CellsPub Date : 2025-01-20DOI: 10.3390/cells14020144
Marco Paolo Donadini, Francesca Calcaterra, Erica Romualdi, Roberta Ciceri, Assunta Cancellara, Corrado Lodigiani, Monica Bacci, Silvia Della Bella, Walter Ageno, Domenico Mavilio
{"title":"The Link Between Venous and Arterial Thrombosis: Is There a Role for Endothelial Dysfunction?","authors":"Marco Paolo Donadini, Francesca Calcaterra, Erica Romualdi, Roberta Ciceri, Assunta Cancellara, Corrado Lodigiani, Monica Bacci, Silvia Della Bella, Walter Ageno, Domenico Mavilio","doi":"10.3390/cells14020144","DOIUrl":"10.3390/cells14020144","url":null,"abstract":"<p><p>Venous thromboembolism (VTE) and arterial thrombosis (AT) are distinct yet closely related pathological processes. While traditionally considered separate entities, accumulating evidence suggests that they share common risk factors, such as inflammation and endothelial dysfunction (ED). This review explores the parallels and differences between venous and arterial thrombosis, with particular attention to the role of unprovoked VTE and its potential links to atherosclerosis and systemic inflammation. A key focus is the role of ED, which is emerging as a critical factor in thrombogenesis across both the venous and arterial systems. We examine the current methods for clinically detecting ED, including the use of biomarkers and advanced imaging techniques. Additionally, we discuss novel research avenues, such as the potential of endothelial colony-forming cells and other innovative methodologies, to further unravel the complex mechanisms of thrombosis. Finally, we propose future clinical scenarios where targeting endothelial health could pave the way for more effective prevention and treatment strategies in thrombosis management.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 2","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032400","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}
CellsPub Date : 2025-01-20DOI: 10.3390/cells14020147
Chenxing S Jiang, Michael Schrader
{"title":"Modelling Peroxisomal Disorders in Zebrafish.","authors":"Chenxing S Jiang, Michael Schrader","doi":"10.3390/cells14020147","DOIUrl":"10.3390/cells14020147","url":null,"abstract":"<p><p>Peroxisomes are ubiquitous, dynamic, oxidative organelles with key functions in cellular lipid metabolism and redox homeostasis. They have been linked to healthy ageing, neurodegeneration, cancer, the combat of pathogens and viruses, and infection and immune responses. Their biogenesis relies on several peroxins (encoded by <i>PEX</i> genes), which mediate matrix protein import, membrane assembly, and peroxisome multiplication. Defects in peroxins or peroxisomal enzymes can result in severe disorders, including developmental and neurological abnormalities. The drive to understand the role of peroxisomes in human health and disease, as well as their functions in tissues and organs or during development, has led to the establishment of vertebrate models. The zebrafish (<i>Danio rerio</i>) has become an attractive vertebrate model organism to investigate peroxisomal functions. Here, we provide an overview of the visualisation of peroxisomes in zebrafish, as well as the peroxisomal metabolic functions and peroxisomal protein inventory in comparison to human peroxisomes. We then present zebrafish models which have been established to investigate peroxisomal disorders. These include model zebrafish for peroxisome biogenesis disorders/Zellweger Spectrum disorders, and single enzyme deficiencies, particularly adrenoleukodystrophy and fatty acid beta-oxidation abnormalities. Finally, we highlight zebrafish models for deficiencies of dually targeted peroxisomal/mitochondrial proteins. Advantages for the investigation of peroxisomes during development and approaches to the application of zebrafish models for drug screening are discussed.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 2","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11764017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032494","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}
CellsPub Date : 2025-01-20DOI: 10.3390/cells14020148
Sofia Hakala, Anna Hämäläinen, Sanne Sandelin, Nikolaos Giannareas, Elisa Närvä
{"title":"Detection of Cancer Stem Cells from Patient Samples.","authors":"Sofia Hakala, Anna Hämäläinen, Sanne Sandelin, Nikolaos Giannareas, Elisa Närvä","doi":"10.3390/cells14020148","DOIUrl":"10.3390/cells14020148","url":null,"abstract":"<p><p>The existence of cancer stem cells (CSCs) in various tumors has become increasingly clear in addition to their prominent role in therapy resistance, metastasis, and recurrence. For early diagnosis, disease progression monitoring, and targeting, there is a high demand for clinical-grade methods for quantitative measurement of CSCs from patient samples. Despite years of active research, standard measurement of CSCs has not yet reached clinical settings, especially in the case of solid tumors. This is because detecting this plastic heterogeneous population of cells is not straightforward. This review summarizes various techniques, highlighting their benefits and limitations in detecting CSCs from patient samples. In addition, methods designed to detect CSCs based on secreted and niche-associated signaling factors are reviewed. Spatial and single-cell methods for analyzing patient tumor tissues and noninvasive techniques such as liquid biopsy and in vivo imaging are discussed. Additionally, methods recently established in laboratories, preclinical studies, and clinical assays are covered. Finally, we discuss the characteristics of an ideal method as we look toward the future.