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Search Results (357)

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Keywords = p16/INK4a

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23 pages, 7598 KB  
Article
Molecular Remodeling of Peritumoral Tissue in Clear Cell Renal Cell Carcinoma: Insights into Inflammaging and Prognostic Markers
by Giuseppe Stefano Netti, Federica Spadaccino, Giuseppe Lucarelli, Valeria Catalano, Andrea Checchia, Alessandra Stasi, Federica De Luca, Valentina Camporeale, Giorgia Leccese, Roberto Cuttano, Dario Troise, Barbara Infante, Giuseppe Carrieri, Walter J. Storkus, Giovanni Stallone and Elena Ranieri
Cancers 2026, 18(3), 414; https://doi.org/10.3390/cancers18030414 (registering DOI) - 28 Jan 2026
Abstract
Background/Objectives: Renal cell carcinoma (RCC) is a common and often asymptomatic malignancy with limited treatment options for advanced stages. Chronic inflammation and cellular senescence—collectively termed “inflammaging”—are emerging as key contributors to tumor progression. This study aimed to investigate the expression of inflammaging-related [...] Read more.
Background/Objectives: Renal cell carcinoma (RCC) is a common and often asymptomatic malignancy with limited treatment options for advanced stages. Chronic inflammation and cellular senescence—collectively termed “inflammaging”—are emerging as key contributors to tumor progression. This study aimed to investigate the expression of inflammaging-related markers in RCC tissues, focusing on the role of PTX3, IL-6, and senescence-associated proteins in the tumor microenvironment. Methods: A retrospective cohort of 57 patients with clear cell RCC who underwent nephrectomy was analyzed. Formalin-fixed paraffin-embedded samples from tumor, peritumoral, and normal renal tissues were examined using confocal immunofluorescence microscopy to assess PTX3, IL-6, p21, and p16 expression. Senescence-associated β-galactosidase staining was performed to identify senescent cells. Serum IL-6 levels were measured by ELISA, and survival analysis was conducted using Kaplan–Meier curves and Cox regression analysis. Results: PTX3 and IL-6 were significantly upregulated in both peritumoral and tumor tissues compared to normal kidney samples (p < 0.001). Expression of senescence markers p21 and p16 were elevated in peritumoral areas (p < 0.001) as compared to normal renal tissues, but their expression was reduced or absent in the tumor core. High-grade and high-stage tumors exhibited stronger PTX3 and IL-6 expression and lower levels of cell cycle inhibitors (p < 0.001). Patients with elevated serum IL-6 levels had significantly lower 5-year cancer-specific survival (p < 0.005) and shorter progression-free survival (p < 0.001). Conclusions: Our findings suggest that peritumoral tissue in RCC exhibits a senescent and proinflammatory phenotype that may support tumor progression. PTX3 and IL-6 are potential biomarkers of disease severity and prognosis. Targeting inflammaging pathways could offer new therapeutic strategies for RCC, particularly in aggressive disease forms. Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
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15 pages, 3299 KB  
Article
Oil-Coated Bubble Flotation for Separating Hydrophilic Particles from Water
by Songcheng Wang, Xue Zong, Xiaotang Du, Sven H. Behrens and J. Carson Meredith
Recycling 2026, 11(1), 12; https://doi.org/10.3390/recycling11010012 - 9 Jan 2026
Viewed by 207
Abstract
Froth flotation is a widely used method for the selective separation of particulates from aqueous dispersions or slurries. This technology is based on the attachment of sufficiently hydrophobic particles to the air–water interface of gas bubbles. However, when the target particles are strongly [...] Read more.
