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Cells
Volume 14
Issue 7
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Cells, Volume 14, Issue 7 (April-1 2025) – 90 articles

Cover Story (view full-size image): The beta-3 adrenoceptor (β3-AR) plays a pivotal role in organ maturation, and its agonism has been shown to counteract hyperoxia-induced large bowel damage. This study investigated the effects of β3-AR agonism in preventing alterations to the ileal enteric nervous system (ENS) in a neonatal rat model of hyperoxia-induced damage. Our findings provided evidence that hyperoxia altered the neurochemical code in both the myenteric and submucosal plexuses and decreased the neuron number and the glia index in the submucosal and the myenteric plexus, respectively. The β3-AR agonism preserved the neuronal chemical coding and mitigated the glia index reduction, while it did not counteract sub-mucosal neuronal loss. Our findings indicate the potential of β3-AR agonism as a new therapeutic strategy for hyperoxia-induced ileal ENS alterations. View this paper
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18 pages, 4083 KiB  
Article
The Assessment of the Effect of Autophagy Inhibitors—Chloroquine and 3-Methyladenine on the Antitumor Activity of Trametinib Against Amelanotic Melanoma Cells
by Dominika Stencel, Justyna Kowalska, Zuzanna Rzepka, Klaudia Banach, Marta Karkoszka-Stanowska and Dorota Wrześniok
Cells 2025, 14(7), 557; https://doi.org/10.3390/cells14070557 - 7 Apr 2025
Viewed by 344
Abstract
Malignant melanoma, particularly amelanotic melanoma, contributes to a very serious problem in public health. One way to find new therapies is to learn about and understand the molecular pathways that regulate cancer growth and development. In the case of a tumor, the autophagy [...] Read more.
Malignant melanoma, particularly amelanotic melanoma, contributes to a very serious problem in public health. One way to find new therapies is to learn about and understand the molecular pathways that regulate cancer growth and development. In the case of a tumor, the autophagy process can lead to the development or inhibition of cancer. This study aimed to assess the cytotoxicity of connection trametinib (MEK1 and MEK2 kinase inhibitor) with autophagy inhibitors—chloroquine (lysosomal clearance of autophagosomes inhibitor) and 3-methyladenine (phosphatidylinositol 3-kinases inhibitor), on two amelanotic melanoma cell lines (C32 and A-375). The results showed that combination therapy had better anti-proliferative effects than alone therapy in both cell lines. The C32 cell line was more sensitive to 3-methyladenine treatment (alone and in combinations), and the A375 line showed sensitivity to chloroquine and 3-methyladenine (alone and in combinations). The anti-proliferative effect was accompanied by dysregulation of the cell cycle, a decrease in the reduced thiols, the depolarization of the mitochondrial membrane and the level of p44/p42 MAPK. Both inhibitors have the ability to induce apoptosis. Differences in the level of LC3A/B and LC3B proteins between the chloroquine and the 3-methyladenine samples indicate that these drugs inhibit autophagy at different stages. The enhancement of the effect of trametinib by autophagy inhibitors suggests the possibility of combining drugs with anti-cancer potential with modulators of the autophagy process. Full article
(This article belongs to the Special Issue Cell Death: Cell–Cell Interactions and Signaling Networks)
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24 pages, 2682 KiB  
Review
Behavioral Cooperation or Conflict of Human Intestinal Roundworms and Microbiomes: A Bio-Activity Perspective
by Meisam Khazaei, Malihe Parsasefat, Aisa Bahar, Hamed Tahmasebi and Valentyn Oksenych
Cells 2025, 14(7), 556; https://doi.org/10.3390/cells14070556 - 7 Apr 2025
Viewed by 357
Abstract
Human infections are greatly impacted by intestinal nematodes. These nematodes, which encompass the large roundworms, have a direct impact on human health and well-being due to their close cohabitation with the host’s microorganisms. When nematodes infect a host, the microbiome composition changes, and [...] Read more.
Human infections are greatly impacted by intestinal nematodes. These nematodes, which encompass the large roundworms, have a direct impact on human health and well-being due to their close cohabitation with the host’s microorganisms. When nematodes infect a host, the microbiome composition changes, and this can impact the host’s ability to control the parasites. We aimed to find out if the small intestinal roundworms produce substances that have antimicrobial properties and respond to their microbial environment, and if the immune and regulatory reactions to nematodes are altered in humans lacking gut microbes. There is no doubt that different nematodes living in the intestines can alter the balance of intestinal bacteria. Nonetheless, our knowledge about the parasite’s influence on the gut microbiome remains restricted. The last two decades of study have revealed that the type of iron utilized can influence the activation of unique virulence factors. However, some roundworm proteins like P43, which makes up a large portion of the worm’s excretory-secretory product, have an unknown role. This review explores how the bacterial iron regulatory network contributes to the adaptability of this opportunistic pathogen, allowing it to successfully infect nematodes in different host environments. Full article
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39 pages, 3070 KiB  
Review
Latest Update on lncRNA in Epithelial Ovarian Cancer—A Scoping Review
by Katarzyna Kwas, Maria Szubert and Jacek Radosław Wilczyński
Cells 2025, 14(7), 555; https://doi.org/10.3390/cells14070555 - 7 Apr 2025
Viewed by 506
Abstract
Long noncoding RNAs (lncRNAs) are RNA molecules exceeding 200 nucleotides that do not encode proteins yet play critical roles in regulating gene expression at multiple levels, such as chromatin modification and transcription. These molecules are significantly engaged in cancer progression, development, metastasis, and [...] Read more.
Long noncoding RNAs (lncRNAs) are RNA molecules exceeding 200 nucleotides that do not encode proteins yet play critical roles in regulating gene expression at multiple levels, such as chromatin modification and transcription. These molecules are significantly engaged in cancer progression, development, metastasis, and chemoresistance. However, the function of lncRNAs in epithelial ovarian cancer (EOC) has not yet been thoroughly studied. EOC remains challenging due to its complex molecular pathogenesis, characterized by genetic and epigenetic alterations. Emerging evidence suggests that lncRNAs, such as XIST, H19, NEAT1, and MALAT1, are involved in EOC by modulating gene expression and signaling pathways, influencing processes like cell proliferation, invasion, migration, and chemoresistance. Despite extensive research, the precise mechanism of acting of lncRNAs in EOC pathogenesis and treatment resistance still needs to be fully understood, highlighting the need for further studies. This review aims to provide an updated overview of the current understanding of lncRNAs in EOC, emphasizing their potential as biomarkers and therapeutic targets. We point out the gaps in the knowledge regarding lncRNAs’ influence on epithelial ovarian cancer (EOC), deliberating on new possible research areas. Full article
(This article belongs to the Special Issue Genetic Disorders in Breast and Ovarian Cancer)
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14 pages, 598 KiB  
Review
The Impact of Microbiota on Musculoskeletal Injuries
by Giada La Placa, Marcello Covino, Marcello Candelli, Antonio Gasbarrini, Francesco Franceschi and Giuseppe Merra
Cells 2025, 14(7), 554; https://doi.org/10.3390/cells14070554 - 7 Apr 2025
Viewed by 745
Abstract
Musculoskeletal injuries comprise a wide range of physical conditions impacting the coordination of bones, muscles, and joints. Estimations suggest that close to one-third of the world’s population will experience a musculoskeletal or non-musculoskeletal injury at some point in their life. Musculoskeletal injuries affect [...] Read more.
