Search Results (2,971)

Skin aging is characterized by decreased collagen synthesis and increased extracellular matrix degradation, leading to wrinkle formation and reduced skin elasticity. This study evaluated the anti-aging potential of hydrolyzed fish skin (HFS) extract through complementary in vitro and clinical investigations. In human dermal fibroblasts, treatment with HFS extract enhanced type I procollagen production and suppressed UVB-induced matrix-degrading enzymes, including matrix metalloproteinase-1 (MMP-1) and elastase, suggesting a mechanism that supports dermal matrix homeostasis. A randomized, double-blind, split-face clinical trial was conducted in 20 female participants over 12 weeks. A formulation containing 0.5% HFS extract was applied to one side of the face, while an identical vehicle control formulation without HFS extract was applied to the contralateral side. Wrinkle parameters were assessed using a three-dimensional imaging system. After 12 weeks, the test group showed significant improvements compared to baseline, with reductions of 12.75% in arithmetic mean roughness (Ra), 12.46% in root mean square roughness (Rq), and 11.32% in maximum wrinkle height (Rmax) (p < 0.05). No adverse events were observed. These findings demonstrate that HFS extract improves wrinkle-related skin parameters, potentially through promoting collagen synthesis while inhibiting matrix degradation. The combined molecular and clinical evidence supports its application as a functional cosmetic ingredient in anti-aging formulations. Full article

Potato (Solanum tuberosum L.) peel, a by-product of the food processing industry, has attracted attention as a potential source of bioactive compounds. This study evaluated the antioxidant and anti-photoaging-related effects of potato peel extracts in human skin cells. Solanum tuberosum L. peel water extract (PPW) and Solanum tuberosum L. ethanol extract (PPE) were prepared and examined in UVB-irradiated human dermal fibroblasts (HDFs) and human keratinocyte cell line (HaCaT) cells. Intracellular reactive oxygen species (ROS) production, matrix metalloproteinase-1 (MMP-1) expression, pro-collagen type I production, and cellular senescence were evaluated in HDF cells, whereas wound closure was assessed in HaCaT cells using a scratch assay. PPE showed higher polyphenol and flavonoid contents and stronger radical scavenging activity. In HDFs, PPW significantly reduced intracellular ROS production, whereas both extracts reduced MMP-1 expression under UVB-irradiated conditions. PPE significantly increased pro-collagen type I production. Both extracts reduced cellular senescence under UVB-irradiated conditions. In addition, PPE enhanced wound closure in HaCaT cells, suggesting a possible improvement in cell migration-related responses. Taken together, these findings suggest that potato peel extracts may exert protective effects against UVB-induced oxidative stress and photoaging-related cellular changes and may serve as potential functional materials associated with skin-protective and anti-photoaging-related cellular effects. Full article

The phenotypic plasticity of epithelial cells along the epithelial–mesenchymal (E-M) axis, or epithelial–mesenchymal transition (EMT), is a critical aspect of tumour progression and therapeutic resistance. During EMT, epithelial cells gradually acquire mesenchymal traits, facilitating vital functions in embryogenesis, wound healing, fibrosis, and tumour metastasis. This review article investigates the potential interplay between hyperglycaemia-induced metabolic stress and EMT in the context of therapeutic resistance. The study examines a complex, multifaceted network of molecular mechanisms regulating EMT, including specialised transcription factors and signalling pathways as well as growth factors, integrins, and matrix metalloproteinases in various epithelial carcinomas. Emerging findings have demonstrated the existence of EMT hybrid states along the continuum, possessing heightened metastatic potential and distinctive metabolic signatures that play critical roles in the development of therapeutic resistance in cancer cells. Hyperglycaemia has been particularly highlighted for its potential to promote EMT-driven therapeutic resistance through various interconnected mechanisms. Elevated glucose levels induce the increased production of reactive oxygen species (ROS), activation of EMT-promoting transcription factors, and a metabolic shift towards glycolysis. This hyperglycaemic stress involves upregulation of glucose transporters and glycolytic enzymes, creating feed-forward loops that support drug efflux mechanisms and help maintain the mesenchymal phenotype. Clinical data also indicate that hyperglycaemia in OSCC patients is associated with more advanced tumour stages, more extended hospital stays, less effective treatments, and higher rates of local recurrence and distant metastasis. Overall, these insights reveal a deleterious feed-forward loop in which hyperglycaemia promotes EMT-driven therapeutic resistance, with the strongest clinical evidence in oral squamous cell carcinoma (OSCC) and supportive data from pancreatic and breast cancers. Although glycaemic control represents a promising low-risk adjunctive approach, its clinical benefit remains to be validated in prospective interventional studies. Full article

