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Cells
Volume 13
Issue 18
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Cells, Volume 13, Issue 18 (September-2 2024) – 16 articles

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31 pages, 3238 KiB  
Review
Treg Cell Therapeutic Strategies for Breast Cancer: Holistic to Local Aspects
by Hanwen Zhang, Oliver Felthaus, Andreas Eigenberger, Silvan Klein and Lukas Prantl
Cells 2024, 13(18), 1526; https://doi.org/10.3390/cells13181526 - 11 Sep 2024
Abstract
Abstract: Regulatory T cells (Tregs) play a key role in maintaining immune homeostasis and preventing autoimmunity through their immunosuppressive function. There have been numerous reports confirming that high levels of Tregs in the tumor microenvironment (TME) are associated with a poor prognosis, highlighting [...] Read more.
Abstract: Regulatory T cells (Tregs) play a key role in maintaining immune homeostasis and preventing autoimmunity through their immunosuppressive function. There have been numerous reports confirming that high levels of Tregs in the tumor microenvironment (TME) are associated with a poor prognosis, highlighting their role in promoting an immunosuppressive environment. In breast cancer (BC), Tregs interact with cancer cells, ultimately leading to the suppression of immune surveillance and promoting tumor progression. This review discusses the dual role of Tregs in breast cancer, and explores the controversies and therapeutic potential associated with targeting these cells. Researchers are investigating various strategies to deplete or inhibit Tregs, such as immune checkpoint inhibitors, cytokine antagonists, and metabolic inhibition. However, the heterogeneity of Tregs and the variable precision of treatments pose significant challenges. Understanding the functional diversity of Tregs and the latest advances in targeted therapies is critical for the development of effective therapies. This review highlights the latest approaches to Tregs for BC treatment that both attenuate Treg-mediated immunosuppression in tumors and maintain immune tolerance, and advocates precise combination therapy strategies to optimize breast cancer outcomes. Full article
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15 pages, 4557 KiB  
Article
DNase II Can Efficiently Digest RNA and Needs to Be Redefined as a Nuclease
by Jingyun Zhuang, Xinmei Du, Kehan Liu, Jing Hao, Haoyu Wang, Ran An and Xingguo Liang
Cells 2024, 13(18), 1525; https://doi.org/10.3390/cells13181525 - 11 Sep 2024
Abstract
DNase II, identified in 1947 and named in 1953, is an acidic DNA endonuclease prevalent across organisms and crucial for normal growth. Despite its expression in nearly all human tissues, as well as its biological significance, DNase II’s detailed functions and corresponding mechanisms [...] Read more.
DNase II, identified in 1947 and named in 1953, is an acidic DNA endonuclease prevalent across organisms and crucial for normal growth. Despite its expression in nearly all human tissues, as well as its biological significance, DNase II’s detailed functions and corresponding mechanisms remain unclear. Although many groups are trying to figure this out, progress is very limited. It is very hard to connect its indispensability with its DNA cleavage activity. In this study, we find that DNase II secreted to saliva can digest RNA in mildly acidic conditions, prompting us to hypothesize that salivary DNase II might digest RNA in the stomach. This finding is consistent with the interesting discovery reported in 1964 that RNA could inhibit DNase II’s activity, which has been largely overlooked. This RNA digestion activity is further confirmed by using purified DNase II, showing activity to digest both DNA and RNA effectively. Here, we suggest redesignating DNase II as DNase II (RNase). The biological functions of DNase II are suggested to recycle intracellular RNA or digest external nucleic acids (both RNA and DNA) as nutrients. This discovery may untangle the mystery of DNase II and its significant biofunctions. Full article
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35 pages, 4785 KiB  
Review
Current Approaches for the Prevention and Treatment of Acute and Chronic GVHD
by Attilio Olivieri and Giorgia Mancini
Cells 2024, 13(18), 1524; https://doi.org/10.3390/cells13181524 - 11 Sep 2024
Abstract
Whereas aGVHD has strong inflammatory components, cGVHD displays autoimmune and fibrotic features; incidence and risk factors are similar but not identical; indeed, the aGVHD is the main risk factor for cGVHD. Calcineurin Inhibitors (CNI) with either Methotrexate (MTX) or Mycophenolate (MMF) still represent [...] Read more.
