Molecular and Cellular Biology最新文献

ZC3H13-Mediated m⁶A Modification of TRIM16 Suppresses EndMT and Atherosclerosis by Destabilizing Ang2 and Inhibiting the TLR4/NLRP3 Pathway. zc3h13介导的m6A修饰TRIM16通过破坏Ang2稳定和抑制TLR4/NLRP3通路抑制EndMT和动脉粥样硬化。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-10-05 DOI: 10.1080/10985549.2026.2733731

Chen Wang, Ying Xing, Lv Wang, Xing Qin, Congye Li, Nan Liu

{"title":"ZC3H13-Mediated m6A Modification of TRIM16 Suppresses EndMT and Atherosclerosis by Destabilizing Ang2 and Inhibiting the TLR4/NLRP3 Pathway.","authors":"Chen Wang, Ying Xing, Lv Wang, Xing Qin, Congye Li, Nan Liu","doi":"10.1080/10985549.2026.2733731","DOIUrl":"https://doi.org/10.1080/10985549.2026.2733731","url":null,"abstract":"The RNA methyltransferase zinc finger CCCH-type containing protein 13 (ZC3H13) is downregulated in atherosclerosis (AS), but its functional mechanism remains unclear. Endothelial-mesenchymal transition (EndMT) is a core pathological driver of endothelial dysfunction in AS. This study aimed to investigate the biological function and molecular mechanism of ZC3H13 in regulating EndMT during AS progression. We found that ZC3H13 expression was reduced in aortic tissues of AS mice and in oxidized low‑density lipoprotein (ox‑LDL)-treated human umbilical vein endothelial cells (HUVECs). In ox-LDL-stimulated HUVECs, overexpression of ZC3H13 markedly upregulated endothelial markers (CD31, VE-cadherin), downregulated mesenchymal markers (α-SMA, vimentin), suppressed cell migration, and restored angiogenesis. Conversely, ZC3H13 silencing induced HUVECs EndMT, enhanced migration and impaired angiogenesis. Mechanistically, ZC3H13 elevated tripartite motif-containing protein 16 (TRIM16) mRNA stability by modulating its N6-methyladenosine (m6A) modification. TRIM16 knockdown abolished the protective effects of ZC3H13 overexpression against ox-LDL-induced EndMT and endothelial dysfunction. Furthermore, TRIM16 interacts with angiopoietin-2 (Ang2) and promotes its K48- and K63-linked ubiquitination, thereby inhibiting TLR4/NLRP3 activation and consequently suppressing EndMT. In vivo, lentivirus-mediated ZC3H13 overexpression attenuated atherosclerotic plaque formation and inhibited EndMT. In conclusion, ZC3H13 alleviates AS by suppressing EndMT via the TRIM16/Ang2/TLR4/NLRP3 pathway, highlighting ZC3H13 as a potential therapeutic target for AS.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"1-20"},"PeriodicalIF":2.8,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Asperulosidic Acid Attenuates Myocardial Ischemia-Reperfusion Injury and Suppresses MAPK Signaling. 曲霉酸减轻心肌缺血再灌注损伤和抑制MAPK信号传导。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-09-15 DOI: 10.1080/10985549.2026.2726768

Junwei Xu, Ning Qin, Wenbo Jiang, Tao Chen

{"title":"Asperulosidic Acid Attenuates Myocardial Ischemia-Reperfusion Injury and Suppresses MAPK Signaling.","authors":"Junwei Xu, Ning Qin, Wenbo Jiang, Tao Chen","doi":"10.1080/10985549.2026.2726768","DOIUrl":"https://doi.org/10.1080/10985549.2026.2726768","url":null,"abstract":"This study evaluated the protective effects of asperulosidic acid (ASP) against myocardial ischemia/reperfusion (I/R) injury and investigated the underlying mechanisms. An in vitro oxygen-glucose deprivation/reoxygenation model was established in H9c2 cells, and an in vivo rat I/R model was generated by left anterior descending coronary artery ligation. ASP treatment significantly improved cell viability and reduced apoptosis in vitro. In vivo, ASP decreased myocardial infarct size, alleviated histopathological damage, and reduced serum creatine kinase and lactate dehydrogenase levels. Additionally, ASP suppressed inflammatory cytokine expression, reduced reactive oxygen species and malondialdehyde levels, enhanced antioxidant enzyme activities, and inhibited myocardial apoptosis. Network pharmacology and molecular docking identified the MAPK signaling pathway as a potential target. Mechanistically, ASP reduced the phosphorylation of p38, ERK, and JNK in myocardial tissue. These findings demonstrate that ASP attenuates myocardial I/R injury by reducing oxidative stress, inflammation, and apoptosis, associated with suppression of the MAPK signaling pathway.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"1-12"},"PeriodicalIF":2.8,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Loss of LRRK2 Protects Against Ox-LDL-Induced Endothelial Oxidative Damage Via NRF2. LRRK2的缺失通过NRF2保护ox - ldl诱导的内皮氧化损伤。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-09-07 DOI: 10.1080/10985549.2026.2718972