Froth flotation is a widely used method for the selective separation of particulates from aqueous dispersions or slurries. This technology is based on the attachment of sufficiently hydrophobic particles to the air–water interface of gas bubbles. However, when the target particles are strongly hydrophilic, the requirement of hydrophobicity limits the effectiveness of conventional froth flotation. A prominent example is the deinking step in paper recycling, where modern hydrophilic inkjet inks are difficult to remove by flotation. In this study, we evaluated oil-coated bubble flotation as an alternative to conventional air flotation for removing inkjet ink from pulped newsprint. We examined the effects of oil type, salt type and concentration, and pH on deinking efficiency. Compared with traditional air flotation, oil-coated bubble flotation produced substantial improvements in standard performance metrics, including ISO brightness, effective residual ink concentration (ERIC), and the fiber retention of recycled paper pads. Full article
(This article belongs to the Topic Converting and Recycling of Waste Materials)
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19 pages, 3591 KB  
Article
Comparison of the Effectiveness of Paper Strengthening with Gelatin, Klucel G, and Tylose Solutions in Combination with Deacidification Using Magnesium Hydroxide Nanoparticles
by Renata Wojech, Aleksandra Kwiatkowska, Grzegorz Cofta and Adam Wójciak
Materials 2026, 19(1), 126; https://doi.org/10.3390/ma19010126 - 30 Dec 2025
Viewed by 220
Abstract
The manuscript concerns modern methods of preserving historical papers and presents research focusing on the effectiveness of paper strengthening with gelatin, Klucel G, and Tylose solutions in combination with deacidification using magnesium hydroxide nanoparticles. The aim of these procedures is to extend the [...] Read more.
The manuscript concerns modern methods of preserving historical papers and presents research focusing on the effectiveness of paper strengthening with gelatin, Klucel G, and Tylose solutions in combination with deacidification using magnesium hydroxide nanoparticles. The aim of these procedures is to extend the durability of historical records on papers, which are an important part of humanity’s cultural heritage. Gelatin and Klucel G dissolved in propyl alcohol were used simultaneously with the dispersion of Mg(OH)2 nanoparticles, and Tylose dissolved in water was applied after deacidification in a separate step. The experiments were conducted on Whatman model papers, artificially acidified or covered with iron gall ink. The evaluation of the effectiveness was based on tests of breaking length, changes in the DPvisc of cellulose, and pH of the aqueous extracts. Additional information was provided by microscopic examinations (SEM-EDX-SE) and measurements of the optical properties of the tested papers before and after the application of strengthening agents. All the strengthening agents tested increased paper strength—Tylose to the greatest extent, followed by Gelatin, and Klucel G to the least extent. Model papers covered with Klucel G showed good dimensional stability. Gelatin-covered papers showed the greatest changes in optical properties. Full article
(This article belongs to the Section Advanced Nanomaterials and Nanotechnology)
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11 pages, 2753 KB  
Article
Impact of 3D-Printed Tricalcium Phosphate Scaffold Polymorphism and Post-Processing Variations on Bone Regenerative Outcomes
by Nicholas Jose Iglesias, Sara E. Munkwitz, Hana Shah, Savanah R. Sturm, Nicholas A. Mirsky, Adriana I. Sandino, Ricky Almada, Vasudev Vivekanand Nayak, Lukasz Witek and Paulo G. Coelho
Bioengineering 2026, 13(1), 34; https://doi.org/10.3390/bioengineering13010034 - 28 Dec 2025
Viewed by 367
Abstract
Tricalcium phosphate (TCP) bioceramics, available as α- and β-polymorphs, are frequently employed in the production of three-dimensionally (3D) printed bone scaffolds. Although hydrothermal immersion processing (HP) and sintering (S) are commonly adopted as post-printing techniques for bioceramics, a comprehensive comparative analysis of their [...] Read more.
