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16 pages, 1560 KiB  
Article
Electromagnetic Transduction Therapy (EMTT) Enhances Tenocyte Regenerative Potential: Evidence for Senolytic-like Effects and Matrix Remodeling
by Matteo Mancini, Mario Vetrano, Alice Traversa, Carlo Cauli, Simona Ceccarelli, Florence Malisan, Maria Chiara Vulpiani, Nicola Maffulli, Cinzia Marchese, Vincenzo Visco and Danilo Ranieri
Int. J. Mol. Sci. 2025, 26(15), 7122; https://doi.org/10.3390/ijms26157122 - 24 Jul 2025
Viewed by 1272
Abstract
Tendinopathies are a significant challenge in musculoskeletal medicine, with current treatments showing variable efficacy. Electromagnetic transduction therapy (EMTT) has emerged as a promising therapeutic approach, but its biological effects on tendon cells remain largely unexplored. Here, we investigated the effects of EMTT on [...] Read more.
Tendinopathies are a significant challenge in musculoskeletal medicine, with current treatments showing variable efficacy. Electromagnetic transduction therapy (EMTT) has emerged as a promising therapeutic approach, but its biological effects on tendon cells remain largely unexplored. Here, we investigated the effects of EMTT on primary cultured human tenocytes’ behavior and functions in vitro, focusing on cellular responses, senescence-related pathways, and molecular mechanisms. Primary cultures of human tenocytes were established from semitendinosus tendon biopsies of patients undergoing anterior cruciate ligament (ACL) reconstruction (n = 6, males aged 17–37 years). Cells were exposed to EMTT at different intensities (40 and 80 mT) and impulse numbers (1000–10,500). Cell viability (MTT assay), proliferation (Ki67), senescence markers (CDKN2a/INK4a), migration (scratch test), cytoskeleton organization (immunofluorescence), and gene expression (RT-PCR) were analyzed. A 40 mT exposure elicited minimal effects, whereas 80 mT treatments induced significant cellular responses. Repeated 80 mT exposure demonstrated a dual effect: despite a moderate decrease in overall cell vitality, increased Ki67 expression (+7%, p ≤ 0.05) and significant downregulation of senescence marker CDKN2a/INK4a were observed, suggesting potential senolytic-like activity. EMTT significantly enhanced cell migration (p < 0.001) and triggered cytoskeletal remodeling, with amplified stress fiber formation and paxillin redistribution. Molecular analysis revealed upregulation of tenogenic markers (Scleraxis, Tenomodulin) and enhanced Collagen I and III expressions, particularly with treatments at 80 mT, indicating improved matrix remodeling capacity. EMTT significantly promotes tenocyte proliferation, migration, and matrix production, while simultaneously exhibiting senolytic-like effects through downregulation of senescence-associated markers. These results support EMTT as a promising therapeutic approach for the management of tendinopathies through multiple regenerative mechanisms, though further studies are needed to validate these effects in vivo. Full article
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25 pages, 3835 KiB  
Article
A Marine-Derived Steroid from Rhodococcus sp., 3,12-Dioxochola-4,6-dien-24-oic Acid, Enhances Skin Re-Epithelialization and Tissue Repair
by Mücahit Varlı, Hui Tan, Chaeyoung Lee, Jeongyun Lee, Ji Young Lee, Jeong-Hyeon Kim, Songyi Lee, Hangun Kim and Sang-Jip Nam
Mar. Drugs 2025, 23(7), 292; https://doi.org/10.3390/md23070292 - 19 Jul 2025
Viewed by 522
Abstract
The discovery of bioactive natural compounds from microbes holds promise for regenerative medicine. In this study, we identified and characterized a steroid-like compound, 3,12-dioxochola-4,6-dien-24-oic acid (DOCDA), from a crude extract of Rhodococcus sp. DOCDA significantly promoted wound healing by enhancing HaCaT cell invasion [...] Read more.