Musculoskeletal injuries comprise a wide range of physical conditions impacting the coordination of bones, muscles, and joints. Estimations suggest that close to one-third of the world’s population will experience a musculoskeletal or non-musculoskeletal injury at some point in their life. Musculoskeletal injuries affect athletes, office workers, industrial workers, older adults, and children every year. Among individuals over the age of 65, musculoskeletal injuries disproportionately affect older women, limiting their ability to maintain an active and professional life or engage in leisure activities during retirement. The field of physical therapy has recently expanded to build an understanding of the complex, non-linear interactions between the gut microbiota and the musculoskeletal system. There is an unexpected connection between the gut microbiota and both the experience of musculoskeletal pain and the healing process following musculoskeletal injuries. Understanding the mechanisms of the microbiota’s influence on these injuries could inform healthcare strategies aimed at prevention and recovery. For patients who suffer from or are at risk of developing musculoskeletal injuries, analyzing the composition of their microbiota plays a crucial role in patient stratification, which can significantly enhance the effectiveness of prevention and treatment strategies. Full article
(This article belongs to the Section Tissues and Organs)
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50 pages, 3293 KiB  
Review
Circulating Non-Coding RNAs as Indicators of Fibrosis and Heart Failure Severity
by Veronika Boichenko, Victoria Maria Noakes, Benedict Reilly-O’Donnell, Giovanni Battista Luciani, Costanza Emanueli, Fabio Martelli and Julia Gorelik
Cells 2025, 14(7), 553; https://doi.org/10.3390/cells14070553 - 7 Apr 2025
Viewed by 625
Abstract
Heart failure (HF) is a leading cause of morbidity and mortality worldwide, representing a complex clinical syndrome in which the heart’s ability to pump blood efficiently is impaired. HF can be subclassified into heart failure with reduced ejection fraction (HFrEF) and heart failure [...] Read more.
Heart failure (HF) is a leading cause of morbidity and mortality worldwide, representing a complex clinical syndrome in which the heart’s ability to pump blood efficiently is impaired. HF can be subclassified into heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF), each with distinct pathophysiological mechanisms and varying levels of severity. The progression of HF is significantly driven by cardiac fibrosis, a pathological process in which the extracellular matrix undergoes abnormal and uncontrolled remodelling. Cardiac fibrosis is characterized by excessive matrix protein deposition and the activation of myofibroblasts, increasing the stiffness of the heart, thus disrupting its normal structure and function and promoting lethal arrythmia. MicroRNAs, long non-coding RNAs, and circular RNAs, collectively known as non-coding RNAs (ncRNAs), have recently gained significant attention due to a growing body of evidence suggesting their involvement in cardiac remodelling such as fibrosis. ncRNAs can be found in the peripheral blood, indicating their potential as biomarkers for assessing HF severity. In this review, we critically examine recent advancements and findings related to the use of ncRNAs as biomarkers of HF and discuss their implication in fibrosis development. Full article
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20 pages, 4176 KiB  
Article
Effects of Anti-CD20 Antibody Therapy on Immune Cell Dynamics in Relapsing-Remitting Multiple Sclerosis
by Alice G. Willison, Ramona Hagler, Margit Weise, Saskia Elben, Niklas Huntemann, Lars Masanneck, Steffen Pfeuffer, Stefanie Lichtenberg, Kristin S. Golombeck, Lara-Maria Preuth, Leoni Rolfes, Menekse Öztürk, Tobias Ruck, Nico Melzer, Melanie Korsen, Stephen L. Hauser, Hans-Peter Hartung, Philipp A. Lang, Marc Pawlitzki, Saskia Räuber and Sven G. Meuthadd Show full author list remove Hide full author list
Cells 2025, 14(7), 552; https://doi.org/10.3390/cells14070552 - 6 Apr 2025
Viewed by 450
Abstract
Introduction: The efficacy of anti-CD20 antibodies has significantly contributed to advancing our understanding of disease pathogenesis and improved treatment outcomes in relapsing-remitting multiple sclerosis (RRMS). A comprehensive analysis of the peripheral immune cell profile, combined with prospective clinical characterization, of RRMS patients treated [...] Read more.
Introduction: The efficacy of anti-CD20 antibodies has significantly contributed to advancing our understanding of disease pathogenesis and improved treatment outcomes in relapsing-remitting multiple sclerosis (RRMS). A comprehensive analysis of the peripheral immune cell profile, combined with prospective clinical characterization, of RRMS patients treated with ocrelizumab (OCR) or ofatumumab (OFA) was performed to further understand immune reconstitution following B-cell depletion. Methods: REBELLION-MS is a longitudinal analysis of RRMS patients treated with either OCR (n = 34) or OFA (n = 25). Analysis of B, T, natural killer (NK) and natural killer T (NKT) cells at baseline, month 1, and 12 was performed by multidimensional flow cytometry. Data were analyzed by conventional gating and unsupervised computational approaches. In parallel, different clinical parameters were longitudinally assessed. Twenty treatment-naïve age/sex-matched RRMS patients were included as the control cohort. Results: B-cell depletion by OCR and OFA resulted in significant reductions in CD20+ T and B cells as well as B-cell subsets, alongside an expansion of CD5+CD19+CD20− B cells, while also elevating exhaustion markers (CTLA-4, PD-1, TIGIT, TIM-3) across T, B, NK, and NKT cells. Additionally, regulatory T-cell (TREG) numbers increased, especially in OCR-treated patients, and reductions in double-negative (CD3+CD4−CD8−) T cells (DN T cells) were observed, with these DN T cells having higher CD20 expression compared to CD4 or CD8 positive T cells. These immune profile changes correlated with clinical parameters, suggesting pathophysiological relevance in RRMS. Conclusions: Our interim data add weight to the argumentation that the exhaustion/activation markers, notably TIGIT, may be relevant to the pathogenesis of MS. In addition, we identify a potentially interesting increase in the expression of CD5+ on B cells. Finally, we identified a population of double-negative T cells (KLRG1+HLADR+, in particular) that is associated with MS activity and decreased with CD20 depletion. Full article
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Central Nervous System Autoimmunity)
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27 pages, 1305 KiB  
Review
FAAH Modulators from Natural Sources: A Collection of New Potential Drugs
by Catalin Nicoara, Filomena Fezza and Mauro Maccarrone
Cells 2025, 14(7), 551; https://doi.org/10.3390/cells14070551 - 5 Apr 2025
Viewed by 444
Abstract
The endocannabinoid system (ECS) plays a crucial role in maintaining homeostasis by regulating immune response, energy metabolism, cognitive functions, and neuronal activity. It consists of endocannabinoids (eCBs), cannabinoid receptors (CBRs), and enzymes involved in eCB biosynthesis and degradation. Increasing evidence highlights the involvement [...] Read more.
