Search Results (2,787)

Neutrophils are the most abundant circulating leukocytes and essential components of innate immunity. Through mechanisms such as phagocytosis, reactive oxygen species (ROS) production, degranulation, and neutrophil extracellular trap (NET) formation, they play a crucial role in host defense. However, dysregulated neutrophil responses are linked to chronic inflammatory conditions, including periodontitis. This review summarizes current evidence on neutrophil biology in periodontal health and disease, focusing on functional mechanisms, recruitment pathways, the influence of dysbiosis, and their potential as biomarkers and therapeutic targets. Neutrophils display a dual role in periodontal tissues: while protecting against microbial invasion, their excessive or impaired activity contributes to tissue destruction. Altered chemotaxis, defective phagocytosis, and uncontrolled NET release perpetuate inflammation and alveolar bone loss. Neutrophil-derived enzymes, including myeloperoxidase, elastase, and matrix metalloproteinases, emerge as promising biomarkers for early diagnosis. In parallel, therapeutic strategies targeting oxidative stress, NET regulation, or neutrophil hyperactivity are being explored to preserve periodontal tissues. Neutrophils are central players in periodontal pathophysiology. Understanding their regulation and interaction with the oral microbiome may enable the development of novel diagnostic and therapeutic approaches, ultimately improving periodontal disease management. Full article

Background: The potential of injectable hydrogels as drug depots lies in their ability to achieve local and sustained co-delivery of chemotherapeutic drugs and immunostimulants for combined tumor therapy. Method: In this study, we devised a localized chemo-immunotherapeutic strategy by co-loading the chemotherapeutic drug, oxaliplatin (OXA), and the immune-checkpoint blockade (ICB) antibody, anti-programmed cell death protein ligand 1 (anti-PD-L1), into a matrix metalloproteinase (MMP)-responsive injectable poly(L-glutamic acid) hydrogel (MMP-gel). Results: The in situ gelation of hydrogels enables local retention of OXA and model antibody IgG, as well as MMP-triggered sustained release. Meanwhile, the OXA-loaded MMP-gel caused the immunogenic cell death (ICD) of tumor cells. When administered intratumorally in mice carrying B16F10 melanoma, the MMP-gel co-loaded with OXA and anti-PD-L1 (OXA&anti-PD-L1@MMP-gel) demonstrated superior tumor suppression efficacy and prolonged the survival time of the animals with low systemic toxicity. Meanwhile, the OXA&anti-PD-L1@MMP-gel induced an increase in CD8⁺ T cells and M1 macrophages within tumors, and a decrease in Treg cells and M2 macrophages, demonstrating that the drug-loaded system enhanced the antitumor immune response. Moreover, the OXA&anti-PD-L1@MMP-gel effectively inhibited the growth of distal tumors in a bilateral-tumor experiment. Conclusions: Consequently, the responsive hydrogel-based chemo-immunotherapy holds potential in tumor treatment. Full article

Interleukin 17 (IL-17) is a crucial mediator at the interface of periodontal dysbiosis and host immunity. This review synthesizes current evidence on IL-17 in periodontitis (PD), its systemic connections, and the role of IL-17 gene variants. Clinical and experimental studies show that IL-17 rises in periodontal disease and is associated with the severity of PD via action on epithelial, stromal and osteoblastic cells to promote chemokine release, neutrophil recruitment, cyclooxygenase 2 and prostaglandin E2 synthesis, RANKL expression, osteoclastogenesis, and matrix metalloproteinase activity. Periodontopathogens Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans pre-activate the local inflammation-maintaining Th17 response. There is converging evidence linking IL-17-centered signaling with rheumatoid arthritis, diabetes mellitus, and psoriasis in favor of a shared inflammatory network in barrier tissues and synovium. Despite these associations, IL-17 biology is contextually determined with mucosal defense and bone homeostatic roles that caution against unidimensional explanations. Evidence on IL-17A and IL-17F polymorphisms is still heterogeneous across populations with modest and variable risk associations with PD. Clinically, IL-17 in gingival crevicular fluid, saliva, or serum is a potential monitoring biomarker when utilized along with conventional indices. Therapeutically, periodontal therapy that reduces microbial burden may inhibit IL-17 function, and IL-17-targeted therapy has to balance potential benefit to inflammation and bone resorption against safety in oral tissues. The following research must utilize harmonized case definitions, standardized sampling, and multiethnic cohorts, and it must include multiomics to be able to differentiate between causal and compensatory IL-17 signals. Full article