Whereas aGVHD has strong inflammatory components, cGVHD displays autoimmune and fibrotic features; incidence and risk factors are similar but not identical; indeed, the aGVHD is the main risk factor for cGVHD. Calcineurin Inhibitors (CNI) with either Methotrexate (MTX) or Mycophenolate (MMF) still represent the standard prophylaxis in HLA-matched allogeneic stem cell transplantation (HSCT); other strategies focused on ATG, Post-Transplant Cyclophosphamide (PTCy), Abatacept and graft manipulation. Despite the high rate, first-line treatment for aGVHD is represented by corticosteroids, and Ruxolitinib is the standard second-line therapy; investigational approaches include Microbiota transplant and the infusion of Mesenchymal stem cells. GVHD is a pleiotropic disease involving any anatomical district; also, Ruxolitinib represents the standard for steroid-refractory cGVHD in this setting. It is a pleiotropic disease involving any anatomical district; also, Ruxolitinib represents the standard for steroid-refractory cGVHD in this setting. Extracorporeal Photopheresis (ECP) is still an option used for steroid refractoriness or to achieve a steroid-sparing. For Ruxolitinib-refractory cGVHD, Belumosudil and Axatilimab represent the most promising agents. Bronchiolitis obliterans syndrome (BOS) still represents a challenge; among the compounds targeting non-immune effectors, Alvelestat, a Neutrophil elastase inhibitor, seems promising in BOS. Finally, in both aGVHD and cGVHD, the association of biological markers with specific disease manifestations could help refine risk stratification and the availability of reliable biomarkers for specific treatments. Full article
(This article belongs to the Special Issue Clinical and Methodological Aspects of HSC Transplantation in Hematological Malignancies)
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17 pages, 22610 KiB  
Article
Bleomycin-Induced Pulmonary Fibrosis in Transgenic Mice Carrying the Human MUC5B rs35705950 Variant
by Suphachai Tharavecharak, Hajime Fujimoto, Taro Yasuma, Corina N. D’Alessandro-Gabazza, Masaaki Toda, Atsushi Tomaru, Haruko Saiki, Mei Uemura, Yurie Kogue, Toshiyuki Ito, Kazuki Furuhashi, Tomohito Okano, Atsuro Takeshita, Kota Nishihama, Ryoichi Ono, Osamu Hataji, Tetsuya Nosaka, Tetsu Kobayashi and Esteban C. Gabazza
Cells 2024, 13(18), 1523; https://doi.org/10.3390/cells13181523 - 11 Sep 2024
Abstract
Idiopathic pulmonary fibrosis (IPF) is a progressive, often fatal lung disease characterized by tissue scarring and declining lung function. The MUC5B promoter polymorphism rs35705950, a significant genetic predisposition for IPF, paradoxically associates with better survival and slower disease progression than other IPF genotypes. [...] Read more.
