Inflammation最新文献_第4页

SIRT6 Overexpression Enhances Diabetic Foot Ulcer Healing via Nrf2 Pathway Activation. SIRT6过表达通过Nrf2通路激活促进糖尿病足溃疡愈合

IF 4.5 2区医学

Inflammation Pub Date : 2025-04-08 DOI: 10.1007/s10753-025-02297-2

Li Wei, Mengyang Kang, Guofeng Zhang, Yan Meng, Hao Qin

{"title":"SIRT6 Overexpression Enhances Diabetic Foot Ulcer Healing via Nrf2 Pathway Activation.","authors":"Li Wei, Mengyang Kang, Guofeng Zhang, Yan Meng, Hao Qin","doi":"10.1007/s10753-025-02297-2","DOIUrl":"https://doi.org/10.1007/s10753-025-02297-2","url":null,"abstract":"Sirtuin-6 (SIRT6) has a pivotal role in a wide array of cellular biological functions and is linked to the progression of various diseases. Previous findings have identified SIRT6 as a protective modulator against numerous diabetic complications. However, whether SIRT6 exerts a protective role in diabetic foot ulcer (DFU) remains unstudied. This work established a rat model of DFU and evaluated the possible role of SIRT6 in mediating the wound healing in DFU. Marked reductions in SIRT6 levels were observed in wound samples from DFU patients and rats. Increasing SIRT6 expression in wound tissues remarkably decreased wound area, accelerated epithelialisation, increased collagen deposition and improved angiogenesis. Moreover, up-modulation of SIRT6 relieved the oxidative stress and inflammation in DFU rats. The increase of SIRT6 in cultured vascular endothelial cells restrained cell apoptosis, oxidative stress and inflammation elicited by high glucose (HG). HG-impaired migration capacity and angiogenesis of vascular endothelial cells was also recovered by increasing SIRT6 expression. Mechanism research revealed that SIRT6 overexpression reinforced the activation of the Nrf2 pathway in wound tissues of DFU rats and HG-exposed vascular endothelial cells. Pharmacological suppression of Nrf2 reversed the protective effect of SIRT6 overexpression on HG-triggered endothelial dysfunction. The findings of this work indicate that the positive role of SIRT6 in DFU wound healing is related to Nrf2 activation which contributes to the suppression of oxidative stress and inflammation and the improvement of angiogenesis in vascular endothelial cells. This study highlights the previously unaddressed role of SIRT6 in DFU wound healing, providing novel insights into its protective functions. The findings hold significant clinical value by identifying SIRT6 as a promising therapeutic target for improving DFU wound healing.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

MLKL-Mediated Necroptosis Predominantly Contributes to Immune-Associated Myocardial Damage. mlkl介导的坏死性上睑下垂主要导致免疫相关心肌损伤。

IF 4.5 2区医学

Inflammation Pub Date : 2025-04-07 DOI: 10.1007/s10753-025-02298-1

Jinglei Sun, Wenting Wu, Yi Wang, Jiali Zhang, Suhua Qiu, Zhengkun Guan, Chenxia Shi, Jingtao Ma, Yanfang Xu