The endocannabinoid system (ECS) plays a crucial role in maintaining homeostasis by regulating immune response, energy metabolism, cognitive functions, and neuronal activity. It consists of endocannabinoids (eCBs), cannabinoid receptors (CBRs), and enzymes involved in eCB biosynthesis and degradation. Increasing evidence highlights the involvement of the ECS under several pathological conditions, making it a promising therapeutic target. Recent research efforts have focused on modulating endogenous eCB levels, particularly through the inhibition of fatty acid amide hydrolase (FAAH), the main catabolic enzyme of the major eCB anandamide. Natural substances, including plant extracts and purified compounds, can inhibit FAAH and represent a promising area of pharmacological research. Natural FAAH inhibitors are particularly attractive due to their potentially lower toxicity compared to synthetic compounds, making them safer candidates for therapeutic applications. Phytocannabinoids, flavonoids, and flavolignans have been shown to efficiently inhibit FAAH. The structural diversity and bioactivity of these natural substances provide a valuable alternative to synthetic inhibitors, and may open new avenues for developing innovative pharmacological tools. Full article
(This article belongs to the Special Issue From Research to Legalization: How Cannabis Exploits the Endocannabinoid System)
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17 pages, 2189 KiB  
Article
Utilisation of Deep Neural Networks for Estimation of Cajal Cells in the Anal Canal Wall of Patients with Advanced Haemorrhoidal Disease Treated by LigaSure Surgery
by Inese Fišere, Edgars Edelmers, Šimons Svirskis and Valērija Groma
Cells 2025, 14(7), 550; https://doi.org/10.3390/cells14070550 - 5 Apr 2025
Viewed by 360
Abstract
Interstitial cells of Cajal (ICCs) play a key role in gastrointestinal smooth muscle contractions, but their relationship with anal canal function in advanced haemorrhoidal disease (HD) remains poorly understood. This study uses deep neural network (DNN) models to estimate ICC presence and quantity [...] Read more.
Interstitial cells of Cajal (ICCs) play a key role in gastrointestinal smooth muscle contractions, but their relationship with anal canal function in advanced haemorrhoidal disease (HD) remains poorly understood. This study uses deep neural network (DNN) models to estimate ICC presence and quantity in anal canal tissues affected by HD. Haemorrhoidectomy specimens were collected from patients undergoing surgery with the LigaSure device. A YOLOv11-based machine learning model, trained on 376 immunohistochemical images, automated ICC detection using the CD117 marker, achieving a mean average precision (mAP50) of 92%, with a recall of 86% and precision of 88%. The DNN model accurately identified ICCs in whole-slide images, revealing that one-third of grade III HD patients and 60% of grade IV HD patients had a high ICC density. Preoperatively, pain was reported in 35% of grade III HD patients and 41% of grade IV patients, with a significant reduction following surgery. A significant decrease in bleeding (p < 0.0001) was also noted postoperatively. Notably, patients with postoperative bleeding, diagnosed with stage IV HD, had high ICC density in their anorectal tissues (p = 0.0041), suggesting a potential link between ICC density and HD severity. This AI-driven model, alongside clinical data, may enhance outcome prediction and provide insights into HD pathophysiology. Full article
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16 pages, 2993 KiB  
Article
Role of Homeobox A1 in Airway Epithelial Generation from Human Airway Basal Cells
by Mohsen Tabasi, Nathaniel Chen and Umadevi Sajjan
Cells 2025, 14(7), 549; https://doi.org/10.3390/cells14070549 - 5 Apr 2025
Viewed by 299
Abstract
Airway basal cells from chronic obstructive pulmonary disease patients show a reduction in HOXA1 expression and generate an abnormal airway epithelium. Because the specific role of HOXA1 in airway basal cells is not known, we investigated the contribution of HOXA1 in the generation [...] Read more.
Airway basal cells from chronic obstructive pulmonary disease patients show a reduction in HOXA1 expression and generate an abnormal airway epithelium. Because the specific role of HOXA1 in airway basal cells is not known, we investigated the contribution of HOXA1 in the generation of the airway epithelium, which depends on basal cell proliferation, polarization, and differentiation. Airway stem cells were transduced with an inducible HOXA1 shRNA lentivector to knock down HOXA1 in either proliferating cells or100% confluent cells. The bronchial epithelium expresses HOXA1 near the basement membrane, likely representing basal cells. HOXA1 knockdown in proliferating basal cells attenuated cell proliferation. HOXA1 knockdown in confluent monolayers of basal cells generated an abnormal airway epithelium characterized by goblet cell hyperplasia and an inflammatory phenotype. Compared to the control, HOXA1 knockdown cells showed a decrease in transepithelial resistance, localization of occludin and E-cadherin to the intercellular junctions, reduced expression of occludin but not E-cadherin, and increased expression of TNF-α. Blocking TNF-α increased the expression of occludin in HOXA1 K/D cells. Based on these results, we conclude that HOXA1 plays an important role in cell proliferation, polarization, and differentiation, which are essential steps in airway epithelial generation. Additionally, HOXA1 may regulate occludin expression by inhibiting TNF-α expression. Full article
(This article belongs to the Section Stem Cells)
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27 pages, 1110 KiB  
Review
Targeting of Extracellular Vesicle-Based Therapeutics to the Brain
by Anastasia Williams, Heather Branscome, Fatah Kashanchi and Elena V. Batrakova
Cells 2025, 14(7), 548; https://doi.org/10.3390/cells14070548 - 4 Apr 2025
Viewed by 920
Abstract
Extracellular vesicles (EVs) have been explored as promising vehicles for drug delivery. One of the most valuable features of EVs is their ability to cross physiological barriers, particularly the blood–brain barrier (BBB). This significantly enhances the development of EV-based drug delivery systems for [...] Read more.
Extracellular vesicles (EVs) have been explored as promising vehicles for drug delivery. One of the most valuable features of EVs is their ability to cross physiological barriers, particularly the blood–brain barrier (BBB). This significantly enhances the development of EV-based drug delivery systems for the treatment of CNS disorders. The present review focuses on the factors and techniques that contribute to the successful delivery of EV-based therapeutics to the brain. Here, we discuss the major methods of brain targeting which includes the utilization of different administration routes, capitalizing on the biological origins of EVs, and the modification of EVs through the addition of specific ligands on to the surface of EVs. Finally, we discuss the current challenges in large-scale EV production and drug loading while highlighting future perspectives regarding the application of EV-based therapeutics for brain delivery. Full article
(This article belongs to the Special Issue Extracellular Vesicle-Based Therapeutics: Current Advances and Future Perspectives)
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17 pages, 4399 KiB  
Article
The Ceramide-Dependent EV Secretome Differentially Affects Prostate Cancer Cell Migration
by Dolma Choezom, Jan-Moritz Plum, Pradhipa Karuna M., Adi Danieli-Mackay, Christof Lenz, Phillipp Brockmeyer and Julia Christina Gross
Cells 2025, 14(7), 547; https://doi.org/10.3390/cells14070547 - 4 Apr 2025
Viewed by 357
Abstract
Tumor-derived extracellular vesicles (EVs) play an important role in cancer progression. Neutral sphingomyelinases (nSMases) are lipid-modifying enzymes that modulate the secretion of EVs from cells. How nSMase activity and therefore ceramide generation affect the composition and functionality of secreted EVs is not fully [...] Read more.
