Frontiers in bioscience (Landmark edition)最新文献

{"title":"The Role of Formononetin in Cerebral Ischemia-Reperfusion Injury: A New Mediator of c-Fos/IL-10/STAT3 Signaling Pathway.","authors":"Ming Yan, Fuyong Ni, Xue Xie, Chenfeng Zhang, Jing Zhu","doi":"10.31083/FBL26274","DOIUrl":"https://doi.org/10.31083/FBL26274","url":null,"abstract":"<p><strong>Backgrounds: </strong>Inflammation plays a pivotal role in the advancement of ischemic stroke, and Formononetin has been recognized for its potential benefits due to its anti-inflammatory effects. Although Formononetin shows promise for reducing cerebral ischemic injury, its precise effectiveness and the underlying molecular mechanisms still need to be thoroughly explored. The research aimed to investigate Formononetin's impact and mechanisms on ischemic brain damage.</p><p><strong>Methods: </strong>In this study, both the ischemia/reperfusion (I/R) mouse model and the oxygen-glucose deprivation/reperfusion (OGD/R) cell model were used. The I/R mouse model was prepared using the middle cerebral artery occlusion (MCAO) method, while the OGD/R SH-SY5Y cell model was established using the oxygen-glucose OGD/R method. Hematoxylin and Eosin (H&E) staining, Tunnel fluorescence staining, and Nissl staining were employed to observe the effects of Formononetin on neuronal damage, apoptosis, and survival in I/R mouse brain tissue. Additionally, the effects of Formononetin on the levels of pro-inflammatory factors in I/R mice and OGD/R cells were detected using Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) and Enzyme-Linked Immunosorbent Assay (ELISA) methods. The c-Fos/Interleukin-10 (IL-10)/Signal Transducer and Activator of Transcription 3 (STAT3) signaling pathway in I/R mice and OGD/R cells was examined using RT-qPCR and Western Blot (WB). Furthermore, rescue validation was performed using targeted interventions of IL-10 and c-Fos, confirming that the c-Fos/IL-10/STAT3 signaling pathway is a key target of Formononetin.</p><p><strong>Results: </strong>Our findings reveal that Formononetin notably decreased infarct size and neuronal damage <i>in vivo</i> (<i>p</i> < 0.001). Additionally, Formononetin decreased inflammation and lowered levels of pro-inflammatory cytokines (<i>p</i> < 0.05). In cell models, Formononetin effectively suppressed neuronal injury induced by OGD/R and the related inflammatory markers (<i>p</i> < 0.001). Mechanistic studies showed that Formononetin enhances IL-10 expression in both models of ischemic brain injury, a process crucial for its protective effects against inflammation (<i>p</i> < 0.05). This regulation is facilitated by increased nuclear translocation of c-Fos, highlighting the c-Fos/IL-10/STAT3 pathway as a crucial mechanism of Formononetin's neuroprotective and anti-inflammatory effects in cerebral ischemia (<i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>We found Formononetin alleviates inflammation associated with I/R injury by activating the c-Fos/IL-10/STAT3 pathway, which highlights the potential of Formononetin as a promising therapeutic approach for I/R injury.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 5","pages":"26274"},"PeriodicalIF":3.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of ERK1/2 and p38 Protein Kinases in Tumors: Biological Insights and Clinical Implications.","authors":"Aleksandra Emelyanova, Alexander Modestov, Anton Buzdin, Elena Poddubskaya","doi":"10.31083/FBL31317","DOIUrl":"https://doi.org/10.31083/FBL31317","url":null,"abstract":"<p><p>Significant advancements have been achieved over recent decades in deciphering the molecular mechanisms driving malignant tumor development. Despite this progress, the precise roles of individual genes, their interactions, and the associated signaling pathways involved in tumor proliferation remain insufficiently characterized. Among these pathways, the mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinase (ERK)1/2 and p38, which regulate essential cellular functions such as growth, differentiation, and apoptosis, have garnered considerable research attention. Building on recent insights into MAPK signaling, we identified components closely linked to ERK1/2 and p38 activity and examined changes in their behavior during tumorigenesis. Furthermore, we developed quantifiable metrics to assess ERK1/2 and p38 activity, including the ERK/p38 ratio, a key indicator of tumor cell proliferative or quiescent states, along with activation levels of these signaling pathways. Our findings underscore the potential of ERK and p38-related gene expression and pathway dynamics as biomarkers for predicting clinical outcomes and informing tailored therapeutic approaches.