{"title":"MLKL-Mediated Necroptosis Predominantly Contributes to Immune-Associated Myocardial Damage.","authors":"Jinglei Sun, Wenting Wu, Yi Wang, Jiali Zhang, Suhua Qiu, Zhengkun Guan, Chenxia Shi, Jingtao Ma, Yanfang Xu","doi":"10.1007/s10753-025-02298-1","DOIUrl":"https://doi.org/10.1007/s10753-025-02298-1","url":null,"abstract":"Activated T cells and macrophages play a critical role in immune-associated myocarditis. However, the molecular and cellular mechanisms driving cardiomyocyte damage by immune cells remain poorly understood. In this study, we co-cultured human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with activated human peripheral blood mononuclear cells (aPBMCs) to recapitulate myocardial infiltration of immune cells. Our results demonstrated that aPBMCs induced hiPSC-CMs death in a dose- and time-dependent manner. Transcriptome analysis revealed the activation of several death pathways, including pyroptosis, apoptosis and necroptosis. The time course of immunofluorescence staining of key proteins related to different death pathways demonstrated that necroptosis was the earliest activated pathway. Pharmacological blockade of necroptosis by targeting mixed lineage kinase domain-like protein (MLKL), receptor-interacting protein kinase 1 (RIPK1) and receptor-interacting protein RIPK1 kinase 3 (RIPK3) protected hiPSC-CMs against injury induced by aPBMCs, while inhibitors of pyroptosis and apoptosis showed no protective effect. Moreover, MLKL knockdown in hiPSC-CMs prevented cell death due to aPBMCs challenge. Additionally, we validated the cardioprotective effects of blocking necroptosis in a mouse model of immune checkpoint inhibitors (ICIs)-related myocarditis using a combination of long-term anti-programmed cell death 1 (PD- 1) and anti-cytotoxic T-lymphocyte antigen- 4 (CTLA- 4) antibodies. ICIs led to elevation of myocardial injury markers in serum and activated immune cells infiltration. Furthermore, in vivo administration of a MLKL inhibitor prevented ICIs-induced myocardial injury. In conclusion, our findings suggested that MLKL-mediated necroptosis predominantly contributed to cardiomyocyte death resulting from activated immune cells. Suppressing necroptosis may be an effective therapeutic approach against myocardial damage in myocarditis.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Protective Effects of Vanillic Acid on LPS-induced Acute Lung Injury by Inhibiting STIM1-mediated NLRP3 Inflammasome Activation. 香草酸通过抑制stim1介导的NLRP3炎性体激活对lps诱导的急性肺损伤的保护作用

IF 4.5 2区医学

Inflammation Pub Date : 2025-04-07 DOI: 10.1007/s10753-025-02293-6

Lei Wang, Hai-Dong Li, Xia Sun, Jia-Hui Ni, Gui-Ze Feng, Xiao-Yan Shen, Hong-Bo Weng, Hao Fang

{"title":"The Protective Effects of Vanillic Acid on LPS-induced Acute Lung Injury by Inhibiting STIM1-mediated NLRP3 Inflammasome Activation.","authors":"Lei Wang, Hai-Dong Li, Xia Sun, Jia-Hui Ni, Gui-Ze Feng, Xiao-Yan Shen, Hong-Bo Weng, Hao Fang","doi":"10.1007/s10753-025-02293-6","DOIUrl":"https://doi.org/10.1007/s10753-025-02293-6","url":null,"abstract":"Acute lung injury (ALI), which can progress to acute respiratory distress syndrome (ARDS), has inflammation as a crucial factor, especially the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome involvement. Stromal interaction molecule 1 (STIM1) can block NLRP3 activation, but the mechanism is unclear. Vanillic acid, possessing anti-inflammatory properties, has a role in acute lung injury (ALI) whose specific mechanism remains unclear. This study aimed to investigate the effectiveness of vanillic acid in ALI induced by lipopolysaccharides (LPS) and to elucidate the potential mechanisms. In vitro and in vivo experiments were conducted using cells and a mouse model to find out the impact and underlying mechanisms. We found that vanillic acid demonstrated significant inhibition of IL-1β and IL-18 release triggered by LPS and nigericin in J774A.1 cells. The in vivo findings indicated that vanillic acid not only mitigated acute lung injury but also suppressed NLRP3 inflammasome activation in mice. Mechanistically, vanillic acid inhibited the LPS-induced increase in STIM1 expression through the lysosomal degradation pathway. The reduced STIM1 expression diminished intracellular Ca2+ levels, thereby suppressing inflammasome activation and impeding the cleavage and maturation of Caspase-1 and GSDMD, and eventually attenuating cell pyroptosis. Vanillic acid exerts its inhibitory effects on NLRP3 inflammasome activation by promoting STIM1 degradation, thereby ameliorates ALI through impeding NLRP3-GSDMD mediated pyroptosis. The STIM1-NLRP3 signaling axis represents a promising avenue for potential therapeutic interventions in ALI.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Inflammatory Axis of LncRNA Ftx/miR-382-5p/NRG1 in the Differential Diagnosis and Prognosis of Multiple Sclerosis and Neuromyelitis Optica. LncRNA Ftx/miR-382-5p/NRG1炎症轴在多发性硬化症和视神经脊髓炎鉴别诊断和预后中的作用

