB/c nude mice. The functions of miR-105-5p were investigated by establishing a xenograft tumor model, H&amp;E staining, TUNEL assay, immunohistochemistry assay, ELISA, RT-PCR, and western blot. In this research, We found that miR-105-5p expressions were upregulated in CC cells. MiR-105-5p depletion notably augmented PTEN expressions and enhanced immune response, while impeded EMT and distinctly declined the levels of p-IκBα and Nuc-NF-κB p65 in LoVo cells. Whereas, these effects were notably counteracted by PTEN depletion. MiR-105-5p upregulation exerted the opposite effects in CaCo2 cells. LPS markedly increased miR-105-5p expressions and suppressed PTEN expressions in LoVo cells. MiR-105-5p depletion offset LPS-triggered promoting effects on EMT and suppressing effects on the immune response. Meanwhile, in vivo assay proved that miR-105-5p depletion markedly impeded tumor growth and EMT, yet facilitated apoptosis and immune response. It also distinctly deactivated the NF-κB pathway. To sum up, these data indicated that miR-105-5p depletion might impede EMT, yet enhance the immune response in CC by elevating PTEN expressions via deactivation of the NF-κB pathway.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882024","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":"Histopathologic and Antioxidant Regulatory Effects of Different Doses of Thymoquinone Against 2,4,6-Trinitrobenzene Sulfonic Acid-Induced Experimental Colitis in Rats","authors":"Ferhat Sirinyıldız,&nbsp;Simge Unay,&nbsp;Adem Keskin","doi":"10.1002/jbt.70110","DOIUrl":"10.1002/jbt.70110","url":null,"abstract":"<div>\u0000 \u0000 <p>The aim of this study was to investigate the potential role of thymoquinone in the treatment of inflammatory bowel disease (IBD) by examining the effects of various doses of thymoquinone on histopathological changes, oxidative stress, and antioxidant markers in basic stamens in a 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model in rats. Thirty-two rats were divided into four groups: control, TNBS, thymoquinone-20 (20 mg/kg), and thymoquinone-50 (50 mg/kg) groups. The basic stamens of 32 rats were used for this experiment. Malondialdehyde, myeloperoxidase, and superoxide dismutase (inhibition rate) levels and histopathological scores (cellular infiltration, tissue integrity disruption, hemorrhagic focus, and mucosal loss) increased in the rats with TNBS, while they decreased with different thymoquinone doses. Glutathione peroxidase levels were decreased in the rats with TNBS, whereas increased with different thymoquinone doses. Furthermore, catalase levels were decreased in the rats with TNBS and increased with a 50 mg/kg thymoquinone dose. Malondialdehyde, catalase, myeloperoxidase, and superoxide dismutase (inhibition rate) levels and cell infiltration, tissue integrity disruption, and hemorrhagic focus scores detected in the thymoquinone-50 group were not different from the healthy control group. In conclusion, thymoquinone may be considered as a potential therapeutic agent in the treatment of IBD.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881904","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":"Sevoflurane Alleviates Myocardial Ischemia/Reperfusion Injury by Targeting the circ_CDR1as/miR-671-5p/HMGA1 Axis","authors":"Zhengnan Zhang,&nbsp;Xi Yang,&nbsp;Baihe Feng,&nbsp;Haibin Huang","doi":"10.1002/jbt.70094","DOIUrl":"10.1002/jbt.70094","url":null,"abstract":"<div>\u0000 \u0000 <p>Sevoflurane (Sev) has a cardioprotective role in myocardial ischemia/reperfusion injury (MI/RI), but its mechanism has not been fully elucidated. This study aimed to investigate whether the circ_CDR1as/miR-671-5p/HMGA1 axis mediates the cardioprotective effect of Sev in MI/RI. Cardiomyocytes underwent hypoxia/reoxygenation (H/R) treatment was used to simulate MI/RI in vitro. H/R cardiomyocytes were then pretreated with Sev to explore the protective effect of Sev on H/R cells. The level of CDR1as/miR-671-5p/HMGA1 axis were detected by RT-qPCR. The proliferation and apoptosis of cardiomyocytes were detected by CCK-8 and flow cytometry. The levels of myocardial injury markers and inflammatory markers were detected by ELISA assay. Finally, the regulatory relationship between CDR1as and miR-671-5p/HMGA1 axis was verified by Dual-luciferase reporting and RNA pull-down assays. Sev Pretreatment can reduce the level of CDR1as and mitigate H/R-induced damage to cardiomyocytes. This Pretreatment lowers the levels of myocardial injury markers, oxidative stress markers, and pro-inflammatory factors in H/R-affected cardiomyocytes. However, CDR1as overexpression inhibits Sev's protective effect on H/R cardiomyocytes. At the molecular mechanism, we found that CDR1as mediates Sev's protective effect through the CDR1as/miR-671-5p/HMGA1 axis. CDR1as increases HMGA1 levels by sponging miR-671-5p, while high HMGA1 levels diminish Sev's protective effect. Sev plays a cardioprotective role in MI/RI by inhibiting the circ_CDR1as/miR-671-5p/HMGA1 axis.