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 5","pages":"31317"},"PeriodicalIF":3.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of <i>SLC1A5</i> Regulation of Glutamine Metabolism to Promote Ferroptosis Sensitivity in Endometriosis.","authors":"Hui-Yu Ma, Huan-Yu Wu, Yu-Ting Xiang, Yu-Yin Liu, Jin Xie, Peng-Yu Cai, Bin Zhang, Yu-Hang Zhang, Ming-Xiu Wu","doi":"10.31083/FBL36781","DOIUrl":"https://doi.org/10.31083/FBL36781","url":null,"abstract":"<p><strong>Background: </strong>Endometriosis (EMs) is a chronic gynecological disorder associated with ectopic endometrial tissue, inflammation, oxidative stress, and mitochondrial dysfunction. A promising strategy for treating EMs is to target ferroptosis, a programmed cell death mechanism regulated by reactive oxygen species (ROS) and glutamine metabolism. Solute carrier family 1 member 5 (<i>SLC1A5</i>), a glutamine transporter, and <i>c-Myc</i> play key roles in ferroptosis, forming a \"ROS/<i>c-Myc</i>/<i>SLC1A5</i>\" feedback loop. The aim of this study was to investigate the regulatory role of <i>SLC1A5</i> in ferroptosis. In addition, we evaluated the ferroptosis inducer Erastin as a potential therapeutic agent for EMs.</p><p><strong>Methods: </strong>The human endometrial stromal cells (ESCs) line hEM15A was used in this study, together with a rat model of EMs. hEM15A cells and rats were treated with Erastin, with or without <i>SLC1A5</i> modulation or ROS scavenging with N-acetylcysteine (NAC). Cell viability, ROS levels, glutamine metabolism, mitochondrial function, and ferroptosis markers (glutathione peroxidase 4 (GPX4)) were subsequently analyzed by Cell Counting Kit-8 (CCK-8) assay, reverse transcription quantitative polymerase chain reaction (RT-qPCR), Western blot, and fluorescent probes. Pathological changes, lesion volumes, and pelvic adhesions in the rat EM model were assessed using hematoxylin and eosin (HE) staining, ultrasound imaging, and Haber scoring.</p><p><strong>Results: </strong>Erastin treatment of ESCs induced ferroptosis by upregulating <i>SLC1A5</i> and <i>c-Myc</i> expression, increasing ROS levels, and altering glutamine metabolism. Overexpression of <i>SLC1A5</i> enhanced sensitivity to ferroptosis, whereas <i>SLC1A5</i> knockdown and NAC treatment reversed these effects. Mechanistically, <i>c-Myc</i> bound to the <i>SLC1A5</i> promoter, forming positive feedback with ROS. In the rat model of EMs, Erastin treatment reduced ectopic lesion volume, pelvic adhesions, and inflammatory markers (TNF-α, IL-6, IL-1β). These therapeutic effects were mitigated by NAC, highlighting the importance of the ROS/<i>c-Myc</i>/<i>SLC1A5</i> pathway.</p><p><strong>Conclusions: </strong>This study confirmed the involvement of the ROS/<i>c-Myc</i>/<i>SLC1A5</i> pathway in regulating EMs sensitivity to ferroptosis and demonstrated the potential of Erastin as a therapeutic agent. Targeting this pathway offers a promising approach for the treatment of EMs.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 5","pages":"36781"},"PeriodicalIF":3.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of Activated Coagulation Factor XII by the Phosphodiesterase-4 Inhibitor Roflumilast: <i>In Vitro</i> and <i>In Silico</i> Studies.","authors":"Hassan A Madkhali, Mohd Nazam Ansari, Mubarak A Alamri","doi":"10.31083/FBL38395","DOIUrl":"https://doi.org/10.31083/FBL38395","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to evaluate the effects of selected phosphodiesterase-4 inhibitors (PDE-4 inhibitors)-roflumilast, ibudilast, and crisaborole-on the activity of blood coagulation factor XII (FXII). In the intrinsic coagulation pathway, FXII is known to initiate the kallikrein-kinin system (KKS), causing an increase in the system expression, which ultimately leads to inflammation and coagulation states. Additionally, the activation of KKS downstream effectors leads to inflammation. Inflammation signaling