The discovery of bioactive natural compounds from microbes holds promise for regenerative medicine. In this study, we identified and characterized a steroid-like compound, 3,12-dioxochola-4,6-dien-24-oic acid (DOCDA), from a crude extract of Rhodococcus sp. DOCDA significantly promoted wound healing by enhancing HaCaT cell invasion and migration. It upregulated key growth factors (EGF, VEGF-A, IGF, TGF-β, and HGF), indicating the activation of regenerative signaling. Additionally, DOCDA increased the expression of genes related to focal adhesion and cytoskeletal regulation (ITGB1, ITGA4, FAK, SRC, RHOA, CDC42, RAC1, and paxillin), supporting enhanced cellular motility and remodeling. Notably, DOCDA promoted stem-like properties in HaCaT cells, as shown by increased spheroid formation and elevated levels of the stemness markers ALDH1 and CD44. Target prediction and molecular docking identified the glucocorticoid receptor (GR) as the primary target of DOCDA, with a docking score of −7.7 kcal/mol. Network and pathway enrichment analysis revealed that GR-linked pathways were significantly associated with wound healing, including steroid hormone signaling, inflammation, immune responses, and cell migration. In vivo, the topical application of DOCDA led to over 70% wound closure in mice by day 5. These findings suggest that DOCDA is a steroid-like compound that accelerates wound healing and may serve as a potential agent in regenerative therapy. Full article
(This article belongs to the Section Structural Studies on Marine Natural Products)
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21 pages, 6233 KiB  
Article
Multispectral Pulsed Photobiomodulation Enhances Diabetic Wound Healing via Focal Adhesion-Mediated Cell Migration and Extracellular Matrix Remodeling
by Jihye Choi, Myung Jin Ban, Chan Hee Gil, Sung Sik Hur, Laurensia Danis Anggradita, Min-Kyu Kim, Ji Won Son, Jung Eun Kim and Yongsung Hwang
Int. J. Mol. Sci. 2025, 26(13), 6232; https://doi.org/10.3390/ijms26136232 - 27 Jun 2025
Viewed by 475
Abstract
Chronic diabetic wounds affect 15–20% of patients and are characterized by impaired healing due to disrupted hemostasis, inflammation, proliferation, and extracellular matrix (ECM) remodeling. Low-level light therapy (LLLT) has emerged as a promising noninvasive strategy for enhancing tissue regeneration. Here, we developed a [...] Read more.
Chronic diabetic wounds affect 15–20% of patients and are characterized by impaired healing due to disrupted hemostasis, inflammation, proliferation, and extracellular matrix (ECM) remodeling. Low-level light therapy (LLLT) has emerged as a promising noninvasive strategy for enhancing tissue regeneration. Here, we developed a multispectral pulsed LED system combining red and near-infrared light to stimulate wound healing. In vitro photostimulation of human keratinocytes and fibroblasts on biomimetic hydrogels enhanced adhesion, spreading, migration, and proliferation via increased focal adhesion kinase (pFAK), paxillin, and F-actin expression. In vivo, daily LED treatment of streptozotocin-induced diabetic wounds accelerated closure and improved ECM remodeling. Histological and molecular analyses revealed elevated levels of MMPs, interleukins, collagen, fibronectin, FGF2, and TGF-β1, supporting regenerative healing without excessive fibrosis. These findings demonstrate that multispectral pulsed photobiomodulation enhances diabetic wound healing through focal adhesion-mediated cell migration and ECM remodeling, offering a cost-effective and clinically translatable approach for chronic wound therapy. Full article
(This article belongs to the Special Issue Advances in Photobiomodulation Therapy)
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19 pages, 3098 KiB  
Article
SHROOM3 Deficiency Aggravates Adriamycin-Induced Nephropathy Accompanied by Focal Adhesion Disassembly and Stress Fiber Disorganization
by Li-Nan Xu, Ying-Ying Sun, Yan-Feng Tan, Xin-Yue Zhou, Tian-Chao Xiang, Ye Fang, Fei Li, Qian Shen, Hong Xu and Jia Rao
Cells 2025, 14(12), 895; https://doi.org/10.3390/cells14120895 - 13 Jun 2025
Viewed by 540
Abstract
SHROOM3 encodes an actin-binding protein involved in kidney development and has been associated with chronic kidney disease through genome-wide association studies. However, its regulatory role in proteinuric kidney diseases and its mechanistic contributions to podocyte homeostasis remain poorly defined. Here, we analyzed single-cell [...] Read more.