</p>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142882035","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":"Vitamin C Ameliorates Potassium Dichromate-Induced Oxidative Stress and Mitochondrial Dysfunction via PGC-1α/Nrf-2/TFAM Pathway","authors":"Sabiha Fatima,&nbsp;Reem H. Alrashoudi,&nbsp;Sana S. Alqarni,&nbsp;Samiyah Alshehri,&nbsp;Sara M. Alsaigh,&nbsp;Abdul Malik,&nbsp;Nikhat J. Siddiqi,&nbsp;Arbila Umrani","doi":"10.1002/jbt.70061","DOIUrl":"10.1002/jbt.70061","url":null,"abstract":"<div>\u0000 \u0000 <p>Exposure to potassium dichromate (K₂Cr₂O₇) is well known for its nephrotoxic effects on humans and animals. This study investigated the protective effects of vitamin C against K₂Cr₂O₇-induced nephrotoxicity, focusing on its impact on altered carbohydrate metabolism, mitochondrial dysfunction, and associated molecular mechanisms in the cortical and medullary kidney segments. Male Wistar rats (<i>n</i> = 8) were divided into four groups: Group I received saline, Group II received a single 250 mg/kg body weight (bwt) intraperitoneal (i.p.) injection of vitamin C, Group III received K₂Cr₂O₇ (15 mg/kg bwt, i.p.), and Group IV received vitamin C 6 h before K₂Cr₂O₇ administration. Vitamin C significantly mitigated K₂Cr₂O₇-induced nephrotoxic effects, restoring normal renal function and histological architecture. It preserved the activities of glycolytic and gluconeogenic enzymes altered by K₂Cr₂O₇. Additionally, vitamin C mitigated K₂Cr₂O₇-induced mitochondrial dysfunction by maintaining tricarboxylic acid (TCA) cycle enzymes, electron transport chain proteins, mitochondrial DNA copy number, and ATP content. It also reduced oxidative stress markers and enhanced antioxidant enzyme activity. The protective mechanism of vitamin C against K₂Cr₂O₇-induced renal damage involved upregulation of the protein expression of peroxisome proliferation-activated receptor-γ coactivator-1α (PGC-1α), which further elevated the protein expression of nuclear factor erythroid 2-related factor-2 (Nrf-2) and transcription factor A, mitochondrial (TFAM), crucial for protecting cells from oxidative stress, enhancing mitochondrial function, and promoting cellular health. Overall, this study highlights the significant protective role of vitamin C against K₂Cr₂O₇-induced renal damage by preserving carbohydrate metabolism and mitigating mitochondrial dysfunction through the PGC-1α/Nrf-2/TFAM pathway, offering valuable insights into its protective mechanisms in nephrotoxicity.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877140","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":"TFAP2A Promotes Cell Progression and Suppresses Ferroptosis in Lung Adenocarcinoma via Activating Transcription of CST1","authors":"Xinyu Luan,&nbsp;Xuxing Peng,&nbsp;Gang Hui,&nbsp;Zichun Wei","doi":"10.1002/jbt.70087","DOIUrl":"10.1002/jbt.70087","url":null,"abstract":"<div>\u0000 \u0000 <p>Lung adenocarcinoma (LUAD) is a common type of lung cancer with complicated pathological mechanism. Transcription Factor AP-2 Alpha (TFAP2A) and Cysteine protease inhibitor 1 (CST1) are upregulated genes in LUAD samples, accordingly, we focused on clarifying the role of TFAP2A/CST1 axis in LUAD. Expression analysis was performed using real-time quantitative polymerase chain reaction and western blot. Cellular behaviors were detected by colony formation assay, EdU assay, wound healing assay and flow cytometry. Ferroptosis was assessed by oxidative indicators, Fe²⁺ level and related proteins. TFAP2A and CST1 interaction was analyzed via ChIP assay and dual-luciferase reporter assay. TFAP2A function in vivo was evaluated by xenograft tumor assay. CST1 was overexpressed in LUAD samples and cells. Downregulation of CST1 inhibited proliferation, migration but it promoted apoptosis and ferroptosis of LUAD cells. TFAP2A interacted with the promoter of CST1 to up-regulate CST1 expression. TFAP2A regulated the malignant behaviors and ferroptosis of LUAD cells by targeting CST1. TFAP2A affected LUAD tumor growth via mediating CST1. All these data proved that TFAP2A/CST1 axis contributed to proliferation, migration while it suppressed apoptosis and ferroptosis in LUAD.