Age-related changes in facial ligaments contribute to altered facial shape and soft tissue descent. Radiofrequency (RF) has been utilized for skin rejuvenation by promoting collagen fiber contraction and synthesis through increased expression of heat shock proteins (HSPs). The primary component of ligamentous collagen fibers undergoes structural modifications with age, exhibiting increased fragmentation and a reduced collagen type I/III ratio. This study aimed to investigate whether RF irradiation alleviates senescence-related changes in facial ligaments through HSP70-mediated molecular remodeling using a UV-induced photoaging rat model. In senescent fibroblasts, RF enhanced the interaction between HSP70 and IκBα kinase (IKK)γ while reducing IκBα phosphorylation, which was associated with decreased nuclear factor-kappa B (NF-κB) activation. These RF-mediated changes were attenuated by an HSP70 inhibitor, suggesting that RF reduces NF-κB activity via HSP70 modulation. RF also suppressed expression levels of matrix metalloproteinases and SMAD7 in senescent fibroblasts. Consistent with in vitro findings, RF increased the interaction between HSP70 and IKKγ while decreasing IκBα phosphorylation and NF-κB activity in the UV-induced photoaging (senescent) facial ligaments of rat models. Furthermore, RF enhanced the collagen type I/III ratio and increased collagen fiber density within the ligaments. Scanning electron microscopy revealed that RF irradiation increased collagen fiber bundle diameter and enhanced the helical structure of those fibers. Overall, RF mitigates senescence-related changes in facial ligaments through HSP70 modulation. Considering that facial ligament laxity contributes to soft tissue descent, facial ligament-targeting approaches may promote a more youthful facial structure. RF demonstrates the possibility in reducing senescence-associated changes within facial ligaments. Full article

Peptides are notable cosmetic ingredients owing to their diverse biological activities and beneficial effects on skin health. Therefore, multifunctional peptides capable of simultaneously exerting antioxidant, whitening, and anti-wrinkle effects are highly desirable. In this study, a scalable and cost-effective chemical synthesis strategy was used for the rapid design and synthesis of linear peptide sequences with skin bioactivity using solid-phase peptide synthesis. Subsequently, liquid-phase peptide synthesis was used to enhance the proteolytic stability and develop a cyclic peptide, cyclic CYGSR (CR5), which was subjected to in vitro biological evaluation. CR5 showed high biocompatibility in water-soluble tetrazolium salt-1 (WST-1) assays, maintaining over 90% cell viability at concentrations up to 400 μg/mL. In the 2,2-Diphenyl-1-picrylhydrazy (DPPH) assay, CR5 exhibited strong antioxidant activity with 83.18% radical scavenging at 200 μg/mL. It also showed 97.79% tyrosinase inhibition at 800 μg/mL, confirming significant whitening potential. Moreover, CR5 inhibited matrix metalloproteinase-1 (MMP-1) expression by 73.55% and increased type I procollagen expression by 44.68% at 400 μg/mL, demonstrating its anti-wrinkle potential. Additionally, molecular docking and dynamic simulation demonstrated stable binding of the peptide to tyrosinase and MMP-1. Collectively, CR5 possesses multifunctional properties with excellent biocompatibility, highlighting its potential as a novel cosmetic active ingredient. Full article

Skin aging is accelerated by both environmental factors—including ultraviolet (UV) radiation and pollution—and intrinsic processes such as chronic inflammaging. N-carbamylglutamate (NCG), an arginine precursor known for its benefits for gut and reproductive health, has not been extensively studied in dermatological applications. To explore its suitability as a multifunctional cosmetic ingredient, this study examines the protective role of NCG in counteracting UV-stimulated oxidative and inflammatory responses in skin cells. NCG significantly reduced UV-induced reactive oxygen species (ROS), indicating strong antioxidant properties. It also inhibited matrix metalloproteinase (MMP) activity, preserving collagen integrity and reducing wrinkle formation. In addition, NCG suppressed nitric oxide (NO) production and downregulated key inflammatory mediators—including cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6)—highlighting its anti-inflammatory potential. Furthermore, NCG reduced melanin production and the expression of melanogenesis-related factors such as the microphthalmia-associated transcription factor (MITF), tyrosinase-related protein 1 (TRP-1), and TRP-2. These findings support the role of NCG as a promising multifunctional cosmetic ingredient with antioxidant, anti-inflammatory, anti-wrinkle, and skin-brightening properties. Full article

