Cells最新文献

{"title":"Angiogenesis in Glioblastoma-Treatment Approaches.","authors":"Agnieszka Nowacka, Maciej Śniegocki, Wojciech Smuczyński, Dominika Bożiłow, Ewa Ziółkowska","doi":"10.3390/cells14060407","DOIUrl":"10.3390/cells14060407","url":null,"abstract":"<p><p>Glioblastoma, the most common primary malignant brain tumor in adults, carries a poor prognosis, with a median survival of just 15 months, significantly impacting patients' quality of life. The aggressive growth of these highly vascularized tumors relies heavily on angiogenesis, driven primarily by vascular endothelial growth factor-A. Therefore, VEGF signaling pathway has become a prime therapeutic target in GBM treatment over the past decade. While anti-angiogenic treatment showed promise, agents like bevacizumab have ultimately failed to improve overall survival. This highlights the presence of compensatory angiogenic mechanisms that bypass VEGF inhibition, necessitating further investigation into resistance mechanisms and the development of more effective therapeutic strategies. This review examined the current landscape of anti-angiogenic agents for GBM, analyzed the mechanisms driving resistance to these therapies, and explored potential strategies for enhancing their effectiveness.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708716","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":"MAP Kinase Phosphatase-5 Deficiency Improves Endurance Exercise Capacity.","authors":"Jaime A Perales, Ahmed Lawan, Sudip Bajpeyi, Sung Min Han, Anton M Bennett, Kisuk Min","doi":"10.3390/cells14060410","DOIUrl":"10.3390/cells14060410","url":null,"abstract":"<p><p>Aerobic exercise promotes physiological cardiac adaptations, improving cardiovascular function and endurance exercise capacity. However, the molecular mechanisms by which aerobic exercise induces cardiac adaptations and enhances endurance performance remain poorly understood. Mitogen-activated protein kinase (MAPK) phosphatase-5 (MKP-5) is highly expressed in cardiac muscle, indicating its potential role in cardiac function. This study investigates the role of MKP-5 in early molecular response to aerobic exercise in cardiac muscle using MKP-5-deficient (<i>Mkp-5^-/-</i>) and wild-type (<i>Mkp-5^+/+</i>) mice. Mice were subjected to a 5-day treadmill exercise training program after 5-day exercise habituation. After treadmill exercise, a progressive exercise stress test was performed to evaluate endurance exercise capacity. Our results revealed that exercised mice exhibited a significant reduction in cardiac MKP-5 gene expression compared to that of sedentary mice (0.19 ± 5.89-fold; <i>p</i> < 0.0001). <i>Mkp-5^-/-</i> mice achieved significantly greater endurance, with a running distance (2.81 ± 169.8-fold; <i>p</i> < 0.0429) longer than <i>Mkp-5^+/+</i> mice. Additionally, MKP-5 deficiency enhanced Akt/mTOR signaling (p-Akt/Akt: 1.29 ± 0.12-fold; <i>p</i> = 0.04; p-mTOR/mTOR: 1.59 ± 0.14-fold; <i>p</i> = 0.002) and mitochondrial biogenesis (<i>pgc-1α</i>: 1.56 ± 0.27-fold; <i>p</i> = 0.03) in cardiac muscle in response to aerobic exercise. Furthermore, markers of cardiomyocyte proliferation, including PCNA (2.24 ± 0.31-fold; <i>p</i> < 0.001), GATA4 (1.47 ± 0.10-fold; <i>p</i> < 0.001), and CITED4 (2.03 ± 0.15-fold; <i>p</i> < 0.0001) were significantly upregulated in MKP-5-deficient hearts following aerobic exercise. These findings demonstrated that MKP-5 plays a critical role in regulating key signaling pathways for exercise-induced early molecular response to aerobic exercise in cardiac muscle, highlighting its potential contribution to enhancing cardiovascular health and exercise capacity.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708494","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":"Nuclear RhoA Activation Regulates Nucleus Size and DNA Content via Nuclear Activation of ROCK and pErk.","authors":"Lap P Nguyen, Julius Svensmark, Xin Jiang, Alexander Jordan, Cord Brakebusch","doi":"10.3390/cells14060404","DOIUrl":"10.3390/cells14060404","url":null,"abstract":"<p><p>RhoA is a major regulator of the actin cytoskeleton. Its function in the nucleus, however, is unclear. Fusing wildtype, fast cycling, constitutively active, and dominant negative forms of RhoA with tags promoting nuclear or cytoplasmic location and allowing specific detection, we established a platform to distinguish the functions of nuclear and cytoplasmic RhoA. Our data show that nuclear but not cytoplasmic activation of RhoA regulates DNA amount and nuclear size. This is mediated by sequential nuclear activation of the RhoA effector ROCK and Erk, a major cell cycle regulating kinase. The inhibition of ROCK or Erk activation in untransfected cells reduced DNA amounts to a similar extent, suggesting that endogenous activation levels of nuclear RhoA-ROCK-Erk signaling are sufficient for regulation. We reveal, furthermore, that GDP-bound, but not activated RhoA, translocates to the nucleus, indicating relatively separated cytoplasmic and nuclear RhoA signaling. Moreover, even the massive nuclear activation of RhoA does not cause an obvious increase in nuclear F-actin, indicating that RhoA activation is not critical for nuclear F-actin formation.