was found to be initiated when the bradykinin (BK) protein binds to its B2 receptor because of the FXII-dependent pathway activation. BK abnormalities can cause a critical condition, hereditary angioedema (HAE), which is characterized by recurring serious swelling. While it is considered unnecessary for hemostasis, FXII is an important enzyme for pathogenic thrombosis. Because of this special characteristic, FXII is a desirable therapeutic target. Our hypothesis is to identify the inhibitory effects of roflumilast, ibudilast, and crisaborole on the activated FXII and to reveal their beneficial impacts in the reduction of the pathogenesis of FXII-related conditions, HAE, and thrombosis. In a current study, we presented the inhibitory effect of tested drugs on the main target activated factor XII (FXIIa) as well as two other plasma protease enzymes included in the target pathway, plasma kallikrein and FXIa.</p><p><strong>Methods: </strong>To achieve our aim, <i>in vitro</i> chromogenic enzymatic assays were utilized to assess the inhibitory effects of these drugs by monitoring the amount of para-nitroaniline (pNA) chromophore released from the substrate of FXIIa, FXIa, or plasma kallikrein.</p><p><strong>Results: </strong>Our study findings exhibited that among assessed PDE-4 inhibitor drugs, roflumilast at micromolar concentrations significantly inhibited FXIIa in a dose-dependent manner. The FXIIa was clearly suppressed by roflumilast, but not the other related KKS members, plasma kallikrein, or the activated factor XI. On the other hand, ibudilast and crisaborole showed no inhibitory effects on the activities of all enzymes.</p><p><strong>Conclusions: </strong>Overall, roflumilast could be used as a lead compound for developing a novel multifunctional therapeutic drug used for the prevention of HAE or thrombotic disorders.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 5","pages":"38395"},"PeriodicalIF":3.3,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inborn Errors of Immunity in Apoptosis.","authors":"Nadia Makkoukdji, Travis Satnarine, Alana Xavier de Almeida, Matthew Wyke, Iris H Kim, Gary I Kleiner, Melissa Gans","doi":"10.31083/FBL27231","DOIUrl":"https://doi.org/10.31083/FBL27231","url":null,"abstract":"<p><p>Inborn errors of immunity (IEIs) are a group of more than 485 disorders that impair immune development and function with variable reported incidence, severity, and clinical phenotypes. A subset of IEIs blend increased susceptibility to infection, autoimmunity, and malignancy and are known collectively as primary immune regulatory disorders (PIRDs). Programmed cell death, or apoptosis, is crucial for maintaining the balance of lymphocytes. Genetic-level identification of several human inherited diseases with impaired apoptosis has been achieved, such as autoimmune lymphoproliferative syndrome (ALPS), caspase-8 deficiency state (CEDS), X-linked lymphoproliferative syndrome (XLP), and Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway disorders. The consequences of this disease are manifested by abnormal lymphocyte accumulation, resulting in clinical features such as lymphadenopathy, hepatomegaly, splenomegaly, and an increased risk of lymphoma. Additionally, these disorders are often associated with autoimmune disease, particularly involving blood cells. Understanding the molecular pathogenesis of these conditions has provided critical insights into the signaling pathways that regulate apoptosis and lymphocyte activation, shedding light on mechanisms of immune dysregulation. This review focuses on the intersection between apoptosis, autoimmunity, and lymphoproliferation, discussing how dysregulation contributes to the development of these immune disorders. These conditions are characterized by excessive lymphocyte accumulation, autoimmunity, and/or immunodeficiency. Understanding their molecular pathogenesis has offered new insights into the signaling mechanisms that regulate apoptosis and lymphocyte activation.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 5","pages":"27231"},"PeriodicalIF":3.