This review will focus on the structure and role of the ECM in physiological conditions and pathological alterations, based on a cardiological case. The patient has a particular case of connective tissue disease (CTD), specifically bicuspid aortic valve type (BAV). The presented clinical case is as follows: a 34-year-old patient has been diagnosed with BAV. The subject is concerned about how his condition may affect his daily life. The subject is worried about passing the disease on to his children. He asked experts for advice on the causes, possible consequences and treatments. BAV is a major congenital heart defect, affecting 1–2% of the global population. This review provides an overview of the structure and function of the ECM, which plays an important role in the architecture of heart valves and vascular structures associated with connective tissue disease. The BAV has been observed to affect the connective tissue, although the underlying causes remain unclear. ECM is a 3-dimensional network of macromolecules that provides structural support for cells and tissues. Extensive research has established the regulatory functions of ECM, given its role in orchestrating cell signalling, functions, properties and morphology. Extracellular and cell-bound factors represent a substantial proportion of the major constituents of the ECM. The following proteins and glycoproteins are of particular interest: collagen, elastin, laminins, tenascins, proteoglycans, glycosaminoglycans and hyaluronan. Relevant cell receptors include CD44. Full article

Polianthes tuberosa L. (PT) flower extracts exhibit considerable bioactivities, yet their application is often constrained by limited bioavailability and efficacy. In this study, fermentation of PT (FPT) using Rhodosporidium toruloides significantly enhanced its phytochemical profile, doubling the total phenol content (697.22 ± 7.51 μg/mL in FPT versus (vs.) 347.61 ± 5.89 μg/mL in non-fermented extract (NF)) and increasing flavonoids by onefold relative to NF (381.44 ± 6.50 μg/mL in FPT vs. 190.25 ± 4.75 μg/mL in NF), resulting in a substantial improvement in radical scavenging capacity (DPPH: 47.59 ± 1.55%; ABTS: 89.87 ± 1.39%). In UVB-irradiated the human keratinocyte cell line, FPT demonstrated superior efficacy over NF by effectively reducing reactive oxygen species and malondialdehyde levels (1.29 ± 0.08 ng/mL at 0.4 mg/mL FPT vs. 1.5 ± 0.1 ng/mL with NF), while concurrently elevating the activity of key antioxidant enzymes. Using human dermal fibroblasts, FPT was further shown to possess notable anti-glycation and anti-carbonylation properties, significantly inhibiting carboxymethyl lysine formation (90.6 ± 3.6% reduction) and protein carbonylation (86.5 ± 2.2% reduction). It also suppressed senescence-associated β-galactosidase activity (67.9 ± 3.0% inhibition), downregulated matrix metalloproteinase-1 expression (62.5 ± 5.1% reduction), and stimulated type I collagen synthesis (166.5 ± 4.2% recovery). Additionally, FPT markedly inhibited UVB-induced melanogenesis in B16F10 melanoma cells by reducing melanin content (36.0 ± 5.3%) and tyrosinase activity (45.7 ± 1.2%), through the downregulation of critical melanogenic genes, including melanocortin 1 receptor, microphthalmia-associated transcription factor, and tyrosinase. Full article

Matrix metalloproteinase-9 (MMP-9) is a zinc-dependent endopeptidase that plays a central role in extracellular matrix (ECM) remodeling, angiogenesis, immune cell trafficking, and cytokine activation. Dysregulated MMP-9 activity has been implicated in the pathogenesis of diverse conditions, including atherosclerosis, aneurysm formation, chronic obstructive pulmonary disease (COPD), asthma, neurodegeneration, and malignancy. Although broad-spectrum synthetic MMP inhibitors were initially developed as therapeutic agents, clinical trials failed due to lack of selectivity, poor tolerability, and impairment with physiological tissue repair. This outcome has shifted attention toward indirect pharmacological modulation of MMP-9 using drugs that are already approved for other indications. In this paper, we review the evidence supporting MMP-9 modulation by established therapeutics and adjunctive strategies. Cardiometabolic agents such as statins, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), metformin, and pioglitazone reduce MMP-9 expression and enzymatic activity, contributing to vascular protection, improved insulin sensitivity, and attenuation of aneurysm progression. Anti-inflammatory and respiratory drugs, including glucocorticoids, phosphodiesterase-4 (PDE4) inhibitors, macrolide antibiotics, montelukast, and nonsteroidal anti-inflammatory drugs (NSAIDs), suppress MMP-9-driven airway inflammation and pathological tissue remodeling in asthma, COPD, and acute lung injury. Tetracycline derivatives, particularly sub-antimicrobial dose doxycycline, directly inhibit MMP-9 activity and are clinically validated in the treatment of periodontal disease and vascular remodeling. Hormone-related therapies such as rapamycin, estradiol, and tamoxifen exert tissue- and disease-specific effects on MMP-9 within endocrine and oncologic pathways. In parallel, nutritional interventions—most notably omega-3 polyunsaturated fatty acids and antioxidant vitamins—provide adjunctive strategies for mitigating MMP-9 activity in chronic inflammatory states. Taken together, these findings position MMP-9 as a modifiable and clinically relevant therapeutic target. The systematic integration of approved pharmacologic agents with lifestyle and nutritional interventions into disease-specific treatment paradigms may facilitate safer, context-specific modulation of MMP-9 activity and unveil novel opportunities for therapeutic repurposing. Full article