Tricalcium phosphate (TCP) bioceramics, available as α- and β-polymorphs, are frequently employed in the production of three-dimensionally (3D) printed bone scaffolds. Although hydrothermal immersion processing (HP) and sintering (S) are commonly adopted as post-printing techniques for bioceramics, a comprehensive comparative analysis of their effects on the osteogenic performance of α- and β-polymorphs in vivo remains inadequately investigated. In this study, α-TCP and β-TCP scaffolds were fabricated via direct ink writing and subjected to hydrothermal immersion processing (α-TCP/HP) and sintering (β-TCP/S) prior to implantation in n = 12 skeletally mature sheep (n = 1 scaffold per group per animal), and the outcome variables were evaluated at 3 and 12 weeks postoperatively (n = 6 sheep per time point). The quantitative results showed no significant differences in bone deposition or scaffold resorption at 3 weeks postoperatively (p = 0.618 and p = 0.898, respectively). However, at 12 weeks, there was a significant increase in osteogenesis and scaffold resorption in the β-TCP/S cohort relative to the α-TCP/HP counterparts (p < 0.001 and p = 0.004, respectively). β-TCP scaffolds subjected to post-print sintering exhibited superior osteoconductive and resorptive profiles compared to hydrothermal immersion-processed α-TCP scaffolds over the 12-week healing period. Full article
(This article belongs to the Section Biomedical Engineering and Biomaterials)
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17 pages, 6202 KB  
Article
Three-Dimensional Printing of Calcium Phosphate-Mesoporous Bioactive Glass Scaffolds for Bone Tissue Engineering
by Ana Beatriz Gomes de Carvalho, Lais Medeiros Cardoso, Igor Paulino Mendes Soares, Joyce Rodrigues de Souza, Arpita Roy, Prabaha Sikder, Aldo R. Boccaccini, Eliandra de Sousa Trichês and Marco C. Bottino
J. Funct. Biomater. 2025, 16(12), 463; https://doi.org/10.3390/jfb16120463 - 16 Dec 2025
Cited by 1 | Viewed by 1627
Abstract
Calcium phosphate cements (CPCs) and biomaterials, such as mesoporous bioactive glass (MBG), are critical for bone tissue engineering. This study aimed to 3D-print CPC scaffolds modified with MBG to enhance their osteogenic potential and regenerative ability. MBG powder was synthesized and characterized using [...] Read more.
Calcium phosphate cements (CPCs) and biomaterials, such as mesoporous bioactive glass (MBG), are critical for bone tissue engineering. This study aimed to 3D-print CPC scaffolds modified with MBG to enhance their osteogenic potential and regenerative ability. MBG powder was synthesized and characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD), and nitrogen adsorption–desorption techniques. A commercial CPC ink (hydroxyapatite/α-tricalcium phosphate) was mixed with 5% MBG (w/w; CPC/MBG), and, after rheological assessment, the mixture was used to obtain scaffolds via 3D printing. These scaffolds were then tested for chemical, morphological, and mechanical properties, as well as ion release analysis. Unmodified CPC 3D-printed scaffolds served as controls. Biological experiments, including cell viability, DNA content, cell adhesion/spreading, and osteogenic gene expression, were performed by seeding alveolar bone-derived mesenchymal stem cells onto the scaffolds. Statistics were performed using Student’s t-test and ANOVA with post hoc tests (α = 5%). MBG characterization showed a typical mesoporous structure with aligned microchannels and an amorphous structure. Both formulations released calcium and phosphate ions; however, CPC/MBG also released silicon. Cell viability, adhesion/spreading, and DNA content were significantly greater in CPC/MBG scaffolds compared to CPC (p < 0.05) after 3 and 7 days of culture. Furthermore, CPC/MBG supported increased expression of key osteogenic genes, including collagen (COL1A1), osteocalcin (OCN), and Runt-related transcription factor 2 (RUNX2), after 14 days (p < 0.05). The combination of CPC ink with MBG particles effectively enhances the biocompatibility and osteogenic potential of the scaffold, making it an innovative bioceramic ink formulation for 3D printing personalized scaffolds for bone regeneration. Full article
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24 pages, 787 KB  
Review
Fundamentals and Functional Applications of 3D and 4D Printing in Food Manufacturing
by Ezequiel José Pérez-Monterroza, Ana María Chaux-Gutiérrez, Márcia Regina de Moura and Fauze Ahmad Aouada
Processes 2025, 13(12), 4043; https://doi.org/10.3390/pr13124043 - 14 Dec 2025
Viewed by 890
Abstract
This review analyzes the critical interdependence among the three key components—ink formulation, printing process parameters, and post-processing—in Three-dimensional (3D) Food Printing (3DFP) and Four-dimensional (4D) Food Printing (4DFP). While extensive research addresses individual phases, a significant opportunity remains to integrate these three pillars [...] Read more.
