Advanced biology最新文献

Hyperoxia Induced Alteration of Chromatin Structure in Human Bone Marrow Derived Primary Mesenchymal Stromal Cells. 高氧诱导人骨髓原代间充质间质细胞染色质结构的改变。

IF 3.2 3区生物学

Advanced biology Pub Date : 2025-06-10 DOI: 10.1002/adbi.202400314

Lauren Monroe, Samantha Kaonis, Natalie Calahan, Neda Kabi, Soham Ghosh

{"title":"Hyperoxia Induced Alteration of Chromatin Structure in Human Bone Marrow Derived Primary Mesenchymal Stromal Cells.","authors":"Lauren Monroe, Samantha Kaonis, Natalie Calahan, Neda Kabi, Soham Ghosh","doi":"10.1002/adbi.202400314","DOIUrl":"https://doi.org/10.1002/adbi.202400314","url":null,"abstract":"In eukaryotic cell nuclei, chromatin exhibits a high degree of structural and functional dynamics. Recent findings suggest that chromatin has the ability to reorganize in response to changes within the cellular microenvironment. Such changes include oxidative stress found in hyperoxia. While hyperoxia is recognized for causing DNA damage and disrupting cellular functions, the effects it has on chromatin structure and the implications thereof remain poorly understood. In this work, an imaging-based technique is developed to visualize and characterize nanoscale chromatin remodeling under hyperoxia in mesenchymal stromal cells, created via hydrogen peroxide treatment. High spatiotemporal variability of remodeling in different chromatin domains is found. Chromatin remodeling is hindered by the GSK126-mediated inhibition of methyltransferase EZH2, which regulates the chromatin compaction. Independent assays such as ATAC seq further revealed that chromatin is compacted by hyperoxia, which is mitigated by GSK126 pretreatment. Epigenetic modifications and DNA damage under hyperoxia is investigated, which is also found to be affected by the pretreatment of GSK126. The techniques and discoveries provide mechanistic insights into chromatin remodeling, potentially paving the way for novel therapeutic strategies to combat genotoxic oxidative stress-commonly associated with degenerative diseases and aging-and to enhance cell-based therapies in regenerative medicine.","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e00314"},"PeriodicalIF":3.2,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144257085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Apolipoprotein A-I Binding Protein: Functions, Mechanisms, and Therapeutic Targets in Neurological Disorders. 载脂蛋白A-I结合蛋白：神经系统疾病的功能、机制和治疗靶点。

IF 3.2 3区生物学

Advanced biology Pub Date : 2025-06-04 DOI: 10.1002/adbi.202500012

Zijian Zhang, Yingjun Wang, Hao Yang, Yanhong Jiang, Guyuan Wang, Renfang Mao

引用次数: 0

HMGB1 Derived from the Pyroptotic Microenvironment Promotes Macrophage Extracellular Traps in Hirschsprung-Associated Enterocolitis. 来自热噬微环境的HMGB1促进巨噬细胞细胞外陷阱在hirschsphen相关的小肠结肠炎。

IF 3.2 3区生物学

Advanced biology Pub Date : 2025-06-04 DOI: 10.1002/adbi.202400761

Rui Zhang, Jing Li, Lili Song, Liya Pan, Chengchen Zhang, Zhiyan Zhan, Li Hong

{"title":"HMGB1 Derived from the Pyroptotic Microenvironment Promotes Macrophage Extracellular Traps in Hirschsprung-Associated Enterocolitis.","authors":"Rui Zhang, Jing Li, Lili Song, Liya Pan, Chengchen Zhang, Zhiyan Zhan, Li Hong","doi":"10.1002/adbi.202400761","DOIUrl":"https://doi.org/10.1002/adbi.202400761","url":null,"abstract":"Hirschsprung-associated enterocolitis (HAEC) is the most common and severe complication in patients with Hirschsprung's disease (HSCR) and is characterized by high morbidity, frequent recurrence and substantial mortality. The formation of macrophage extracellular traps (METs), a novel inflammatory mode of cell death, plays a significant role in the progression of various inflammatory diseases. However, the mechanisms underlying METs formation and their role in the progression of HAEC remain unclear. Here, the findings indicate that METs formation induced by the pyroptotic microenvironment enhances inflammatory responses and induces colonic epithelial cells (CECs) injury in HAEC. Mechanistically, high mobility group box 1 protein (HMGB1), derived from this pyroptotic environment, mediates METs formation through toll-like receptor 4 (TLR4)-p38 MAPK/p65 NF-kB signaling pathways. Furthermore, incubation of CECs with METs induces suppression of cell viability, more production of reactive oxygen species (ROS) and pyroptosis. In conclusion, HMGB1 mediates the communication between pyroptotic microenvironment and METs formation, triggering enhanced inflammatory responses and damage to CECs. Targeting HMGB1 presents a potential therapeutic strategy for HAEC.","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e00761"},"PeriodicalIF":3.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Using a Supramolecular Approach to Engineer Modular Hydrogel Platforms for Culturing Protoplasts - from General Tissue Engineering to Cellular Agriculture. 利用超分子方法设计模块化水凝胶平台用于培养原生质体-从一般组织工程到细胞农业。