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Analysis of the Bioactivity and Anti-Inflammatory Effects Against Endotoxin in Mitochondria for Transplantation: Impact of Muscle Origin in Rats.","authors":"Da-Wei Huang, Heng-Juei Hsu, Pei-Wen Chen, Ming-Tse Wu, Chia-En Wong, Chi-Chen Huang, Po-Hsuan Lee, Hui-Fang Chen, Jung-Shun Lee","doi":"10.31083/FBL37367","DOIUrl":"https://doi.org/10.31083/FBL37367","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Mitochondria are essential for cellular energy production and cell survival. Mitochondrial dysfunction has been implicated in various neurological disorders, prompting the development of novel therapeutic approaches targeting these organelles. Among these, mitochondrial transplantation (MT), which replaces dysfunctional mitochondria with healthy counterparts from donor tissues, has emerged as a promising strategy. While skeletal muscle is a rich source of mitochondria, the optimal muscle tissue for MT remains unidentified, and the potential functional differences among mitochondria from various muscle types are not fully understood. This study investigates the quantity, size, respiratory function, energy production, and anti-inflammatory effects of mitochondria isolated from red skeletal muscle (RSM), mixed skeletal muscle (MSM), and white skeletal muscle (WSM).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Mitochondria were extracted from the soleus muscle (RSM), pectoralis major and rectus abdominis (MSM), and biceps brachii and gastrocnemius (WSM) of healthy 8-week-old male Sprague Dawley rats. Nanoparticle tracking analysis was employed to determine mitochondrial quantity and size. The activities of mitochondrial complexes I, II, and IV and adenosine triphosphate (ATP) content were assessed. The protective effects of mitochondria (100 μg/mL) from each muscle type against lipopolysaccharide (LPS, 5 μg/mL)-induced cell death and mitochondrial membrane potential disruption were evaluated in PC-12 neuronal cells.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;RSM-derived mitochondria exhibited a smaller average size and significantly higher mitochondrial content compared to those from MSM (mean size: &lt;i&gt;p&lt;/i&gt; = 0.0056, vs. pectoralis major; &lt;i&gt;p&lt;/i&gt; = 0.0056, vs. rectus abdominis; count of mitochondria: &lt;i&gt;p&lt;/i&gt; &lt; 0.0001, vs. pectoralis major; &lt;i&gt;p&lt;/i&gt; &lt; 0.0001, vs. rectus abdominis) and WSM (mean size: &lt;i&gt;p&lt;/i&gt; = 0.0006, vs. biceps brachii; &lt;i&gt;p&lt;/i&gt; &lt; 0.0001, vs. gastrocnemius; count of mitochondria: &lt;i&gt;p&lt;/i&gt; &lt; 0.0001, vs. biceps brachii; &lt;i&gt;p&lt;/i&gt; &lt; 0.0001, vs. gastrocnemius). Additionally, RSM mitochondria demonstrated the highest activity of mitochondrial complex I among the three muscle types (&lt;i&gt;p&lt;/i&gt; = 0.0001, vs. pectoralis major; &lt;i&gt;p&lt;/i&gt; = 0.0095, vs. rectus abdominis; &lt;i&gt;p&lt;/i&gt; &lt; 0.0001, vs. biceps brachii; &lt;i&gt;p&lt;/i&gt; &lt; 0.0001, vs. gastrocnemius). WSM-derived mitochondria showed relatively lower complex II activity (&lt;i&gt;p&lt;/i&gt; = 0.0006, biceps brachii vs. soleus; &lt;i&gt;p&lt;/i&gt; = 0.0218, biceps brachii vs. rectus abdominis), while complex IV activity and ATP content were comparable across all groups. Supplementation with mitochondria isolated from RSM and WSM, but not MSM, effectively mitigated LPS-induced cell death (mitochondria isolated from soleus: &lt;i&gt;p&lt;/i&gt; = 0.0031; biceps brachii: &lt;i&gt;p&lt;/i&gt; = 0.0046; gastrocnemius: &lt;i&gt;p&lt;/i&gt; = 0.0169) and preserved mitochondrial membrane potential (mitochondria isolated from soleus: &lt;i&gt;p&lt;/i&gt; = 0.0204; bicep","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 5","pages":"37367"},"PeriodicalIF":3.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Matrix Metalloproteinases in Liver Function and Disease.","authors":"Gregoria Mitropoulou, Vasiliki Kompoura, Francesca Saffioti, Vasileios K Mavroeidis","doi":"10.31083/FBL27127","DOIUrl":"https://doi.org/10.31083/FBL27127","url":null,"abstract":"<p><p>Matrix metalloproteinases (MMPs) and the tissue inhibitors of metalloproteinases (TIMPs) play critical roles in the pathogenesis of liver diseases, particularly in conditions such as fibrosis, cirrhosis, and liver cancer. This review highlights the diagnostic and prognostic potential of MMPs, emphasizing their involvement in metastasis, de-differentiation, and hepatic cell proliferation. Utilizing advanced reporter mouse models has