IF 4.5 2区医学

Inflammation Pub Date : 2025-04-07 DOI: 10.1007/s10753-025-02284-7

Nadia Mangoud, Mohamed I Hegazy, Shady Estfanous, Sahar A Ali

{"title":"The Inflammatory Axis of LncRNA Ftx/miR-382-5p/NRG1 in the Differential Diagnosis and Prognosis of Multiple Sclerosis and Neuromyelitis Optica.","authors":"Nadia Mangoud, Mohamed I Hegazy, Shady Estfanous, Sahar A Ali","doi":"10.1007/s10753-025-02284-7","DOIUrl":"https://doi.org/10.1007/s10753-025-02284-7","url":null,"abstract":"Multiple sclerosis (MS) and Neuromyelitis Optica (NMO) are immune-related CNS inflammatory diseases that often present with overlapping clinical symptoms, leading to frequent misdiagnosis, particularly in aquaporin-4 seronegative NMO patients. Identifying the underlying mechanisms of these diseases is critical for discovering biomarkers that enable timely diagnosis and effective treatment. This study included 252 participants, divided into four groups. Group I (Relapsing-Remitting MS: RRMS group), Group II (Secondary Progressive MS: SPMS group), Group III (NMO group), and Group IV (Healthy controls). Blood samples were collected from all participants to measure the expression levels of Neuregulin-1 (NRG1), lncRNA Ftx, and miR-382-5p. The results showed that NRG1 levels were significantly lower in the RRMS, SPMS, NMO groups compared to healthy controls, with the most pronounced reduction observed in NMO, suggesting NRG1 may serve as a potential biomarker for differentiating NMO from MS, especially in cases where traditional diagnostic criteria are inconclusive. lncRNA Ftx, a sponge for miR-382-5p, exhibited an opposite trend to miR-382-5p and was significantly downregulated in NMO compared to MS, SPMS, RRMS, and healthy controls, suggesting its potential as a promising biomarker. Our findings highlight the potential of NRG1, lncRNA Ftx, and miR-382-5p expression as diagnostic, screening, and prognostic biomarkers, as well as tools for the differential diagnosis of NMO and MS.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CRISPR/Cas9-Mediated Knockout and Overexpression Studies Unveil the Role of PD-L1 in Immune Modulation in a Psoriasis-like Mouse Model. CRISPR/ cas9介导的敲除和过表达研究揭示了PD-L1在银屑病样小鼠模型中的免疫调节作用。

IF 4.5 2区医学

Inflammation Pub Date : 2025-04-03 DOI: 10.1007/s10753-025-02281-w

Chunjie Gao, Yunxi Cai, Xinxin Wu, Jiankun Song, Qi Zheng, Mingxia Wang, Ying Luo, Yue Luo, Xiaoya Fei, Ying Zhang, Yang Yang, Le Kuai, Yi Ru, Seokgyeong Hong, Na Tian, Bin Li, Zhan Zhang

