Search Results (682)

Ozone (O₃) has re-emerged in periodontology for its antimicrobial, oxygenating, and immunomodulatory actions, yet its role in regeneration remains contentious. This narrative review synthesizes current evidence on adjunctive ozone use in periodontal therapy, delineates cellular constraints—especially in periodontal ligament fibroblasts (PDLFs)—and explores mitigation strategies using bioactive compounds and advanced delivery platforms. Two recent meta-analyses indicate that adjunctive ozone with scaling and root planing yields statistically significant reductions in probing depth and gingival inflammation, with no significant effects on bleeding on probing, plaque control, or clinical attachment level; interpretation is limited by heterogeneity of formulations, concentrations, and delivery methods. Mechanistically, ozone imposes a dose-dependent oxidative burden that depletes glutathione and inhibits glutathione peroxidase and superoxide dismutase, precipitating lipid peroxidation, mitochondrial dysfunction, ATP depletion, and PDLF apoptosis. Concurrent activation of NF-κB and upregulation of IL-6/TNF-α, together with matrix metalloproteinase-mediated extracellular matrix degradation and tissue dehydration (notably with gaseous applications), further impairs fibroblast migration, adhesion, and ECM remodeling, constraining regenerative potential. Emerging countermeasures include co-administration of polyphenols (epigallocatechin-3-gallate, resveratrol, curcumin, quercetin), coenzyme Q10, vitamin C, and hyaluronic acid to restore redox balance, stabilize mitochondria, down-modulate inflammatory cascades, and preserve ECM integrity. Nanocarrier-based platforms (nanoemulsions, polymeric nanoparticles, liposomes, hydrogels, bioadhesive films) offer controlled ozone release and co-delivery of protectants, potentially widening the therapeutic window while minimizing cytotoxicity. Overall, current evidence supports ozone as an experimental adjunct rather than a routine regenerative modality. Priority research needs include protocol standardization, dose–response definition, long-term safety, and rigorously powered randomized trials evaluating bioactive-ozone combinations and nanocarrier systems in clinically relevant periodontal endpoints. Full article

Background/Objectives: The design of scaffolds that mimic the extracellular matrix has gained increasing attention in regenerative medicine. This study aims to develop and characterize electrospun nanofibrous scaffolds based on pullulan blended with either gelatin or gliadin and doped with selenium nanoparticles (Se NPs), to assess the influence of protein type and Se NP doping on scaffold performance and regenerative potential. Methods: Se NPs were synthesized via redox reaction and stabilized using pullulan. Electrospun scaffolds were then prepared by blending pullulan-stabilized Se NPs with either gelatin or gliadin. The resulting fibers were characterized using a multidisciplinary approach, including physicochemical (morphology, fiber dimension, swelling capacity, surface zeta potential, mechanical properties) and preclinical properties (antioxidant properties, fibroblast adhesion and proliferation, collagen expression). Results: Protein type influenced fiber morphology and dimensions, as well as mechanical behavior, with gelatin-based scaffolds demonstrating smaller fiber diameters and higher mechanical properties. The doping with Se NPs enhanced scaffold antioxidant properties without affecting fiber formation. Moreover, all scaffolds supported fibroblast proliferation, but those containing Se NPs showed enhanced modulation of ECM gene expression. Conclusions: The results show that scaffolds doped with Se NPs exhibited superior performance compared to the undoped counterparts, offering promising platforms for chronic wound reparation. Full article