IF 3.2 3区生物学

Advanced biology Pub Date : 2025-06-04 DOI: 10.1002/adbi.202400690

Maritza M Rovers, Erik J Slootweg, Ferdinand C O Los, Patricia Y W Dankers

{"title":"Using a Supramolecular Approach to Engineer Modular Hydrogel Platforms for Culturing Protoplasts - from General Tissue Engineering to Cellular Agriculture.","authors":"Maritza M Rovers, Erik J Slootweg, Ferdinand C O Los, Patricia Y W Dankers","doi":"10.1002/adbi.202400690","DOIUrl":"https://doi.org/10.1002/adbi.202400690","url":null,"abstract":"Protoplast regeneration into plant cells and further into plants is an ongoing challenge in agricultural biotechnology. Inspired by mammalian tissue engineering, a strategic shift is proposed in plant tissue engineering to steer protoplast culture using fully synthetic materials-based culture platforms. Here a supramolecular materials method to engineer modular culture methods for protoplasts is chosen to use. Supramolecular monomers as modular building blocks allow to make various hydrogel formulations and to study different protoplast cultures; including 2D cultures on top of supramolecular hydrogels, 2.5D cultures using supramolecular fibers in solution, and 3D cultures when encapsulated in bulk hydrogels or microgels. Importantly, the need is shown for bioactive functionalization of the supramolecular hydrogels with a peptide additive in 2D protoplast cultures. After 11 days, the bioactive hydrogel induced protoplast enlargement, which is absent on pristine hydrogels. The opposite effect is present for protoplasts cultured in 3D, showing plasmolysis as a result of the bioactive additive. Interestingly, in 2.5D lower bioactive additive concentrations in supramolecular fibers stimulated protoplast enlargement, demonstrated by similar morphological changes as in 2D. Finally, protoplast encapsulation in supramolecular microgels is showcased. This work demonstrates the potential to modularly engineer various synthetic platforms to facilitate cellular agriculture.","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e00690"},"PeriodicalIF":3.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oncogenic miR-182-5p Targets NCOA4 to Disrupt the NCOA4-FTH1 Axis-Mediated Ferroptosis in Head and Neck Squamous Cell Carcinoma. 致癌性miR-182-5p靶向NCOA4破坏NCOA4- fth1轴介导的头颈部鳞状细胞癌中铁下垂。

IF 3.2 3区生物学

Advanced biology Pub Date : 2025-06-04 DOI: 10.1002/adbi.202400832

Wulin Wen, Jia Zhao, Wuxia Zhao, Simin Zhu, Yongchun Li, Le Wang, Lina Xie, Tian Liu, Mengyu Zhang, Ruixia Ma