{"title":"CRISPR/Cas9-Mediated Knockout and Overexpression Studies Unveil the Role of PD-L1 in Immune Modulation in a Psoriasis-like Mouse Model.","authors":"Chunjie Gao, Yunxi Cai, Xinxin Wu, Jiankun Song, Qi Zheng, Mingxia Wang, Ying Luo, Yue Luo, Xiaoya Fei, Ying Zhang, Yang Yang, Le Kuai, Yi Ru, Seokgyeong Hong, Na Tian, Bin Li, Zhan Zhang","doi":"10.1007/s10753-025-02281-w","DOIUrl":"https://doi.org/10.1007/s10753-025-02281-w","url":null,"abstract":"The role of programmed death-ligand 1 (PD-L1), an essential immune checkpoint protein, has garnered considerable interest in recent years due to its influence on immune responses, particularly inhibiting immature Th cells into Th17 cells. This study aims to examine the effect of PD-L1 on psoriasis progress, which is the condition characterized by an immune response dominated by Th17 cells. We constructed the PD-L1 knockout (PD-L1KO) and overexpression (PD-L1OE) mice through CRISPR/Cas9 technology to assess the impact of PD-L1 in an imiquimod (IMQ)-induced psoriasis-like mouse model. In comparison to IMQ, the ear thickness exhibited a reduction, the PASI score decreased, and HE sections revealed a thinning of the epidermal spines in PD-L1OE mice. PD-L1KO mice, however, showed opposite results. Moreover, immunohistochemical assessments of the skin lesion tissues demonstrated heightened epidermal proliferation and inflammatory infiltration in the PD-L1KO group, accompanied by elevated tissue expression of proliferating cell nuclear antigen (PCNA), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) p50, and F4/80 in comparison to IMQ-treated and WT mice. The absence of PD-L1 in IMQ-induced mice was found to intensify the immune response, as evidenced by heightened expression of phosphorylated signal transducers and activators of transcription 3 (pSTAT3) and CD3 in the affected tissues compared to both IMQ-treated and WT mice. According to our findings, PD-L1 plays important roles in inhibiting inflammation, proliferation, and regulating immune responses. Targeting PD-L1 may present a promising therapeutic strategy for the management of psoriasis.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LRRK2 Mediates α-Synuclein-Induced Neuroinflammation and Ferroptosis through the p62-Keap1-Nrf2 Pathway in Parkinson's Disease. LRRK2通过p62-Keap1-Nrf2通路介导帕金森病α-突触核蛋白诱导的神经炎症和铁下垂。

IF 4.5 2区医学

Inflammation Pub Date : 2025-04-02 DOI: 10.1007/s10753-025-02291-8

Xinjie Liu, Zijian Zheng, Cheng Xue, Xiangrong Wang, Jianwei Li, Zheng Liu, Wenqiang Xin, Xinping Xu, Dongwei Zhou, Longping Yao, Guohui Lu

{"title":"LRRK2 Mediates α-Synuclein-Induced Neuroinflammation and Ferroptosis through the p62-Keap1-Nrf2 Pathway in Parkinson's Disease.","authors":"Xinjie Liu, Zijian Zheng, Cheng Xue, Xiangrong Wang, Jianwei Li, Zheng Liu, Wenqiang Xin, Xinping Xu, Dongwei Zhou, Longping Yao, Guohui Lu","doi":"10.1007/s10753-025-02291-8","DOIUrl":"https://doi.org/10.1007/s10753-025-02291-8","url":null,"abstract":"Parkinson's disease (PD) is the second most prevalent neurodegenerative disorder worldwide, characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta and the abnormal aggregation of α-synuclein (α-syn). Despite extensive research, the mechanisms underlying microglial-mediated neuroinflammation and ferroptosis in PD remain inadequately understood. In particular, the role of leucine-rich repeat kinase 2 (LRRK2) in microglial cells and its modulation of the p62-Keap1-Nrf2 signaling pathway warrant further investigation.In this study, we present novel findings demonstrating that LRRK2 regulates microglial neuroinflammation and ferroptosis through the p62-Keap1-Nrf2 signaling axis in the context of PD. Using α-syn-stimulated BV2 microglial cells, we found that LRRK2 inhibition significantly reduced the production of pro-inflammatory cytokines and enhanced the activation of the p62-Keap1-Nrf2 pathway, thereby mitigating ferroptosis and oxidative stress. Furthermore, conditioned medium from LRRK2-inhibited microglia conferred neuroprotective effects on cultured neurons, highlighting the therapeutic potential of targeting LRRK2 in microglia.Importantly, these in vitro findings were corroborated in the MPTP-induced PD mouse model, where LRRK2 inhibition led to diminished microglial activation, decreased apoptosis of midbrain dopaminergic neurons, and upregulation of the p62-Keap1-Nrf2 pathway.Our study fills a critical gap in understanding the microglial mechanisms mediated by LRRK2 and provides novel insights into the pathogenesis of PD. These findings suggest that targeting LRRK2 in microglia may represent a promising therapeutic strategy for PD.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Non-Canonical STING-PERK Pathway Modulation of Cellular Senescence and Therapeutic Response in Sepsis-Associated Acute Kidney Injury. 脓毒症相关急性肾损伤中细胞衰老和治疗反应的非典型 STING-PERK 通路调控