Tumor-derived extracellular vesicles (EVs) play an important role in cancer progression. Neutral sphingomyelinases (nSMases) are lipid-modifying enzymes that modulate the secretion of EVs from cells. How nSMase activity and therefore ceramide generation affect the composition and functionality of secreted EVs is not fully understood. Here, we aimed to investigate the expression of nSMases 1 and 2 in prostate cancer (PCa) tissue and their role in EV composition and secretion for prostate cancer cell migration. Reduced nSMase 1 and 2 expression was found in prostate cancer and correlated with the age of the patient. When nSMase 2 was inhibited by GW4869 in PCa cells (PC3 and DU145), the EV secretome was significantly altered, while the number of EVs and the total protein content of released EVs were not significantly changed. Using proteomic analysis, we found that extracellular matrix proteins, such as SDC4 (Syndecan-4) and SRPX-2, were differentially secreted on EVs from GW4869-treated PC3 cells. In scratch wound migration assays, GW4869 significantly increased migration compared to control PC3 cells but not DU145 cells, while SDC4 knockdown significantly reduced the migration of PC3 cells. These and other nSMase-2-dependent secreted proteins are interesting candidates for understanding the role of stress-induced EVs in the progression of prostate cancer. Full article
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19 pages, 2932 KiB  
Article
Transcriptome Analysis Reveals the Requirement of the TGFβ Pathway in Ascidian Tail Regression
by Wenjie Shi, Penghui Liu, Dongyu Yang, Yuan Zhuang, Boyan Lin and Bo Dong
Cells 2025, 14(7), 546; https://doi.org/10.3390/cells14070546 - 4 Apr 2025
Viewed by 304
Abstract
Metamorphosis is a common developmental process in invertebrate development. It is essential for the degeneration of larval organs, formation of adult organs, and adaptation transformation of the living environment. However, the underlying molecular regulatory mechanism remains to be elucidated. In this study, we [...] Read more.
Metamorphosis is a common developmental process in invertebrate development. It is essential for the degeneration of larval organs, formation of adult organs, and adaptation transformation of the living environment. However, the underlying molecular regulatory mechanism remains to be elucidated. In this study, we used tail regression of ascidian Styela clava as a model to understand the gene regulation pathway and molecular mechanism in organ metamorphosis. The TGFβ signaling pathway was screened and demonstrated to be involved in tail regression based on RNA sequencing on the different larval stages and verification with inhibitor treatment experiments. We further investigated the downstream gene network of the TGFβ signaling pathway through comparative transcriptome data analysis on the TGFβ pathway inhibition samples. Together with qRT-PCR verification, we identified four critical gene functional categories, including ion transporters/water channel, extracellular matrix structural constituent, extracellular matrix organization, and cell polarity establishment. Furthermore, a cross-species comparative analysis between Ciona robusta and S. clava was performed to understand the conservation and divergence of gene regulation in ascidians. Overall, our work identifies a crucial gene regulation pathway in ascidian tail regression and provides several potential downstream targets for understanding the molecular mechanism of larval metamorphosis. Full article
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22 pages, 925 KiB  
Review
The Emerging Role of Water Loss in Dog Aging
by Gabriella Guelfi, Camilla Capaccia, Vicente Francisco Ratto, Antonello Bufalari, Leonardo Leonardi, Luca Mechelli, Simone Cenci and Margherita Maranesi
Cells 2025, 14(7), 545; https://doi.org/10.3390/cells14070545 - 4 Apr 2025
Viewed by 657
Abstract
Aging involves progressive physiological changes, including the dysregulation of water homeostasis, essential for cellular function, neuronal signaling, and musculoskeletal integrity. This review explores the emerging role of water loss as a central and underestimated driver of functional decline in aging, with a focus [...] Read more.
Aging involves progressive physiological changes, including the dysregulation of water homeostasis, essential for cellular function, neuronal signaling, and musculoskeletal integrity. This review explores the emerging role of water loss as a central and underestimated driver of functional decline in aging, with a focus on the dog, both as a clinically relevant target species and as a model for human aging. Age-related alterations in water metabolism—driven by changes in body composition, aquaporin (AQP) expression, electrolyte imbalances, reduced thirst perception, and impaired urine concentration—lead to intracellular and extracellular dehydration, exacerbating functional decline. We examine molecular mechanisms of water regulation involving AQPs and osmolytes, and describe how dehydration contributes to structural and metabolic dysfunction across key biological compartments, including the kidney, brain, bone, and skeletal muscle. Physiological dehydration, a hallmark of aging, intensifies inflammaging, accelerating tissue degeneration. In particular, we highlight how water loss impairs solvent capacity, solute transport, protein conformation, and cellular communication. Despite the known role of macronutrients in geriatric nutrition, hydration remains an often-overlooked factor in aging management. We argue for its inclusion as a fourth pillar in the nutritional approach to veterinary geriatrics, alongside protein, fat, and fiber. By investigating aging-associated water loss in dogs—species that share environments and lifestyle patterns with humans—we propose hydration-centered strategies to promote healthy aging in both veterinary and comparative medicine. Full article
(This article belongs to the Special Issue Understanding Aging Mechanisms to Prevent Age-Related Diseases: 2nd Edition)
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16 pages, 843 KiB  
Review
The Role of A20 in Cancer: Friend or Foe?
by Jinju Lee and Heesun Cheong
Cells 2025, 14(7), 544; https://doi.org/10.3390/cells14070544 - 4 Apr 2025
Viewed by 428
Abstract
A20 is a ubiquitin-editing enzyme that has emerged as a key regulator of inflammatory signaling with paradoxical roles in cancer. Acting as both an oncogene and a tumor suppressor gene depending on the cellular context, A20 modulates important cell pathways, such as NF-κB [...] Read more.
A20 is a ubiquitin-editing enzyme that has emerged as a key regulator of inflammatory signaling with paradoxical roles in cancer. Acting as both an oncogene and a tumor suppressor gene depending on the cellular context, A20 modulates important cell pathways, such as NF-κB signaling and autophagy. In this review, we summarize the dual roles of A20 in tumorigenesis, highlighting its ability to promote tumor progression in cancers, such as breast and melanoma, while functioning as a tumor suppressor in lymphomas and hepatocellular carcinoma. We discuss the interplay of A20 with autophagy, a process that is important for maintaining cellular homeostasis and influencing tumor dynamics. By integrating recent findings, we provide insight into how dysregulation of A20 and its associated pathways can either suppress or drive cancer development, which may lead to improved therapeutic intervention. Full article
(This article belongs to the Special Issue Cellular Mechanisms of Anti-Cancer Therapies)
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20 pages, 2940 KiB  
Article
Targeted Control of Gene Expression Using CRISPR-Associated Endoribonucleases
by Sagar J. Parikh, Heather M. Terron, Luke A. Burgard, Derek S. Maranan, Dylan D. Butler, Abigail Wiseman, Frank M. LaFerla, Shelley Lane and Malcolm A. Leissring
Cells 2025, 14(7), 543; https://doi.org/10.3390/cells14070543 - 3 Apr 2025
Viewed by 294
Abstract
CRISPR-associated endoribonucleases (Cas RNases) cleave single-stranded RNA in a highly sequence-specific manner by recognizing and binding to short RNA sequences known as direct repeats (DRs). Here, we investigate the potential of exploiting Cas RNases for the regulation of target genes with one or [...] Read more.