{"title":"Oncogenic miR-182-5p Targets NCOA4 to Disrupt the NCOA4-FTH1 Axis-Mediated Ferroptosis in Head and Neck Squamous Cell Carcinoma.","authors":"Wulin Wen, Jia Zhao, Wuxia Zhao, Simin Zhu, Yongchun Li, Le Wang, Lina Xie, Tian Liu, Mengyu Zhang, Ruixia Ma","doi":"10.1002/adbi.202400832","DOIUrl":"https://doi.org/10.1002/adbi.202400832","url":null,"abstract":"Head and neck squamous cell carcinoma (HNSCC) is characterized by a high recurrence rate and poor prognosis. Ferroptosis, a regulated cell death, plays a significant role in inhibiting tumor progression. However, its role and regulatory mechanisms in HNSCC remain unclear. In this study, the expression of ferroptosis-related molecules in HNSCC is analysed and NCOA4 and FTH1 are identified as prognostic markers. TU177 and TU686 cells are transfected with plasmids for the overexpression or knockdown of NCOA4 and FTH1. MTT assays demonstrated reduced cell viability following either NCOA4 overexpression or FTH1 knockdown alone. Concurrently, ferroptosis hallmarks such as iron overload and ROS overproduction are upregulated in these conditions. Conversely, NCOA4 knockdown or FTH1 overexpression has the opposite effects. Furthermore, miR-182-5p is found to be significantly upregulated in HNSCC tissues. Mechanistic studies revealed that miR-182-5p directly binding to the NCOA4 3' UTR, leading to the downregulation of NCOA4 expression and suppression of NCOA4/FTH1-mediated ferroptosis. In conclusion, the finding elucidate the role of miR-182-5p/NCOA4/FTH1 signaling axis in regulating ferroptosis in HNSCC and provide insights into the molecular mechanism underlying ferroptosis in HNSCC cells.","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e00832"},"PeriodicalIF":3.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Retrotransposon Expression Is Upregulated in Adulthood and Suppressed during Regeneration of the Limb in the Axolotl (Ambystoma mexicanum). 反转录转座子的表达在成年期上调，在蝾螈（Ambystoma mexicanum）肢体再生期间被抑制。

IF 3.2 3区生物学

Advanced biology Pub Date : 2025-05-29 DOI: 10.1002/adbi.202400502

Samuel Ruiz-Pérez, Nicolás Alcaraz, Karla Torres-Arciga, José Antonio Ocampo-Cervantes, Alejandra Cervera, Clementina Castro-Hernández, Cynthia Gabriela Sámano-Salazar, Ernesto Soto-Reyes, Rodrigo González-Barrios

{"title":"Retrotransposon Expression Is Upregulated in Adulthood and Suppressed during Regeneration of the Limb in the Axolotl (Ambystoma mexicanum).","authors":"Samuel Ruiz-Pérez, Nicolás Alcaraz, Karla Torres-Arciga, José Antonio Ocampo-Cervantes, Alejandra Cervera, Clementina Castro-Hernández, Cynthia Gabriela Sámano-Salazar, Ernesto Soto-Reyes, Rodrigo González-Barrios","doi":"10.1002/adbi.202400502","DOIUrl":"https://doi.org/10.1002/adbi.202400502","url":null,"abstract":"The axolotl (Ambystoma mexicanum) has a great capacity to regenerate its tissues; however, the fidelity and success of its regenerative process diminish with age. Retrotransposons make up the largest portion of the axolotl genome, and their expression may be involved in this age-related decline. Through an integrative analysis of repetitive element expression using RNA sequencing, it is shown that Ty3 retrotransposons are highly upregulated in the axolotl as an effect of chronological aging. Other non-long-terminal-repeat transposons, including long interspersed nuclear element 1, function as hubs of gene coexpression networks involved in muscle development and regulation of apoptosis and connective tissue replacement, which are also suppressed in adulthood. By contrast, it is found that during regeneration of the limb, these pathways and the expression of Ty3 retrotransposons are distinctly downregulated. Although the blastema can readjust most of the transposon differential expression in adulthood, several elements remain affected and may have an impact in the immune response during regeneration. This analysis provides a profile of retrotransposon expression through chronological aging and during limb regeneration in the axolotl and indicates that transposons are responsive to physiological changes in a tissue-specific way and may participate in the gene coregulatory networks underlying the regenerative process.","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e00502"},"PeriodicalIF":3.2,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IFN-γ Synergizes with TNF-α to Induce RIPK1-Independent Necroptosis of Mesenchymal Stem/Stromal Cells. IFN-γ与TNF-α协同诱导间充质干细胞/间质细胞不依赖ripk1的坏死凋亡

IF 3.2 3区生物学

Advanced biology Pub Date : 2025-05-28 DOI: 10.1002/adbi.202400577

Ren Xiang, Huo Jiali, Li Xingxin, Wang Min, Jin Peng, Nie Neng, Zhang Jing, Zheng Yizhou, Huang Jinbo, Ge Meili