SHROOM3 encodes an actin-binding protein involved in kidney development and has been associated with chronic kidney disease through genome-wide association studies. However, its regulatory role in proteinuric kidney diseases and its mechanistic contributions to podocyte homeostasis remain poorly defined. Here, we analyzed single-cell transcriptomic datasets and the Nephroseq database to delineate SHROOM3 expression patterns in proteinuric kidney diseases. Using podocyte-specific SHROOM3 knockout mice and an Adriamycin (ADR)-induced nephropathy mouse model, we demonstrated that glomerular SHROOM3, specifically in podocytes, was upregulated following ADR treatment during the acute injury phase but downregulated in chronic kidney disease. Clinically, the glomerular SHROOM3 expression positively correlated with glomerular filtration rates in focal segmental glomerulosclerosis patients. Genetic ablation of SHROOM3 in podocytes exacerbated ADR-induced proteinuria, diminished podocyte markers (nephrin, podocin, and WT1), and accelerated glomerulosclerosis. In vitro, SHROOM3 deficiency impaired podocyte size and adhesion, concomitant with the downregulation of focal adhesion molecules (talin1, vinculin, and paxillin) and stress fiber regulators (synaptopodin and RhoA), as well as calpain activation and RhoA inactivation. Our findings reveal a critical role for SHROOM3 in maintaining podocyte integrity and suggest its therapeutic potential in mitigating proteinuric kidney disease progression. Full article
(This article belongs to the Special Issue Cellular and Molecular Basis in Chronic Kidney Disease)
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14 pages, 4335 KiB  
Article
Impact of Atomic Layer-Deposited Hydroxyapatite-Coated Titanium on Expression of Focal Adhesion Molecules of Human Gingival Fibroblasts
by Nagat Areid, Faleh Abushahba, Sini Riivari, Elisa Närvä, Elina Kylmäoja, Mikko Ritala, Juha Tuukkanen, Pekka K. Vallittu and Timo O. Närhi
Nanomaterials 2025, 15(12), 887; https://doi.org/10.3390/nano15120887 - 8 Jun 2025
Viewed by 551
Abstract
This study investigated the impact of the nanocrystalline atomic layer-deposited hydroxyapatite (ALD-HA) coating of titanium (Ti) surface on the attachment and proliferation of human gingival fibroblasts (HGFs). Ti discs were divided into ALD-HA-coated and non-coated (NC) controls. HGFs were harvested from gingival biopsies [...] Read more.
This study investigated the impact of the nanocrystalline atomic layer-deposited hydroxyapatite (ALD-HA) coating of titanium (Ti) surface on the attachment and proliferation of human gingival fibroblasts (HGFs). Ti discs were divided into ALD-HA-coated and non-coated (NC) controls. HGFs were harvested from gingival biopsies of patients subjected to extraction of their third molar. The cells were cultivated on the Ti discs for 2 and 24 h to evaluate the initial cell attachment using confocal microscopy. Spreading of cells and the signals of focal adhesion proteins were measured. Moreover, the adhesion proteins vinculin and paxillin expression levels were evaluated using Western blot after 3 d of cultivation. In addition, the proliferation of HGF was assessed by cultivating the cells on Ti discs for 1, 3, and 7 d. Fibroblast spreading was significantly greater on ALD-HA surfaces than on NC surfaces after 2 h (p < 0.001). In addition, the signals of vinculin and paxillin were significantly higher on the ALD-HA than on the NC surfaces at 2 and 24 h. The confocal microscope analysis also revealed significantly higher expression of focal adhesion molecules on ALD-HA surfaces at both time points. Furthermore, the cell proliferation rate was significantly higher at d 3 (p = 0.022) and d 7 (p < 0.001) on the ALD-HA compared to the NC surfaces. These findings indicate that ALD-HA coating enhances focal adhesion formation, cell spreading, and proliferation on Ti surfaces, suggesting its potential to improve gingival tissue attachment to Ti implant surfaces. Full article
(This article belongs to the Special Issue Advances in Nanotechnology for Medical Implants)
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19 pages, 5008 KiB  
Article
Targeting Ion Channels: Blockers Suppress Calcium Signals and Induce Cytotoxicity Across Medulloblastoma Cell Models
by Darani Ashley Thammavongsa, Taylor N. Jackvony, Markus J. Bookland and Min D. Tang-Schomer
Bioengineering 2025, 12(3), 268; https://doi.org/10.3390/bioengineering12030268 - 9 Mar 2025
Cited by 1 | Viewed by 1115
Abstract
Medulloblastoma (MB) groups 3 and 4 lack targeted therapies despite their dismal prognoses. Ion channels and pumps have been implicated in promoting MB metastasis and growth; however, their roles remain poorly understood. In this study, we repurposed FDA-approved channel blockers and modulators to [...] Read more.