Pingfeng Wang, Xuesi Chen, Xiaoyu Chen, Yimin Shu, Yanjin Song

{"title":"Loss of LRRK2 Protects Against Ox-LDL-Induced Endothelial Oxidative Damage Via NRF2.","authors":"Pingfeng Wang, Xuesi Chen, Xiaoyu Chen, Yimin Shu, Yanjin Song","doi":"10.1080/10985549.2026.2718972","DOIUrl":"https://doi.org/10.1080/10985549.2026.2718972","url":null,"abstract":"This study investigated the role of LRRK2, a protein implicated in cancers but poorly understood in atherosclerosis, in oxidized low-density lipoprotein (Ox-LDL)-induced endothelial dysfunction. An in vitro model was established using HUVECs treated with Ox-LDL. Cell viability, apoptosis, reactive oxygen species (ROS) levels, and mitochondrial membrane potential were assessed using standard assays. Results showed that Ox-LDL exposure caused dose- and time-dependent decreases in cell viability and concurrent upregulation of LRRK2 expression. Silencing LRRK2 significantly improved cell survival and suppressed Ox-LDL-induced apoptosis, as evidenced by modulation of key apoptotic proteins (decreased cleaved-caspase-3, cleaved-caspase-9, and Bax; increased Bcl-2). LRRK2 silencing alleviated oxidative stress by elevating antioxidant superoxide dismutase and glutathione levels, reducing malondialdehyde and ROS production, and restoring mitochondrial membrane potential. Mechanistically, si-LRRK2 enhanced NRF2 expression and nuclear translocation, leading to increased levels of its downstream targets heme oxygenase-1 and NAD(P)H quinone dehydrogenase 1. The critical role of this pathway was confirmed, as pharmacological inhibition of NRF2 with ML385 reversed all protective effects of si-LRRK2. LRRK2 is a key mediator of Ox-LDL-induced endothelial damage. Its inhibition protects HUVECs by activating the NRF2 signaling pathway, suggesting LRRK2 as a promising novel therapeutic target for combating endothelial dysfunction in atherosclerosis and related cardiovascular diseases.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"1-12"},"PeriodicalIF":2.8,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Sinomenine Ameliorates Mitochondrial Dysfunction in PD-1 Inhibitor-Induced Myocardial Injury in Mice via the TLR4/NF-κB Pathway. 青藤碱通过TLR4/NF-κB通路改善PD-1抑制剂诱导的小鼠心肌损伤的线粒体功能障碍

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-08-21 DOI: 10.1080/10985549.2026.2717162