CRISPR-associated endoribonucleases (Cas RNases) cleave single-stranded RNA in a highly sequence-specific manner by recognizing and binding to short RNA sequences known as direct repeats (DRs). Here, we investigate the potential of exploiting Cas RNases for the regulation of target genes with one or more DRs introduced into the 3′ untranslated region, an approach we refer to as DREDGE (direct repeat-enabled downregulation of gene expression). The DNase-dead version of Cas12a (dCas12a) was identified as the most efficient among five different Cas RNases tested and was subsequently evaluated in doxycycline-regulatable systems targeting either stably expressed fluorescent proteins or an endogenous gene. DREDGE performed superbly in stable cell lines, resulting in up to 90% downregulation with rapid onset, notably in a fully reversible and highly selective manner. Successful control of an endogenous gene with DREDGE was demonstrated in two formats, including one wherein both the DR and the transgene driving expression of dCas12a were introduced in one step by CRISPR-Cas. Our results establish DREDGE as an effective method for regulating gene expression in a targeted, highly selective, and fully reversible manner, with several advantages over existing technologies. Full article
(This article belongs to the Section Cell Methods)
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25 pages, 2073 KiB  
Review
Extracellular Vesicles in Asthma: Intercellular Cross-Talk in TH2 Inflammation
by Naila Arif Cheema, Annalisa Castagna, Francesca Ambrosani, Giuseppe Argentino, Simonetta Friso, Marco Zurlo, Ruggero Beri, Matteo Maule, Rachele Vaia, Gianenrico Senna and Marco Caminati
Cells 2025, 14(7), 542; https://doi.org/10.3390/cells14070542 - 3 Apr 2025
Viewed by 449
Abstract
Asthma is a complex, multifactorial inflammatory disorder of the airways, characterized by recurrent symptoms and variable airflow obstruction. So far, two main asthma endotypes have been identified, type 2 (T2)-high or T2-low, based on the underlying immunological mechanisms. Recently, extracellular vesicles (EVs), particularly [...] Read more.
Asthma is a complex, multifactorial inflammatory disorder of the airways, characterized by recurrent symptoms and variable airflow obstruction. So far, two main asthma endotypes have been identified, type 2 (T2)-high or T2-low, based on the underlying immunological mechanisms. Recently, extracellular vesicles (EVs), particularly exosomes, have gained increasing attention due to their pivotal role in intercellular communication and distal signaling modulation. In the context of asthma pathobiology, an increasing amount of experimental evidence suggests that EVs secreted by eosinophils, mast cells, dendritic cells, T cells, neutrophils, macrophages, and epithelial cells contribute to disease modulation. This review explores the role of EVs in profiling the molecular signatures of T2-high and T2-low asthma, offering novel perspectives on disease mechanisms and potential therapeutic targets. Full article
(This article belongs to the Special Issue Novel Insights into Molecular Mechanisms and Therapy of Asthma)
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18 pages, 4857 KiB  
Article
The Growth of Soybean (Glycine max) Under Salt Stress Is Modulated in Simulated Microgravity Conditions
by Setsuko Komatsu, Haruka Misaki, Wei Zhu, Hisateru Yamaguchi, Keisuke Hitachi, Kunihiro Tsuchida and Atsushi Higashitani
Cells 2025, 14(7), 541; https://doi.org/10.3390/cells14070541 - 3 Apr 2025
Viewed by 206
Abstract
The role of a simulated microgravity environment on soybean growth was investigated. The root grew more under simulated microgravity conditions than in the presence of gravity. However, root shortening due to salt stress did not occur in simulated microgravity conditions. To reveal these [...] Read more.
The role of a simulated microgravity environment on soybean growth was investigated. The root grew more under simulated microgravity conditions than in the presence of gravity. However, root shortening due to salt stress did not occur in simulated microgravity conditions. To reveal these mechanisms by simulated microgravity environment on soybean root, a proteomic analysis was conducted. Proteomic analysis revealed that among 1547 proteins, the abundances of proteins related to phytohormone, oxidative stress, ubiquitin/proteasome system, cell organization, and cell wall organization were altered under stimulated microgravity compared with gravity. Membrane-localized proteins and redox-related proteins were inversely correlated in protein numbers due to salt stress under gravity and the simulated microgravity condition. Proteins identified by proteomics were validated for protein accumulation by immunoblot analysis. Superoxide dismutase and ascorbate peroxidases, which are reactive oxygen species-scavenging proteins, increased in soybean root under salt stress but not in the simulated microgravity conditions even under stress. The accumulation of 45 kDa aquaporin and 70 kDa calnexin in soybean root under salt stress were increased in the simulated microgravity conditions compared to gravity. These findings suggest that soybean growth under salt stress may be regulated through improved water permeability, mitigation of reactive oxygen species production, and restoration of protein folding under simulated microgravity conditions. Full article
(This article belongs to the Section Cell Methods)
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23 pages, 1766 KiB  
Review
Insights into Autophagy in Microbiome Therapeutic Approaches for Drug-Resistant Tuberculosis
by Md Abdur Rahim, Hoonhee Seo, Indrajeet Barman, Mohammed Solayman Hossain, Md Sarower Hossen Shuvo and Ho-Yeon Song
Cells 2025, 14(7), 540; https://doi.org/10.3390/cells14070540 - 3 Apr 2025
Viewed by 291
Abstract
Tuberculosis, primarily caused by Mycobacterium tuberculosis, is an airborne lung disease and continues to pose a significant global health threat, resulting in millions of deaths annually. The current treatment for tuberculosis involves a prolonged regimen of antibiotics, which leads to complications such [...] Read more.
Tuberculosis, primarily caused by Mycobacterium tuberculosis, is an airborne lung disease and continues to pose a significant global health threat, resulting in millions of deaths annually. The current treatment for tuberculosis involves a prolonged regimen of antibiotics, which leads to complications such as recurrence, drug resistance, reinfection, and a range of side effects. This scenario underscores the urgent need for novel therapeutic strategies to combat this lethal pathogen. Over the last two decades, microbiome therapeutics have emerged as promising next-generation drug candidates, offering advantages over traditional medications. In 2022, the Food and Drug Administration approved the first microbiome therapeutic for recurrent Clostridium infections, and extensive research is underway on microbiome treatments for various challenging diseases, including metabolic disorders and cancer. Research on microbiomes concerning tuberculosis commenced roughly a decade ago, and the scope of this research has broadened considerably over the last five years, with microbiome therapeutics now viewed as viable options for managing drug-resistant tuberculosis. Nevertheless, the understanding of their mechanisms is still in its infancy. Although autophagy has been extensively studied in other diseases, research into its role in tuberculosis is just beginning, with preliminary developments in progress. Against this backdrop, this comprehensive review begins by succinctly outlining tuberculosis’ characteristics and assessing existing treatments’ strengths and weaknesses, followed by a detailed examination of microbiome-based therapeutic approaches for drug-resistant tuberculosis. Additionally, this review focuses on establishing a basic understanding of microbiome treatments for tuberculosis, mainly through the lens of autophagy as a mechanism of action. Ultimately, this review aims to contribute to the foundational comprehension of microbiome-based therapies for tuberculosis, thereby setting the stage for the further advancement of microbiome therapeutics for drug-resistant tuberculosis. Full article
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15 pages, 1782 KiB  
Review
Decoding B Cells in Autoimmune Diseases Through ScRNA + BCR-Seq: Current Knowledge and Future Directions
by Kai Quan, Huifang Wang, Peng Su, Yuanyuan Xu and Xinsheng Yao
Cells 2025, 14(7), 539; https://doi.org/10.3390/cells14070539 - 3 Apr 2025
Viewed by 457
Abstract
The combined application of single-cell RNA sequencing (scRNA-seq) and single-cell B-cell receptor sequencing (scBCR-seq) offers a multidimensional perspective for dissecting the immunopathological mechanisms of B cells in autoimmune diseases. This review systematically summarizes the principles of these techniques, the analytical framework, and their [...] Read more.