Idiopathic pulmonary fibrosis (IPF) is a progressive, often fatal lung disease characterized by tissue scarring and declining lung function. The MUC5B promoter polymorphism rs35705950, a significant genetic predisposition for IPF, paradoxically associates with better survival and slower disease progression than other IPF genotypes. This study investigates the potential paradoxical protective effects of this MUC5B variant in lung fibrosis. For this purpose, we developed a transgenic mouse model overexpressing the human MUC5B rs35705950 variant in the proximal large airways. Lung fibrosis was induced through subcutaneous injection of bleomycin. Results demonstrated significantly reduced lung fibrosis severity in transgenic mice compared to wild-type mice, assessed by trichrome staining, Ashcroft scoring, and hydroxyproline levels. Additionally, transgenic mice showed significantly lower levels of inflammatory cells and cytokines (TNFα, IL-6, IFNγ) and growth factors (PDGF, CTGF, IL-13) in the bronchoalveolar lavage fluid and lung tissues. There was also a significant decrease in mRNA expressions of fibrosis-related markers (periostin, fibronectin, Col1a1). In summary, this study reveals that mucin overexpression related to the MUC5B rs35705950 variant in the large airways significantly attenuates lung fibrosis and inflammatory responses in transgenic mice. These findings suggest that the rs35705950 variant modulates inflammatory and fibrotic responses in the proximal airways, which may contribute to the slower disease progression observed in IPF patients carrying this variant. Our study offers a possible explanation for the paradoxical beneficial effects of the MUC5B variant despite its role as a significant predisposing factor for IPF. Full article
(This article belongs to the Special Issue Idiopathic Pulmonary Fibrosis: Pathogenic Pathways and Treatment Strategies)
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28 pages, 9988 KiB  
Article
Concurrent Oncolysis and Neurolesion Repair by Dual Gene-Engineered hNSCs in an Experimental Model of Intraspinal Cord Glioblastoma
by Xiang Zeng, Alexander E. Ropper, Zaid Aljuboori, Dou Yu, Theodore W. Teng, Serdar Kabatas, Esteban Usuga, Jamie E. Anderson and Yang D. Teng
Cells 2024, 13(18), 1522; https://doi.org/10.3390/cells13181522 - 11 Sep 2024
Abstract
Intramedullary spinal cord glioblastoma (ISCG) is lethal due to lack of effective treatment. We previously established a rat C6-ISCG model and the antitumor effect of F3.CD-TK, an hNSC line expressing CD and TK, via producing cytocidal 5FU and GCV-TP. However, the neurotherapeutic potential [...] Read more.
Intramedullary spinal cord glioblastoma (ISCG) is lethal due to lack of effective treatment. We previously established a rat C6-ISCG model and the antitumor effect of F3.CD-TK, an hNSC line expressing CD and TK, via producing cytocidal 5FU and GCV-TP. However, the neurotherapeutic potential of this hNSC approach has remained uninvestigated. Here for the first time, cultured F3.CD-TK cells were found to have a markedly higher oncolytic effect, which was GJIC-dependent, and BDNF expression but less VEGF secretion than F3.CD. In Rowett athymic rats, F3.CD-TK (1.5 × 106 cells/10 µL × 2), injected near C6-ISCG (G55 seeding 7 days earlier: 10 K/each) and followed by q.d. (×5/each repeat; i.p.) of 5FC (500 mg/kg/5 mL/day) and GCV (25 mg/kg/1 mL/day), robustly mitigated cardiorespiratory, locomotor, and sensory deficits to improve neurofunction and overall survival compared to animals receiving either F3.CD or F3.CD-TK+F3.CD debris formula. The F3.CD-TK regimen exerted greater tumor penetration and neural inflammation/immune modulation, reshaped C6-ISCG topology to increase the tumor’s surface area/volume ratio to spare/repair host axons (e.g., vGlut1+ neurites), and had higher post-prodrug donor self-clearance. The multimodal data and mechanistic leads from this proof-of-principle study suggest that the overall stronger anti-ISCG benefit of our hNSC-based GDEPT is derived from its concurrent oncolytic and neurotherapeutic effects. Full article
(This article belongs to the Special Issue Understanding Spinal Cord Injury and Repair: From Molecules to Neurocircuits and Multimodal Prostheses)
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5 pages, 209 KiB  
Editorial
Health Effect of Low-Dose-Rate Irradiation with Cumulative Threshold Dose: A Promising Area to Explore in Nuclear Emergency and Environmental Contamination
by Feng Ru Tang
Cells 2024, 13(18), 1521; https://doi.org/10.3390/cells13181521 - 11 Sep 2024
Abstract
Humans live in an environment in which they are constantly exposed to meagre dose rates of radiation [...] Full article
(This article belongs to the Special Issue Radiation-Induced Brain Injury: Molecular Mechanisms and Therapeutic Strategies)
20 pages, 3445 KiB  
Review
Deciphering the Pathophysiological Mechanisms Underpinning Myoclonus Dystonia Using Pluripotent Stem Cell-Derived Cellular Models
by Zongze Li, Laura Abram and Kathryn J. Peall
Cells 2024, 13(18), 1520; https://doi.org/10.3390/cells13181520 - 10 Sep 2024
Viewed by 214
Abstract
Dystonia is a movement disorder with an estimated prevalence of 1.2% and is characterised by involuntary muscle contractions leading to abnormal postures and pain. Only symptomatic treatments are available with no disease-modifying or curative therapy, in large part due to the limited understanding [...] Read more.