Background/Objectives: Oral squamous cell carcinoma (OSCC) is a common and aggressive oral cancer with high recurrence and mortality rates, largely due to late diagnosis and metastasis. Epigenetic regulation, particularly aberrant DNA methylation, plays a critical role in cancer progression. Altered methylation patterns disrupt cancer-related gene regulation. Our previous study found that oral cancer patients exhibit increased synthesis of S-adenosyl-L-methionine, a key methyl donor for cytosine methylation. Therefore, the aim of this study was to explore the relationship between global DNA methylation and OSCC progression and to evaluate the impact of DNA methylation heterogeneity on oral cancer cells. Methods: Immunohistochemistry (IHC) and immunofluorescence (IF) staining were used to examine 5-methylcytosine (5-mC) expression in OSCC clinical specimens and oral cancer cells. The DNA methyltransferase inhibitor 5-Aza-dC was used to assess the effects of DNA methylation on cell function and gene expression. RNA sequencing was used to identify key differentially expressed genes affected by 5-Aza-dC treatment. Cell migration was assessed using a wound closure assay. Protein and gene expression were analyzed using Western blotting and quantitative PCR. Results: An inverse relationship was found between 5-mC levels and cancer differentiation—poorly differentiated OSCC exhibited higher 5-mC levels. Additionally, higher 5-mC staining was observed at the invasion front of oral cancer tissues. In OSCC cells, 5-mC content correlated with migration ability. Furthermore, conditioned medium from cancer-associated fibroblasts enhanced both methylation levels and migration of OSCC cells. Treatment with 5-Aza-dC significantly increased epithelial differentiation, reduced epithelial-to-mesenchymal transition and cell adhesion-related genes, and inhibited OSCC cell migration. Conclusions: The findings highlight the critical role of DNA hypermethylation in OSCC progression, particularly in regulating differentiation, migration, and EMT. The interplay between the tumor microenvironment and epigenetic modifications underscores the complexity of OSCC biology and opens avenues for innovative therapeutic strategies. Full article

Background: To overcome the esthetic limitations of dental monolithic zirconia restorations, multichromatic systems were developed to combine improved structural integrity with a natural shade gradient that mimics the optical properties of natural teeth. In response to the clinical demand for time-efficient, i.e., chairside fabrication of zirconia restorations, rapid sintering protocols have become necessary to adjust clinical efficiency along with material performance. This study addresses the challenges of a rapid sintering protocol related to optical performance and phase transformation of the final restoration and the zirconia–cell interaction. Methods: The influence of a rapid sintering protocol on the color stability of the final dental restoration was evaluated by the CIE L*a*b* color space. Phase transformation was assessed through X-ray diffraction analysis. Cellular behavior was evaluated by measuring wettability, the material’s surface energy, and a cell mitochondrial activity assay on human gingival fibroblasts. Results: Optical measurements demonstrated that the total color change in all layers after rapid sintering was above the perceptibility threshold (ΔE* > 1.2), while only the polished enamel layer (ΔE* = 3.01) exceeded the acceptability threshold (ΔE* > 2.7), resulting in a clinically perceptible mismatch. Results of X-ray diffraction analysis, performed for fixed occupancy at Z_0.935Y_0.065O_0.984, revealed that rapid sintering caused a decrease in the cubic (C-) phase and an increase in the total amount of tetragonal (T-) phases. Conventionally sintered zirconia consists of 54% tetragonal (T-) and 46% cubic (C-) phase, whereas in the speed-sintered specimens, an additional T1 phase was detected (T = 49%; T1 = 27%), along with a reduced cubic fraction (C = 24%). Additionally, a small amount of the monoclinic (M) phase is noticed. Although glazing as a surface finishing procedure resulted in increased hydrophilicity, both polished and glazed surface-treated specimens showed statistically comparable cell adhesion and proliferation (p > 0.05). Conclusions: Rapid sintering induced perceptible color changes only in the enamel layer of multichromatic zirconia, suggesting that even layer-specific alterations may have an impact on the overall esthetic outcome of the final prosthetic restoration. Five times higher heating and cooling rates caused difficulty in reaching equilibrium, leading to changes in lattice parameters and the formation of the metastable T1 phase. Full article

