Journal of Cellular Physiology最新文献

{"title":"Bypassing Blood-Brain Barrier and Glucose Dependency of Anti-Glioblastoma Drug Candidates Targeting Mitochondrial Respiration","authors":"Charles H. Ingraham,&nbsp;Diana Polania Villanueva,&nbsp;Annamarie Macaluso,&nbsp;Annelise Tramuta,&nbsp;Cecilia Vittori,&nbsp;Jean-Jacques Hunter,&nbsp;Monika Rak,&nbsp;Pier Paolo Claudio,&nbsp;Mohamed A. Ibrahim,&nbsp;Luis Del Valle,&nbsp;Francesca Peruzzi,&nbsp;Branko S. Jursic,&nbsp;Krzysztof Reiss","doi":"10.1002/jcp.70062","DOIUrl":"https://doi.org/10.1002/jcp.70062","url":null,"abstract":"<div>\u0000 \u0000 <p>We attempt to address two key therapeutic obstacles affecting glioblastoma patients: low ability of anticancer drugs to penetrate the blood-brain barrier (BBB), and temozolomide (TMZ) resistance, by targeting mitochondrial respiration of glioblastoma cells. We designed and tested over 100 new compounds based on the chemical structure of fenofibrate (FF), which in its prodrug form is cytotoxic to cancer cells by causing severe impairment of mitochondrial respiration. The compounds were designed using two key predictive tools: central nervous system–multiparameter optimization (CNS-MPO) and BBB_SCORE. These algorithms assess how effectively compounds can penetrate the BBB. We initially selected PP1 as a lead compound by testing its BBB penetration, metabolic performance, and antitumoral efficacy. PP1 accumulated in brain tumors and triggered glioblastoma cell death. However, PP1-induced inhibition of mitochondrial respiration was followed by an immediate glycolytic response, which attenuated PP1 toxicity in a glucose-dependent manner. To bypass this limitation, we tested two strategies: (1) the use of PP1 in combination with glycolysis inhibitors; and (2) introduction of a new compound, PP211, which inhibited mitochondrial respiration in the absence of a concomitant increase of glycolysis. Although the combination of PP1 with glycolysis inhibitors was very effective in vitro, this drug combination demonstrated elevated toxicity in mice. PP211, instead, attenuated TMZ-resistant tumor growth and prolonged mouse survival with only minimal general animal toxicity. In summary, we developed and tested a novel mitochondria-targeting drug candidate, PP211, which effectively crosses the BBB, overcomes TMZ resistance, and induces tumor cell death independently of glucose levels—while exhibiting minimal systemic toxicity in preclinical models. These findings support further development of PP211 for glioblastoma therapy.</p></div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144635419","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}

{"title":"The Role of Mitochondrial Dynamics in Doxorubicin-Induced Disease: Implications for Therapy","authors":"Huan Yue,&nbsp;Yousheng Chen,&nbsp;Junxiao Feng,&nbsp;Weiying Yue,&nbsp;Xingjuan Shi","doi":"10.1002/jcp.70064","DOIUrl":"https://doi.org/10.1002/jcp.70064","url":null,"abstract":"<div>\u0000 \u0000 <p>As an anthracycline chemotherapy drug, doxorubicin (Dox) is generally prescribed to treat a variety of malignant tumors. Nevertheless, Dox exhibited toxicity at a high dosage, which might eventually lead to injury of the body. Mitochondrial dynamics, including mitochondrial fission and fusion, regulates mitochondrial homeostasis and cellular function. Mounting evidence has demonstrated that imbalance in mitochondrial dynamics, manifested by increased mitochondrial fission or decreased mitochondrial fusion, is associated with the development of Dox-induced diseases. In this paper, we will elaborate the role of mitochondrial dynamics in Dox-induced diseases, and discuss the regulatory mechanism of mitochondrial dynamics in Dox-induced diseases, including apoptosis, fibrosis, myocardial atrophy and inflammation. Elucidating these issues may provide important value in the diagnosis and potential therapeutic strategies for Dox-induced diseases through regulation of mitochondria dynamics.</p></div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144615259","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}