The combined application of single-cell RNA sequencing (scRNA-seq) and single-cell B-cell receptor sequencing (scBCR-seq) offers a multidimensional perspective for dissecting the immunopathological mechanisms of B cells in autoimmune diseases. This review systematically summarizes the principles of these techniques, the analytical framework, and their key applications in diseases such as systemic lupus erythematosus et. al. It reveals the dynamic correlations between the transcriptome of B-cell subsets and B-cell receptor (BCR) clones. Furthermore, we focus on the potential roles of dual BCR B cells and B/T biphenotypic cells in autoimmunity, emphasizing their exacerbation of disease progression through abnormal clonal expansion and autoantibody secretion. By sorting through cutting-edge advancements and bottleneck issues, this article aims to propel the innovation of multi-omics research and precision treatment paradigms for autoimmune diseases. Full article
(This article belongs to the Special Issue Immune Functions and Therapeutic Potential of B Lymphocytes in Autoimmune Disorders)
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40 pages, 2165 KiB  
Review
Stem Cells in Cancer: From Mechanisms to Therapeutic Strategies
by Laurence Haddadin and Xueqin Sun
Cells 2025, 14(7), 538; https://doi.org/10.3390/cells14070538 - 3 Apr 2025
Viewed by 675
Abstract
Stem cells have emerged as a pivotal area of research in the field of oncology, offering new insights into the mechanisms of cancer initiation, progression, and resistance to therapy. This review provides a comprehensive overview of the role of stem cells in cancer, [...] Read more.
Stem cells have emerged as a pivotal area of research in the field of oncology, offering new insights into the mechanisms of cancer initiation, progression, and resistance to therapy. This review provides a comprehensive overview of the role of stem cells in cancer, focusing on cancer stem cells (CSCs), their characteristics, and their implications for cancer therapy. We discuss the origin and identification of CSCs, their role in tumorigenesis, metastasis, and drug resistance, and the potential therapeutic strategies targeting CSCs. Additionally, we explore the use of normal stem cells in cancer therapy, focusing on their role in tissue regeneration and their use as delivery vehicles for anticancer agents. Finally, we highlight the challenges and future directions in stem cell research in cancer. Full article
(This article belongs to the Special Issue Stem Cells in Cancer)
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17 pages, 4041 KiB  
Article
Characterization and Biological Evaluation of Composite Nanofibrous Membranes Prepared from Hemp Salmon (Oncorhynchus keta) Skin Collagen
by Yu Liu, Mochi Zhu, Rui Duan and Junjie Zhang
Cells 2025, 14(7), 537; https://doi.org/10.3390/cells14070537 - 3 Apr 2025
Viewed by 346
Abstract
Aquatic collagen, a natural macromolecule protein with excellent biocompatibility, has attracted attention in the field of medical materials. Compared to mammalian collagen, aquatic collagen offers unique advantages, including the absence of zoonotic disease risks and religious concerns. In this study, salmon skin collagen [...] Read more.
Aquatic collagen, a natural macromolecule protein with excellent biocompatibility, has attracted attention in the field of medical materials. Compared to mammalian collagen, aquatic collagen offers unique advantages, including the absence of zoonotic disease risks and religious concerns. In this study, salmon skin collagen nanofiber membrane (GS) was prepared by electrostatic spinning. Then, skin collagen was combined with silk sericin (SS) and sodium hyaluronate (HA) to fabricate composite collagen nanofiber membrane (GF) using electrostatic spinning technology. GF membranes were further cross-linked (GFL) for use in a mouse wound healing model. The physicochemical properties and biocompatibility of GS, GF, and GFL were evaluated. FTIR analysis revealed that GFL exhibited a more stable secondary structure compared to GS and GF. DSC and TGA results indicated that GFL had the highest thermal stability, followed by GF. Cytotoxicity tests confirmed that GS, GF, and GFL were non-cytotoxic, with GF showing the highest cell viability rate of 175.23 ± 1.77%. In the wound healing model, GFL group achieved nearly complete healing by day 14 (98 ± 0.1%), compared to 76.04 ± 0.01% in the blank group. Measurement of TGF-β1 and VEGF levels in the healing tissue on day 14 indicated that the GFL group had progressed to the late stage of healing, whereas the blank group remained in the early stage. These results suggest that GFL holds significant potential as a medical biomaterial for wound healing applications. Full article
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20 pages, 1701 KiB  
Review
Translational Regulators in Pulmonary Fibrosis: MicroRNAs, Long Non-Coding RNAs, and Transcript Modifications
by Sumeen Kaur Gill and Richard H. Gomer
Cells 2025, 14(7), 536; https://doi.org/10.3390/cells14070536 - 3 Apr 2025
Viewed by 463
Abstract
Fibrosing disorders including idiopathic pulmonary fibrosis (IPF) are progressive irreversible diseases, often with poor prognoses, characterized by the accumulation of excessive scar tissue and extracellular matrix. Translational regulation has emerged as a critical aspect of gene expression control, and the dysregulation of key [...] Read more.
Fibrosing disorders including idiopathic pulmonary fibrosis (IPF) are progressive irreversible diseases, often with poor prognoses, characterized by the accumulation of excessive scar tissue and extracellular matrix. Translational regulation has emerged as a critical aspect of gene expression control, and the dysregulation of key effectors is associated with disease pathogenesis. This review examines the current literature on translational regulators in IPF, focusing on microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and RNA transcript modifications including alternative polyadenylation and chemical modification. Some of these translational regulators potentiate fibrosis, and some of the regulators inhibit fibrosis. In IPF, some of the profibrotic regulators are upregulated, and some of the antifibrotic regulators are downregulated. Correcting these defects in IPF-associated translational regulators could be an intriguing avenue for therapeutics. Full article
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2 pages, 1030 KiB  
Correction
Correction: Sumarni et al. Targeting Cutaneous T-Cell Lymphoma Cells by Ingenol Mebutate (PEP005) Correlates with PKCδ Activation, ROS Induction as Well as Downregulation of XIAP and c-FLIP. Cells 2021, 10, 987
by Uly Sumarni, Ulrich Reidel and Jürgen Eberle
Cells 2025, 14(7), 535; https://doi.org/10.3390/cells14070535 - 3 Apr 2025
Viewed by 142
Abstract
In the original publication [...] Full article
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53 pages, 4308 KiB  
Review
PPAR-γ in Melanoma and Immune Cells: Insights into Disease Pathogenesis and Therapeutic Implications
by Vladimir Sobolev, Ekaterina Tchepourina, Anna Soboleva, Elena Denisova, Irina Korsunskaya and Alexandre Mezentsev
Cells 2025, 14(7), 534; https://doi.org/10.3390/cells14070534 - 2 Apr 2025
Viewed by 339
Abstract
Changes in skin pigmentation, like hyperpigmentation or moles, can affect appearance and social life. Unlike locally containable moles, malignant melanomas are aggressive and can spread rapidly, disproportionately affecting younger individuals with a high potential for metastasis. Research has shown that the peroxisome proliferator-activated [...] Read more.