proven instrumental in assessing intraglandular MMP activity and predicting metastatic risks, paving the way for targeted therapeutic interventions. Current research indicates that specific MMPs and TIMPs can serve as valuable biomarkers for liver function and disease progression, although a clear consensus on their clinical utility remains elusive. Ongoing studies explore MMP-targeted therapies with potential applications in liver disease management, particularly in reducing fibrosis and enhancing liver regeneration. Future directions in this field involve elucidating the roles of MMPs in ischemia and transplantation, with the aim of improving clinical outcomes. Emerging therapeutic strategies focus on achieving a balance between MMP activity and TIMP expression to optimize liver function, highlighting the need for organ-specific targeting. Overall, this comprehensive overview underscores the importance of MMPs and TIMPs in liver function and liver disease, as well as the necessity for further research to harness their potential in clinical practice.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 5","pages":"27127"},"PeriodicalIF":3.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of CEBPD in Oxidative Stress and Angiogenesis Regulation in Endometriosis.","authors":"Jing Su, Peipei Tang, Jixiang Zhong, Rongxue Zhang, Huiying Xue, Hong Zhang","doi":"10.31083/FBL33488","DOIUrl":"https://doi.org/10.31083/FBL33488","url":null,"abstract":"<p><strong>Background: </strong>Endometriosis (EM) is a prevalent gynecological disorder in women. Although the underlying mechanisms have yet to be fully elucidated, EM may be related to oxidative stress. The current research aimed to identify possible pathways that control oxidative stress in EM, thereby providing a theoretical foundation for its clinical diagnosis and treatment.</p><p><strong>Methods: </strong>High-throughput RNA sequencing (RNA-seq) data were integrated with GeneCards online data to screen for oxidative stress-related genes and potential targets in EM. The reverse transcription-quantitative polymerase chain reaction (RT-qPCR), Western blotting, and immunohistochemistry assays confirmed the expression of candidate genes. The <i>in vivo</i> and <i>in vitro</i> effects of CCAAT enhancer binding protein delta (CEBPD, C/EBP-delta) and DNA damage-inducible transcript 4 (DDIT4) on oxidative stress, cell proliferation, and angiogenesis in endometriotic cells were validated using loss- or gain-of-function approaches.</p><p><strong>Results: </strong>CEBPD was highly expressed in ectopic and eutopic endometrial tissue from patients with endometriosis. Loss- or gain-of-function experiments showed that CEBPD promoted oxidative stress, cell proliferation, and angiogenesis <i>in</i> <i>vitro</i> and <i>in vivo</i>. Integration of RNA-seq and online data revealed that <i>CEBPD</i> regulates <i>DDIT4</i> expression, subsequently increasing oxidative stress, cell proliferation, and angiogenesis in endometriotic cells. Finally, CEBPD and DDIT4 were found to regulate the expression of extracellular signal-regulated kinase 1/2 (ERK1/2) proteins associated with the mitogen-activated protein kinase (MAPK) signaling pathway.</p><p><strong>Conclusions: </strong>These results suggest that CEBPD may promote oxidative stress, cell proliferation, and angiogenesis in EM by activating MAPK via DDIT4. Hence, CEBPD may be a potential target for diagnosing and treating EM.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 5","pages":"33488"},"PeriodicalIF":3.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neutrophil Extracellular Trap Formation Suppressed by Ro 106-9920 Enhances Diabetic Wound Healing by Blocking NLRP3 Inflammasome Activation.","authors":"Hua Li, Lihua Xu, Jingying Chen, Huijuan Huang, Feiteng Liang, Shuxiao Li, Fuda Huang, Junyu Guo","doi":"10.31083/FBL37393","DOIUrl":"https://doi.org/10.31083/FBL37393","url":null,"abstract":"<p><strong>Background: </strong>The excessive formation of neutrophil extracellular traps (NETs) is involved in delayed wound healing under diabetic conditions. However, potential therapeutic agents remain underexplored. Our present study aimed to explore the effects of Ro 106-9920, a specific nuclear factor kappa B (NF-κB) inhibitor, on diabetic wound healing and to elucidate the underlying mechanisms.