Search Results (152)

Polydeoxyribonucleotide (PDRN) is a DNA-derived biological therapy gaining prominence in the treatment of musculoskeletal disorders. It functions as an adenosine A2A receptor (A2AR) agonist and serves as a substrate in the nucleotide salvage pathway. These mechanisms drive anti-inflammatory effects, stimulate angiogenesis via vascular endothelial growth factor, and promote collagen synthesis. In osteoarthritis, PDRN reduces cartilage degradation and promotes the chondrogenic differentiation of stem cells. PDRN has shown therapeutic potential in tendinopathies, including Achilles and rotator cuff injuries, by supporting tissue repair. Preliminary reports suggest it may offer a non-steroidal alternative for managing spinal radiculopathy when corticosteroids are contraindicated, though robust comparative trials are needed. Preclinical and clinical evidence indicate favorable preliminary safety profiles and potential pain reduction. Future large-scale trials are needed to standardize the dosing protocols for integrated orthopedic rehabilitation. Full article

Skin photoaging is primarily induced by ultraviolet (UV) radiation and is accompanied by extracellular matrix (ECM) degradation, abnormal pigmentation, and loss of skin elasticity. Excessive melanin synthesis represents a key cause of pigmentary skin disorders. Natural polyphenols with dual skin-whitening and anti-photoaging activities have attracted increasing attention as cosmetic ingredients. This study examined the effects of polyphenol-enriched fraction from the brown alga Sargassum fusiforme (SFP). Zebrafish embryos and human melanoma A375 cells were used to evaluate the depigmenting efficacy of SFP, while UVA-induced human dermal fibroblasts (HDFs) were employed to assess its anti-photoaging activity. SFP significantly decreased melanin levels in both models in a dose-dependent and reversible manner by suppressing tyrosinase activity. In terms of anti-photoaging effects, SFP markedly suppressed UVA-induced matrix metalloproteinases (MMPs) expression and elevated key ECM components, including type I collagen, elastin, and hyaluronic acid. In conclusion, SFP exerts dual beneficial effects by attenuating melanogenesis via tyrosinase inhibition and alleviating photoaging damage by suppressing MMPs to protect ECM. These results provide a scientific foundation for the use of SFP as a dual-purpose natural cosmetic ingredient with significant potential in the cosmetics sector. Full article

Excessive ultraviolet A (UVA) irradiation disrupts extracellular matrix (ECM) homeostasis in skin photoaging by impairing the balance between synthesis and degradation, yet whether silk fibroin peptide (SF), a small bioactive peptide from Bombyx mori, can restore this balance through mechanotransduction pathways remains unknown. Herein, we demonstrate that SF dose-dependently rescues human dermal fibroblasts (HDFs) from UVA-induced oxidative stress, senescence, and ECM disintegration. Notably, SF not only suppresses reactive oxygen species (ROS) and restores activities of antioxidant enzymes, but is also associated with the recovery of the ITGB1-FAK mechanotransduction axis, as evidenced by restored fibronectin levels and increased focal adhesion kinase (FAK) phosphorylation, whereas integrin β1 (ITGB1) expression itself was not significantly altered. This mechanosensory recovery is accompanied by restoration of downstream transforming growth factor-β (TGF-β)/Smad signaling, upregulation of COL1A1, COL3A1 and ELN transcription, and simultaneous suppression of MMP1, MMP3 and MMP9. Unlike conventional antioxidants or exogenous collagen supplements that merely counteract oxidative damage or provide structural substitutes, SF may facilitate recovery of the disrupted cell–matrix interface potentially through modulation of integrin-mediated mechanochemical signal conversion, which may contribute to ECM homeostasis restoration. Collectively, SF promotes mechanotransduction, offering a potential paradigm for anti-aging strategies that target ECM homeostasis through integrin signaling. Full article