IF 4.5 2区医学

Inflammation Pub Date : 2025-04-01 Epub Date: 2024-06-24 DOI: 10.1007/s10753-024-02081-8

Yuxin Dong, Guanghe Liu, Xiaonan Situ, Lei Xia, Tianyi Zhang, Xiangxi Zhu, Heng Jin, Yancun Liu, Songtao Shou

{"title":"Non-Canonical STING-PERK Pathway Modulation of Cellular Senescence and Therapeutic Response in Sepsis-Associated Acute Kidney Injury.","authors":"Yuxin Dong, Guanghe Liu, Xiaonan Situ, Lei Xia, Tianyi Zhang, Xiangxi Zhu, Heng Jin, Yancun Liu, Songtao Shou","doi":"10.1007/s10753-024-02081-8","DOIUrl":"10.1007/s10753-024-02081-8","url":null,"abstract":"Abstract-This study explored the role of the non-canonical STING-PERK signaling pathway in sepsis-associated acute kidney injury (SA-AKI). Gene expression data from the GEO database and serum STING protein levels in patients with SA-AKI were analyzed. An LPS-induced mouse model and an in vitro model using HK-2 cells were used to investigate the role of STING in SA-AKI. STING expression was suppressed using shRNA silencing technology and the STING inhibitor C176. Kidney function, inflammatory markers, apoptosis, and senescence were measured. The role of the STING-PERK pathway was investigated by silencing PERK in HK-2 cells and administering the PERK inhibitor GSK2606414. STING mRNA expression and serum STING protein levels were significantly higher in patients with SA-AKI. Suppressing STING expression improved kidney function, reduced inflammation, and inhibited apoptosis and senescence. Silencing PERK or administering GSK2606414 suppressed the inflammatory response, cell apoptosis, and senescence, suggesting that PERK is a downstream effector in the STING signaling pathway. The STING-PERK signaling pathway exacerbates cell senescence and apoptosis in SA-AKI. Inhibiting this pathway could provide potential therapeutic targets for SA-AKI treatment.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"696-712"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dibenzazepine, a γ-Secretase Enzyme Inhibitor, Protects Against Doxorubicin-Induced Cardiotoxicity by Suppressing NF-κB, iNOS, and Hes1/Hey1 Expression. γ-分泌酶抑制剂二苯扎西平通过抑制 NF-κB、iNOS 和 Hes1/Hey1 的表达来防止多柔比星诱发的心脏毒性

IF 4.5 2区医学

Inflammation Pub Date : 2025-04-01 Epub Date: 2024-07-30 DOI: 10.1007/s10753-024-02046-x