</p><p><strong>Methods: </strong>A diabetic mouse model was established, and full-thickness wounds were created. Ro 106-9920 was administered, and wound healing was monitored. Protein levels of NET markers and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome components were assessed via western blotting and histological analysis. Functional assays were conducted to evaluate the effect of NETs on fibroblasts, endothelial cells, and keratinocytes using conditioned media (CM) from a phorbol 12-myristate 13-acetate (PMA)-treated neutrophil-macrophage coculture model (NET-CM). CM collected from the coculture model after Ro 106-9920 treatment ((NET+Ro 106-9920)-CM) was used to determine its therapeutic potential.</p><p><strong>Results: </strong>NET formation and NLRP3 inflammasome activation were significantly elevated in wound tissues of diabetic mice from day 7 (<i>p</i> < 0.001). Similar results were observed in PMA-treated neutrophils and macrophages (<i>p</i> < 0.001). The viability and migration of endothelial cells, fibroblasts, and keratinocytes, as well as the angiogenic potential of endothelial cells, were significantly impaired by NET-CM treatment (all <i>p</i> < 0.001), whereas Ro 106-9920 effectively attenuated these alterations (NET-CM vs. (NET+Ro 106-9920)-CM, cell viability, <i>p</i> < 0.001; cell migration, <i>p</i> < 0.01; tube formation, <i>p</i> < 0.001). <i>In vivo</i>, Ro 106-9920 treatment inhibited NET formation, as evidenced by the decreased citrullinated histone H3 (CitH3) and peptidyl arginine deiminase 4 (PAD4) expression (<i>p</i> < 0.05). This was followed by a decrease in NLRP3 inflammasome activation (<i>p</i> < 0.05), an increase in angiogenesis in wound tissues (<i>p</i> < 0.001), and improved wound healing (<i>p</i> < 0.001) compared with those in Ro 106-9920-untreated mice.</p><p><strong>Conclusions: </strong>Ro 106-9920 enhances diabetic wound healing by suppressing NET formation and inhibiting NLRP3 inflammasome activation, providing a novel therapeutic choice for improving chronic wound healing in patients with diabetes.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 5","pages":"37393"},"PeriodicalIF":3.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217772","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oleandrin Promotes Apoptosis in an Autophagy-Dependent Manner in Gastric Cancer.","authors":"Xiaoyan Huang, Liting Yan, Xiangrong Zhao, Ying Wang, Huiting Li, Xinlu Jiang, Yangmeng Feng, Dandan Ouyang, Cuixiang Xu, Jianhua Wang","doi":"10.31083/FBL26608","DOIUrl":"https://doi.org/10.31083/FBL26608","url":null,"abstract":"<p><strong>Background: </strong>The medicinal phytochemical oleandrin (Ole) is obtained from the Nerium oleander plant. The exact relationship between Ole-induced apoptosis and autophagy in gastric cancer (GC) is unclear despite the fact that it has outstanding anti-tumor capabilities. This research aimed to demonstrate how autophagy and Ole-induced apoptosis interact in GC.</p><p><strong>Methods: </strong>The Cell Counting Kit (CCK)-8 assay and colony formation assays were employed to evaluate cell proliferation. Cellular apoptosis was evaluated with Calcein/Propidium Iodide (PI) assays and flow cytometry. Confocal and electron microscopes were employed to examine the morphology of autophagy. Protein concentrations were assessed by western blotting. Luciferase-positive HGC-27 cells were administered subcutaneously to Balb/c nude mice to evaluate Ole's anti-tumor activity. Immunohistochemistry assessed Ki67 expression and H&E staining in tumor tissue.</p><p><strong>Results: </strong>Ole causes GC cells to undergo intracellular apoptosis and autophagy at low nanomolar doses, halting the cell cycle at the G0/G1 phase. Whereas 3-methyladenine (3-MA), the inhibitor of autophagy, counteracts the apoptosis generated by Ole <i>in vitro</i> and <i>in vivo</i>.</p><p><strong>Conclusions: </strong>Ole may trigger apoptosis through the activation of autophagy in GC. It offers a secure and efficacious candidate drug for the treatment of tumors in the digestive system.</p>","PeriodicalId":73069,"journal":{"name":"Frontiers in bioscience (Landmark edition)","volume":"30 5","pages":"26608"},"PeriodicalIF":3.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}