Mengjiao Gao, Xinya Liu, Li Wu, Yun Jiang, Jian Yu, Yuanming Zhang

{"title":"Sinomenine Ameliorates Mitochondrial Dysfunction in PD-1 Inhibitor-Induced Myocardial Injury in Mice via the TLR4/NF-κB Pathway.","authors":"Mengjiao Gao, Xinya Liu, Li Wu, Yun Jiang, Jian Yu, Yuanming Zhang","doi":"10.1080/10985549.2026.2717162","DOIUrl":"10.1080/10985549.2026.2717162","url":null,"abstract":"Immune checkpoint inhibitors (ICIs) are widely used in cancer treatment but can cause severe cardiotoxicity. Anti-inflammatory and cardioprotective effects of sinomenine have been documented in existing research. However, it remains unclear what role sinomenine plays in myocardial injury induced by PD-1 inhibitors. Myocardial injury in mice, induced by PD-1 inhibitors, was used to establish an experimental model. After administering sinomenine to the mice, assessments of cardiac function were conducted using echocardiographic techniques. Histological examination and ELISA were performed to evaluate myocardial injury, inflammation, and mitochondrial dysfunction. The expression of key proteins in the TLR4/NF-κB pathway was determined via Western blotting. Treatment with sinomenine notably enhanced cardiac function and mitigated myocardial injury in mice subjected to PD-1 inhibitors. It also attenuated myocardial inflammation and mitochondrial dysfunction. Mechanistic studies shed light on the fact that the activation of the TLR4/NF-κB pathway was inhibited by sinomenine. The alleviation of PD-1 inhibitor-induced myocardial injury by sinomenine is achieved through the reduction of inflammation and the restoration of mitochondrial function, with this process being regulated by the inhibition of the TLR4/NF-κB signaling pathway. These observations imply that sinomenine has the potential to serve as a therapeutic option for managing cardiotoxicity linked to immune checkpoint inhibitors.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"1-14"},"PeriodicalIF":2.8,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

The Emerging Role of mTOR in Shaping the Cancer Cell Secretome and Plasticity. mTOR在塑造癌细胞分泌组和可塑性中的新作用。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-07-14 DOI: 10.1080/10985549.2026.2699146

Tyler T Cooper, Ivan Topisirovic, Lynne M Postovit

{"title":"The Emerging Role of mTOR in Shaping the Cancer Cell Secretome and Plasticity.","authors":"Tyler T Cooper, Ivan Topisirovic, Lynne M Postovit","doi":"10.1080/10985549.2026.2699146","DOIUrl":"https://doi.org/10.1080/10985549.2026.2699146","url":null,"abstract":"As tumors expand and encounter hypoxia and nutrient deprivation, cancer cells must establish tight coordination between metabolic reprogramming, protein synthesis and secretory activity to enable effective adaptation. The mechanistic target of rapamycin (mTOR) pathway plays a major role in coordinating protein synthesis and energy metabolism. Dysregulation of mTOR signaling is a hallmark of neoplasia and it contributes to tumorigenesis, metastasis, and therapeutic resistance. In this review, we discuss the emerging role of mTOR in shaping the cancer secretome and examine the implications of mTOR-dependent secretory regulation within the tumor microenvironment. Specifically, we highlight how alterations in secretory output downstream of mTOR influence extracellular matrix remodeling, angiogenesis, immune evasion, and the development of chemoresistance. This review integrates current evidence to provide a comprehensive perspective on the intersection between mTOR signaling, metabolism, protein synthesis and secretory remodeling in cancer. Specifically, we emphasize emerging links between aberrant mTOR function in cancer and secretory programs in the context of cancer cell plasticity and therapeutic resistance.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"1-22"},"PeriodicalIF":2.8,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Silybin Improves Acute Kidney Injury by Regulating HDAC6/NF-κB/NLRP3 Signaling to Reduce Inflammation and Ferroptosis. 水飞蓟宾通过调节HDAC6/NF-κB/NLRP3信号减少炎症和铁下垂改善急性肾损伤。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2025-12-08 DOI: 10.1080/10985549.2025.2594183