Medulloblastoma (MB) groups 3 and 4 lack targeted therapies despite their dismal prognoses. Ion channels and pumps have been implicated in promoting MB metastasis and growth; however, their roles remain poorly understood. In this study, we repurposed FDA-approved channel blockers and modulators to investigate their potential anti-tumor effects in MB cell lines (DAOY and D283) and primary cell cultures derived from a patient with MB. For the first time, we report spontaneous calcium signaling in MB cells. Spontaneous calcium signals were significantly reduced by mibefradil (calcium channel blocker), paxilline (calcium-activated potassium channel blocker), and thioridazine (potassium channel blocker). These drugs induced dose-dependent cytotoxicity in both the DAOY and D283 cell lines, as well as in primary cell cultures of a patient with group 3 or 4 MB. In contrast, digoxin and ouabain, inhibitors of the Na/K pump, reduced the calcium signaling by over 90% in DAOY cells and induced approximately 90% cell death in DAOY cells and 80% cell death in D283 cells. However, these effects were significantly diminished in the cells derived from a patient with MB, highlighting the variability in drug sensitivity among MB models. These findings demonstrate that calcium signaling is critical for MB cell survival and that the targeted inhibition of calcium pathways suppresses tumor cell growth across multiple MB models. Full article
(This article belongs to the Special Issue Advancing Treatment for Brain Tumors)
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24 pages, 4906 KiB  
Review
Modulating PAK1: Accessory Proteins as Promising Therapeutic Targets
by Amin Mirzaiebadizi, Rana Shafabakhsh and Mohammad Reza Ahmadian
Biomolecules 2025, 15(2), 242; https://doi.org/10.3390/biom15020242 - 7 Feb 2025
Viewed by 1407
Abstract
The p21-activated kinase (PAK1), a serine/threonine protein kinase, is critical in regulating various cellular processes, including muscle contraction, neutrophil chemotaxis, neuronal polarization, and endothelial barrier function. Aberrant PAK1 activity has been implicated in the progression of several human diseases, including cancer, heart disease, [...] Read more.
The p21-activated kinase (PAK1), a serine/threonine protein kinase, is critical in regulating various cellular processes, including muscle contraction, neutrophil chemotaxis, neuronal polarization, and endothelial barrier function. Aberrant PAK1 activity has been implicated in the progression of several human diseases, including cancer, heart disease, and neurological disorders. Increased PAK1 expression is often associated with poor clinical prognosis, invasive tumor characteristics, and therapeutic resistance. Despite its importance, the cellular mechanisms that modulate PAK1 function remain poorly understood. Accessory proteins, essential for the precise assembly and temporal regulation of signaling pathways, offer unique advantages as therapeutic targets. Unlike core signaling components, these modulators can attenuate aberrant signaling without completely abolishing it, potentially restoring signaling to physiological levels. This review highlights PAK1 accessory proteins as promising and novel therapeutic targets, opening new horizons for disease treatment. Full article
(This article belongs to the Special Issue Cellular Signaling in Cancer)
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25 pages, 1337 KiB  
Review
Paxillin and Kindlin: Research Progress and Biological Functions
by Zijian Li, Ruonan Shao, Honglei Xin, Yilin Zhu, Suyu Jiang, Jiao Wu, Han Yan, Tongyu Jia, Mengyu Ge and Xiaofeng Shi
Biomolecules 2025, 15(2), 173; https://doi.org/10.3390/biom15020173 - 24 Jan 2025
Viewed by 1891
Abstract
Paxillin and kindlin are essential regulatory proteins involved in cell adhesion, migration, and signal transduction. Paxillin influences cytoskeletal dynamics by interacting with multiple signaling proteins, while kindlin regulates integrin activation, affecting adhesion and motility. This review examines the structures and functions of these [...] Read more.