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 2","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11764358/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032332","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}
CellsPub Date : 2025-01-20DOI: 10.3390/cells14020146
Damien Le Nihouannen, Claudine Boiziau, Sylvie Rey, Nicole Agadzhanian, Nathalie Dusserre, Fabrice Cordelières, Muriel Priault, Helene Boeuf
{"title":"Inhibiting Autophagy by Chemicals During SCAPs Osteodifferentiation Elicits Disorganized Mineralization, While the Knock-Out of <i>Atg5/7</i> Genes Leads to Cell Adaptation.","authors":"Damien Le Nihouannen, Claudine Boiziau, Sylvie Rey, Nicole Agadzhanian, Nathalie Dusserre, Fabrice Cordelières, Muriel Priault, Helene Boeuf","doi":"10.3390/cells14020146","DOIUrl":"https://doi.org/10.3390/cells14020146","url":null,"abstract":"<p><p>SCAPs (Stem Cells from Apical Papilla), derived from the apex of forming wisdom teeth, extracted from teenagers for orthodontic reasons, belong to the MSCs (Mesenchymal Stromal Cells) family. They have multipotent differentiation capabilities and are a potentially powerful model for investigating strategies of clinical cell therapies. Since autophagy-a regulated self-eating process-was proposed to be essential in osteogenesis, we investigated its involvement in the SCAP model. By using a combination of chemical and genetic approaches to inhibit autophagy, we studied early and late events of osteoblastic differentiation. We showed that blocking the formation of autophagosomes with verteporfin did not induce a dramatic alteration in early osteoblastic differentiation monitored by ALP (alkaline phosphatase) activity. However, blocking the autophagy flux with bafilomycin A1 led to ALP repression. Strikingly, the mineralization process was observed with both compounds, with calcium phosphate (CaP) nodules that remained inside cells under bafilomycin A1 treatment and numerous but smaller CaP nodules after verteporfin treatment. In contrast, deletion of <i>Atg5</i> or <i>Atg7</i>, two genes involved in the formation of autophagosomes and essential to trigger canonical autophagy, indicated that both genes could be involved differently in the mineralization process with a modification of the ALP activity while final mineralization was not altered.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 2","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032387","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}
CellsPub Date : 2025-01-20DOI: 10.3390/cells14020145
Judit Bovari-Biri, Judith A Miskei, Zsanett Kover, Alexandra Steinerbrunner-Nagy, Kinga Kardos, Peter Maroti, Judit E Pongracz
{"title":"Advancements in Bone Replacement Techniques-Potential Uses After Maxillary and Mandibular Resections Due to Medication-Related Osteonecrosis of the Jaw (MRONJ).","authors":"Judit Bovari-Biri, Judith A Miskei, Zsanett Kover, Alexandra Steinerbrunner-Nagy, Kinga Kardos, Peter Maroti, Judit E Pongracz","doi":"10.3390/cells14020145","DOIUrl":"10.3390/cells14020145","url":null,"abstract":"<p><p>Maxillofacial bone defects can have a profound impact on both facial function and aesthetics. While various biomaterial scaffolds have shown promise in addressing these challenges, regenerating bone in this region remains complex due to its irregular shape, intricate structure, and differing cellular origins compared to other bones in the human body. Moreover, the significant and variable mechanical loads placed on the maxillofacial bones add further complexity, especially in cases of difficult-to-treat medical conditions. This review provides a brief overview of medication-related osteonecrosis of the jaw (MRONJ), highlighting the medication-induced adverse reactions and the associated clinical challenges in treating this condition. The purpose of this manuscript is to emphasize the role of biotechnology and tissue engineering technologies in therapy. By using scaffold materials and biofactors in combination with autologous cells, innovative solutions are explored for the repair of damaged facial bones. The ongoing search for effective scaffolds that can address these challenges and improve in vitro bone preparation for subsequent regeneration in the maxillofacial region remains critical. The primary purpose of this review is to spotlight current research trends and novel approaches in this area.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 2","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143031974","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}