Bioactive collagen peptides and collagen hydrolysates are dietary proteins whose degradation products also carry signaling activity. This second part of a two-part narrative review addresses the translational dimensions of their bioactivity, integrating veterinary clinical trials, controlled animal-model studies, and human biomedical data, with evidence strictly stratified by type. The gastrointestinal tract acts not only as the absorption site but as a target organ. In cell culture and rodent models, luminal collagen fragments restore tight-junction integrity, alter the microbiome, and shift the enterohepatic bile acid pool; increased secondary bile acid synthesis is proposed to engage the farnesoid X receptor (FXR) and Takeda G-protein-coupled receptor 5 (TGR5). None of these steps have been demonstrated in veterinary clinical patients. The accompanying GLP-1 and PYY response may reflect direct amino acid stimulation of enteroendocrine cells as much as a bile acid-dependent route, and current data do not separate the two. Veterinary trials show objective kinetic improvement in osteoarthritic dogs and horses. Taurine-responsive dilated cardiomyopathy is a reversible, diet-amenable condition; as the principal bile acid conjugation substrate in carnivores, taurine acts on the same bile acid pool as a mechanistically separate input. Recent data implicate prolyl-hydroxyproline in brown adipogenesis, collagen peptides in hippocampal neurogenesis, and taurine in platelet normalisation. The gut–collagen peptide axis is an evolving model linking dietary collagen to systemic metabolic, endocrine, and immune signaling, with implications for companion-animal, equine, and livestock practice. Full article

Background: Continuous chelation with etidronic acid (1-Hydroxyethylidene-1,1-diphosphonic acid, HEDP) has been proposed as a less aggressive alternative to sequential irrigation with ethylenediaminetetraacetic acid (EDTA) in endodontics. This systematic review and meta-analysis aimed to compare the effects of these two protocols on the mechanical properties and structure of root dentin. Methods: PubMed, Scopus, and Cochrane Central databases were searched up to June 2026 for in vitro studies comparing continuous chelation (NaOCl + HEDP mixture) with sequential irrigation (NaOCl and EDTA) on root dentin of permanent teeth. Studies on coronal dentin and those not using NaOCl + HEDP as a mixture were excluded. Risk of bias was assessed using the QUIN tool. Meta-analyses were performed for fracture resistance using a random-effects model. This review was registered in PROSPERO (CRD420250630663). Results: Twenty studies with a total of 572 specimens were included. Six studies had a low risk of bias and thirteen had a medium risk. The qualitative synthesis showed that HEDP generally resulted in similar or lower levels of erosion, microhardness reduction, demineralization, and collagen degradation compared to EDTA. The meta-analysis revealed no significant difference in fracture resistance (5 studies; SMD = 0.28; 95% CI: −0.37 to 0.92; p = 0.40); however, substantial heterogeneity was observed (I² = 66.7%). Conclusions: The evidence was limited by substantial heterogeneity and mainly medium risk of bias. Within the limitations, in vitro evidence suggests that continuous chelation with HEDP is comparable to EDTA in terms of root dentin mechanical properties and composition, supporting its use as a chelating agent in endodontic practice. This research received no external funding. Full article

Osteoarthritis (OA) is a chronic, debilitating degenerative joint disease whose prevalence is rising markedly with the rapid aging of the global population. In this study, we investigated the chondroprotective efficacy of NP-2007, an enzymatically hydrolyzed low-molecular-weight collagen from Cervi cornu, using IL-1β-stimulated SW1353 human chondrocyte cells and a medial meniscal transection (MMT)-induced OA rat model. In SW1353 cells, NP-2007 considerably suppressed the expression of inflammatory mediators (iNOS, COX-2) and cytokines (TNF-α, IL-6) without cytotoxicity. Crucially, it restored matrix homeostasis by downregulating catabolic enzymes (MMP-3, MMP-13, and ADAMTS-5) and upregulating anabolic markers (COL2A1, aggrecan), a process associated with the modulation of the Wnt/β-catenin and phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathways and the recovery of the master chondrogenic factor SOX9. These in vitro findings were consistent with the in vivo results from the MMT model, where oral administration of NP-2007 (50 and 200 mg/kg) for 8 weeks effectively preserved articular cartilage structure and proteoglycan content while markedly reducing serum levels of catabolic biomarkers, including MMP-13 and COMP. Collectively, our findings demonstrate that NP-2007 exerts potent chondroprotective effects by modulating the balance between cartilage degradation and synthesis, suggesting its potential as a therapeutic candidate for the management of OA. Full article