Background: Myocardial fibrosis (MF) is a dynamic remodeling process characterized by excessive extracellular matrix (ECM) deposition, fibroblast activation, and dysregulated matrix turnover. Although initially reparative, persistent fibrotic remodeling promotes myocardial stiffening, electrical instability, and progressive cardiac dysfunction across diverse cardiovascular diseases. Circulating biomarkers reflecting collagen synthesis, degradation, proteolytic regulation, and inflammatory activation have emerged as potential tools for assessing fibrotic activity and risk stratification. Methods: This targeted narrative review was based on manually guided searches of PubMed and Scopus, supplemented by citation chaining and inclusion of landmark mechanistic and translational studies. Publications addressing myocardial extracellular matrix remodeling, circulating fibrosis-related biomarkers and imaging-derived fibrosis phenotypes were selected for qualitative synthesis. Results: Myocardial fibrosis reflects interconnected inflammatory, neurohormonal, oxidative, and extracellular matrix remodeling pathways. Among circulating biomarkers, C-terminal propeptide of procollagen type I (PICP) showed the most consistent association with myocardial collagen burden and adverse outcomes, whereas carboxy-terminal telopeptide of type I collagen (CITP), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), galectin-3, osteopontin, soluble suppression of tumorigenicity 2 (sST2), and natriuretic peptides provided more context-dependent signals. Standalone interpretation remains limited by restricted cardiac specificity, renal dysfunction, systemic inflammation, assay heterogeneity, and lack of standardized thresholds. Integration with cardiac magnetic resonance (CMR)-derived late gadolinium enhancement (LGE), T1 mapping, and extracellular volume (ECV) may improve biological and structural phenotyping. Conclusions: Circulating biomarkers capture complementary dimensions of myocardial remodeling but cannot replace structural imaging. We propose an updated, hypothesis-generating biomarker–imaging framework integrating inflammatory activation, collagen turnover, matrix quality, hemodynamic stress, and structural imaging to support phenotypic stratification and future validation of antifibrotic strategies. Full article

The endothelial glycocalyx (EG) is a dynamic endothelial surface layer composed of proteoglycans, glycosaminoglycans, glycoproteins, and adsorbed plasma proteins that regulates permeability, mechanotransduction, leukocyte trafficking, coagulation, and nitric oxide signaling. In kidney transplantation (KT), the EG is exposed to cumulative injury from recipient uremia, donor instability, preservation, machine perfusion, reperfusion, rejection, and immunosuppressive toxicity. This narrative review summarizes EG biology in KT, with emphasis on biomolecular findings relevant to ischemia–reperfusion injury, delayed graft function, rejection, and chronic allograft injury. Particular attention is given to syndecan-1, heparan sulfate, heparanase, soluble thrombomodulin, matrix metalloproteinases, angiopoietin-2/Tie2 signaling, selectins, miR-126, extracellular vesicles, and urinary or perfusate-derived readouts. Current evidence is biologically coherent but uneven: human data are largely observational, whereas many therapeutic concepts remain preclinical or exploratory. Glycocalyx-centered phenotyping may eventually improve risk stratification and trial enrichment, but clinical implementation will require standardized sampling, sample-source-aware biomarker panels, prospective validation, and clear separation between mechanistic plausibility and proven clinical utility. Full article