Dystonia is a movement disorder with an estimated prevalence of 1.2% and is characterised by involuntary muscle contractions leading to abnormal postures and pain. Only symptomatic treatments are available with no disease-modifying or curative therapy, in large part due to the limited understanding of the underlying pathophysiology. However, the inherited monogenic forms of dystonia provide an opportunity for the development of disease models to examine these mechanisms. Myoclonus Dystonia, caused by SGCE mutations encoding the ε-sarcoglycan protein, represents one of now >50 monogenic forms. Previous research has implicated the involvement of the basal ganglia–cerebello-thalamo-cortical circuit in dystonia pathogenesis, but further work is needed to understand the specific molecular and cellular mechanisms. Pluripotent stem cell technology enables a patient-derived disease modelling platform harbouring disease-causing mutations. In this review, we discuss the current understanding of the aetiology of Myoclonus Dystonia, recent advances in producing distinct neuronal types from pluripotent stem cells, and their application in modelling Myoclonus Dystonia in vitro. Future research employing pluripotent stem cell-derived cellular models is crucial to elucidate how distinct neuronal types may contribute to dystonia and how disruption to neuronal function can give rise to dystonic disorders. Full article
(This article belongs to the Special Issue Pluripotent Stem Cells: Current Applications and Future Directions)
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14 pages, 2899 KiB  
Review
YAP/TAZ Signaling in the Pathobiology of Pulmonary Fibrosis
by Kostas A. Papavassiliou, Amalia A. Sofianidi, Fotios G. Spiliopoulos, Vassiliki A. Gogou, Antonios N. Gargalionis and Athanasios G. Papavassiliou
Cells 2024, 13(18), 1519; https://doi.org/10.3390/cells13181519 - 10 Sep 2024
Viewed by 110
Abstract
Pulmonary fibrosis (PF) is a severe, irreversible lung disease characterized by progressive scarring, with idiopathic pulmonary fibrosis (IPF) being the most prevalent form. IPF’s pathogenesis involves repetitive lung epithelial injury leading to fibroblast activation and excessive extracellular matrix (ECM) deposition. The prognosis for [...] Read more.
Pulmonary fibrosis (PF) is a severe, irreversible lung disease characterized by progressive scarring, with idiopathic pulmonary fibrosis (IPF) being the most prevalent form. IPF’s pathogenesis involves repetitive lung epithelial injury leading to fibroblast activation and excessive extracellular matrix (ECM) deposition. The prognosis for IPF is poor, with limited therapeutic options like nintedanib and pirfenidone offering only modest benefits. Emerging research highlights the dysregulation of the yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) signaling pathway as a critical factor in PF. YAP and TAZ, components of the Hippo pathway, play significant roles in cell proliferation, differentiation, and fibrosis by modulating gene expression through interactions with TEA domain (TEAD) transcription factors. The aberrant activation of YAP/TAZ in lung tissue promotes fibroblast activation and ECM accumulation. Targeting the YAP/TAZ pathway offers a promising therapeutic avenue. Preclinical studies have identified potential treatments, such as trigonelline, dopamine receptor D1 (DRD1) agonists, and statins, which inhibit YAP/TAZ activity and demonstrate antifibrotic effects. These findings underscore the importance of YAP/TAZ in PF pathogenesis and the potential of novel therapies aimed at this pathway, suggesting a new direction for improving IPF treatment outcomes. Further research is needed to validate these approaches and translate them into clinical practice. Full article
(This article belongs to the Special Issue Cellular Signaling and Therapeutic Approaches of Pulmonary Fibrosis)
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23 pages, 9095 KiB  
Article
Characterizing the Tumor Microenvironment and Its Prognostic Impact in Breast Cancer
by Wenjuan Zhang, Alex Lee, Amit K. Tiwari and Mary Qu Yang
Cells 2024, 13(18), 1518; https://doi.org/10.3390/cells13181518 - 10 Sep 2024
Viewed by 254
Abstract
The tumor microenvironment (TME) is crucial in cancer development and therapeutic response. Immunotherapy is increasingly recognized as a critical component of cancer treatment. While immunotherapies have shown efficacy in various cancers, including breast cancer, patient responses vary widely. Some patients receive significant benefits, [...] Read more.