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

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

Skin aging, pigmentation disorders and skin barrier dysfunction are strongly associated with oxidative stress, chronic inflammation and extracellular matrix degradation. In this context, plant sprouts have gained popularity as a rich source of bioactive compounds and are becoming promising candidates for dermatological applications. The aim of this review was to summarize current scientific research on the potential of sprout extracts in skin care and to identify the biological mechanisms underlying their dermatological activity. A comprehensive literature search was conducted in Medline, Scopus, and Google Scholar databases up to February 2026. Studies assessing the effects of topical sprout extracts on skin structure, inflammation, pigmentation, and hair growth were included. A total of 31 studies met the inclusion criteria and were subjected to qualitative analysis. Available evidence indicates that sprout extracts have multifaceted effects relevant to skin health, including stimulation of collagen synthesis, inhibition of matrix metalloproteinases, improvement of epidermal hydration, melanogenesis, and suppression of inflammatory signaling pathways. These effects are largely attributed to bioactive compounds such as phenolic acids, flavonoids, isothiocyanates, and other antioxidant phytochemicals, which exhibit antioxidant, anti-inflammatory, and anti-aging properties. Preliminary clinical studies suggest that ingredients derived from sprouts may improve skin elasticity, hydration, and photoprotection. Although most of the evidence comes from in vitro and animal studies, it preliminarily supports the emerging concept of “food for skin” and highlights the potential of sprouted plant materials as multifunctional ingredients in dermatology. Full article

Skin aging is driven by both intrinsic and extrinsic factors, including ultraviolet (UV) radiation and environmental stressors. Tumor necrosis factor-alpha (TNF-α) is a key pro-aging cytokine that promotes reactive oxygen species (ROS) production, leading to collagen degradation and inflammatory responses in skin cells. In this study, we investigated the protective effects of Prunus persica flower extract and its major constituents (1–4) against TNF-α–induced oxidative and inflammatory responses in human dermal fibroblasts (HDFs) and human epidermal keratinocytes (HEKs). In HDFs, the extract and isolated compounds significantly suppressed TNF-α–induced ROS generation and matrix metalloproteinase-1 (MMP-1) secretion while enhancing collagen synthesis. Notably, mandelamide (4) markedly reduced MMP-1 secretion (from 7.53 ± 0.28 to 2.97 ± 0.12, p < 0.001) and restored collagen levels (from 3.3 ± 0.03 to 19.1 ± 0.58, p < 0.001). In HEKs, mandelamide attenuated the production of inflammatory mediators under TNF-α stimulation and further suppressed MMP expression while restoring the mRNA expression of hyaluronan synthase genes under TNF-α/ interferon-γ (IFN-γ) co-stimulation. Importantly, mandelamide exhibited selective activity under inflammatory conditions without affecting basal cellular states. Collectively, these findings demonstrate that mandelamide is a key bioactive constituent of Prunus persica (P. persica) flowers and exerts protective effects against inflammation-associated skin aging through the modulation of oxidative stress and extracellular matrix homeostasis. Full article