Paxillin and kindlin are essential regulatory proteins involved in cell adhesion, migration, and signal transduction. Paxillin influences cytoskeletal dynamics by interacting with multiple signaling proteins, while kindlin regulates integrin activation, affecting adhesion and motility. This review examines the structures and functions of these proteins, focusing on their roles in cancer progression, immune response, and therapeutic potential. The cooperation between paxillin and kindlin in integrin activation and focal adhesion dynamics offers valuable insights into tumor metastasis, immune function, and tissue repair. Full article
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14 pages, 2853 KiB  
Article
Dysregulation of Podocyte BK Channels and Nephrosis: Effects of Circulating Factors and Auxiliary β4 Subunits
by Eun Young Kim, Patrycja Rachubik and Stuart E. Dryer
Cells 2025, 14(1), 22; https://doi.org/10.3390/cells14010022 - 30 Dec 2024
Cited by 1 | Viewed by 913
Abstract
Podocytes express large-conductance Ca2+-activated K+ channels (BK channels) and at least two different pore-forming KCa1.1 subunit C-terminal splice variants, known as VEDEC and EMVYR, along with auxiliary β and γ subunits. Podocyte KCa1.1 subunits interact directly with TRPC6 channels and [...] Read more.
Podocytes express large-conductance Ca2+-activated K+ channels (BK channels) and at least two different pore-forming KCa1.1 subunit C-terminal splice variants, known as VEDEC and EMVYR, along with auxiliary β and γ subunits. Podocyte KCa1.1 subunits interact directly with TRPC6 channels and BK channels become active in response to Ca2+ influx through TRPC6. Here, we confirmed that Ca2+ influx through TRPC channels is reduced following the blockade of BK channels by paxilline. The overall abundance of KCa1.1 subunits, as well as that of β4 and γ3 subunits, were increased in glomeruli isolated from Sprague Dawley rats during chronic puromycin aminonucleoside (PAN) nephrosis. Exposing cultured mouse podocytes for 24 h to recombinant TNFα, a circulating factor implicated in pediatric nephrotic syndromes, did not affect the total abundance of KCa1.1, but did evoke significant increases in both β4 and γ3. However, TNFα evoked a marked increase in the surface abundance of KCa1.1 subunits, similar to that of its previously reported effects on TRPC6 channels. The effect of TNFα on the surface expression of KCa1.1 was eliminated following siRNA knockdown of the β4 subunits, suggesting a role for this subunit in KCa1.1 trafficking to the cell surface. By contrast, treating podocytes with suPAR did not affect the total or surface expression of KCa1.1. The coordinated activation of KCa1.1 channels may promote Ca2+ influx through TRPC channels during normal and abnormal podocyte function by maintaining a membrane potential that allows for the efficient permeation of divalent cations through TRPC pores. Full article
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15 pages, 6275 KiB  
Article
O-GlcNAcylation of Focal Adhesion Kinase Regulates Cell Adhesion, Migration, and Proliferation via the FAK/AKT Pathway
by Zhiwei Zhang, Tomoya Isaji, Yoshiyuki Oyama, Jianwei Liu, Zhiwei Xu, Yuhan Sun, Tomohiko Fukuda, Haojie Lu and Jianguo Gu
Biomolecules 2024, 14(12), 1577; https://doi.org/10.3390/biom14121577 - 10 Dec 2024
Cited by 2 | Viewed by 1654
Abstract
Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase pivotal in cellular signal transduction, regulating cell adhesion, migration, growth, and survival. However, the regulatory mechanisms of FAK during tumorigenesis and progression still need to be fully understood. Our previous study demonstrated that O [...] Read more.
Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase pivotal in cellular signal transduction, regulating cell adhesion, migration, growth, and survival. However, the regulatory mechanisms of FAK during tumorigenesis and progression still need to be fully understood. Our previous study demonstrated that O-GlcNAcylation regulates integrin-mediated cell adhesion. To further elucidate the underlying molecular mechanism, we focused on FAK in this study and purified it from 293T cells. Using liquid chromatography–mass spectrometry (LC-MS/MS), we identified the O-GlcNAcylation of FAK at Ser708, Thr739, and Ser886. Compared with wild-type FAK expressed in FAK-knockout 293T cells, the FAK mutant, in which Ser708, Thr739, and Ser886 were replaced with Ala, exhibited lower phosphorylation levels of Tyr397 and AKT. Cell proliferation and migration, assessed through MTT and wound healing assays, were significantly suppressed in the FAK mutant cells compared to the wild-type FAK cells. Additionally, the interaction among FAK, paxillin, and talin was enhanced, and cell adhesion was increased in the mutant cells. These data indicate that specific O-GlcNAcylation of FAK plays a critical regulatory role in integrin-mediated cell adhesion and migration. This further supports the idea that O-GlcNAcylation is essential for tumorigenesis and progression and that targeting the O-GlcNAcylation of FAK could offer a promising therapeutic strategy for cancer treatment. Full article
(This article belongs to the Section Biomacromolecules: Carbohydrates)
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20 pages, 18147 KiB  
Article
CD38 Inhibitor 78c Attenuates Pro-Inflammatory Cytokine Expression and Osteoclastogenesis in Macrophages
by William Lory, Nityananda Chowdhury, Bridgette Wellslager, Subramanya Pandruvada, Yan Huang, Özlem Yilmaz and Hong Yu
Cells 2024, 13(23), 1971; https://doi.org/10.3390/cells13231971 - 28 Nov 2024
Cited by 2 | Viewed by 1808
Abstract
CD38, a nicotinamide adenine dinucleotide (NAD+) glycohydrolase, increases during infection or inflammation. Therefore, we aimed to evaluate the effects of a CD38 inhibitor (78c) on NAD+ levels, IL-1β, IL-6, TNF-α cytokine expressions, and osteoclastogenesis. The results show that treatment with [...] Read more.
CD38, a nicotinamide adenine dinucleotide (NAD+) glycohydrolase, increases during infection or inflammation. Therefore, we aimed to evaluate the effects of a CD38 inhibitor (78c) on NAD+ levels, IL-1β, IL-6, TNF-α cytokine expressions, and osteoclastogenesis. The results show that treatment with 78c on murine BMMs dose-dependently reduced CD38, reversed the decline of NAD+, and inhibited IL-1β, IL-6, and TNF-α pro-inflammatory cytokine levels induced by oral pathogen Porphyromonas gingivalis (Pg) or Aggregatibacter actinomycetemcomitans (Aa) or by advanced glycation end products (AGEs). Additionally, treatment with 78c dose-dependently suppressed osteoclastogenesis and bone resorption induced by RANKL. Treatment with 78c suppressed CD38, nuclear factor kappa-B (NF-κB), phosphoinositide 3-kinase (PI3K), and mitogen-activated protein kinases (MAPKs) induced by Pg, Aa, or AGEs, and suppressed podosome components (PI3K, Pyk2, Src, F-actin, integrins, paxillin, and talin) induced by RANKL. These results from our studies support the finding that the inhibition of CD38 by 78c is a promising therapeutic strategy to treat inflammatory bone loss diseases. However, treatment with a CD38 shRNA only significantly reduced IL-1β, IL-6, and TNF-α pro-inflammatory cytokine levels induced by AGEs. Compared with controls, it had limited effects on cytokine levels induced by Pg or Aa. Treatment with the CD38 shRNA enhanced RANKL-induced osteoclastogenesis, suggesting that 78c has some off-target effects. Full article
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13 pages, 3283 KiB  
Article
Laser Emission at 675 nm: Molecular Counteraction of the Aging Process
by Lorenzo Notari, Laura Pieri, Francesca Cialdai, Irene Fusco, Chiara Risaliti, Francesca Madeddu, Stefano Bacci, Tiziano Zingoni and Monica Monici
Biomedicines 2024, 12(12), 2713; https://doi.org/10.3390/biomedicines12122713 - 27 Nov 2024
Cited by 2 | Viewed by 1198
Abstract
Background/Objectives: Many lasers applied in skin rejuvenation protocols show emissions with wavelengths falling in the red or near-infrared (NIR) bands. To obtain further in vitro data on the potential therapeutic benefits regarding rejuvenation, we employed a 675 nm laser wavelength on cultured human [...] Read more.