This review analyzes the critical interdependence among the three key components—ink formulation, printing process parameters, and post-processing—in Three-dimensional (3D) Food Printing (3DFP) and Four-dimensional (4D) Food Printing (4DFP). While extensive research addresses individual phases, a significant opportunity remains to integrate these three pillars systematically to bridge the gap between initial design and final product viability. The analysis reveals that successful 3D printing demands a formulation optimized to resist thermal and mechanical stresses; thus, printability assessments must be extended to include post-processing stability. Conversely, 4D printing intentionally exploits this relationship, utilizing post-processing (e.g., heat or pH) as a strategic trigger to activate programmed deformation. Joint optimization of formulation, printed food microstructure, and final post-processing stages is necessary to produce foods with the desired final quality. Full article
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15 pages, 1932 KB  
Article
SpyCatcher-Multiplicity Tunes Nanoscaffold Hydrogels for Enhanced Catalysis of Regulated Enzymes
by Xue Yin, Bei Liao, Hui Li, Ming-Yue Huang and Fu-Xing Niu
Processes 2025, 13(12), 4009; https://doi.org/10.3390/pr13124009 - 11 Dec 2025
Viewed by 318
Abstract
This study presents a strategy for enhancing hydrogel formation through SpyCatcher-mediated conjugation of nanoscale scaffold proteins. We demonstrate that SpyCatcher can facilitate hydrogel assembly with various nano-scaffolds of diverse structural configurations. By conjugating one, two, or three SpyCatcher units to the P9 protein [...] Read more.
This study presents a strategy for enhancing hydrogel formation through SpyCatcher-mediated conjugation of nanoscale scaffold proteins. We demonstrate that SpyCatcher can facilitate hydrogel assembly with various nano-scaffolds of diverse structural configurations. By conjugating one, two, or three SpyCatcher units to the P9 protein nanoscaffold, hydrogel yield was substantially increased, allowing for the simultaneous co-immobilization of a larger number of enzymes. Characterization using cell-free biosynthesis, electron microscopy, and rheological analysis revealed that the resulting SpyCatcher-mediated nanoscaffold hydrogels exhibit soft solid-like behavior, high elasticity, and an “ink-bottle” pore morphology, which collectively promote and regulate enzymatic activity. Notably, hydrogels crosslinked via the P9 scaffold with two SpyCatcher units showed the most balanced properties, leading to a 149% increase in pyruvic acid production. These findings not only advance the efficient design of hydrogels for enzyme co-immobilization but also provide a foundation for developing more sophisticated models and expanding the scope of biocatalytic systems. Full article
(This article belongs to the Section Materials Processes)
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67 pages, 8757 KB  
Review
Chemical Transformations and Papermaking Potential of Recycled Secondary Cellulose Fibers for Circular Sustainability
by Corina-Iuliana Pătrăucean-Patrașcu, Dan-Alexandru Gavrilescu and Maria Gavrilescu
Appl. Sci. 2025, 15(24), 13034; https://doi.org/10.3390/app152413034 - 10 Dec 2025
Viewed by 1186
Abstract
The papermaking and recycling industries face increasing demands to improve efficiency, product quality, and environmental performance under conditions of water closure and high furnish variability. This study presents a comprehensive assessment of process control and management strategies for optimizing fines behavior, retention and [...] Read more.