Background: Anterior cruciate ligament (ACL) injuries are increasing in young athletes and many are related to non-contact, spontaneous mechanical fatigue-related ruptures. The objective of this narrative review is to identify and synthesize the anatomical, histological, physiological, and biomechanical basis of extracellular matrix (ECM) factors that contribute to ACL injuries and suggest ways to decrease their occurrence. Methods: The primary investigator searched PubMed, Web of Science, and Google Scholar database titles and abstracts using search phrases with Boolean operators: “anterior cruciate ligament” OR “ACL”, OR “cranial cruciate ligament” AND “disease”; “anterior cruciate ligament” OR “ACL”, OR “cranial cruciate ligament” AND “spontaneous rupture” OR “non-contact injury”; and “anterior cruciate ligament” OR ACL, OR cranial cruciate ligament” AND “crosslink”, “collagen” OR “extracellular matrix”; and “anterior cruciate ligament” OR “ACL”, OR “cranial cruciate ligament” AND “microtrauma”, OR “sudden” OR “fatigue failure”. The primary investigator and a sports orthopedic surgeon reviewed titles and abstracts of diverse evidence sources. From these identified sources, the study team performed full text reviews, selected contributing articles, performed Strength of Recommendation Taxonomy (SORT) grading, and synthesized the following themes: A Hostile Environment, ACL Strain, and Poor Nutrient Delivery; Accumulative ACL Microtrauma and Mechanical Failure; The ACL Differs From Other Ligaments; Collagen, the ECM, and ACL Mechanobiology; Crimps and ACL ECM Stretch; Crosslinks Improve ECM Mechanical Properties; The Delicate Collagen Synthesis and Degradation Balance; Exercise Training and the ACL; Can Nutraceuticals Help Restore the Balance?; Training Induced ACL Hypoxia; Estrogen and the Female Athlete; Counting Pitches or Counting Collagen Fiber Ruptures; and Restoring A Positive Anabolic–Catabolic Collagen Balance. Results: Regular exercise training within a physiologically safe loading range is vital to ACL ECM health. However, low or moderate evidence suggested that poor blood supply, slow metabolism, and a hypoxic environment may unbalance anabolic and catabolic homeostasis. Active rest and recovery concepts that prevent youth baseball shoulder and elbow injuries may help prevent non-contact ACL injuries. Conclusions: More prescriptive active rest and recovery intervals and neuromuscular control training may restore the anabolic–catabolic balance that increases mature crosslink density and improves ACL ECM strength. Confirmatory studies are needed to better establish therapeutic intervention mode(s), timing, dosage, and frequency optimization. Full article

Skin aging and wound healing are the result of intricate and interconnected processes involving chronic inflammation, oxidative stress, cellular senescence and extracellular matrix degradation. Mesenchymal stem cell (MSC)-derived exosomes are rich in bioactive components, particularly microRNAs (miRNAs), which play a crucial role in regulating gene expression and key signaling pathways critical for maintaining skin homeostasis. This article reviews the current evidence regarding the roles of MSC-derived exosomal miRNAs (MSC-Exo-miRNAs) in cutaneous repair and rejuvenation. Specific exosomal miRNAs are analyzed for their ability to modulate inflammatory responses, promote fibroblast proliferation and collagen synthesis, enhance angiogenesis, and facilitate keratinocyte migration and re-epithelialization. Their roles in regulating key signaling pathways are discussed in the context of skin regeneration and aging, including nuclear factor-κB (NF-κB), PI3K/Akt, TGF-β/Smad, Wnt/β-catenin, and nuclear factor erythroid 2-related factor 2 (Nrf2). Additionally, emerging engineering strategies aimed at optimizing miRNA cargo loading, improving delivery efficiency, and advancing clinical translation are highlighted. Overall, MSC-Exo-miRNAs represent a promising cell-free therapeutic strategy for skin repair and rejuvenation; however, further mechanistic investigations and rigorous clinical studies are necessary to fully realize their translational potential. Full article