Background/Objectives: This study proposes a framework for building a statistical prediction model for dental clinics to facilitate the diagnosis of periodontitis and its stages. The method is based on active-matrix metalloproteinase-8 (aMMP-8) mouth rinse point-of-care testing (POCT). Methods: A complete model was created within a three-step modeling scenario: (i) the first function differentiates healthy patients from those with periodontitis; (ii) the second function differentiates stage I and II patients from stage III patients; and (iii) the third function separates stage I and II patients from each other. The model was developed using logistic regression analysis, and the aMMP-8 POCT results utilized in the predictive functions were obtained from an Oralyzer digital reader. Sample data comprised 149 adult patients who visited dental clinics in Thessaloniki, Greece. Results: Patients without periodontitis were identified in 74.2% of cases (95% CI: 55.1–87.5%). Patients with periodontitis were revealed with a success rate of 94.1% (95% CI: 87.7–97.4%), and of these, the correct stage was determined in 71.2% of cases (95% CI: 61.7–79.2%). The complete model was tested on the same patient data from which it was formed. Conclusions: The results of the study showed that logistic regression can be used in the development of a model for dental clinics to reveal and stage periodontitis with sufficient accuracy. In the complete model created, aMMP-8 mouth rinse POCT results in ng/mL, visible plaque index (VPI), and the information on the patient’s missing teeth were statistically important factors in determining the presence and stage of periodontitis. Full article

Background/Objectives: Conventional two-dimensional (2D) cell cultures offer valuable insights into cancer cell biology; however, they lack in replicating the complex interactions present in solid tumors. Therefore, research has shifted towards the development of three-dimensional (3D) cell models that recapitulate the dynamic cell–cell and cell–matrix interactions within the complex tumor microenvironment (TME), better resembling tumor growth and initial stages of dissemination. Extracellular matrix, a key component within the TME, regulates cell morphology and signaling, influencing key functional properties. Breast cancer remains the most frequently diagnosed cancer type in women and a leading cause of cancer-related mortality. Methods: The aim of the present study was the development of breast cancer cell-derived spheroids, utilizing two breast cancer cell lines with differential estrogen receptor (ER) expression profile, and their characterization in terms of morphology, functional properties, and expression of epithelial-to-mesenchymal transition (EMT) markers and matrix signatures implicated in breast cancer progression. To this end, the ERα-positive MCF-7, and ERβ-positive MDA-MB-231 breast cancer cell lines were utilized. Results: Our findings revealed notable phenotypic transitions between 2D and 3D cultures, which were further supported by differential EMT markers expression. Moreover, spheroids exhibited distinct expression profiles of key receptors [ERs, epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor (IGF1R)] and matrix molecules (syndecans, and matrix metalloproteinases), accompanied by altered functional cell properties. Bioinformatic tools further emphasized the interplay between the studied matrix regulators and their prognostic relevance in breast cancer. Conclusions: Overall, this study introduces a simple yet informative 3D breast cancer model that captures key TME features to better predict cell behavior in vitro. Full article

Narrowband ultraviolet B (NB-UVB) phototherapy, used for treating skin diseases, can induce skin aging, cause inflammation, and reduce cell viability due to reactive oxygen species (ROS) generation. To mitigate these adverse effects, a multi-target polyherbal mixture for topical application was developed. This study investigated the effects of a polyherbal combination comprising Zingiber officinale (ZH), Garcinia mangostana (GE), and Centella asiatica (CAEw) extracts against NB-UVB-induced damage in HaCaT cells. Extracts were prepared to obtain high levels of specific biomarkers (compound D, α-mangostin, and asiaticoside). They were characterized for total phenolic and total flavonoid content, antioxidant properties, and anti-collagenase activity. The ability to enhance HaCaT cell viability after NB-UVB exposure was evaluated to determine the optimal polyherbal mixture ratios. Both the individual extracts and polyherbal formulations significantly improved irradiated HaCaT cell viability. Subsequent treatment with 100 µg/mL of the polyherbal mixture ZH:GE:CAEw (1:1:1) increased cell viability from 62.3% to 80.1% and decreased intracellular ROS (63.6%) without reducing cell apoptosis. It also downregulated the gene expression of cyclooxygenase-2, inducible nitric oxide synthase, matrix metalloproteinase-1 (MMP-1), and MMP-9, allowing their expression to reach the normal level of the non-irradiated cells. In conclusion, the polyherbal mixture effectively attenuated NB-UVB-induced damage and premature aging in HaCaT keratinocytes. Full article