The papermaking and recycling industries face increasing demands to improve efficiency, product quality, and environmental performance under conditions of water closure and high furnish variability. This study presents a comprehensive assessment of process control and management strategies for optimizing fines behavior, retention and fixation efficiency, de-inking performance, and ash balance in modern papermaking systems. The surface chemistry of fines was found to play a pivotal role in regulating charge distribution, additive demand, and drainage behavior, acting both as carriers and sinks for dissolved and colloidal substances. Results show that light, targeted refining enhances external fibrillation and produces beneficial fines that strengthen fiber bonding, while excessive refining generates detrimental fines and impairs drainage. Sequential retention programs involving polyamines, polyaluminum compounds, and microparticle systems significantly improve fines capture and drainage stability when operated under controlled pH and ionic strength. In recycling operations, optimized flotation conditions coupled with detackifiers and mineral additives such as talc effectively reduce micro-stickies formation and deposition risks. Ash management strategies based on partial purge and coordinated filler make-up maintain bonding, optical properties, and energy efficiency. Overall, the findings emphasize the need for an integrated wet-end management framework combining chemical, mechanical, and operational controls. Perspectives for future development include the application of biodegradable additives, nanocellulose-based reinforcements, and data-driven optimization tools to achieve sustainable, high-performance paper manufacturing. Full article
(This article belongs to the Section Chemical and Molecular Sciences)
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21 pages, 6640 KB  
Article
The Effect of 2′-Fucosyllactose on Gut Health in Aged Mice
by Songsong Jiang, Yang Li, Tingting Luo, Yutong Huang, Huilian Che, Jinzhu Pang and Xiangren Meng
Foods 2025, 14(24), 4184; https://doi.org/10.3390/foods14244184 - 5 Dec 2025
Viewed by 492
Abstract
This study aimed to explore the effect of 2′-Fucosyllactose (2′-FL) on the gut health of aged mice. The results revealed that 2′-FL intervention effectively improved the intestinal permeability and reduced the serum diamine oxidase (DAO) level in aged mice (p < 0.05); [...] Read more.
This study aimed to explore the effect of 2′-Fucosyllactose (2′-FL) on the gut health of aged mice. The results revealed that 2′-FL intervention effectively improved the intestinal permeability and reduced the serum diamine oxidase (DAO) level in aged mice (p < 0.05); in addition, 2′-FL increased the IgA level and decreased the IgG level (p < 0.05). Meanwhile, 2′-FL reduced the serum levels of IL-6, IL-1β, TNF-α, and IFN-γ (p < 0.05). Histopathological analysis indicated that 2′-FL successfully reversed intestinal damage in the jejunum and colon. Additionally, 2′-FL increased the expression of the tight-junction proteins ZO-1 and Claudin-1 both at mRNA and protein levels (p < 0.05), and also down-regulated the expression of pro-inflammatory factors (IL-6, IL-1β) (p < 0.05), and decreased aging-related markers P16INK4α and P21Cip1. Furthermore, 16S rRNA results showed that 2′-FL increased the relative abundance of beneficial bacteria in the gut, such as Lachnospiraceae_UCG-006, norank_f__Muribaculaceae and Lachnospiraceae_NK4A136_group. In conclusion, 2′-FL effectively improved the intestinal immune health of the aged mice and provided a theoretical basis for its application as a functional component in the treatment of intestinal diseases. Full article
(This article belongs to the Section Food Nutrition)
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23 pages, 9803 KB  
Article
Metformin Mitigates Diabetes-Driven Renal Senescence via Immunomodulation and the FABP4/FOXO1 Axis
by Nawal M. Alrasheed, Lama A. Almuthanbi, Rana R. Alotaibi, Asma S. Alonazi, Maha A. Alamin, Tahani K. Alshammari, Dalal A. Alkhelb, Anfal F. Bin Dayel, Hatun A. Alomar, Doaa M. Elnagar and Nouf M. Alrasheed
Pharmaceuticals 2025, 18(12), 1834; https://doi.org/10.3390/ph18121834 - 1 Dec 2025
Viewed by 647
Abstract
Background: Diabetic nephropathy (DN) accelerates renal aging through chronic inflammation and metabolic dysregulation; however, the role of metformin in this process remains incompletely understood. This study investigated whether metformin attenuates diabetes-driven renal senescence through the modulation of the fatty acid-binding protein 4 (FABP4)/forkhead [...] Read more.