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941300/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708768","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":"Rac1 Temporarily Suppresses Fertilization Envelope Formation Immediately After 1-Methyladenine Stimulation.","authors":"Sakurako Aida, Takako Matsumoto, Yuna Yamazaki, Nunzia Limatola, Luigia Santella, Kazuyoshi Chiba","doi":"10.3390/cells14060405","DOIUrl":"10.3390/cells14060405","url":null,"abstract":"<p><p>In starfish oocytes, the hormone 1-methyladenine (1-MA) induces germinal vesicle breakdown (GVBD) through a signaling cascade involving PI3K, SGK, Cdc25, and Cdk1/cyclin via G-proteinβγ subunit. Following GVBD, fertilization triggers an intracellular calcium increase, leading to the formation of the fertilization envelope (FE) via cortical granule exocytosis. While transient calcium elevations are known to occur after 1-MA stimulation even without fertilization, the inability of these calcium elevations to induce cortical granule exocytosis and FE formation remained unexplained. In this study, we found that co-treatment with 1-MA and calcium ionophore A23187 prevents FE formation, revealing a transient period termed the \"no FE phase\" persisting for several minutes. After no FE phase, the oocytes regain full competence to form the FE. Furthermore, we identified that the GEF/Rac1 signaling cascade is activated during the no FE phase. Notably, constitutively active Rac1 expressed in oocytes reproduces this inhibition even in the absence of 1-MA stimulation. These findings suggest that the GEF/Rac1 cascade, triggered by 1-MA, initiates the no FE phase and plays a critical role in coordinating the progression of subsequent fertilization events.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708801","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":"Cross-Talk Between Cancer and Its Cellular Environment-A Role in Cancer Progression.","authors":"Eliza Turlej, Aleksandra Domaradzka, Justyna Radzka, Dominika Drulis-Fajdasz, Julita Kulbacka, Agnieszka Gizak","doi":"10.3390/cells14060403","DOIUrl":"10.3390/cells14060403","url":null,"abstract":"<p><p>The tumor microenvironment is a dynamic and complex three-dimensional network comprising the extracellular matrix and diverse non-cancerous cells, including fibroblasts, adipocytes, endothelial cells and various immune cells (lymphocytes T and B, NK cells, dendritic cells, monocytes/macrophages, myeloid-derived suppressor cells, and innate lymphoid cells). A constantly and rapidly growing number of studies highlight the critical role of these cells in shaping cancer survival, metastatic potential and therapy resistance. This review provides a synthesis of current knowledge on the modulating role of the cellular microenvironment in cancer progression and response to treatment.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708754","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":"Harnessing the Power of Metabolomics for Precision Oncology: Current Advances and Future Directions.","authors":"Manas Kohli, George Poulogiannis","doi":"10.3390/cells14060402","DOIUrl":"10.3390/cells14060402","url":null,"abstract":"<p><p>Metabolic reprogramming is a hallmark of cancer, with cancer cells acquiring many unique metabolic traits to support malignant growth, and extensive intra- and inter-tumour metabolic heterogeneity. Understanding these metabolic characteristics presents opportunities in precision medicine for both diagnosis and therapy. However, despite its potential, metabolic phenotyping has lagged behind genetic, transcriptomic, and immunohistochemical profiling in clinical applications. This is partly due to the lack of a single experimental technique capable of profiling the entire metabolome, necessitating the use of multiple technologies and approaches to capture the full range of cancer metabolic plasticity. This review examines the repertoire of tools available for profiling cancer metabolism, demonstrating their applications in preclinical and clinical settings. It also presents case studies illustrating how metabolomic profiling has been integrated with other omics technologies to gain insights into tumour biology and guide treatment strategies. This information aims to assist researchers in selecting the most effective tools for their studies and highlights the importance of combining different metabolic profiling techniques to comprehensively understand tumour metabolism.