Over the past years, with the growing interest in sustainable biomaterials, marine collagen has been emerging as an interesting alternative to bovine collagen. It is more easily absorbed by the body and has higher bioavailability. In this study, collagen was extracted from Dicentrarchus labrax (sea bass) skin, a fishery by-product, thus valorizing waste streams while reducing environmental impact. To overcome the intrinsic weak mechanical of collagen, it was combined with chitosan to produce composite scaffolds for skin tissue engineering. The incorporation of collagen proved crucial for scaffold performance: (i) it promoted the formation of an open-pore architecture, favorable for cell infiltration and proliferation; (ii) it enhanced swelling behavior suitable for exudate absorption and maintenance of a moist wound environment; (iii) by tuning the chitosan/collagen ratio, it enabled us to control the degradation rate; (iv) it conferred antioxidant properties; and (iv) by adjusting collagen/chitosan concentrations, it allowed fine-tuning of mechanical properties, ensuring sufficient strength to resist stresses encountered during wound healing. In vitro assays demonstrated that the scaffolds were non-cytotoxic and effectively supported mouse adipose tissue fibroblasts’ adhesion and proliferation. Finally, all formulations exhibited marked bactericidal activity against the human pathogen Staphylococcus aureus and the methicillin-resistant Staphylococcus aureus, with a Log reduction greater than 3 (a reduction of at least 99.9% in bacterial growth) compared to the control. Collectively, these findings highlight collagen not only as a sustainable resource but also as a functional component that drives the structural, physicochemical, biological, and antimicrobial performance of chitosan/collagen scaffolds for skin tissue engineering. Full article

This study evaluated a biomimetic filler strategy for two-step universal dental adhesives by integrating amine-functionalized mesoporous silica nanoparticles (MSNs) loaded with polyacrylic acid-stabilized amorphous calcium phosphate (PA–ACP) into the primer phase. MSNs were synthesized and characterized by FTIR, N₂ sorption (BET), and HRTEM to confirm structural integrity and effective PA–ACP loading. Two commercial adhesives (G2 Bond and OptiBond eXTRa) were modified by incorporating different volumes fractions (10, 15, 20 vol%) of PA–ACP/MSN. Wettability (contact angle), microtensile bond strength (μTBS), and cytotoxicity (indirect MTT assay using human periodontal ligament fibroblasts, HPLFs) were assessed. The results demonstrated that incorporating up to 15 vol% PA–ACP/MSN maintained favorable wettability and bond strength, comparable to those of the unmodified controls. At 20 vol%, significant increases in contact angles and reductions in bond strength indicated impaired primer infiltration. Cytotoxicity testing confirmed high fibroblast viability (>70%) across all tested concentrations, verifying the biocompatibility of PA–ACP/MSN-filled primers. This work confirms the feasibility of a biomimetic adhesive design using PA–ACP/MSN in the primer phase without compromising immediate wettability and immediate μTBS up to 15 vol%. Remineralization is a potential capability that requires verification in future studies. Full article

CD44, a multi-isoform adhesion receptor for hyaluronic acid (HA), plays a crucial role in regulating cell interactions with the extracellular matrix, cell migration, differentiation, and survival in both physiological and pathological contexts. Accumulating experimental evidence suggests that CD44 is not merely a passive marker of mesenchymal cell activation but rather an active signaling hub driving fibrosis in many organs, including the lung, skin, heart, and liver. Its involvement in fibroblast differentiation into myofibroblasts, as well as induction of the invasive phenotype of these cells, shows striking analogies to the mechanisms of epithelial-to-mesenchymal transition (EMT) known from cancer progression. In this paper, we discuss both the molecular mechanisms of CD44-dependent signaling (including through EGFR, MAPK/ERK, CaMKII, lipid rafts, and Smad) and the influence of its modulation (knockout, antibodies, blockade of HA synthesis) on the course of fibrosis in in vitro and in vivo models. In addition, we present the influence of environmental pollutants—such as heavy metals, particulate matter, endocrine disruptors, and microplastics—on the activation of the HA-CD44 axis in connective tissue, with particular emphasis on their role in the induction of chronic inflammation, EMT, and extracellular matrix deposition. The collected evidence suggests that CD44 serves as a central integrator of inflammatory and fibrogenic signals, and its pharmacological modulation may represent a novel therapeutic strategy for treating fibrotic diseases and chronic inflammatory conditions. Full article