Background: Diabetic nephropathy (DN) accelerates renal aging through chronic inflammation and metabolic dysregulation; however, the role of metformin in this process remains incompletely understood. This study investigated whether metformin attenuates diabetes-driven renal senescence through the modulation of the fatty acid-binding protein 4 (FABP4)/forkhead box protein O1 (FOXO1) axis and key immunometabolic enzymes. Methods: Thirty-two male Wistar rats were divided into healthy and diabetic groups and treated with either saline or metformin (200 mg/kg) for 10 weeks. Type 2 diabetes was induced by multiple low doses of streptozotocin (30 mg/kg, intraperitoneally) and high-fat diet. Renal function indices, lipid profile, inflammatory cytokines, succinate dehydrogenase (SDH), ATP-citrate lyase (ACLY), and senescence markers were measured, while FABP4 and FOXO1 expression, macrophage infiltration, and kidney histology were assessed using immunoassays and microscopy. Results: Metformin considerably reduced serum creatinine, urea, and blood urea nitrogen; normalized the lipid profile; suppressed interleukin (IL)-6 and tumor necrosis factor-α; and increased IL-10 levels. Additionally, it reversed DN-associated alterations in SDH and ACLY; downregulated FABP4, FOXO1, and P16INK4a; decreased macrophage infiltration; promoted M2 polarization; and improved renal architecture. Conclusions: This study is the first to demonstrate that metformin mitigates diabetic renal senescence by simultaneously targeting the FABP4/FOXO1 axis and immunometabolic enzymes SDH and ACLY. These findings highlight the translational significance of metformin as a prototype for immunometabolic and immunosenescence-directed therapies in DN. Full article
(This article belongs to the Section Pharmacology)
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18 pages, 2128 KB  
Review
The Emerging Role of Senolysis in Atherosclerosis
by Sylvia Vagena, Giorgos Theocharous, Alexios Theodorou, Pavlos Pantelis, Miltiadis Gravanis, Linnea Tscheuschner, Andreas Theodorou, George Galyfos, Frangiska Sigala, Nefeli Lagopati and Athanassios Kotsinas
Medicina 2025, 61(12), 2137; https://doi.org/10.3390/medicina61122137 - 29 Nov 2025
Viewed by 769
Abstract
Atherosclerosis, a major contributor to vascular damage and plaque formation, is brought on by cellular senescence and chronic inflammation. A crucial matter that emerges is the classification of the disease in order to understand the pathogenic mechanisms before treatment. Given that oxidative stress, [...] Read more.
Atherosclerosis, a major contributor to vascular damage and plaque formation, is brought on by cellular senescence and chronic inflammation. A crucial matter that emerges is the classification of the disease in order to understand the pathogenic mechanisms before treatment. Given that oxidative stress, DNA damage, and inflammation contribute to cellular senescence, an increase in pro-inflammatory factors is detected in the atherosclerotic plaque, which exacerbates its instability while impeding vascular repair. This study emphasizes the importance of pathways such as Nrf2, ICAM-1, and p38 MAPK/p16INK4A in the development of atherosclerosis. It also underscores the potential of senescence-targeting interventions to complement the conventional treatments for atherosclerosis. The study promotes using senolytic approaches that may serve as effective adjuncts to conventional pharmacological treatments for atherosclerosis. Particularly, quercetin, a flavonoid, demonstrates a potential action as senolytic agent by mitigating macrophage senescence, improving lipid profiles, and reducing plaque size of up to 56% in experimental models. This review article advocates for integrating senolytic approaches, including nutraceuticals like quercetin and combination therapies, to improve cardiovascular health and age-related vascular disorders. Full article
(This article belongs to the Section Cardiology)
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22 pages, 5849 KB  
Article
Hyperosmolarity-Induced Oxidative Stress Leads to Senescence in Human Corneal Epithelial Cells (HCEPC) via DNA Damage, Metabolic Disturbance and Mitophagy Decline
by Yongjie Zhang and Tingjun Fan
Antioxidants 2025, 14(11), 1381; https://doi.org/10.3390/antiox14111381 - 19 Nov 2025
Viewed by 978
Abstract
Background: Dry eye disease (DED), characterized by tear film hyperosmolarity, can lead to corneal epithelial damage. The mechanisms linking hyperosmotic stress to human corneal epithelial cell (HCEPC) damage are not fully understood. Methods: A DED model was established by exposing HCEPCs to sustained [...] Read more.