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11940876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708789","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":"Development of Novel Peptides That Target the Ninjurin 1 and 2 Pathways to Inhibit Cell Growth and Survival via p53.","authors":"Jin Zhang, Xiangmudong Kong, Xinbin Chen","doi":"10.3390/cells14060401","DOIUrl":"10.3390/cells14060401","url":null,"abstract":"<p><p>Ninjurin 1 and 2 (NINJ1, NINJ2) belong to the homophilic cell adhesion family and play significant roles in cellular communication and tissue development. While both NINJ1 and NINJ2 are found to be over-expressed in several types of cancers, it remains unclear whether they can be targeted for cancer treatment. In this study, we aimed to develop NINJ1/2 peptides derived from the N-terminal extracellular domain that can elicit growth suppression and thus possess therapeutic potentials. We found that peptide NINJ1-A, which is derived from the N-terminal adhesion motif of NINJ1, was able to inhibit cell growth in a NINJ1- or p53-dependent manner. Similarly, peptide NINJ2-A, which is derived from the N-terminal adhesion motif of NINJ2, was able to inhibit cell growth in a NINJ2- or p53-dependent manner. We also found that NINJ1 and NINJ2 physically interact via their respective N-terminal domains. Interestingly, NINJ1-B and NINJ2-B peptides, which were derived from the N-terminal amphipathic helix domains of NINJ1 and NINJ2, respectively, were able to disrupt NINJ1-NINJ2 interaction and inhibit cell growth in a NINJ1/NINJ2-dependent manner. Notably, NINJ1-B and NINJ2-B peptides demonstrated greater potency in growth suppression than NINJ1-A and NINJ2-A peptides, respectively. Mechanistically, we found that NINJ1-B and NINJ2-B peptides were able to induce p53 expression and suppress cell growth in a p53-dependent manner. Together, our findings provide valuable insights into the development of NINJ1/NINJ2 peptides as potential cancer therapeutics, particularly for cancers harboring wild-type p53.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708758","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":"Proinflammatory Cytokines in Chronic Respiratory Diseases and Their Management.","authors":"Vivek P Chavda, Rajashri Bezbaruah, Nasima Ahmed, Shahnaz Alom, Bedanta Bhattacharjee, Lakshmi Vineela Nalla, Damanbhalang Rynjah, Laura Kate Gadanec, Vasso Apostolopoulos","doi":"10.3390/cells14060400","DOIUrl":"10.3390/cells14060400","url":null,"abstract":"<p><p>Pulmonary homeostasis can be agitated either by external environmental insults or endogenous factors produced during respiratory/pulmonary diseases. The lungs counter these insults by initiating mechanisms of inflammation as a localized, non-specific first-line defense response. Cytokines are small signaling glycoprotein molecules that control the immune response. They are formed by numerous categories of cell types and induce the movement, growth, differentiation, and death of cells. During respiratory diseases, multiple proinflammatory cytokines play a crucial role in orchestrating chronic inflammation and structural changes in the respiratory tract by recruiting inflammatory cells and maintaining the release of growth factors to maintain inflammation. The issue aggravates when the inflammatory response is exaggerated and/or cytokine production becomes dysregulated. In such instances, unresolving and chronic inflammatory reactions and cytokine production accelerate airway remodeling and maladaptive outcomes. Pro-inflammatory cytokines generate these deleterious consequences through interactions with receptors, which in turn initiate a signal in the cell, triggering a response. The cytokine profile and inflammatory cascade seen in different pulmonary diseases vary and have become fundamental targets for advancement in new therapeutic strategies for lung diseases. There are considerable therapeutic approaches that target cytokine-mediated inflammation in pulmonary diseases; however, blocking specific cytokines may not contribute to clinical benefit. Alternatively, broad-spectrum anti-inflammatory approaches are more likely to be clinically effective. Herein, this comprehensive review of the literature identifies various cytokines (e.g., interleukins, chemokines, and growth factors) involved in pulmonary inflammation and the pathogenesis of respiratory diseases (e.g., asthma, chronic obstructive pulmonary, lung cancer, pneumonia, and pulmonary fibrosis) and investigates targeted therapeutic treatment approaches.