{"title":"IFN-γ Synergizes with TNF-α to Induce RIPK1-Independent Necroptosis of Mesenchymal Stem/Stromal Cells.","authors":"Ren Xiang, Huo Jiali, Li Xingxin, Wang Min, Jin Peng, Nie Neng, Zhang Jing, Zheng Yizhou, Huang Jinbo, Ge Meili","doi":"10.1002/adbi.202400577","DOIUrl":"https://doi.org/10.1002/adbi.202400577","url":null,"abstract":"IFN-γ and TNF-α are two vital inflammatory factors elevated aberrantly in many diseases. Such an inflammatory microenvironment is detrimental to residual cells such as mesenchymal stem cells (MSCs), yet the precise mechanisms are not fully understood. IFN-γ and TNF-α have distinct effects on the immunoregulatory properties of MSCs, and they have been proposed as optimal priming factors to enhance the immunosuppressive capacity of engineered MSCs. Thus, the overall effects of IFN-γ and/or TNF-α exposure on MSCs needs to be elucidated. Here, it is found that IFN-γ and TNF-α synergistically induce cell death of MSCs via necroptosis. When MSCs are exposed to both IFN-γ and TNF-α, their morphological features and biological functions are impaired. Mechanistically revealed by RNA-Sequencing, the injured MSCs undergo a unique cell death process, namely necroptosis. Compared with controls, IFN-γ synergized with TNF-α to increase the expression of RIPK1, RIPK3, MLKL, and all other genes associated with necroptosis. Rescue experiments further demonstrate that this process can be reversed by RIPK3 and MLKL inhibitors but not by the RIPK1 inhibitor, suggesting a RIPK1-independent pathway. Collectively, this study discloses an inflammatory injury mechanism of MSCs, which may shed new light on revealing the MSCs deficits in many inflammatory diseases with expectations to inspire potential targeted therapies. In addition, inflammatory impairment should be taken into consideration when delivering cell therapy based on MSCs primed with IFN-γ and TNF-α.","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e00577"},"PeriodicalIF":3.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting Ferroptosis Alleviates Pulmonary Arterial Hypertension, Insights from Transcriptomic and Experimental Analyses. 靶向铁下垂减轻肺动脉高压，转录组学和实验分析的见解。

IF 3.2 3区生物学

Advanced biology Pub Date : 2025-05-28 DOI: 10.1002/adbi.202500001

Xiaowan Wang, Qiang Guo

{"title":"Targeting Ferroptosis Alleviates Pulmonary Arterial Hypertension, Insights from Transcriptomic and Experimental Analyses.","authors":"Xiaowan Wang, Qiang Guo","doi":"10.1002/adbi.202500001","DOIUrl":"https://doi.org/10.1002/adbi.202500001","url":null,"abstract":"Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling driven by endothelial cell injury. This study investigates the role of ferroptosis in PAH development and its underlying molecular mechanisms. Ferroptosis-related gene expression is analyzed using transcriptomic and single-cell RNA sequencing data. A PAH mouse model is induced by combined hypoxia and Semaxanib (SU5416) treatment. The impact of ferroptosis on pulmonary vascular remodeling is evaluated by measuring right ventricular systolic pressure (RVSP), the Fulton index, vascular wall thickness, and histological changes in pulmonary arteries. Transcriptomic analysis reveals downregulation of SLC7A11 and upregulation of ACSL1 and ACSL4 in PAH patients. Endothelial cells are identified as key mediators of ferroptosis, and inhibiting ferroptosis alleviates endothelial damage and vascular remodeling. Additionally, HIF1α signaling plays a crucial role in ferroptosis induction in PAH. These findings highlight ferroptosis as a critical mechanism of endothelial injury and a key contributor to PAH pathogenesis. Targeting ferroptosis offers promising new strategies for early intervention and targeted therapy in PAH.","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e00001"},"PeriodicalIF":3.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Flow Cytometry and Gene Expression Modulation by Euphorbia rigida Methanol Extract in A549 Lung Cancer Cells: Induction of Apoptosis Through Bax, Caspase-9, and Bcl-2 Pathways. 大大麻甲醇提取物对A549肺癌细胞的流式细胞术和基因表达调控：通过Bax、Caspase-9和Bcl-2途径诱导凋亡

IF 3.2 3区生物学

Advanced biology Pub Date : 2025-05-28 DOI: 10.1002/adbi.202500136

Zeynep Betül Sarı, Muhammed Emin Sarı, Erdi Can Aytar, Abidin Gümrükçüoğlu, Emine Incilay Torunoğlu, Tuba Ozdemir-Sanci, Gamze Demirel, Alper Durmaz