Ying Wei, Mingjing Yin, Guojiang Chen, Menghua Chen

{"title":"Silybin Improves Acute Kidney Injury by Regulating HDAC6/NF-κB/NLRP3 Signaling to Reduce Inflammation and Ferroptosis.","authors":"Ying Wei, Mingjing Yin, Guojiang Chen, Menghua Chen","doi":"10.1080/10985549.2025.2594183","DOIUrl":"10.1080/10985549.2025.2594183","url":null,"abstract":"Inflammation and ferroptosis play a crucial role in cisplatin (CP)-induced acute kidney injury (AKI). Silybin (SYB), a polyphenolic flavonoid, has shown renal protective effects, but its underlying mechanisms remain unclear. CP-induced HK-2 cell and mouse AKI models were used to explore the role of SYB. CCK-8, lactate dehydrogenase release, flow cytometry, and calcein/PI staining, were performed to evaluate cell viability, proliferation, and apoptosis. Oxidative stress and ferroptosis markers were measured, while renal function was assessed by serum creatinine and urea nitrogen. Mitochondrial ultrastructure was examined, and histological staining was conducted to analyze renal pathology and iron deposition. Western blotting detected HDAC6, NF-κB, NLRP3, and ferroptosis-related proteins expression. SYB treatment alleviated CP-induced mitochondrial damage, reduced lactate dehydrogenase release, inflammatory cytokines, oxidative stress, and ferroptosis, and improved proliferation and viability in HK-2 cells. In mice, 100 mg/kg SYB decreased serum creatinine, urea nitrogen, and cytokine levels, while ameliorating renal tissue injury. Mechanistically, SYB downregulated HDAC6 and inhibited NF-κB/NLRP3 activation, thereby suppressing ferroptosis. Notably, overexpression of HDAC6 restored NF-κB/NLRP3 activity and attenuated the protective effects of SYB. In conclusion, SYB mitigates CP-induced AKI by reducing inflammation and ferroptosis by modulating the HDAC6/NF-κB/NLRP3 pathway.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"546-565"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145701035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Aberrant Expression of miR-25-3p/EZH2 Is Involved in T Cell Activation in Aplastic Anemia. miR-25-3p/EZH2的异常表达参与再生障碍性贫血中T细胞的活化

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2026-06-16 DOI: 10.1080/10985549.2026.2677548

Jian Gao, Ping Li, Huanyu Guo, Wenye Shao, Zhiqiang Zhong

{"title":"Aberrant Expression of miR-25-3p/EZH2 Is Involved in T Cell Activation in Aplastic Anemia.","authors":"Jian Gao, Ping Li, Huanyu Guo, Wenye Shao, Zhiqiang Zhong","doi":"10.1080/10985549.2026.2677548","DOIUrl":"10.1080/10985549.2026.2677548","url":null,"abstract":"This research aims to investigate how aberrantly expressed miR-25-3p and EZH2 regulate T cell activation in aplastic anemia (AA) patients and to explore the underlying mechanisms. The study enrolled 26 severe AA (SAA) patients and 22 healthy subjects. Quantitative reverse transcription polymerase chain reaction was used to detect the miR-25-3p, EZH2 and CD69 expression. After establishing an AA mouse model, cell viability, proteins expression levels and cytokines levels were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, Western blot analysis, and enzyme-linked immunosorbent assay. A luciferase reporter assay was performed to verify the interaction between miR-25-3p and EZH2. Serum miR-25-3p expression was decreased in SAA patients (P < 0.001). Overexpression of miR-25-3p reduced cell viability and decreased CD69, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) levels; conversely, inhibition of miR-25-3p exerted the opposite effect (P < 0.001). EZH2 was a downstream target gene of miR-25-3p. Overexpression of EZH2 partially reversed the decrease in cell viability and the inhibition of CD69, IFN-γ and TNF-α levels caused by miR-25-3p upregulation (P < 0.01). MiR-25-3p was downregulated in SAA patients and regulated CD4+ T cell activation and proliferation by targeting EZH2. These findings provide novel insights into potential therapeutic targets for AA.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"711-723"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148258888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Importance of E3 Ligases for Preserving Genome Integrity: Progress and Challenges. E3连接酶对保持基因组完整性的重要性：进展和挑战。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2026-03-17 DOI: 10.1080/10985549.2026.2638203

Rumpa Mahata, Manas Kumar Santra

引用次数: 0

Global Profiling of Remodeled Subcellular Structures Due to Drug Treatment and Disease. 药物治疗和疾病引起的亚细胞结构重塑的全局分析。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2026-08-03 DOI: 10.1080/10985549.2026.2705873

Rachel A Victor, Jesse J Altemus, Michelle A Lay, Sarah N Shepherd, Valery F Thompson, Mozani Zianti, Marco Padilla-Rodriguez, Austin Lipinski, Ghassan Mouneimne, Paul R Langlais, Jacob C Schwartz