Changes in skin pigmentation, like hyperpigmentation or moles, can affect appearance and social life. Unlike locally containable moles, malignant melanomas are aggressive and can spread rapidly, disproportionately affecting younger individuals with a high potential for metastasis. Research has shown that the peroxisome proliferator-activated receptor gamma (PPAR-γ) and its ligands exhibit protective effects against melanoma. As a transcription factor, PPAR-γ is crucial in functions like fatty acid storage and glucose metabolism. Activation of PPAR-γ promotes lipid uptake and enhances sensitivity to insulin. In many cases, it also inhibits the growth of cancer cell lines, like breast, gastric, lung, and prostate cancer. In melanoma, PPAR-γ regulates cell proliferation, differentiation, apoptosis, and survival. During tumorigenesis, it controls metabolic changes and the immunogenicity of stromal cells. PPAR-γ agonists can target hypoxia-induced angiogenesis in tumor therapy, but their effects on tumors can be suppressive or promotional, depending on the tumor environment. Published data show that PPAR-γ-targeting agents can be effective in specific groups of patients, but further studies are needed to understand lesser-known biological effects of PPAR-γ and address the existing safety concerns. This review provides a summary of the current understanding of PPAR-γ and its involvement in melanoma. Full article
(This article belongs to the Section Cellular Pathology)
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29 pages, 27509 KiB  
Article
Repurposed Drugs to Enhance the Therapeutic Potential of Oligodendrocyte Precursor Cells Derived from Adult Rat Adipose Tissue
by J. Pascual-Guerra, M. Torres-Rico, B. Marín-Rodríguez, M. S. Arasmou-Idrovo, A. G. García, J. A. Rodríguez-Navarro and C. L. Paíno
Cells 2025, 14(7), 533; https://doi.org/10.3390/cells14070533 - 2 Apr 2025
Viewed by 449
Abstract
Failure in the proliferation, recruitment, mobilization, and/or differentiation of oligodendrocyte precursor cells (OPCs) impedes remyelination in central nervous system (CNS) demyelinating diseases. Our group has recently achieved the generation of functional oligodendroglia through direct lineage conversion by expressing Sox10, Olig2, and [...] Read more.
Failure in the proliferation, recruitment, mobilization, and/or differentiation of oligodendrocyte precursor cells (OPCs) impedes remyelination in central nervous system (CNS) demyelinating diseases. Our group has recently achieved the generation of functional oligodendroglia through direct lineage conversion by expressing Sox10, Olig2, and Zfp536 genes in adult rat adipose tissue-derived stromal cells. The present study aimed to determine whether various repurposed drugs or molecules could enhance the myelinating capacities of these induced OPCs (iOPCs). We report that kainate, benztropine, miconazole, clobetasol, and baclofen promote in vitro iOPCs migration, differentiation, and ensheathing abilities through mechanisms similar to those observed in rat neural stem cell-derived OPCs. This research supports the potential use of iOPCs as they provide an alternative and reliable cell source for testing the effects of in vitro promyelinating repurposed drugs and for assessing the molecular and cellular mechanisms involved in therapeutic strategies for demyelinating diseases. Full article
(This article belongs to the Special Issue Glial Cells: Physiological and Pathological Perspective)
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16 pages, 5333 KiB  
Article
The Influence of Interleukin 6 Knockout on Age-Related Degenerative Changes in the Cerebellar Cortex of Mice
by Magdalena Wiktoria Cieślińska, Izabela Bialuk, Magdalena Dziemidowicz, Beata Szynaka, Joanna Reszeć-Giełażyn, Maria Małgorzata Winnicka and Tomasz Andrzej Bonda
Cells 2025, 14(7), 532; https://doi.org/10.3390/cells14070532 - 2 Apr 2025
Viewed by 268
Abstract
This study investigates age-related neurodegeneration in the cerebellar cortex, emphasizing the role of IL-6 deficiency in preserving Purkinje cells. We found that apoptosis plays a minimal role in Purkinje cell loss by using 4-month- and 24-month-old wild-type (WT) and IL-6 knockout (IL-6KO) mice. [...] Read more.
This study investigates age-related neurodegeneration in the cerebellar cortex, emphasizing the role of IL-6 deficiency in preserving Purkinje cells. We found that apoptosis plays a minimal role in Purkinje cell loss by using 4-month- and 24-month-old wild-type (WT) and IL-6 knockout (IL-6KO) mice. At 24 months, WT mice exhibited severe Purkinje cell degeneration, including atrophic cell bodies, eosinophilic cytoplasm, pyknotic nuclei, mitochondrial disruption, and increased levels of lipofuscin-rich lysosomes. In contrast, IL-6KO mice showed fewer lysosomes, reduced mitochondrial damage, and less neuronal atrophy, indicating a neuroprotective effect. Lower p53 expression and decreased levels of its downstream effectors (p21, and Bax) in IL-6KO mice correlated with reduced cellular stress. Minimal changes in apoptotic markers (Bax and caspase-3) further reinforce the limited role of apoptosis. Neuroinflammation, marked by elevated GFAP, was prominent in aged WT mice but attenuated in IL-6KO mice. Reduced p53 accumulation, less severe neuroinflammation, and preserved metabolic homeostasis in IL-6KO mice correlated with improved Purkinje cell survival. These findings suggest that IL-6 accelerates neurodegeneration via p53-associated stress and inflammation, while IL-6 deficiency mitigates these effects. Targeting IL-6 signaling through anti-inflammatory strategies or IL-6 inhibition may offer a therapeutic approach for age-related neurodegenerative disorders. Full article
(This article belongs to the Section Cells of the Nervous System)
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41 pages, 3013 KiB  
Review
Zebrafish as a Versatile Model for Cardiovascular Research: Peering into the Heart of the Matter
by Ramcharan Singh Angom, Meghna Singh, Huzaifa Muhammad, Sai Manasa Varanasi and Debabrata Mukhopadhyay
Cells 2025, 14(7), 531; https://doi.org/10.3390/cells14070531 - 2 Apr 2025
Viewed by 600
Abstract
Cardiovascular diseases (CVDs) are the leading cause of death in the world. A total of 17.5 million people died of CVDs in the year 2012, accounting for 31% of all deaths globally. Vertebrate animal models have been used to understand cardiac disease biology, [...] Read more.