{"title":"New Trick for the Old COP: Cellular Physiology of COPII Condensation in Lipoprotein Secretion","authors":"Xiao Wang,&nbsp;Ke Yang,&nbsp;Xiao-Wei Chen","doi":"10.1002/jcp.70061","DOIUrl":"https://doi.org/10.1002/jcp.70061","url":null,"abstract":"<div>\u0000 \u0000 <p>Products encoded by approximately 30% of the mammalian genome exit the endoplasmic reticulum via the coat complex II (COPII) system en route to their functional destination. Among these cargoes, APOB-containing lipoproteins stand out as abundant and bulky secretory particles with profound implications for human health and diseases. Recent insights into the specialized intracellular itinerary of lipoprotein metabolism and transport not only shed light on longstanding questions of lipid dynamics, but also highlight challenges faced by the COPII machinery in accommodating these complex, unconventional cargoes. Emerging evidence supports that tightly-regulated COPII condensation enables maximal capacity of cargo transport, providing a potential solution tailored for efficient lipoprotein delivery without affecting general protein secretion. This distinction suggests that targeting COPII condensation may provide new therapeutic strategies for lipid-associated diseases. Indeed, recent studies have identified manganese as a key modulator of this process, offering novel insights into its physiological relevance and potential translations.</p></div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 7","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144574150","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}

{"title":"Response to the Letter “Classification and Characterization of Platelet-Rich Fibrin in Regenerative Medicine”","authors":"Sahar Baniameri,&nbsp;Hossein Aminianfar,&nbsp;Niusha Gharehdaghi,&nbsp;Amir-Ali Yousefi-Koma,&nbsp;Sadra Mohaghegh,&nbsp;Hanieh Nokhbatolfoghahaei,&nbsp;Arash Khojasteh","doi":"10.1002/jcp.70059","DOIUrl":"https://doi.org/10.1002/jcp.70059","url":null,"abstract":"","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515009","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}

{"title":"Classification and Characterization of Platelet-Rich Fibrin in Regenerative Medicine","authors":"Shajahan Amitha Banu,&nbsp;Khan Sharun","doi":"10.1002/jcp.70060","DOIUrl":"https://doi.org/10.1002/jcp.70060","url":null,"abstract":"","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515010","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}

{"title":"Dapagliflozin Interrupts Pro-Fibroinflammatory Interleukin 11-Tenascin C Mutual Reinforcement in Fibroblasts by Antagonizing Interleukin-11 Receptor Subunit Alpha","authors":"Yen-Chen Lin,&nbsp;Wei-Jan Chen,&nbsp;Yu-Juei Hsu,&nbsp;Ying-Ju Lai,&nbsp;Cheng-Chin Kuo,&nbsp;Yung-Hsin Yeh","doi":"10.1002/jcp.70052","DOIUrl":"https://doi.org/10.1002/jcp.70052","url":null,"abstract":"<div>\u0000 \u0000 <p>Sodium/glucose cotransporter 2 inhibitors (SGLT2i) protect against heart failure and fibroinflammation with an unclear mechanistic. Recombinant interleukin-11 (IL11) therapy for thrombocytopenia induces heart failure symptoms and signs. Profibrotic IL11 upregulates extracellular matrix (ECM) proteins, whereas pro-inflammatory tenascin-C (TNC) is an ECM-derived alarmin. We hypothesized IL11 upregulated TNC to induce fibroinflammation via Toll-like receptor 4 (TLR4) and prototype SGLT2i dapagliflozin counteracted the effects. We stimulated fibroblasts with IL11 and confirmed TNC upregulation. NADPH oxidase 2 (NOX2) is known to participate in TNC-TLR4 signaling. We treated IL11-stimulated fibroblasts with inhibitors of TLR4 (TLR4i) and NOX2 (NOX2i) and found IL11 induced an imperative profibrotic TNC-TLR4-NOX2 auto-amplification loop. IL11 is known to induce ERK-dependent positive autofeedback. By finding TLR4i and NOX2i inhibited IL11-induced ERK phosphorylation, we suspected IL11-ERK joined TNC-TLR4-NOX2 auto-amplification fibroinflammatory pathway. We stimulated fibroblasts with TNC and found IL11 upregulation. We treated TNC-stimulated fibroblasts with TLR4i, NOX2i, or neutralizing IL11 antibody and confirmed TLR4-NOX2 and IL11 were indispensable for TNC-induced fibrosis. We concluded that IL11-ERK, TNC-TLR4, and NOX2 are interdependent in fibroblasts and together make a positive-feedback loop to sustain fibroinflammation. We checked mRNA expression of relevant proteins from proteinatlas.org and found fibroblasts are overwhelming producers of IL11 and TNC in the heart. IL11 receptor subunit alpha (IL11RA) and TLR4 are highly differentially expressed with the former on cardiomyocytes and the latter on macrophages. We therefore proposed a model of differentially activated IL11RA and TLR4 signaling in response to mutually reinforcing IL11-TNC alarmins, to explain how activated fibroblasts pivotally support fibroinflammatory microenvironment and how danger signals induce cell-type-specific responses. Next, we showed dapagliflozin prevented fibroinflammation induced by IL11 or TNC. Mechanistically, we showed dapagliflozin antagonized IL11RA by molecular docking, fluorescence quenching, and grading-dose IL11-signaling inhibitor cocktails studies. In conclusion, dapagliflozin interrupts pro-fibroinflammatory IL11-TNC bi-alarmin mutual reinforcement in human cardiac fibroblasts by antagonizing IL11RA.</p>\u0000 </div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144514960","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}