This study investigated the toxicity of ten polymer materials intended for the development of invasive neural interfaces improving the treatment of neurological diseases. Most of the materials for neural implants can cause traumatization of the surrounding tissue, inflammation, and foreign body reaction. In this study, in vitro and in vivo toxicity assessment was performed for nylon 618 (NY), polycaprolactone (PCL), polyethylene glycol diacrylate (PEGDA), polydimethylsiloxane (PDMS), polyethylene terephthalate (PET), polylactide (PLA), thermoplastic polyurethane (TPU), polypropylene (PP), polyethylene terephthalate glycol (PET-G), and polyimide (PI). The biocompatibility of these ten materials was assessed based on cell adhesion, growth and cytotoxicity on neural (PC-12) and fibroblast (NRK-49F) cultures. Furthermore, brain tissue responses to the implanted phantom scaffolds were analyzed in rats. According to these measurements, PI showed the highest compatibility for both cell types. PEGDA exhibited cytotoxic effects, low cell adhesion and the strongest foreign body reaction, including fibrosis and multinucleated cell formation. The other polymers showed lower pathological responses which makes them potentially usable for neural interfacing. We conclude that PEGDA appears to be unsuitable for long-term use due to adverse tissue and cellular reactions, whereas PI, PLA, PDMS and TPU hold promise as materials for safe and effective neural interface applications. Full article

Glass ionomers are utilized extensively within the domain of dentistry, for instance, as provisional restorations, liners, or bases, in addition to their application as pit and fissure sealers. It is imperative that this type of material exhibits favorable physico-chemical and biological properties. The primary objective of the presented study is to modify commercial resin-modified glass ionomer (Riva Light Cure, RMGIC) by doping it with copper particles (RMGIC + Cu) and to evaluate its properties in terms of potential beneficial clinical applications. Susceptibility to adhesion of microbial species and potential antimicrobial activity was evaluated against the Candida albicans, Streptococcus mutans, and Lactobacillus rhamnosus strains. Antiviral properties were evaluated against two viruses: Herpes simplex virus type 1 and human Adenovirus 5. Cytotoxicity of the materials was assessed using Balb/3T3 mouse fibroblast cell line. Temporal fluoride release up to 168 h in water and artificial saliva of different pH levels were also measured and assessed using statistical analysis. Samples were also subjected to Attenuated Total Reflectance Fourier-Transform Infrared Spectroscopy and Fourier-Transform Raman Spectroscopy. The findings of the present study demonstrate that RMGIC + Cu displays reduced biofilm formation against the tested strains when compared to non-modified material. The influence of the Cu presence on fluoride release is most pronounced in artificial saliva with a low pH (4.5), where the difference is significantly higher in samples with Cu than in samples without it. No reduction in herpes simplex 1 titers under the influence of either material was observed, whereas both materials exhibited virucidal properties against human adenovirus 5. Commercial glass ionomer presented no cytotoxicity, while the modified biomaterial caused changes in the fibroblast culture only under the sample (slight cytotoxicity, grade 1). Considering all the acquired results, doping glass ionomer with copper may be an interesting modification enhancing antimicrobial properties of the biomaterial, but it requires further evaluation in terms of long-term cytotoxicity before further in vivo studies. Full article

Plasma technology is an emerging method for implant surface decontamination and modification. This in vitro study evaluates the effects of plasma treatment on fibroblast and osteoblast adhesion, proliferation, and differentiation on titanium surfaces. Plasma was applied to machined and rough titanium discs, followed by surface characterization using scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS), and hydrophilicity testing. SEM imaging, cell viability assays, and immunohistologic staining were used to assess cell behaviour in response to treatment, while RNA sequencing evaluated gene expression related to differentiation. Although no significant architecture changes were observed with plasma treatment, XPS revealed a significant reduction in carbon content (p < 0.001), indicating decreased hydrocarbon contamination. Plasma treatment significantly increased surface hydrophilicity in both machined and rough surfaces (p < 0.0001). SEM and IHC imaging showed greater early-stage cell attachment for both fibroblasts and osteoblasts, though differences diminished after 12 h. RNA sequencing revealed time-dependent gene expression in both cell types, with Apln and Crabp2 significantly upregulated at 6 h in the plasma-treated fibroblast group. In conclusion, plasma treatment reduces hydrocarbon buildup, enhances hydrophilicity, promotes early cell attachment, and upregulates genes linked to angiogenesis and proliferation. Further studies are needed to determine its clinical significance in managing peri-implant disease. Full article