Background: Dry eye disease (DED), characterized by tear film hyperosmolarity, can lead to corneal epithelial damage. The mechanisms linking hyperosmotic stress to human corneal epithelial cell (HCEPC) damage are not fully understood. Methods: A DED model was established by exposing HCEPCs to sustained hyperosmotic stress (400 mOsm/L) over multiple passages in vitro. Senescence was assessed using senescence-associated-β-galactosidase (SA-β-gal) staining, 5-ethynyl-2′-deoxyuridine (EdU) assays, p16INK4A and senescence-associated secretory phenotypes (SASP) analysis. Mechanisms were investigated by measuring reactive oxygen species (ROS), mitochondrial function, energy metabolism, DNA damage, and inflammatory signaling. The role of autophagy was probed pharmacologically. Results: Hyperosmotic stress induced HCEPC senescence, driven by mitochondrial dysfunction, oxidative stress, DNA damage, bioenergetic crisis, and compromised autophagy (especially mitophagy). Autophagy and mitophagy play a key role in regulating senescence progression. Enhancing autophagy with LYN-1604 ameliorated oxidative stress, improved energy homeostasis, and attenuated senescence. Inhibiting autophagy exacerbated these states. Conclusion: Hyperosmolarity promotes HCEPC senescence via mitochondrial dysfunction and oxidative damage. Autophagy serves a critical protective role, and its enhancement represents a promising therapeutic strategy for DED. Full article
(This article belongs to the Special Issue Oxidative Stress in Cell Senescence)
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15 pages, 10967 KB  
Article
Protective Role of p66Shc Deletion in Physiological Renal Aging: Effects on G Protein-Coupled Receptor 124 Expression and Associated Cellular Senescence
by Carla Iacobini, Martina Vitale, Federica Sentinelli, Antonietta Lucarelli, Jonida Haxhi, Ilaria Sergio, Giuseppe Pugliese and Stefano Menini
Int. J. Mol. Sci. 2025, 26(22), 11096; https://doi.org/10.3390/ijms262211096 - 17 Nov 2025
Viewed by 549
Abstract
The adaptor protein p66Shc regulates oxidative stress and aging, but its role in renal aging is unclear. We investigated the effects of p66Shc deletion on age-related kidney changes, focusing on G protein-coupled receptor 124 (GPR124) and cellular senescence. Using kidney and urine samples [...] Read more.
The adaptor protein p66Shc regulates oxidative stress and aging, but its role in renal aging is unclear. We investigated the effects of p66Shc deletion on age-related kidney changes, focusing on G protein-coupled receptor 124 (GPR124) and cellular senescence. Using kidney and urine samples from p66Shc−/− and wild-type mice aged 5–24 months, we found that p66Shc deficiency slows renal aging. Compared to wild-type mice, p66Shc−/− mice showed better kidney function and reduced glomerular sclerosis and mesangial expansion from 18 months, alongside attenuated fibrosis, oxidative stress, and podocyte loss. Age-related declines in GPR124 were also smaller in p66Shc−/− mice, correlating with lower p16INK4a levels in glomeruli and cultured podocytes. These findings suggest that p66Shc deletion provides kidney protection by limiting oxidative stress and senescence, potentially through the preservation of GPR124. This study links p66Shc to natural kidney aging and identifies GPR124 as a mediator of p66Shc-driven senescence, suggesting potential targets for interventions in age-related renal decline. Full article
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20 pages, 682 KB  
Review
Genetic and Epigenetic Biomarkers for the Early Oral Cancerization Risk in Periodontitis Patients
by Giorgia M. Marmo, Morena Munzone, Alessandro Polizzi, Roberto Campagna, Marco Mascitti and Gaetano Isola
Curr. Issues Mol. Biol. 2025, 47(11), 933; https://doi.org/10.3390/cimb47110933 - 9 Nov 2025
Cited by 1 | Viewed by 894
Abstract
Oral squamous cell carcinoma (OSCC) remains one of the most prevalent and aggressive malignancies worldwide, with late diagnosis contributing to poor survival rates. Recent evidence suggests that periodontitis may act as a co-factor in development of OSCC through persistent inflammation, microbial dysbiosis, and [...] Read more.