Henosepilachna vigintioctopunctata is a major pest of solanaceous crops. Matrix metalloproteinase 2 (MMP2) is a zinc ion-dependent endopeptidase that plays a crucial role in the remodeling process of the extracellular matrix (ECM) within cells. However, the function of HvMMP2 in H. vigintioctopunctata remains unknown. In this study, we cloned and characterized the HvMMP2 gene in H. vigintioctopunctata and investigated its function using RNA interference (RNAi). HvMMP2 exists as two transcript variants that differ at the 5′ end. HvMMP2 is highly expressed in the prepupal stage, the pupal stage and the intestine. Silencing HvMMP2 expression in fourth-instar larvae led to approximately 54% mortality at the prepupal stage, with the remaining larvae dying after pupation. RNAi with HvMMP2 in third-instar larvae did not affect their development to the fourth instar, but caused mortality in the majority of larvae during the prepupal and pupal stages, and most of these pupae exhibited wing deformities. Examination of these stunted larvae by dissection showed that their fat bodies were abnormally shaped and that yellow uric acid crystals had accumulated in the Malpighian tubules. Collectively, our findings indicate that HvMMP2 plays a critical role in pupation and eclosion in H. vigintioctopunctata and support HvMMP2 as a potential molecular target for further RNAi-based control studies. Full article

Colorectal cancer (CRC) remains a major cause of cancer-related morbidity and mortality worldwide. Metastasis regulators and matrix metalloproteinases have been implicated in tumor progression; however, their clinical significance in CRC remains incompletely defined. In this study, the prognostic value of MACC1 and MMP8 expression levels was investigated. A total of 140 patients diagnosed with CRC and 48 healthy controls were included. Serum levels of MACC1 and MMP8 were measured using ELISA. Clinicopathological parameters were recorded, and their associations with biomarker expression were analyzed. Both MACC1 and MMP8 levels demonstrated moderate diagnostic performance with comparable area under the curve values. A strong positive correlation between MACC1 and MMP8 expression was observed. MACC1 expression was significantly associated with metastasis status and tumor stage, whereas MMP8 expression was associated with tumor localization. In survival analyses, established clinicopathological factors, particularly tumor stage and metastasis status, were identified as the primary determinants of overall survival. In multivariate analysis, tumor stage remained the only consistent independent prognostic factor, while MMP8 showed a modest independent association in a separate model. MACC1 did not retain independent prognostic significance. Although MACC1 and MMP8 may have diagnostic and biological relevance in CRC, their prognostic utility appears limited compared to established clinical parameters. Further large-scale prospective studies are needed. Full article

Ultraviolet (UV) radiation is a main environmental factor responsible for skin damage, leading to oxidative stress, inflammation, and impairment of the skin barrier function. Furthermore, many components in sunscreen may accumulate in aquatic systems, causing environmental pollution. Therefore, the identification of novel natural bioactives that counteract these effects and can be useful as effective adjuvants in sunscreen formulations is of particular interest. Morin (1), a natural flavonoid, represents an attractive scaffold for modifications to enhance its biological activity. Herein, we aimed to investigate the effects of combining the flavonoid 1 and its derivative, morin semicarbazone (2), with the carotenoid fucoxanthin (FX) on UVB-exposed HaCaT keratinocytes. All compounds exhibited higher radical scavenging activity compared to Trolox. In this cell model, the phenolic–carotenoid combinations provided greater photoprotection than individual compounds, significantly enhancing cell viability and reducing necrosis, FX-2 emerged as the most potent combination, as evidenced by a marked reduction in reactive oxygen species (ROS) and malondialdehyde (MDA) levels, likely mediated through the activation of the nuclear factor erythroid 2-related factor 2/Heme oxygenase-1 (Nrf2/HO-1) signaling pathway. Furthermore, the tested treatments exerted enhanced anti-inflammatory effects by significantly reducing interleukin-6 (IL-6), cyclooxygenase 2 (COX-2), and matrix metalloproteinase-9 (MMP-9) mediators, with FX-2 being the most active combination. In conclusion, our findings highlight the protective effects of the combinations of these phenolics with the carotenoid FX against UVB radiation and support their potential application as natural active ingredients in sunscreen formulations. Full article