Cardiovascular diseases (CVDs) are the leading cause of death in the world. A total of 17.5 million people died of CVDs in the year 2012, accounting for 31% of all deaths globally. Vertebrate animal models have been used to understand cardiac disease biology, as the cellular, molecular, and physiological aspects of human CVDs can be replicated closely in these organisms. Zebrafish is a popular model organism offering an arsenal of genetic tools that allow the rapid in vivo analysis of vertebrate gene function and disease conditions. It has a short breeding cycle, high fecundity, optically transparent embryos, rapid internal organ development, and easy maintenance. This review aims to give readers an overview of zebrafish cardiac biology and a detailed account of heart development in zebrafish and its comparison with humans and the conserved genetic circuitry. We also discuss the contributions made in CVD research using the zebrafish model. The first part of this review focuses on detailed information on the morphogenetic and differentiation processes in early cardiac development. The overlap and divergence of the human heart’s genetic circuitry, structure, and physiology are emphasized wherever applicable. In the second part of the review, we overview the molecular tools and techniques available to dissect gene function and expression in zebrafish, with special mention of the use of these tools in cardiac biology. Full article
(This article belongs to the Special Issue Advances in Zebrafish Cardiac Disease Models)
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30 pages, 1092 KiB  
Review
B7H3 in Gastrointestinal Tumors: Role in Immune Modulation and Cancer Progression: A Review of the Literature
by Sylwia Mielcarska, Anna Kot, Agnieszka Kula, Miriam Dawidowicz, Piotr Sobków, Daria Kłaczka, Dariusz Waniczek and Elżbieta Świętochowska
Cells 2025, 14(7), 530; https://doi.org/10.3390/cells14070530 - 2 Apr 2025
Viewed by 531
Abstract
B7-H3 (CD276), a member of the B7 immune checkpoint family, plays a critical role in modulating immune responses and has emerged as a promising target in cancer therapy. It is highly expressed in various malignancies, where it promotes tumor evasion from T cell [...] Read more.
B7-H3 (CD276), a member of the B7 immune checkpoint family, plays a critical role in modulating immune responses and has emerged as a promising target in cancer therapy. It is highly expressed in various malignancies, where it promotes tumor evasion from T cell surveillance and contributes to cancer progression, metastasis, and therapeutic resistance, showing a correlation with the poor prognosis of patients. Although its receptors were not fully identified, B7-H3 signaling involves key intracellular pathways, including JAK/STAT, NF-κB, PI3K/Akt, and MAPK, driving processes crucial for supporting tumor growth such as cell proliferation, invasion, and apoptosis inhibition. Beyond immune modulation, B7-H3 influences cancer cell metabolism, angiogenesis, and epithelial-to-mesenchymal transition, further exacerbating tumor aggressiveness. The development of B7-H3-targeting therapies, including monoclonal antibodies, antibody–drug conjugates, and CAR-T cells, offers promising avenues for treatment. This review provides an up-to-date summary of the B7H3 mechanisms of action, putative receptors, and ongoing clinical trials evaluating therapies targeting B7H3, focusing on the molecule’s role in gastrointestinal tumors. Full article
(This article belongs to the Special Issue Gastrointestinal Cancer: From Cellular and Molecular Mechanisms to Therapeutic Opportunities)
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34 pages, 13134 KiB  
Article
Induced Pluripotent Stem Cell-Derived Exosomes Promote Peripheral Nerve Regeneration in a Rat Sciatic Nerve Crush Injury Model: A Safety and Efficacy Study
by Fatima Aldali, Yujie Yang, Chunchu Deng, Xiangling Li, Xiaojian Cao, Jia Xu, Yajie Li, Jianlin Ding and Hong Chen
Cells 2025, 14(7), 529; https://doi.org/10.3390/cells14070529 - 2 Apr 2025
Viewed by 513
Abstract
Peripheral nerve injury (PNI) remains a significant clinical challenge, often leading to long-term functional impairment. Despite advances in therapies, current repair strategies offer unsatisfactory clinical outcomes. Exosomes derived from induced pluripotent stem cells (iPSC-Exos) have emerged as a promising therapeutic approach in regenerative [...] Read more.
Peripheral nerve injury (PNI) remains a significant clinical challenge, often leading to long-term functional impairment. Despite advances in therapies, current repair strategies offer unsatisfactory clinical outcomes. Exosomes derived from induced pluripotent stem cells (iPSC-Exos) have emerged as a promising therapeutic approach in regenerative medicine. This study assesses the efficacy and safety of iPSC-Exos in a rat model of sciatic nerve crush injury. Briefly, iPSCs were generated from peripheral blood mononuclear cells (PBMCs) of healthy donors using Sendai virus vectors and validated for pluripotency. iPSC-Exos were characterized and injected at the injury site. Functional recovery was assessed through gait analysis, grip strength, and pain response. Histological and molecular analyses were used to examine axonal regeneration, myelination, Schwann cell (SC) activation, angiogenesis, and changes in gene expression. iPSC-Exos were efficiently internalized by SC, promoting their proliferation. No adverse effects were observed between groups on body weight, organ histology, or hematological parameters. iPSC-Exos injection significantly enhanced nerve regeneration, muscle preservation, and vascularization, with RNA sequencing revealing activation of PI3K-AKT and focal adhesion pathways. These findings support iPSC-Exos as a safe and effective non-cell-based therapy for PNIs, highlighting their potential for clinical applications in regenerative medicine. Full article
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19 pages, 2523 KiB  
Article
Immunopathological Dysregulation in Acute Myeloid Leukemia: The Impact of T-bet, RORγt, and FOXP3 on Disease Dynamics
by Amira M. Mohamed Mohy El-Din, Buthayna Ahmad AlShaarawy, Eman Zaghloul Kandeel, Dalia Mahmoud AlDewi, Lobna Abdel Azeem Refaat, Borros Arneth and Hussein Sabit
Cells 2025, 14(7), 528; https://doi.org/10.3390/cells14070528 - 1 Apr 2025
Viewed by 366
Abstract
The etiology of acute myeloid leukemia (AML) is complex, including genetic and environmental abnormalities. The immune system anomalies play an essential role in the process of leukemogenesis. However, the immunopathological factors, including abnormal T helper (Th) subsets, contributing to the initiation and progression [...] Read more.
The etiology of acute myeloid leukemia (AML) is complex, including genetic and environmental abnormalities. The immune system anomalies play an essential role in the process of leukemogenesis. However, the immunopathological factors, including abnormal T helper (Th) subsets, contributing to the initiation and progression of this neoplasm, require further investigation. Considering the previously mentioned data, we decided to study the expression pattern of transcription factors T-bet, Foxp3, and RORγt that regulate Th1, Treg, and Th17, respectively, in acute myeloid leukemia with correlation to clinical and other investigation data and treatment outcomes. This study was conducted on 80 newly diagnosed patients with AML recruited from the National Cancer Institute, Cairo University, and 25 healthy control subjects. The AML patient cohort consisted of 30 females (37.5%) and 50 males (62.5%), ranging from 18 to 74 years old. The control group was 8 females (32%) and 17 males (68%), with ages ranging from 23 to 40 years old. Samples were provided from the bone marrow of donor cases for allogeneic bone marrow transplantation. The diagnosis of acute myeloid leukemia was based on morphologic and cytochemical evaluation, immunophenotyping, and complementary cytogenetics according to WHO criteria. Upshift from the normal T-bet intensity of power (MFI), RORγt+ CD4+ T lymphocyte frequency (%) with downshift from the normal FOXP3 intensity of power (MFI), may suggest a state of inflammation. In contrast, an upshift from the normal FOXP3+ CD4+ T lymphocyte frequency (%) may reflect a state of immunosuppression in the bone marrow microenvironment of AML. Combined, they constitute a sophisticated scenario of immunological disorder in AML. Co-expression of T-bet and RORγt transcription factors in CD4+ T lymphocytes in both normal and AML groups may suggest CD4+ T lymphocyte plasticity. Full article
(This article belongs to the Special Issue Cellular Mechanisms and Targeted Therapy of Acute Myeloid Leukemia)
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