{"title":"Flow Cytometry and Gene Expression Modulation by Euphorbia rigida Methanol Extract in A549 Lung Cancer Cells: Induction of Apoptosis Through Bax, Caspase-9, and Bcl-2 Pathways.","authors":"Zeynep Betül Sarı, Muhammed Emin Sarı, Erdi Can Aytar, Abidin Gümrükçüoğlu, Emine Incilay Torunoğlu, Tuba Ozdemir-Sanci, Gamze Demirel, Alper Durmaz","doi":"10.1002/adbi.202500136","DOIUrl":"https://doi.org/10.1002/adbi.202500136","url":null,"abstract":"Non-small cell lung cancer (NSCLC) remains a major cause of cancer-related mortality. This study investigates the cytotoxic effects of Euphorbia rigida extract on A549 NSCLC cells and its potential as a therapeutic agent. Cellular morphology was observed microscopically, and cell viability was evaluated using dose-dependent proliferation assays. Apoptosis-related gene expression-including Bax, Bcl-2, and Caspase-9-was analyzed via quantitative PCR (qPCR). Chromatographic methods identified bioactive flavonoids, and molecular docking assessed their binding to cancer-related proteins. Additionally, absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles were evaluated. The extract induced apoptotic morphological changes such as cell shrinkage and loss of intercellular contact. A dose-dependent reduction in A549 viability was observed, with an IC50 of 0.5 mg mL-1. Gene expression indicated activation of the intrinsic mitochondrial apoptotic pathway, with increased Bax and Caspase-9 and decreased Bcl-2 expression. Flow cytometry using Annexin V-allophycocyanin (V-APC) staining revealed selective cytotoxicity: significant apoptosis in A549 cells while preserving viability in BEAS-2B normal lung epithelial cells. Identified flavonoids included quercetin, apigenin, and myricetin, which showed strong binding affinities in docking studies. ADMET profiling supported their drug-likeness. These findings highlight E. rigida potential in NSCLC treatment via apoptosis induction and selective cytotoxicity.","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e00136"},"PeriodicalIF":3.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144155558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Guilongwan Ameliorates Experimental Diabetic Foot Ulcer in Rats via the Inhibition of Delta-Like 4/Notch1 Signaling in M1 Macrophages. 桂龙丸通过抑制M1巨噬细胞中delta -样4/Notch1信号通路改善实验性糖尿病足溃疡大鼠

IF 3.2 3区生物学

Advanced biology Pub Date : 2025-05-19 DOI: 10.1002/adbi.202400819

Xi-Ting Lv, Wen-Xiu Yang, Xiao Zhang, Bao-Ling Li, Wen-Ying Wang, Guo-En Wang

{"title":"Guilongwan Ameliorates Experimental Diabetic Foot Ulcer in Rats via the Inhibition of Delta-Like 4/Notch1 Signaling in M1 Macrophages.","authors":"Xi-Ting Lv, Wen-Xiu Yang, Xiao Zhang, Bao-Ling Li, Wen-Ying Wang, Guo-En Wang","doi":"10.1002/adbi.202400819","DOIUrl":"https://doi.org/10.1002/adbi.202400819","url":null,"abstract":"Guilongwan (GLW), a representative of traditional Chinese Medicine (TCM) has been utilized to treating diabetic foot ulcer (DFU)-related syndrome including an intolerance of cold with cold limbs, blood circulation disorder, and immune dysfunction for decades. However, the chemical and biological mechanisms of GLW remain unclear. This study aims to discover the biological mechanisms of GLW on DFU by using streptozotocin- and skin-puncher-induced DFU rat models, in vitro macrophage models, and in silico analysis. The alterations in pathology, Notch1 signaling, and macrophage polarization are detected. The results indicated that GLW promoted wound healing, cutaneous cell proliferation, and angiogenesis in DFU rats by inhibiting delta-like (DLL) 4/Notch1 signaling. In addition, GLW inhibited M1 polarization and promoted M2 polarization in diabetic wounds. Seventeen chemical compounds in GLW-medicated serum are identified. In silico analysis and in vitro experiments demonstrated that GLW-medicated serum and its main compounds inhibited the expression of DLL4 in matrix metalloproteinase-9-induced M1 macrophages. In conclusion, GLW ameliorated experimental DFU rats via the inhibition of DLL4/Notch1 signaling in M1 macrophages. This study provided a new biologic mechanism for GLW in the treatment of DFU.","PeriodicalId":7234,"journal":{"name":"Advanced biology","volume":" ","pages":"e70004"},"PeriodicalIF":3.2,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0