{"title":"In Old Mice, Exercise Induces Inflammation and Fibrosis Unless Alk5-Inhibitor and Oxytocin Are Used","authors":"Joana Marie C. Cruz,&nbsp;Hayden Yeung,&nbsp;Rana Alzalzalee,&nbsp;Qile Yang,&nbsp;Hannaneh Kabir,&nbsp;Samantha Annaliese McDonough,&nbsp;Xiaoyue Mei,&nbsp;Michael J. Conboy,&nbsp;Irina M. Conboy","doi":"10.1002/jcp.70054","DOIUrl":"https://doi.org/10.1002/jcp.70054","url":null,"abstract":"<p>Exercise and diet are the best-known methods for attenuating aging-related health decline. However, exercise in older age has diminished gains of strength and agility, and a danger of unrepaired muscle damage. Improving the understanding of age-related differences in response to exercise, our results demonstrate that in old mice, downhill treadmill (eccentric) exercise causes increased influx of CD45+ cells (inflammation) and fibrotic index (fibrosis) in the heart and skeletal muscles. To explain these changes, we identified newly synthesized proteins through bio-orthogonal noncanonical amino acid tagging (BONCAT) and established that exercise exacerbated age-associated protein patterns through a dysregulated transforming growth factor (TGF)-β, Ras/MAPK/PI3Akt, and JAK/STAT pathways. Testing causality, we found that an inhibitor of TGF-β (Alk5 inhibitor, A5i) in combination with the age-diminished peptide oxytocin, previously shown to rejuvenate muscle and brain in sedentary animals, allowed aged mice to exercise without pathologies of skeletal and heart muscles and youthfully restored their de novo proteomes.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Potential Dual Roles of Metallothionein-1/-2 in Diabetic Osteoarthritis","authors":"Yu-Ping Su,&nbsp;Rong-Ze Hsieh,&nbsp;Kuo-Ti Peng,&nbsp;Chung-Sheng Shi,&nbsp;Kuo-Chin Huang,&nbsp;Shun-Fu Chang","doi":"10.1002/jcp.70056","DOIUrl":"https://doi.org/10.1002/jcp.70056","url":null,"abstract":"<div>\u0000 \u0000 <p>Osteoarthritis (OA) is increasingly recognized as a chronic inflammatory degenerative joint disease. Recent evidence exhibits a higher prevalence of OA among patients with type II diabetes mellitus (T2DM). Metallothioneins (MTs) are important proteins involved in controlling physiology and pathophysiology. MT-1/MT-2 have been further found their positive correlation with OA progression, but their precise roles need more examination. This study aimed to investigate the role of MT-1/MT-2 in the development of diabetic OA and the underlying mechanisms. Cartilage was collected from patients with OA-only and T2DM-OA, and from rats classified as healthy, T2DM, and T2DM with destabilization of medial meniscus (DMM) surgery. Additionally, a cell model treated with high glucose (HG) or advanced glycation end products (AGEs) was used to investigate underlying mechanisms. Our results revealed that MT-1/MT-2 levels were elevated in cartilage from T2DM-OA patients and rats, as well as in T2DM rats subjected to DMM surgery. Similarly, primary chondrocytes treated with HG and AGE showed increased expression of MT-1/MT-2, with distinct distributions and regulatory mechanisms: (a) MT-1 enhanced MMP and transcription factor activity without affecting their expressions, whereas MT-2 increased both the activity and expression of MMPs and transcription factors; (b) MT-1 reduced IL6/IL8 expression, while MT-2 promoted it. Furthermore, this differential regulation appears to be mediated by BMP2 autocrine stimulation. These findings underscore the dual role of MT-1/MT-2 in simultaneously activating self-repair and degenerative processes, potentially influencing diabetic cartilage pathogenesis. Our study suggests that MT-1/MT-2 may serve as valuable theranostic targets for diabetic OA in future clinical applications.</p>\u0000 </div>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292701","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}