{"title":"Global Profiling of Remodeled Subcellular Structures Due to Drug Treatment and Disease.","authors":"Rachel A Victor, Jesse J Altemus, Michelle A Lay, Sarah N Shepherd, Valery F Thompson, Mozani Zianti, Marco Padilla-Rodriguez, Austin Lipinski, Ghassan Mouneimne, Paul R Langlais, Jacob C Schwartz","doi":"10.1080/10985549.2026.2705873","DOIUrl":"10.1080/10985549.2026.2705873","url":null,"abstract":"Cellular biochemistry arises from various interactions between macromolecules, including proteins, nucleic acids, and lipids. These make up membrane-bound organelles, membrane-less compartments, and molecular assemblies and scaffolds. Changes due to stimuli or disease can significantly impact cell fate and metabolism. We recently reported our protocol combining crosslinking and size exclusion chromatography with mass spectrometry (SEC-MS). In this study, we explore global changes to subcellular structure in Ewing sarcoma cell lines or in response to drug treatment. Crosslinking-dependent differential enrichment across four human cell lines is seen for proteins involved in splicing, mitochondria function, and cell division. We confirmed changes to nucleoli structure. We also examine structures affected by a transcription inhibitor, flavopiridol. Following flavopiridol treatment, we observed changes to the levels of transcription and mRNA processing machinery present in large subcellular structures. Unexpected effects were also found, including structural changes to a cytoplasmic organelle, the peroxisome. Along with a reduction in peroxisome function, dissociation of peroxisome pore proteins PEX13 and PEX14 was detected by STORM microscopy. We conclude that SEC-MS combined with crosslinking is a valuable method to detect and quantify drug or disease effects on subcellular structures and may shed light on new aspects to mechanisms underlying their biologic outcomes.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"1054-1069"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148664220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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

Pharmacological Modulation of Autophagy Corrects Cellular Defects in Pediatric Crohn's Disease. 自噬的药理调节纠正儿童克罗恩病的细胞缺陷。

IF 2.8 2区生物学

Molecular and Cellular Biology Pub Date : 2026-01-01 Epub Date: 2025-11-13 DOI: 10.1080/10985549.2025.2583173

Mara Creoli, Pietro Buono, Sabrina Cenni, Marianna Casertano, Alessandra Vitale, Mariantonia Maglio, Roman Polishchuk, Elena Polishchuk, Laura Cinque, Erasmo Miele, Massimo Martinelli, Carmine Settembre, Annamaria Staiano, Pasquale Dolce, Caterina Strisciuglio

{"title":"Pharmacological Modulation of Autophagy Corrects Cellular Defects in Pediatric Crohn's Disease.","authors":"Mara Creoli, Pietro Buono, Sabrina Cenni, Marianna Casertano, Alessandra Vitale, Mariantonia Maglio, Roman Polishchuk, Elena Polishchuk, Laura Cinque, Erasmo Miele, Massimo Martinelli, Carmine Settembre, Annamaria Staiano, Pasquale Dolce, Caterina Strisciuglio","doi":"10.1080/10985549.2025.2583173","DOIUrl":"10.1080/10985549.2025.2583173","url":null,"abstract":"Crohn's disease (CD) is an inflammatory gastrointestinal disorder marked by impaired autophagy due to inefficient bacterial uptake. We studied the effects of autophagy modulation using Tat-beclin-1 and carbamazepine (CBZ) on dendritic cells (DCs) and Paneth cell functionality in pediatric CD patients. Twenty CD children genotyped for the ATG16L1 rs2241880 polymorphism and 10 healthy controls were enrolled. DCs were incubated with fluorochrome-conjugated particles of Escherichia coli or DQ-ovalbumin after pretreatment with CBZ or Tat-beclin-1 to evaluate antigen processing. Treated DCs were stained for P62, LAMP1, and LC3, and analyzed by confocal microscopy. Paneth cells from biopsies were pretreated with both drugs, stained for lysozyme, and analyzed by transmission electron microscopy. Antigen processing increased after Tat-beclin-1 and CBZ treatment in all groups. DCs expressed higher activation markers HLA-DR and CD86+, notably in high-risk patients, who also showed increased DQ-OVA processing. The number of lysozymes in Paneth cells from controls did not change after Tat-beclin-1 treatment, while in the CD group, it decreased significantly, suggesting increased exocytosis. CBZ treatment increased secretory granules only in CD inflamed tissue. Our results indicate that CBZ and Tat-beclin-1 enhance autophagic flux, representing a novel approach to treating pediatric CD patients.","PeriodicalId":18658,"journal":{"name":"Molecular and Cellular Biology","volume":" ","pages":"270-280"},"PeriodicalIF":2.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145505646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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