Background/Objectives: Many lasers applied in skin rejuvenation protocols show emissions with wavelengths falling in the red or near-infrared (NIR) bands. To obtain further in vitro data on the potential therapeutic benefits regarding rejuvenation, we employed a 675 nm laser wavelength on cultured human dermal fibroblasts to understand the mechanisms involved in the skin rejuvenation process’s signaling pathways by analyzing cytoskeletal proteins, extracellular matrix (ECM) components, and membrane integrins. Methods: Normal human dermal fibroblasts (NHDFs) were irradiated with a 675 nm laser 24 h after seeding, and immunofluorescence microscopy and Western blotting were applied. Results: The results demonstrate that the laser treatment induces significant changes in human dermal fibroblasts, affecting cytoskeleton organization and the production and reorganization of ECM molecules. The cell response to the treatment appears to predominantly involve paxillin-mediated signaling pathways. Conclusions: These changes suggest that laser treatment can potentially improve the structure and function of skin tissue, with interesting implications for treating skin aging. Full article
(This article belongs to the Special Issue Photodynamic Therapy (3rd Edition))
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13 pages, 2497 KiB  
Article
Yohimbine Inhibits PDGF-Induced Vascular Smooth Muscle Cell Proliferation and Migration via FOXO3a Factor
by Leejin Lim, Hyeonhwa Kim, Jihye Jeong, Sung Hee Han, Young-Bob Yu and Heesang Song
Int. J. Mol. Sci. 2024, 25(13), 6899; https://doi.org/10.3390/ijms25136899 - 24 Jun 2024
Cited by 2 | Viewed by 1846
Abstract
Yohimbine (YHB) has been reported to possess anti-inflammatory, anticancer, and cardiac function-enhancing properties. Additionally, it has been reported to inhibit the proliferation, migration, and neointimal formation of vascular smooth muscle cells (VSMCs) induced by platelet-derived growth factor (PDGF) stimulation by suppressing the phospholipase [...] Read more.
Yohimbine (YHB) has been reported to possess anti-inflammatory, anticancer, and cardiac function-enhancing properties. Additionally, it has been reported to inhibit the proliferation, migration, and neointimal formation of vascular smooth muscle cells (VSMCs) induced by platelet-derived growth factor (PDGF) stimulation by suppressing the phospholipase C-gamma 1 pathway. However, the transcriptional regulatory mechanism of YHB controlling the behavior of VSMCs is not fully understood. In this study, YHB downregulated the expression of cell cycle regulatory proteins, such as proliferating cell nuclear antigen (PCNA), cyclin D1, cyclin-dependent kinase 4 (CDK4), and cyclin E, by modulating the transcription factor FOXO3a in VSMCs induced by PDGF. Furthermore, YHB decreased p-38 and mTOR phosphorylation in a dose-dependent manner. Notably, YHB significantly reduced the phosphorylation at Y397 and Y925 sites of focal adhesion kinase (FAK), and this effect was greater at the Y925 site than Y397. In addition, the expression of paxillin, a FAK-associated protein known to bind to the Y925 site of FAK, was significantly reduced by YHB treatment in a dose-dependent manner. A pronounced reduction in the migration and proliferation of VSMCs was observed following co-treatment of YHB with mTOR or p38 inhibitors. In conclusion, this study shows that YHB inhibits the PDGF-induced proliferation and migration of VSMCs by regulating the transcription factor FOXO3a and the mTOR/p38/FAK signaling pathway. Therefore, YHB may be a potential therapeutic candidate for preventing and treating cardiovascular diseases such as atherosclerosis and vascular restenosis. Full article
(This article belongs to the Section Biochemistry)
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15 pages, 3798 KiB  
Article
α-Catenin and Piezo1 Mediate Cell Mechanical Communication via Cell Adhesions
by Mingxing Ouyang, Qingyu Zhang, Yiming Zhu, Mingzhi Luo, Bing Bu and Linhong Deng
Biology 2024, 13(5), 357; https://doi.org/10.3390/biology13050357 - 19 May 2024
Viewed by 2015
Abstract
Cell-to-cell distant mechanical communication has been demonstrated using in vitro and in vivo models. However, the molecular mechanisms underlying long-range cell mechanoresponsive interactions remain to be fully elucidated. This study further examined the roles of α-Catenin and Piezo1 in traction force-induced rapid branch [...] Read more.