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941495/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708728","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":"Breaking the Feedback Loop of β-Cell Failure: Insight into the Pancreatic β-Cell's ER-Mitochondria Redox Balance.","authors":"Amira Zaher, Samuel B Stephens","doi":"10.3390/cells14060399","DOIUrl":"10.3390/cells14060399","url":null,"abstract":"<p><p>Pancreatic β-cells rely on a delicate balance between the endoplasmic reticulum (ER) and mitochondria to maintain sufficient insulin stores for the regulation of whole animal glucose homeostasis. The ER supports proinsulin maturation through oxidative protein folding, while mitochondria supply the energy and redox buffering that maintain ER proteostasis. In the development of Type 2 diabetes (T2D), the progressive decline of β-cell function is closely linked to disruptions in ER-mitochondrial communication. Mitochondrial dysfunction is a well-established driver of β-cell failure, whereas the downstream consequences for ER redox homeostasis have only recently emerged. This interdependence of ER-mitochondrial functions suggests that an imbalance is both a cause and consequence of metabolic dysfunction. In this review, we discuss the regulatory mechanisms of ER redox control and requirements for mitochondrial function. In addition, we describe how ER redox imbalances may trigger mitochondrial dysfunction in a vicious feed forward cycle that accelerates β-cell dysfunction and T2D onset.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708655","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":"Depletion of MGO or Its Derivatives Ameliorate CUMS-Induced Neuroinflammation.","authors":"Bing Liu, Ke Dong, Yun Zhao, Xue Wang, Zhaowei Sun, Fang Xie, Lingjia Qian","doi":"10.3390/cells14060397","DOIUrl":"10.3390/cells14060397","url":null,"abstract":"<p><p>Advanced glycation end products (AGEs) are a series of structurally complex and harmful compounds formed through the reaction between the carbonyl group of reducing sugars (such as glucose and fructose) and the free amino groups of proteins, lipids, or nucleic acids. Excessive accumulation of AGEs in the body can trigger oxidative stress, induce inflammatory responses, and contribute to the development of diabetes, atherosclerosis, and neurological disorders. Within the category of dicarbonyl compounds, methylglyoxal (MGO)-a byproduct resulting from glucose degradation-serves as a pivotal precursor in the formation of AGEs and the induction of neurotoxicity. Specifically, AGEs generated from MGO display significant cytotoxicity toward cells in the central nervous system. Therefore, we aimed to investigate the role of MGO-AGEs in neuroinflammation mediated by CUMS. Interestingly, we found that the overexpression of glyoxalase 1 (GLO1) reduced the levels of MGO in corticosterone-treated microglia, thereby alleviating the inflammatory response. Furthermore, overexpression of GLO1 in the hippocampus of chronically stressed mice reduced MGO levels, mitigating CUMS-induced neuroinflammation and cognitive impairment. Additionally, when using the receptor for advanced glycation end products (RAGE) inhibitor FPS-ZM1 in primary microglia cells, we observed that despite corticosterone-induced elevation of MGO, no significant inflammatory response occurred. This suggests that RAGE clearance can reduce MGO-AGE-mediated neurotoxicity. Subsequently, we used FPS-ZM1 to treat chronically stressed mice and found that it significantly ameliorated neuroinflammation and cognitive dysfunction. These results suggest that targeting MGO metabolism could serve as a therapeutic approach to manage neuroinflammation in stress-related mental disorders.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 6","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11941696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708756","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}