Background/Objectives: Matrix metalloproteinases (MMP-8 and MMP-9) are key mediators of periodontal tissue degradation and have been proposed as salivary biomarkers of disease activity. However, their comparative responsiveness to non-surgical periodontal therapy remains insufficiently clarified. This study aimed to assess short-term changes in salivary MMP-8 and MMP-9 following full-mouth disinfection (FMD), to evaluate their association with clinical periodontal parameters, and to explore potential differences according to depressive comorbidity. Methods: Eighty patients were included and divided into two groups: 40 patients without depressive disorder (PAR group) and 40 patients with depressive disorder (DEP group). Clinical periodontal parameters (probing depth and clinical attachment loss) and salivary levels of MMP-8 and MMP-9 were assessed at baseline and 12 weeks following FMD. Salivary MMP-8 and MMP-9 levels were determined using the enzyme-linked immunosorbent assay (ELISA). Results: Significant reductions in probing depth and clinical attachment loss were observed following therapy (p < 0.01). Salivary MMP-9 levels decreased significantly in both groups (PAR: 2.4 to 1.1 ng/mL, p = 0.002; DEP: 2.6 to 1.5 ng/mL, p = 0.004), whereas MMP-8 did not show statistically significant changes (p > 0.05). Moderate positive correlations were identified between MMP-9 and clinical parameters (r = 0.46–0.51), while MMP-8 showed no significant associations. No significant differences in treatment response or biomarker dynamics were observed between groups. Conclusions: The findings indicate a differential salivary biomarker response to periodontal therapy, with MMP-9 showing greater responsiveness than MMP-8 under the conditions of this study. These results suggest a potential role for salivary MMP-9 in reflecting short-term periodontal changes; however, further longitudinal and controlled studies are required to establish its clinical applicability. Depressive comorbidity did not appear to influence short-term outcomes, although this finding should be interpreted cautiously due to the lack of a standardized severity assessment. Full article

Background and Objectives: Autologous matrix-induced chondrogenesis (AMIC) is an established technique for the treatment of focal cartilage defects of the knee, with well-documented clinical outcomes. However, the biological processes underlying early postoperative cartilage remodeling remain poorly characterized, and the role of synovial fluid biomarkers in this setting is not well defined. This study aimed to assess short-term changes in selected synovial fluid and serum biomarkers of cartilage turnover after AMIC and to examine their associations with clinical outcomes. Materials and Methods: Fifteen patients undergoing AMIC for focal knee chondral or osteochondral defects were prospectively enrolled. Synovial fluid and serum samples were collected intraoperatively and at 6 and 12 weeks postoperatively. Concentrations of matrix metalloproteinase-3 (MMP-3), tissue inhibitor of metalloproteinases-2 (TIMP-2), cartilage oligomeric matrix protein (COMP), and procollagen type II C-terminal propeptide (PIICP) were measured using multiplex flow luminescence immunoassay. Clinical outcomes were evaluated using the International Knee Documentation Committee (IKDC) and Lysholm scores preoperatively and at 6 and 12 months. Results: Both IKDC and Lysholm scores improved significantly during follow-up. Absolute biomarker concentrations in synovial fluid were low and did not change significantly over time. Nevertheless, higher MMP-3 levels, higher COMP concentrations, and a higher MMP-3/TIMP-2 ratio were associated with poorer clinical improvement. Correlations between synovial fluid and serum biomarker levels were generally weak. Total synovial fluid protein increased postoperatively but did not account for the low biomarker concentrations. Conclusions: Early biomarker profiles after AMIC were characterized by low absolute concentrations without significant temporal changes. However, associations of COMP, MMP-3, and the MMP-3/TIMP-2 ratio with clinical outcomes suggest that relative biomarker patterns may reflect early intra-articular remodeling. Synovial fluid analysis may provide more informative insight into local joint biology than serum measurements in this setting. These findings should be interpreted cautiously and require confirmation in larger cohorts. Full article