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846649","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":"Targeting the SIRT3/MnSOD and JNK/HMGB1/Beclin 1 Axes: Role of Apigenin in Multifaceted Metabolic Intervention in Colorectal Cancer","authors":"Nourhan M. Abdelmaksoud,&nbsp;Ahmed I. Abulsoud,&nbsp;Tamer M. Abdelghany,&nbsp;Shereen Saeid Elshaer,&nbsp;Ahmed Samaha,&nbsp;Nadine W. Maurice,&nbsp;Sherine Maher Rizk,&nbsp;Mahmoud A. Senousy","doi":"10.1002/jbt.70095","DOIUrl":"10.1002/jbt.70095","url":null,"abstract":"<div>\u0000 \u0000 <p>Colorectal cancer (CRC) is the third most prevalent cancer worldwide. While chemotherapy remains the standard treatment approach, natural products have emerged as a promising alternative. Among these, apigenin, a natural flavonoid, has garnered significant attention due to its pro-oxidant and antioxidant properties in various types of cancer. This study aimed to assess the potential impact of apigenin in CRC treatment by targeting mitochondrial SIRT3, HMGB1, and beclin 1-mediated autophagy in a mouse model of CRC. We administered 20 mg/kg of dimethyl hydrazine (DMH) intraperitoneally once weekly for 20 weeks to induce CRC in C57BL/6 mice. After 6 weeks of initiating the study, apigenin was intragastrically co-administered by oral gavage at 25 and 50 mg/kg until the end of week 20. The results revealed significant weight loss, shortening of the colon, and diarrhea in DMH-induced CRC, which are considered the marks of CRC. In addition, histopathological examination revealed dysplastic changes in the DMH-treated group, while no dysplasia was found in the apigenin-treated CRC groups. Importantly, the administration of apigenin to DMH-treated animals has led to a significant reduction of SIRT3 and MnSOD expression levels with a significant increase in LC3-II at either dose and a significant dose-dependent increase in the levels of MDA, c-JNK, HMGB1, and beclin 1 compared to the DMH-treated group. In conclusion, apigenin may have a promising role in suppressing DMH-induced CRC. It elicits a pro-oxidant activity by suppressing the gene expression of SIRT3 and subsequently, its target MnSOD, resulting in increased reactive oxygen species (ROS) and lipid peroxidation. The released ROS, in turn, activates JNK-mediated autophagy by enhancing HMGB1, beclin 1, and LC3-II protein levels.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846647","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":"Dexmedetomidine Regulates Macrophage Phenotype Remodeling Through AMPK/SIRT1 to Alleviate Inflammatory Mediators and Lung Injury","authors":"Yi-si Zhao,&nbsp;Ya-kang Shi,&nbsp;Ke-feng Li,&nbsp;Bei Ma,&nbsp;Shi-hui Lin,&nbsp;Yu Xing,&nbsp;Fang Xu","doi":"10.1002/jbt.70108","DOIUrl":"10.1002/jbt.70108","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is associated with high morbidity and mortality in the intensive care unit (ICU) and can cause excessive inflammation. Dexmedetomidine (DEX) is a drug that exerts anti-inflammatory effects. Identifying the anti-inflammatory mechanism of DEX in the context of ALI/ARDS possesses potential significance for the prevention and treatment of ARDS. In this study, DEX was used to treat mouse models of cecal ligation and puncture (CLP) and lipopolysaccharide (LPS)-stimulated cells. Immunofluorescence, western blot analysis, and flow cytometry were used to detect macrophage phenotypic markers in mice, and western blot analysis, real-time qPCR (RT-qPCR), ELISA, and immunofluorescence were used to detect macrophage phenotype markers in RAW264.7 cells. Flow cytometry was used to detect phenotypic markers of bone marrow-derived macrophages (BMDM). Culture medium collected from macrophages was used to cultivate human non-small cell adenocarcinoma epithelial cells (A549) to detect their aquaporins 1 (AQP1) expression and apoptosis status. Western blot analysis was used to detect the activation of the AMP-activated protein kinase (AMPK)/sirtuin 1(SIRT1) signaling pathway both in vivo and in vitro. The regulatory effect of DEX on macrophage phenotype remodeling was detected by knocking down AMPK expression in cells using AMPK shRNA. The results showed that in both in vivo and in vitro experiments, DEX downregulated the expression of M1 markers (tumor necrosis factor-α [TNF-α], nitric oxide synthase [iNOS], and cluster of differentiation [CD]-86) and upregulated the expression of M2 markers (arginase-1 [ARG-1], interleukin [IL]-10, and CD206) in macrophages. The culture medium of macrophages treated with DEX alleviated the edema and apoptosis of A549 cells. DEX activates the AMPK/SIRT1 signaling pathway in macrophages. After AMPK knockdown, the ability of DEX to regulate macrophage phenotype remodeling decreased. Together, this study suggests that DEX regulates macrophage phenotype remodeling by activating the AMPK/SIRT1 pathway, thereby reducing ALI/ARDS.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142846634","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}