CellsPub Date : 2025-01-19DOI: 10.3390/cells14020143
Pavel P Tregub, Yulia K Komleva, Maria V Kukla, Anton S Averchuk, Anna S Vetchinova, Natalia A Rozanova, Sergey N Illarioshkin, Alla B Salmina
{"title":"Brain Plasticity and Cell Competition: Immediate Early Genes Are the Focus.","authors":"Pavel P Tregub, Yulia K Komleva, Maria V Kukla, Anton S Averchuk, Anna S Vetchinova, Natalia A Rozanova, Sergey N Illarioshkin, Alla B Salmina","doi":"10.3390/cells14020143","DOIUrl":"10.3390/cells14020143","url":null,"abstract":"<p><p>Brain plasticity is at the basis of many cognitive functions, including learning and memory. It includes several mechanisms of synaptic and extrasynaptic changes, neurogenesis, and the formation and elimination of synapses. The plasticity of synaptic transmission involves the expression of immediate early genes (IEGs) that regulate neuronal activity, thereby supporting learning and memory. In addition, IEGs are involved in the regulation of brain cells' metabolism, proliferation, and survival, in the establishment of multicellular ensembles, and, presumably, in cell competition in the tissue. In this review, we analyze the current understanding of the role of IEGs (c-Fos, c-Myc, Arg3.1/Arc) in controlling brain plasticity in physiological and pathological conditions, including brain aging and neurodegeneration. This work might inspire new gene therapy strategies targeting IEGs to regulate synaptic plasticity, and potentially prevent or mitigate neurodegenerative diseases.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 2","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763428/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032300","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}
CellsPub Date : 2025-01-18DOI: 10.3390/cells14020141
Ravinder Kumar, Colin Arrowood, Micah B Schott, Taras Y Nazarko
{"title":"Microlipophagy from Simple to Complex Eukaryotes.","authors":"Ravinder Kumar, Colin Arrowood, Micah B Schott, Taras Y Nazarko","doi":"10.3390/cells14020141","DOIUrl":"10.3390/cells14020141","url":null,"abstract":"<p><p>Lipophagy is a selective degradation of lipid droplets in lysosomes or vacuoles. Apart from its role in generating energy and free fatty acids for membrane repair, growth, and the formation of new membranes, lipophagy emerges as a key player in other cellular processes and disease pathogenesis. While fungal, plant, and algal cells use microlipophagy, the most prominent form of lipophagy in animal cells is macrolipophagy. However, recent studies showed that animal cells can also use microlipophagy to metabolize their lipid droplets. Therefore, to no surprise, microlipophagy is conserved from simple unicellular to the most complex multicellular eukaryotes, and many eukaryotic cells can operate both forms of lipophagy. Macrolipophagy is the most studied and better understood at the molecular level, while our understanding of microlipophagy is very sparse. This review will discuss microlipophagy from the perspective of its conservation in eukaryotes and its importance in diseases. To better appreciate the conserved nature of microlipophagy, different organisms and types of cells in which microlipophagy has been reported are also shown in a tabular form. We also point toward the gaps in our understanding of microlipophagy, including the signaling behind microlipophagy, especially in the cells of complex multicellular organisms.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 2","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11764314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032464","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}
CellsPub Date : 2025-01-18DOI: 10.3390/cells14020140
Arshag D Mooradian, Michael J Haas
{"title":"Role of Thyroid Hormone in Neurodegenerative Disorders of Older People.","authors":"Arshag D Mooradian, Michael J Haas","doi":"10.3390/cells14020140","DOIUrl":"10.3390/cells14020140","url":null,"abstract":"<p><p>Thyroid dysfunction is associated with a number of neuropsychiatric manifestations. Cognitive decline is a common feature of hypothyroidism and clinical or subclinical hyperthyroidism. In addition, there is a significant association between thyroid hormone (TH) levels and the degree of cognitive impairment in Parkinson's disease (PD). The pathophysiology of TH-related neurodegeneration include changes in the blood-brain barrier, increased cellular stress, altered processing of β-amyloid precursor protein and the effect of TH on neuronal cell viability. The neurotoxicity of TH is partially mediated by the thyroid hormone responsive protein (THRP). This protein is 83% homologous to mouse c-Abl-interacting protein-2 (Abi2), a c-Abl-modulating protein with tumor suppressor activity. In cell cultures, increasing THRP expression either with TH treatment or exogenously through transfecting neuronal or PC 12 cells causes cell necrosis. The expression of exogenous THRP in other cells such as the colonic epithelial cell line Caco-2 and the glial cell line U251 has no effect on cell viability. The effect of THRP on cell viability is not modulated by c-Abl tyrosine kinase. The causal relationship between specific biochemical perturbations in cerebral tissue and thyroid dysfunction remains to be elucidated.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 2","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032293","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}