Uterine stromal-derived tumors encompass a spectrum of rare neoplasms, ranging from benign endometrial stromal nodules to aggressive high-grade endometrial stromal sarcomas and undifferentiated uterine sarcomas. The classification of these tumors has advanced through molecular and immunohistochemical profiling, but the role of the extracellular matrix (ECM) in their biology is only beginning to be understood. The ECM provides both structural support and dynamic signaling cues, regulating tumor cell proliferation, invasion, angiogenesis, and immune evasion. Altered expression of collagens, proteoglycans, glycosaminoglycans, and matricellular proteins reshapes stromal architecture and contributes to disease progression. Moreover, ECM remodeling enzymes such as matrix metalloproteinases, together with cross-linking factors, create a stiff and pro-tumorigenic microenvironment that facilitates invasion and therapeutic resistance. Furthermore, these matrix alterations intersect with angiogenesis, mechanotransduction pathways, and immune modulation. Studies to date describe the role of ECM molecules in the function of the physiological uterine tissue and data for the uterine stroma-derived tumors is scarce. This review summarizes the existing knowledge in classification, prognosis and diagnosis, and summarizes the ECM-driven mechanisms in tumors described so far, aiming to identify new and prognostic biomarkers and novel therapeutic targets in uterine sarcomas. Full article

Matrix metalloproteinases (MMPs) are proteolytic enzymes involved in connective tissue remodeling. Matrix metalloproteinase 3 (MMP3) belongs to the MMP family and is associated with the pathogenesis of tendinopathy. Moreover, MMP3 gene polymorphisms have been associated with the risk of tendinopathy development. The goal of this study was to investigate whether this gene polymorphisms could also affect the effectiveness of platelet-rich plasma (PRP) tendinopathy treatment. 107 patients (132 elbows) with lateral elbow tendinopathy underwent PRP injection and were followed for two years at specific follow-up weeks (2, 4, 8, 12, 24, 52, 104). The effectiveness of the therapy was assessed based on patient-reported outcome measures (PROMs) values, specifically visual analogue scale (VAS), quick version of the disabilities of the arm, shoulder and hand (QDASH), patient-rated tennis elbow evaluation (PRTEE), and the achievement of minimal clinically important difference (MCID). Three MMP3 single nucleotide polymorphisms (SNPs) (rs520540, rs591058, rs679620) were genotyped using the TaqMan method. All studied polymorphisms were found to present strong linkage disequilibrium and were associated with the effectiveness of therapy on the VAS scale (week 4) and PRTEE (week 104), as well as with MCID achievement (PRTEE week 4); however, these were not strong associations. The studied SNPs also showed an association with the frequency of hand pain before treatment. MMP3 gene polymorphisms are associated with pain experienced before PRP therapy, but do not show a clear association with treatment effectiveness. Full article

Obesity is a multifactorial metabolic disease characterized by chronic low-grade inflammation, extracellular matrix (ECM) dysfunction, and systemic metabolic dysregulation. Matrix metalloproteinases (MMPs), especially MMP-2 and MMP-9, are key regulators of ECM remodeling and inflammation in obesity. This narrative review aimed to synthesize and critically discuss current evidence on the effects of bariatric surgery and pharmacological therapies, including GLP-1 and dual GLP-1/GIP receptor agonists, on MMP activity and metabolic outcomes. Literature from PubMed and Scopus and Web of Science (2015–2024) was analyzed, focusing on studies evaluating MMPs, inflammation, and metabolic parameters. Bariatric surgery consistently reduces MMP-9 levels and normalizes MMP-2 activity, contributing to improved ECM integrity, reduced inflammation, and enhanced insulin sensitivity. Pharmacological therapies achieve substantial weight loss and glycemic control, but evidence regarding their direct effects on MMP activity remains limited. This review highlights bariatric surgery as the most effective strategy for modulating obesity-related MMP dysregulation and emphasizes the need for further research into the mechanistic effects of modern pharmacotherapy on ECM remodeling. Full article