{"title":"Targeting Heparanase Attenuates Podocyte Injury Induced by Puromycin Aminonucleoside","authors":"Xing-Yun Huang,&nbsp;Yu-Hsien Lu,&nbsp;Hsiao-Hui Lee","doi":"10.1002/jcp.70053","DOIUrl":"https://doi.org/10.1002/jcp.70053","url":null,"abstract":"<p>Podocytes are highly specialized glomerular visceral epithelial cells critical for maintaining the structure and function of the glomerular filtration barrier. These cells adhere to the glomerular basement membrane (GBM) and envelop the outer surfaces of the glomerular capillaries to prevent protein leakage during blood ultrafiltration. The GBM is a dense network of extracellular matrix composed of type IV collagen, laminin, nidogen, and heparan sulfate proteoglycans. In this study, we investigated the protective effect of a heparanase inhibitor on puromycin aminonucleoside (PAN)-induced podocyte injury. Our results demonstrate that PAN treatment significantly disrupted the cytoskeletal architecture of cultured podocytes, reducing the formation of focal adhesions and stress fibers. Interdigitating intercellular junctions were replaced by dot-like structures with accumulated filamentous actin. Co-treatment with the heparanase inhibitor PI-88 effectively prevented these PAN-induced cytoskeletal abnormalities. Furthermore, a BSA filtration assay revealed that PI-88 attenuated PAN-induced increases in podocyte monolayer permeability. Taken together, our findings suggest that heparanase inhibition protects against podocyte injury and may represent a potential therapeutic strategy for glomerular diseases.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 6","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70053","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144255810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTION: Evaluation of Anticancer Effects of Cerium Oxide Nanoparticles on Mouse Fibrosarcoma Cell Line","authors":"","doi":"10.1002/jcp.70051","DOIUrl":"https://doi.org/10.1002/jcp.70051","url":null,"abstract":"<p><b>RETRACTION</b>: E. Nourmohammadi, H. Khoshdel–Sarkarizi, R. Nedaeinia, H. R. Sadeghnia, L. Hasanzadeh, M. Darroudi and R. K. Oskuee, “Evaluation of Anticancer Effects of Cerium Oxide Nanoparticles on Mouse Fibrosarcoma Cell Line,” <i>Journal of Cellular Physiology</i> 234, no. 4 (2019): 4987–4996, https://doi.org/10.1002/jcp.27303.</p><p>The above article, published online on 06 September 2018 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Robert Heath; and Wiley Periodicals LLC. The retraction has been agreed upon following an investigation into concerns raised by a third party. The investigation revealed duplication between the L929-Control flow cytometry plot and the L929-Conc30 plot shown in Figure 7b. Furthermore, duplications were identified between the Conc 30 BAX western blot band presented in Figures 9a and the Control BAX western blot band in Figure 9b. These two figures represent different cell lines. An additional duplication was observed between the Control BCL2 band and the Conc 60 BAX band in Figure 9a. The authors provided an explanation and some data, but this was not deemed sufficient. The editors consider the results and conclusions from this study to be substantially compromised. The authors disagree with the retraction.</p>","PeriodicalId":15220,"journal":{"name":"Journal of Cellular Physiology","volume":"240 5","pages":""},"PeriodicalIF":4.5,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcp.70051","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144140598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}