The tumor microenvironment (TME) is crucial in cancer development and therapeutic response. Immunotherapy is increasingly recognized as a critical component of cancer treatment. While immunotherapies have shown efficacy in various cancers, including breast cancer, patient responses vary widely. Some patients receive significant benefits, while others experience minimal or no improvement. This disparity underscores the complexity and diversity of the immune system. In this study, we investigated the immune landscape and cell–cell communication within the TME of breast cancer through integrated analysis of bulk and single-cell RNA sequencing data. We established profiles of tumor immune infiltration that span across a broad spectrum of adaptive and innate immune cells. Our clustering analysis of immune infiltration identified three distinct patient groups: high T cell abundance, moderate infiltration, and low infiltration. Patients with low immune infiltration exhibited the poorest survival rates, while those in the moderate infiltration group showed better outcomes than those with high T cell abundance. Moreover, the high cell abundance group was associated with a greater tumor burden and higher rates of TP53 mutations, whereas the moderate infiltration group was characterized by a lower tumor burden and elevated PIK3CA mutations. Analysis of an independent single-cell RNA-seq breast cancer dataset confirmed the presence of similar infiltration patterns. Further investigation into ligand–receptor interactions within the TME unveiled significant variations in cell–cell communication patterns among these groups. Notably, we found that the signaling pathways SPP1 and EGF were exclusively active in the low immune infiltration group, suggesting their involvement in immune suppression. This work comprehensively characterizes the composition and dynamic interplay in the breast cancer TME. Our findings reveal associations between the extent of immune infiltration and clinical outcomes, providing valuable prognostic information for patient stratification. The unique mutations and signaling pathways associated with different patient groups offer insights into the mechanisms underlying diverse tumor immune infiltration and the formation of an immunosuppressive tumor microenvironment. Full article
(This article belongs to the Collection Cell-to-Cell Metabolic Cross-Talk in Physiology and Pathology—2nd Edition)
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16 pages, 5075 KiB  
Article
The Oncoprotein Fra-2 Drives the Activation of Human Endogenous Retrovirus Env Expression in Adult T-Cell Leukemia/Lymphoma (ATLL) Patients
by Julie Tram, Laetitia Marty, Célima Mourouvin, Magali Abrantes, Ilham Jaafari, Raymond Césaire, Philippe Hélias, Benoit Barbeau, Jean-Michel Mesnard, Véronique Baccini, Laurent Chaloin and Jean-Marie Jr. Peloponese
Cells 2024, 13(18), 1517; https://doi.org/10.3390/cells13181517 - 10 Sep 2024
Viewed by 172
Abstract
Human endogenous retroviruses (HERVs) are retroviral sequences integrated into 8% of the human genome resulting from ancient exogenous retroviral infections. Unlike endogenous retroviruses of other mammalian species, HERVs are mostly replication and retro-transposition defective, and their transcription is strictly regulated by epigenetic mechanisms [...] Read more.