Oral squamous cell carcinoma (OSCC) remains one of the most prevalent and aggressive malignancies worldwide, with late diagnosis contributing to poor survival rates. Recent evidence suggests that periodontitis may act as a co-factor in development of OSCC through persistent inflammation, microbial dysbiosis, and subsequent tissue remodeling. Identifying molecular signatures that link periodontitis with early oral cancerization is therefore of paramount importance for risk assessment, prevention, and timely intervention. This narrative review aims to provide an integrative overview of the current knowledge on molecular, genetic, and epigenetic biomarkers associated with oral cancer risk in patients with periodontitis. Specifically, periodontal pathogens such as Porphyromonas gingivalis and Fusobacterium nucleatum promote oral cancerization by modulating molecular, genetic, and epigenetic pathways, including p53, Cyclin D1, Ki-67, p16INK4A, DNA methylation, histone modifications, and microRNA regulation. Therefore, this review provides a discussion about the role of inflammatory mediators, oxidative stress-related molecules, microbial-derived products, genetic markers and epigenetic mechanisms as early molecular signals of malignant transformation. The study of these salivary biomarkers (salivaomics) has emerged as a promising non-invasive diagnostic tool, although variability in sampling, biomarker stability, and confounding factors such as coexisting periodontal disease remain significant limitations. By synthesizing the available evidence, this review summarizes recent evidence linking periodontitis to oral cancerization, highlights potential salivary, proteomic, and inflammatory biomarkers, and considers the role of periodontal therapy in improving inflammatory profiles and modulating tumor-related biomarkers. Finally, it explores future perspectives, including the integration of Artificial Intelligence (AI) to enhance biomarker-based diagnosis and risk stratification in OSCC patients. Full article
(This article belongs to the Collection Molecular Mechanisms in Human Diseases)
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16 pages, 1334 KB  
Article
Development of a Paper-Based Electrochemical Immunosensor for Cardiac Troponin I Determination Using Gold Nanoparticle-Modified Screen-Printed Electrodes
by Mayra Asevedo Campos de Resende, Ana Elisa Ferreira Oliveira, Thaís Cristina de Oliveira Cândido, Daniela Nunes da Silva, Scarlat Ohanna Dávila da Trindade, Lucas Franco Ferreira and Arnaldo César Pereira
Chemosensors 2025, 13(11), 383; https://doi.org/10.3390/chemosensors13110383 - 31 Oct 2025
Cited by 1 | Viewed by 1317
Abstract
Acute Myocardial Infarction (AMI) is a critical cardiac condition that poses a substantial threat to myocardial function. Expedient diagnosis of AMI is paramount and relies on serological assays for rapid and accurate quantification of relevant biomarkers. Electrochemical sensors have emerged as promising candidates [...] Read more.
Acute Myocardial Infarction (AMI) is a critical cardiac condition that poses a substantial threat to myocardial function. Expedient diagnosis of AMI is paramount and relies on serological assays for rapid and accurate quantification of relevant biomarkers. Electrochemical sensors have emerged as promising candidates for this application, owing to their accessibility, operational simplicity, and high specificity. In this study, we developed a paper-based electrochemical immunosensor to detect cardiac troponin I in serum and saliva specimens. The electrode was fabricated using screen-printing technology with photographic paper as the substrate, employing graphite-based ink, nail polish, and acetone as the solvent. A quasi-reference electrode was constructed using silver powder-based ink, nail polish, and acetone. The immunosensor was prepared by modifying the working electrode with gold nanoparticles (AuNP) functionalized with cardiac troponin I antibodies (anti-cTnI) and bovine serum albumin (BSA). This modified electrode was subsequently used to detect the troponin I antigen. The analyses were performed in 0.1 mol L−1 phosphate buffer medium, pH 7.00, in the presence of 5.0 mmol L−1 of the potassium ferrocyanide probe. The immunosensor exhibited a sensitivity of 0.006 µA/fg mL−1, a limit of detection of 9.83 fg mL−1, and a limit of quantification of 32.79 fg mL−1. Specificity studies conducted in the presence of other macromolecules demonstrated minimal interference, with relative standard deviations (RSD) below 5.00%, indicating a specific interaction with troponin I. Furthermore, the immunosensor demonstrated excellent reproducibility and stability. Upon application to serum and saliva samples, the immunosensor presented recoveries of approximately 99–105%, suggesting its potential applicability in clinical analyses. Full article
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