CellsPub Date : 2025-01-18DOI: 10.3390/cells14020139
Melanie A Simpson
{"title":"Impacts of Hyaluronan on Extracellular Vesicle Production and Signaling.","authors":"Melanie A Simpson","doi":"10.3390/cells14020139","DOIUrl":"10.3390/cells14020139","url":null,"abstract":"<p><p>Hyaluronan (HA) is a critical component of cell and tissue matrices and an important signaling molecule. The enzymes that synthesize and process HA, as well as the HA receptors through which the signaling properties of HA are transmitted, have been identified in extracellular vesicles and implicated in context-specific processes associated with health and disease. The goal of this review is to present a comprehensive summary of the research on HA and its related receptors and enzymes in extracellular vesicle biogenesis and the cellular responses to vesicles bearing these extracellular matrix modulators. When present in extracellular vesicles, HA is assumed to be on the outside of the vesicle and is sometimes found associated with CD44 or the HAS enzyme itself. Hyaluronidases may be inside the vesicles or present on the vesicle surface via a transmembrane domain or GPI linkage. The implication of presenting these signals in extracellular vesicles is that there is a greater range of systemic distribution and more complex delivery media than previously thought for secreted HA or hyaluronidase alone. Understanding the context for these HA signals offers new diagnostic and therapeutic insight.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 2","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11763598/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032382","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}
CellsPub Date : 2025-01-18DOI: 10.3390/cells14020142
Mai Thi Nguyen, Quoc Kiet Ly, Thanh Huu Phan Ngo, Wan Lee
{"title":"Calponin 3 Regulates Myoblast Proliferation and Differentiation Through Actin Cytoskeleton Remodeling and YAP1-Mediated Signaling in Myoblasts.","authors":"Mai Thi Nguyen, Quoc Kiet Ly, Thanh Huu Phan Ngo, Wan Lee","doi":"10.3390/cells14020142","DOIUrl":"10.3390/cells14020142","url":null,"abstract":"<p><p>An actin-binding protein, known as Calponin 3 (CNN3), modulates the remodeling of the actin cytoskeleton, a fundamental process for the maintenance of skeletal muscle homeostasis. Although the roles of CNN3 in actin remodeling have been established, its biological significance in myoblast differentiation remains largely unknown. This study investigated the functional significance of CNN3 in myogenic differentiation, along with its effects on actin remodeling and mechanosensitive signaling in C2C12 myoblasts. CNN3 knockdown led to a marked increase in filamentous actin, which promoted the nuclear localization of Yes-associated protein 1 (YAP1), a mechanosensitive transcriptional coactivator required for response to the mechanical cues that drive cell proliferation. Subsequently, CNN3 depletion enhanced myoblast proliferation by upregulating the expression of the YAP1 target genes related to cell cycle progression, such as cyclin B1, cyclin D1, and PCNA. According to a flow cytometry analysis, CNN3-deficient cells displayed higher S and G2/M phase fractions, which concurred with elevated proliferation rates. Furthermore, CNN3 knockdown impaired myogenic differentiation, as evidenced by reduced levels of MyoD, MyoG, and MyHC, key markers of myogenic commitment and maturation, and immunocytochemistry showed that myotube formation was diminished in CNN3-suppressed cells, which was supported by lower differentiation and fusion indices. These findings reveal that CNN3 is essential for myogenic differentiation, playing a key role in regulating actin remodeling and cellular localization of YAP1 to orchestrate the proliferation and differentiation in myogenic progenitor cells. This study highlights CNN3 as a critical regulator of skeletal myogenesis and suggests its therapeutic potential as a target for muscle atrophy and related disorders.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":"14 2","pages":""},"PeriodicalIF":5.1,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11764405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143032303","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}