Human endogenous retroviruses (HERVs) are retroviral sequences integrated into 8% of the human genome resulting from ancient exogenous retroviral infections. Unlike endogenous retroviruses of other mammalian species, HERVs are mostly replication and retro-transposition defective, and their transcription is strictly regulated by epigenetic mechanisms in normal cells. A significant addition to the growing body of research reveals that HERVs’ aberrant activation is often associated with offsetting diseases like autoimmunity, neurodegenerative diseases, cancers, and chemoresistance. Adult T-cell leukemia/lymphoma (ATLL) is a very aggressive and chemoresistant leukemia caused by the human T-cell leukemia virus type 1 (HTLV-1). The prognosis of ATLL remains poor despite several new agents being approved in the last few years. In the present study, we compare the expression of HERV genes in CD8+-depleted PBMCs from HTLV-1 asymptomatic carriers and patients with acute ATLL. Herein, we show that HERVs are highly upregulated in acute ATLL. Our results further demonstrate that the oncoprotein Fra-2 binds the LTR region and activates the transcription of several HERV families, including HERV-H and HERV-K families. This raises the exciting possibility that upregulated HERV expression could be a key factor in ATLL development and the observed chemoresistance, potentially leading to new therapeutic strategies and significantly impacting the field of oncology and virology. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Lymphomas)
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12 pages, 2033 KiB  
Review
Revolutionizing Cancer Treatments through Stem Cell-Derived CAR T Cells for Immunotherapy: Opening New Horizons for the Future of Oncology
by Hemant K. Mishra and Alex Kalyuzhny
Cells 2024, 13(18), 1516; https://doi.org/10.3390/cells13181516 - 10 Sep 2024
Viewed by 232
Abstract
Recent advances in cellular therapies have paved the way for innovative treatments of various cancers and autoimmune disorders. Induced pluripotent stem cells (iPSCs) represent a remarkable breakthrough, offering the potential to generate patient-specific cell types for personalized as well as allogeneic therapies. This [...] Read more.
Recent advances in cellular therapies have paved the way for innovative treatments of various cancers and autoimmune disorders. Induced pluripotent stem cells (iPSCs) represent a remarkable breakthrough, offering the potential to generate patient-specific cell types for personalized as well as allogeneic therapies. This review explores the application of iPSC-derived chimeric antigen receptor (CAR) T cells, a cutting-edge approach in allogeneic cancer immunotherapies. CAR T cells are genetically engineered immune cells designed to target specific tumor antigens, and their integration with iPSC technology holds immense promise for enhancing the efficacy, safety, and scalability of cellular therapies. This review begins by elucidating the principles behind iPSC generation and differentiation into T cells, highlighting the advantage of iPSCs in providing a uniform, inexhaustible source of CAR T cells. Additionally, we discuss the genetic modification of iPSC-derived T cells to express various CARs, emphasizing the precision and flexibility this affords in designing customized therapies for a diverse range of malignancies. Notably, iPSC-derived CAR T cells demonstrate a superior proliferative capacity, persistence, and anti-tumor activity compared to their conventionally derived counterparts, offering a potential solution to challenges associated with conventional CAR T cell therapies. In conclusion, iPSC-derived CAR T cells represent a groundbreaking advancement in cellular therapies, demonstrating unparalleled potential in revolutionizing the landscape of immunotherapies. As this technology continues to evolve, it holds the promise of providing safer, more effective, and widely accessible treatment options for patients battling cancer and other immune-related disorders. This review aims to shed light on the transformative potential of iPSC-derived CAR T cells and inspire further research and development in this dynamic field. Full article
(This article belongs to the Section Stem Cells)
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19 pages, 10349 KiB  
Article
FGF23 and Cell Stress in SaOS-2 Cells—A Model Reflecting X-Linked Hypophosphatemia Dynamics
by Lisanne Brueck, Sascha Roocke, Veronika Matschke, Annette Richter-Unruh, Katrin Marcus-Alic, Carsten Theiss and Sarah Stahlke
Cells 2024, 13(18), 1515; https://doi.org/10.3390/cells13181515 - 10 Sep 2024
Viewed by 204
Abstract
Our study investigates the impact of FGF23 overexpression on SaOS-2 cells to elucidate its role in cellular stress and morphology, contributing to the understanding of skeletal pathologies like X-linked hypophosphatemia (XLH). Using transmission electron microscopy and protein analysis (Western blot), we analyzed the [...] Read more.