Epidermal Growth Factor (EGF) plays an important role in skin regeneration and repair by promoting cell proliferation and collagen synthesis. However, its topical application is limited by low stability, susceptibility to degradation, and poor penetration through the stratum corneum due to its hydrophilic nature and relatively large molecular size. Microencapsulation offers a strategy to protect sensitive bioactives and improve their delivery in cosmetic formulations. In this study, EGF was encapsulated in Arabic gum/gelatine A (AG/GE) coacervate microcapsules and incorporated into a hydrating cream. The work extends previous studies using the same microcapsule composition for lipophilic compounds, demonstrating its applicability for a hydrophilic bioactive and highlighting the versatility of the encapsulation platform. The resulting microcapsules exhibited spherical, multinucleated morphology with an encapsulation efficiency of 78.8 + 1.0%. Although diffusion of microencapsulated EGF in the cream could not be directly determined, the formulation showed trends towards improvement in several skin parameters during the volunteer evaluation, including reduction in surface spots (31%), brown spots (21%) and pore visibility (10%), and improved texture (22%). A 25% decrease in transepidermal water loss and a 33% increase in elasticity suggested improved skin barrier function. Volunteers reported high acceptance regarding non-irritancy, texture, and sensory experience. Full article

Hyaluronic acid (HA) is a biologically active glycosaminoglycan with recognized roles in wound healing and inflammation modulation, and its adjunctive use in dental and periodontal therapy has gained interest, particularly in medically compromised patients. This narrative review critically evaluated preclinical and clinical evidence on locally applied HA in periodontal, oral surgical, peri-implant, and oral medicine treatments in patients with systemic conditions. A literature search of PubMed/MEDLINE, Scopus, and Web of Science (January 2015–December 2025) identified in vivo translational studies, randomized and controlled clinical trials, and selected systematic reviews involving medically compromised populations. Qualitative synthesis focused on biological plausibility, clinical outcomes, and safety. Nine core studies were included, comprising two preclinical in vivo investigations and seven clinical trials. In diabetic models, cross-linked high-molecular-weight HA reduced macrophage infiltration and delayed collagen membrane degradation without impairing angiogenesis. Clinically, adjunctive HA use in patients with type 2 diabetes mellitus was associated with modest but statistically significant short-term improvements in clinical attachment level (CAL) and enhanced early soft tissue healing following tooth extraction. In peri-implantitis therapy and oncology-related oral complications, HA application was linked to reduced inflammatory markers, decreased lesion severity, and improved patient-reported symptoms. No systemic adverse effects were reported. Overall, HA appears to be a locally safe adjunct that may support early healing and inflammation control in medically compromised patients, although its effects are primarily short-term and do not indicate disease-modifying potential. Full article

Thin, dry skin is characterized by impaired barrier integrity, loss of dermal density, and accelerated aging driven by intrinsic and extrinsic factors. Biomimetic collagen peptides mimic native collagen sequences, stimulating fibroblasts to enhance synthesis while limiting matrix metalloproteinase-mediated degradation. This study evaluated the clinical efficacy and safety of a multi-ingredient cosmetic product for thin, dry, aging skin, formulated as a dual-purpose body and face serum lotion containing 0.1% biomimetic collagen tripeptide (Tripeptide-29) along with Niacinamide, Citrullus lanatus fruit extract, and Selaginella lepidophylla extract. In this prospective, single-center study, 47 healthy women, aged 36–65 years with Fitzpatrick skin types I–IV, applied the formula twice daily to the face and body over four weeks. Objective measurements—including elasticity, wrinkle depth and volume, hydration, trans-epidermal water loss (TEWL), and texture—were collected weekly alongside clinical grading and self-assessments. Significant improvements were observed across all parameters, with facial dryness decreasing immediately (−74.6%) and continuing to week 4 (−93.7%), hydration increasing up to 72.5%, softness improving up to 37.7%, roughness decreasing up to 37.9%, and TEWL reductions indicating strengthened barrier function. Desquamation improved by 75.5% by week 3, and no adverse effects occurred. The serum lotion demonstrated robust, well-tolerated benefits for enhancing multiple markers of thin, dry, aging skin. Full article