CXCL14 is a highly conserved chemokine with potential roles in tumor progression and immune modulation. This study investigates the functional impact of CXCL14 on colon cancer by exploring its effects on tumor cell behavior and the immune microenvironment. We generated stable cell lines overexpressing CXCL14 in mouse MC38 and CT26 cells and human HCT15 colon cancer cells, and used these models to assess tumor growth, invasion, and immune cell infiltration. Our results demonstrate that CXCL14 suppresses colon cancer cell proliferation, migration, and metastasis. In vitro, CXCL14 inhibited the expression of matrix metalloproteinases (MMPs), key regulators of epithelial–mesenchymal transition (EMT), suggesting a role in promoting mesenchymal–epithelial transition (MET). Additionally, in vivo studies using a subcutaneous tumor model showed that CXCL14 not only suppressed tumor growth but also enhanced the infiltration of immune cells, including NK cells, dendritic cells (DCs), and T cells, converting the tumor microenvironment from a “cold” to a “hot” phenotype. RNA sequencing and pathway analyses revealed that CXCL14 regulates the expression of genes associated with angiogenesis, immune response, and cell signaling, particularly through the MAPK pathway. Furthermore, CXCL14’s influence on tumor progression was confirmed in a spleen-to-liver metastasis model, where its overexpression reduced metastatic spread. In conclusion, CXCL14 inhibits colon cancer progression by modulating both tumor cell behavior and the immune landscape, making it a promising candidate for targeted immunotherapy. Our findings highlight CXCL14’s potential to enhance anti-tumor immunity and provide new insights into its therapeutic applications in colon cancer. Full article

Background/Objectives: Traditional breast cancer prognostic tools relying on clinical staging often miss molecular heterogeneity, leading to divergent patient outcomes. Extracellular matrix (ECM) remodeling, driven by the Matrix Metalloproteinase (MMP), ADAM, and ADAMTS enzyme families, is critical to tumor progression. This study evaluates whether integrating ECM protease transcript abundance with standard clinical variables improves survival prediction accuracy and personalized risk stratification. Methods: Clinical and transcriptomic data from The Cancer Genome Atlas (TCGA) breast cancer cohort were analyzed. We integrated the protein-coding transcripts per million (pTPM) of top-ranked protease genes with standard clinical covariates (age, ordinal stage). Cox Proportional Hazards (CoxPH), penalized Cox (CoxNet), Random Survival Forest (RSF), and Gradient Boosting Survival (GBS) models were evaluated under a stratified 70/30 train–test split, followed by five-fold cross-validation. The locked final RSF model was then externally tested in METABRIC without retraining or risk-cutoff optimization. Results: Univariate screening identified ADAM15, MMP15, and ADAMTSL1 as global risk factors, whereas ADAMTS8 and MMP7 were protective. Prognostic signals were subtype-dependent. Integrated multivariable models outperformed transcript-only approaches in internal testing. The integrative RSF achieved the highest held-out discrimination (C-index = 0.797), outperforming a clinical-only Cox baseline trained on age and stage alone (C-index = 0.742, 95% CI 0.636–0.826). In METABRIC, the external C-index was 0.581 (95% CI 0.562–0.598), with significant survival separation across training-defined risk groups (log-rank p < 0.0001). Conclusions: ECM protease transcript profiles provide complementary prognostic information in TCGA-BRCA and show partial transportability to METABRIC. However, the modest external C-index indicates limited individual-level discrimination across platforms, so these candidate markers should be interpreted as hypothesis-generating and require further validation before clinical implementation. Full article

Inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis, is a chronic inflammatory disorder of the gastrointestinal tract that imposes an increasing global health burden. Conventional pharmacological treatments are often limited by systemic side effects and insufficient drug accumulation at inflamed intestinal sites. Enzyme-responsive polymeric drug delivery systems have emerged as a promising strategy to overcome these limitations by enabling site-specific and controlled drug release within the pathological microenvironment of the colon. This review summarizes recent advances in enzyme-responsive polymeric platforms designed for IBD therapy. We first discuss the altered enzymatic landscape in the intestinal microenvironment of IBD, including host-derived inflammatory enzymes such as esterases, matrix metalloproteinases, and hyaluronidase, as well as microbiota-derived enzymes such as azoreductase, cellulase, and amylase. These enzymes provide intrinsic biological triggers for selective polymer degradation and drug release. We then categorize enzyme-responsive polymeric delivery systems according to the enzymes involved and highlight representative material design strategies, including polymer prodrugs, core–shell nanocarriers, enzyme-degradable hydrogels, and polysaccharide-based carriers. Particular emphasis is placed on the multifunctional roles of polymers that enable targeted delivery, mucosal adhesion, and therapeutic synergy through bioactive degradation products. Finally, current challenges and future directions toward multi-stimuli-responsive systems and clinically translatable polymeric nanomedicine for precision IBD therapy are discussed. Full article

The accumulation of oxidative damage and inflammation, induced by internal and external factors, represents a major mechanism underlying the aging of skin. Excessive reactive oxygen species (ROS) trigger mitogen-activated protein kinase (MAPK) pathways, upregulating matrix metalloproteinase (MMP) expression and facilitating extracellular matrix degradation. Although nicotinamide mononucleotide (NMN) and hyaluronic acid (HA) possess antioxidant and dermoprotective properties, their potential combinational effects remain largely obscure. This study evaluated the impact of NMN and HA co-treatment on ROS production, MAPK signaling, MMP-1 secretion, and type I collagen secretion in TNF-α-stimulated human epidermal keratinocytes. ROS levels were assessed via DCFDA assay, while MMP-1 and COL1A1 secretion were quantified using ELISA. Additionally, the regulatory effects on ERK, JNK, and p38 phosphorylation were determined by Western blot. Synergy prediction was analyzed using the SynergyFinder platform via Highest Single Agent and Loewe models. While NMN and HA individually attenuated TNF-α-induced ROS and MMP-1 levels, co-treatment provided superior suppression and exhibited combinational interactions at specific concentrations. These findings suggest that NMN and HA combination treatment effectively modulates oxidative stress and skin-aging-related responses by regulating ROS levels and MAPK signaling pathways. Full article

Objectives: To investigate whether Porphyromonas gingivalis gingipains contribute to the activation of MMP-8 and MMP-9 in patients with cancer and to evaluate the potential of aMMP-8 chair-side test for early detection of active periodontal inflammation in cancer care. Methods: This cross-sectional study enrolled 89 of 119 initially assessed patients with cancer at Dr. Sardjito Hospital, Yogyakarta, Indonesia (2023–2024). Active MMP-8 was quantified using a chair-side test on oral rinse samples. Total MMP-8 was measured by ELISA, MMP-9 activation by gelatin zymography, and gingipain presence by Western immunoblotting. Associations with periodontal parameters (PPD, GI, OHI-S, and VPI) were analyzed using linear regression. Results: aMMP-8 chair-side test demonstrated 91% positive results in 89 patients with cancer. Western blotting revealed the co-localization of gingipains with fragmented MMP-8. aMMP-8 levels were significantly associated with MMP-9 activation (p = 0.003, R² = 0.097), suggesting proteolytic cascade activation. Oral hygiene indices showed stronger associations (OHI-S: p = 0.003, R² = 0.100; VPI: p = 0.014, R² = 0.067) than deeper periodontal parameters (PPD: p = 0.094; GI: p = 0.358), suggesting early-stage inflammation detection. Conclusions: Gingipain presence may be associated with the activation of MMP-8 and MMP-9 in patients with cancer, which links bacterial virulence to amplified tissue destruction. aMMP-8 chair-side test enables rapid identification of active inflammation, facilitating timely periodontal intervention during cancer care. Full article