Focal adhesion kinase (FAK) is a crucial protein component of focal adhesions (FAs) and belongs to the cytoplasmic non-receptor protein tyrosine kinase family. FAK primarily regulates adhesion signaling and cell migration and is highly expressed in various tumors, including lung, liver, gastric, and colorectal cancers, as well as in conditions such as acute lung injury (ALI) and pulmonary fibrosis (PF). Recent research on FAK and its small-molecule inhibitors has revealed that targeting FAK provides a novel approach for treating various lung diseases. FAK inhibitors can obstruct signaling pathways, demonstrating anti-tumor, anti-inflammatory, and anti-fibrotic effects. In lung cancer, FAK inhibitors suppress tumor growth and metastasis; in ALI, they exert protective effects by alleviating inflammatory responses and oxidative stress; and in pulmonary fibrosis, FAK inhibitors reduce fibroblast activation and inhibit collagen deposition. The findings demonstrate promising efficacy and an acceptable safety profile in preclinical models. However, these early-stage results require further validation through clinical studies. Additionally, the underlying mechanisms, as well as the toxic effects and side effects, necessitate further in-depth investigation. Some have progressed to clinical trials (Defactinib (Phase II), PF-562271 (Phase I), CEP-37440 (Phase I), PND-1186 (Phase I), GSK-2256098 (Phase II), BI-853520 (Phase I)), offering potential therapeutic targets for lung diseases. Collectively, these findings establish a foundational basis for the advancement of FAK inhibitor discovery. Emerging methodologies, such as PROTAC degraders and combination regimens, demonstrate significant potential for future research. Based on a comprehensive analysis of the relevant literature from 2015 to the present, this review briefly introduces the structure and function of FAK and discusses recent research advancements regarding FAK and its inhibitors in the context of pulmonary diseases. Full article

The Tumour Microenvironment (TME) is pivotal for melanoma progression and contributes to therapy resistance. While dermal cell involvement is well established, the role of epidermal cells remains less defined. To explore the contribution of Normal Human Keratinocytes (NHKs) to melanoma biology, we investigated the modification of gene and protein expression of NHKs exposed to melanoma-conditioned medium or maintained in a co-culture system. The analysis focused on pathways related to proliferation, inflammation, Extracellular Matrix (ECM) remodelling, and cell adhesion. Due to the well-documented melanoma–fibroblast crosstalk, Normal Human Fibroblasts (NHFs) and Cancer-Associated Fibroblasts (CAFs) were used as comparative references. Keratinocyte gene expression changes under the influence of melanoma secretome only partially overlapped with those of NHFs and CAFs, indicating cell-type-specific responses. Exposure to melanoma-conditioned medium induced the upregulation of bFGF, CXCL-16, TIMP-2, and E-cadherin in NHKs, alongside downregulating TGF-β and MMP-9. Although bFGF is a recognized pro-tumorigenic factor, the modulation of CXCL-16, TIMP-2, and TGF-β may reflect a protective response. Notably, under co-culture conditions, NHKs exhibited a pronounced pro-inflammatory and ECM-remodelling phenotype, characterized by elevated production of cytokines (IL-1α, IL-1β, and IL-8) and ECM-degrading enzymes (MMP-7, 9, 12, and 13), indicative of a pro-tumoral feature. Collectively, these findings underscore an active role for NHKs in melanoma initiation and progression. Full article