Cell-to-cell distant mechanical communication has been demonstrated using in vitro and in vivo models. However, the molecular mechanisms underlying long-range cell mechanoresponsive interactions remain to be fully elucidated. This study further examined the roles of α-Catenin and Piezo1 in traction force-induced rapid branch assembly of airway smooth muscle (ASM) cells on a Matrigel hydrogel containing type I collagen. Our findings demonstrated that siRNA-mediated downregulation of α-Catenin or Piezo1 expression or chemical inhibition of Piezo1 activity significantly reduced both directional cell movement and branch assembly. Regarding the role of N-cadherin in regulating branch assembly but not directional migration, our results further confirmed that siRNA-mediated downregulation of α-Catenin expression caused a marked reduction in focal adhesion formation, as assessed by focal Paxillin and Integrin α5 localization. These observations imply that mechanosensitive α-Catenin is involved in both cell–cell and cell-matrix adhesions. Additionally, Piezo1 partially localized in focal adhesions, which was inhibited by siRNA-mediated downregulation of α-Catenin expression. This result provides insights into the Piezo1-mediated mechanosensing of traction force on a hydrogel. Collectively, our findings highlight the significance of α-Catenin in the regulation of cell-matrix interactions and provide a possible interpretation of Piezo1-mediated mechanosensing activity at focal adhesions during cell–cell mechanical communication. Full article
(This article belongs to the Section Cell Biology)
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19 pages, 9910 KiB  
Article
Quercetin Induces Mitochondrial Apoptosis and Downregulates Ganglioside GD3 Expression in Melanoma Cells
by Sang Young Seo, Won Seok Ju, Kyongtae Kim, Juhwan Kim, Jin Ok Yu, Jae-Sung Ryu, Ji-Su Kim, Hyun-A Lee, Deog-Bon Koo and Young-Kug Choo
Int. J. Mol. Sci. 2024, 25(10), 5146; https://doi.org/10.3390/ijms25105146 - 9 May 2024
Cited by 8 | Viewed by 2077
Abstract
Malignant melanoma represents a form of skin cancer characterized by a bleak prognosis and heightened resistance to traditional therapies. Quercetin has demonstrated notable anti-carcinogenic, anti-inflammatory, anti-oxidant, and pharmacological effects across various cancer types. However, the intricate relationship between quercetin’s anti-cancer properties and ganglioside [...] Read more.
Malignant melanoma represents a form of skin cancer characterized by a bleak prognosis and heightened resistance to traditional therapies. Quercetin has demonstrated notable anti-carcinogenic, anti-inflammatory, anti-oxidant, and pharmacological effects across various cancer types. However, the intricate relationship between quercetin’s anti-cancer properties and ganglioside expression in melanoma remains incompletely understood. In this study, quercetin manifests specific anti-proliferative, anti-migratory, and cell-cycle arrest effects, inducing mitochondrial dysfunction and apoptosis in two melanoma cancer cell lines. This positions quercetin as a promising candidate for treating malignant melanoma. Moreover, our investigation indicates that quercetin significantly reduces the expression levels of ganglioside GD3 and its synthetic enzyme. Notably, this reduction is achieved through the inhibition of the FAK/paxillin/Akt signaling pathway, which plays a crucial role in cancer development. Taken together, our findings suggest that quercetin may be a potent anti-cancer drug candidate for the treatment of malignant melanoma. Full article
(This article belongs to the Section Molecular Oncology)
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