Our study investigates the impact of FGF23 overexpression on SaOS-2 cells to elucidate its role in cellular stress and morphology, contributing to the understanding of skeletal pathologies like X-linked hypophosphatemia (XLH). Using transmission electron microscopy and protein analysis (Western blot), we analyzed the rough endoplasmic reticulum (rER) and mitochondria in SaOS-2 cells with FGF23 overexpression compared to controls. We found significant morphological changes, including enlarged and elongated rER and mitochondria, with increased contact zones, suggesting enhanced interaction and adaptation to elevated protein synthesis and secretion demands. Additionally, we observed higher apoptosis rates of the cells after 24–72 h in vitro and upregulated proteins associated with ER stress and apoptosis, such as CHOP, XBP1 (spliced and unspliced), GRP94, eIF2α, and BAX. These findings indicate a robust activation of the unfolded protein response (UPR) and apoptotic pathways due to FGF23 overexpression. Our results highlight the critical role of ER and mitochondrial interactions in cellular stress responses and provide new insights into the mechanistic link between FGF23 signaling and cellular homeostasis. In conclusion, our study underscores the importance of analyzing UPR-related pathways in the development of therapeutic strategies for skeletal and systemic diseases and contributes to a broader understanding of diseases like XLH. Full article
(This article belongs to the Special Issue Molecular Mechanism of Bone Disease)
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22 pages, 1943 KiB  
Review
Small Extracellular Vesicles and Oral Mucosa: The Power Couple in Regenerative Therapies?
by Blanka Maria Borowiec, Marta Dyszkiewicz-Konwińska, Dorota Bukowska, Michał Nowicki and Joanna Budna-Tukan
Cells 2024, 13(18), 1514; https://doi.org/10.3390/cells13181514 - 10 Sep 2024
Viewed by 239
Abstract
Although ongoing debates persist over the scope of phenomena classified as regenerative processes, the most up-to-date definition of regeneration is the replacement or restoration of damaged or missing cells, tissues, organs, or body parts to full functionality. Despite extensive research on this topic, [...] Read more.
Although ongoing debates persist over the scope of phenomena classified as regenerative processes, the most up-to-date definition of regeneration is the replacement or restoration of damaged or missing cells, tissues, organs, or body parts to full functionality. Despite extensive research on this topic, new methods in regenerative medicine are continually sought, and existing ones are being improved. Small extracellular vesicles (sEVs) have gained attention for their regenerative potential, as evidenced by existing studies conducted by independent research groups. Of particular interest are sEVs derived from the oral mucosa, a tissue renowned for its rapid regeneration and minimal scarring. While the individual regenerative potential of both sEVs and the oral mucosa is somewhat understood, the combined potential of sEVs derived from the oral mucosa has not been sufficiently explored and highlighted in the existing literature. Serving as a broad compendium, it aims to provide scientists with essential and detailed information on this subject, including the nature of the materials employed, isolation and analysis methodologies, and clinical applications. The content of this survey aims to facilitate the comparison of diverse methods for working with sEVs derived from the oral mucosa, aiding in the planning of research endeavors and identifying potential research gaps. Full article
(This article belongs to the Special Issue Extracellular Vesicles in Tissue Repair and Regeneration)
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20 pages, 6452 KiB  
Article
Dynamic Mitotic Localization of the Centrosomal Kinases CDK1, Plk, AurK, and Nek2 in Dictyostelium amoebae
by Stefan Krüger, Nathalie Pfaff, Ralph Gräf and Irene Meyer
Cells 2024, 13(18), 1513; https://doi.org/10.3390/cells13181513 - 10 Sep 2024
Viewed by 209
Abstract
The centrosome of the amoebozoan model Dictyostelium discoideum provides the best-established model for an acentriolar centrosome outside the Opisthokonta. Dictyostelium exhibits an unusual centrosome cycle, in which duplication is initiated only at the G2/M transition and occurs entirely during the M phase. [...] Read more.