Amira M Badr, Hind N Alotaibi, Naglaa El-Orabi

{"title":"Dibenzazepine, a γ-Secretase Enzyme Inhibitor, Protects Against Doxorubicin-Induced Cardiotoxicity by Suppressing NF-κB, iNOS, and Hes1/Hey1 Expression.","authors":"Amira M Badr, Hind N Alotaibi, Naglaa El-Orabi","doi":"10.1007/s10753-024-02046-x","DOIUrl":"10.1007/s10753-024-02046-x","url":null,"abstract":"Doxorubicin (DOX) is an effective chemotherapeutic drug; however, its cardiotoxicity and resistance compromise its therapeutic index. The Notch pathway was reported to contribute to DOX cancer resistance. The role of Notch pathway in DOX cardiotoxicity has not been identified yet. Notch receptors are characterized by their extracellular (NECD) and intracellular (NICD) domains (NICD). The γ-secretase enzyme helps in the release of NICD. Dibenzazepine (DBZ) is a γ-secretase inhibitor. The present study investigated the effect of Notch pathway inhibition on DOX cardiotoxicity. Twenty-four male Wistar rats were divided into four groups: control group, DOX group, acute cardiotoxicity was induced by a single dose of DOX (20 mg/kg) i.p., DOX (20 mg/kg) plus DBZ group, and DBZ group. The third and fourth groups received i.p. injection of DBZ daily for 14 days at 2 mg/kg dose. DOX cardiotoxicity increased the level of serum creatine kinase-MB and cardiac troponin I, and it was confirmed by the histopathological examination. Moreover, the antioxidants glutathione peroxidase and superoxide dismutase levels were markedly decreased, and the inflammatory markers, inducible nitric oxide synthase, nuclear factor-ķB, and tumor necrosis factor-α were markedly increased. Furthermore, DOX increased BAX protein and downregulated BCL-2. In addition, DOX upregulated Notch pathway-related parameters: Hes1 and Hey1 mRNA levels, and increased Hes1 protein levels. DBZ ameliorated DOX-induced cardiotoxicity, evidenced by reducing the cardiac injury biomarkers, improving cardiac histopathological changes, correcting antioxidant levels, and reducing inflammatory and apoptotic proteins. Our study indicates the protective effect of Notch inhibitor against DOX-induced cardiotoxicity.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"557-574"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141792454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Increased Tryptophan Catabolism Provides Predictive Value to Chronic Heart Failure Patients with Low-Grade Inflammation. 色氨酸分解增加可预测慢性心力衰竭患者的低度炎症。

IF 4.5 2区医学

Inflammation Pub Date : 2025-04-01 Epub Date: 2024-07-16 DOI: 10.1007/s10753-024-02100-8

Huiqing Wang, Junfang Wu, Haoran Wei, Yuxuan Zhang, Yinhui Wang, Dao Wen Wang

{"title":"Increased Tryptophan Catabolism Provides Predictive Value to Chronic Heart Failure Patients with Low-Grade Inflammation.","authors":"Huiqing Wang, Junfang Wu, Haoran Wei, Yuxuan Zhang, Yinhui Wang, Dao Wen Wang","doi":"10.1007/s10753-024-02100-8","DOIUrl":"10.1007/s10753-024-02100-8","url":null,"abstract":"Kynurenine to tryptophan ratio (KTR), which serves as an indicator for evaluating indoleamine-2,3-dioxygenase activity and inflammation, has been reported to be linked with cardiovascular incidences. However, its correlation with cardiovascular outcomes in patients suffering from heart failure (HF) remains to be explored. The objective of this study was to investigate the prognostic value of KTR in HF. The concentration of tryptophan and kynurenine were quantified by liquid chromatography-tandem mass spectrometry, and the KTR value was calculated in a population of 3150 HF patients. The correlation between plasma KTR levels and the occurrence of adverse cardiovascular events was evaluated for its prognostic value. We also assessed the role of KTR in addition to the classic inflammatory biomarker hypersensitive C-reactive protein (hs-CRP) in different subtypes of HF. We found that increased KTR levels were associated with an elevated risk and severity of the primary endpoints in different subtypes of HF. The simultaneous evaluation of KTR and hs-CRP levels enhanced risk categorization among HF patients. Furthermore, the KTR index presented complementary prognostic value for those HF patients with low-grade inflammation (hs-CRP ≤ 6 mg/L). Our results indicated plasma KTR is an independent risk factor for cardiovascular events. Plasma KTR levels in patients with HF can provide both concurrent and complementary prognostic value to hs-CRP.","PeriodicalId":13524,"journal":{"name":"Inflammation","volume":" ","pages":"963-973"},"PeriodicalIF":4.5,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Melatonin via MTNR1B regulates METTL3 to protect ileum cell differentiation. 褪黑激素通过MTNR1B调节METTL3，保护回肠细胞分化。

IF 4.5 2区医学

Inflammation Pub Date : 2025-04-01 Epub Date: 2024-07-17 DOI: 10.1007/s10753-024-02098-z

Yuanyuan Li, Yan Sun, Yaoxing Chen, Yulan Dong

引用次数: 0