Atherosclerosis is a multifactorial, chronic inflammatory disorder characterized by the progressive accumulation of plaque within the arterial wall. Recent research has highlighted the pivotal role of bioactive peptides in modulating vascular homeostasis and inflammation. Among these, salusin-α and salusin-β have emerged as critical regulators of atherogenesis. These peptides are generated via differential proteolytic processing of preprosalusin: an amino acid precursor encoded by the torsin family 2 member A gene. Despite their common origin, salusin-α and salusin-β exhibit divergent biological activities. Salusin-β promotes vascular inflammation by enhancing oxidative stress, activating the nuclear factor kappa B signaling pathway, and upregulating proinflammatory cytokines as well as adhesion molecules, and it also facilitates foam cell formation by increasing the expression of acyl-CoA/cholesterol acyltransferase 1 and scavenger receptors, thereby contributing to plaque progression. In contrast, salusin-α appears to exert protective, anti-inflammatory, and anti-atherogenic effects by increasing the expression of the interleukin-1 receptor antagonist and inhibiting key proinflammatory mediators. Additionally, these peptides modulate the proliferation of vascular smooth muscle cells and fibroblasts, with salusin-β promoting cellular proliferation and fibrosis via calcium and 3′,5′-cyclic adenosine monophosphate-mediated pathways, while the role of salusin-α in these processes is less well defined. Altered plasma levels of salusins have been correlated with the presence and severity of atherosclerotic lesions, suggesting their potential as diagnostic biomarkers and therapeutic targets. This review provides a comprehensive overview of biosynthesis, tissue distribution, and dual roles of salusins in vascular inflammation and remodeling, emphasizing their significance in the pathogenesis and early detection of atherosclerotic cardiovascular disease. Full article

The biocompatibility of orthodontic archwires is crucial for ensuring patient safety and the long-term success of orthodontic treatment. This study evaluated the biocompatibility of stainless steel (SS) and nickel–titanium (Ni-Ti) orthodontic archwires, as well as stainless steel metal brackets, before and after the application of a graphene coating. The assessment was based on the materials’ effects on a fibroblast cell line and on the development of a foetal chicken egg embryo. Fibroblasts that had been in temporary contact with steel and NiTi archwires after CW-CVD (cold wall chemical vapour deposition) treatment exhibited changes in morphology in the presence of the material. The materials exhibited moderate cytotoxicity. For metal brackets, the treated samples caused stronger cytotoxic changes in the culture. Unlike graphene-coated implants, where cells were found to directly adhere to the surface, the embryonic tissues did not treat the non-graphene-coated implants as an adhesive material. This study suggests that depositing carbon-based coatings, including graphene, on stainless steel archwires may reduce the cytotoxicity of orthodontic components. Using graphene increases adhesion of the implant surface to membrane-derived cells and the embryonic yolk and does not inhibit the further development of the chicken egg embryo. Full article

Background/Objectives: Dietary supplements are sources of nutrients or other substances that added to a healthy lifestyle help to preserve human homeostasis. Since inflammation is one of the major contributors to the alteration of homeostasis, this work investigated the effects of a multi-ingredient dietary supplement on human macrophages, cells involved in the inflammatory response. Methods: THP-1 cells were differentiated into macrophage-like cells and polarized in M₁ or M₂ phenotypes. Cell migration was evaluated by Boyden chamber assay; phenotypic markers by qRT-PCR; cytokine release by ELISA and LPS/ATP-induced pyroptosis by LDH assay. The antioxidant properties of the supplement were evaluated in human and mouse fibroblasts by DCF-DA assay. After supplement treatment, cell extracts were analyzed by HPLC-PDA-MS/MS and GC-MS to evaluate the presence of the ingredients. Results: Our results showed that the dietary supplement promoted M₂ migration and polarization and significantly reduced migration of M₁. In a model of LPS-induced inflammation in M₀, it significantly reduced NF-κB activation, COX-2 expression, and cytokine release. The supplement was not a specific inhibitor of NLRP-3, but it was able to modulate LPS priming. In addition, the supplement decreased granulocyte adhesion to HUVEC and reduced the oxidative stress in fibroblasts. The analysis of cell extracts showed the presence of the following ingredients of the formulation inside the cells: CoQ10, spermidine, resveratrol, 5-hydroxytryptophan from Griffonia simplicifolia (Vahl ex DC.) Baill., bacosides from Bacopa monnieri (L.) Wettst, vit B₂, B₅, E acetate. Conclusions: Our results demonstrate how a combination of natural active ingredients may contribute to the maintenance of homeostasis in human cells. Full article