The centrosome of the amoebozoan model Dictyostelium discoideum provides the best-established model for an acentriolar centrosome outside the Opisthokonta. Dictyostelium exhibits an unusual centrosome cycle, in which duplication is initiated only at the G2/M transition and occurs entirely during the M phase. Little is known about the role of conserved centrosomal kinases in this process. Therefore, we have generated knock-in strains for Aurora (AurK), CDK1, cyclin B, Nek2, and Plk, replacing the endogenous genes with constructs expressing the respective green fluorescent Neon fusion proteins, driven by the endogenous promoters, and studied their behavior in living cells. Our results show that CDK1 and cyclin B arrive at the centrosome first, already during G2, followed by Plk, Nek2, and AurK. Furthermore, CDK1/cyclin B and AurK were dynamically localized at kinetochores, and AurK in addition at nucleoli. The putative roles of all four kinases in centrosome duplication, mitosis, cytokinesis, and nucleolar dynamics are discussed. Full article
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18 pages, 1468 KiB  
Article
The Role of Tumor Suppressor p53 Protein in HIV–Host Cell Interactions
by Mary Bakhanashvili
Cells 2024, 13(18), 1512; https://doi.org/10.3390/cells13181512 - 10 Sep 2024
Viewed by 167
Abstract
The virus–host relationship is indispensable for executing successful viral infection. The pathogenesis of HIV is determined by an intricate interaction between the host and the virus for the regulation of HIV infection, thereby influencing various aspects, including the regulation of signaling pathways. High [...] Read more.
The virus–host relationship is indispensable for executing successful viral infection. The pathogenesis of HIV is determined by an intricate interaction between the host and the virus for the regulation of HIV infection, thereby influencing various aspects, including the regulation of signaling pathways. High mutation rates and population heterogeneity characterize HIV with consequences for viral pathogenesis and the potential to escape the immune system and anti-viral inhibitors used in therapy. The origin of the high mutation rates exhibited by HIV may be attributed to a limited template-copied fidelity that likely operates in the cytoplasm. HIV-1 infection induces upregulation and activation of tumor suppressor p53 protein in the early stages of HIV-1 infection. p53 plays a multifaceted role in the context of HIV infection, thereby affecting viral replication. p53 is involved in maintaining genetic integrity, actively participating in various DNA repair processes through its various biochemical activities and via its ability to interact with components of the repair machinery. This report focuses on the impact of the p53 protein on the HIV-1 reverse transcription process while incorporating various incorrect and non-canonical nucleotides. The presence of functional host-coded p53 protein with proofreading–repair activities in the cytoplasm may lead to various biological outcomes. Full article
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15 pages, 1354 KiB  
Article
Postencephalitic Parkinsonism: Unique Pathological and Clinical Features—Preliminary Data
by Sabrina Strobel, Jeswinder Sian-Hulsmann, Dennis Tappe, Kurt Jellinger, Peter Riederer and Camelia-Maria Monoranu
Cells 2024, 13(18), 1511; https://doi.org/10.3390/cells13181511 - 10 Sep 2024
Viewed by 209
Abstract
Postencephalitic parkinsonism (PEP) is suggested to show a virus-induced pathology, which is different from classical idiopathic Parkinson’s disease (PD) as there is no α-synuclein/Lewy body pathology. However, PEP shows a typical clinical representation of motor disturbances. In addition, compared to PD, there is [...] Read more.
Postencephalitic parkinsonism (PEP) is suggested to show a virus-induced pathology, which is different from classical idiopathic Parkinson’s disease (PD) as there is no α-synuclein/Lewy body pathology. However, PEP shows a typical clinical representation of motor disturbances. In addition, compared to PD, there is no iron-induced pathology. The aim of this preliminary study was to compare PEP with PD regarding iron-induced pathology, using histochemistry methods on paraffin-embedded post-mortem brain tissue. In the PEP group, iron was not seen, except for one case with sparse perivascular depositions. Rather, PEP offers a pathology related to tau-protein/neurofibrillary tangles, with mild to moderate memory deficits only. It is assumed that this virus-induced pathology is due to immunological dysfunctions causing (neuro)inflammation-induced neuronal network disturbances as events that trigger clinical parkinsonism. The absence of iron deposits implies that PEP cannot be treated with iron chelators. The therapy with L-Dopa is also not an option, as L-Dopa only leads to an initial slight improvement in symptoms in isolated cases. Full article
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