Search Results (1,887)

Salmon skin, a high-volume by-product of seafood processing, offers a circular-bioeconomy route to sustainable, value-added ingredients. This study aimed to generate low-molecular-weight collagen peptides (LMWCPs) from salmon skin using a stepwise enzymatic process and to evaluate their safety and pro-extracellular-matrix (ECM) activity in human BJ fibroblasts. LMWCPs were produced by sequential hydrolysis (alcalase/papain, then collagenase) and characterized as low-molecular-weight peptide preparations with a mean dispersed particle diameter of approximately 117 nm. LMWCPs display negatively charged peptide dispersions with a mass centered around ~1 kDa. Cytocompatibility (MTT) showed no toxicity up to 1.5 mg/mL over 48 h. Gene expression by reverse transcription–quantitative polymerase chain reaction (RT-qPCR) revealed a robust, dose-dependent ECM response: collagen type I alpha 1 chain (COL1A1) increased by approximately 7-fold, with additional rises of 5–6-fold in versican (VCAN) levels and modest increases in elastin (ELN) and transforming growth factor-β (TGF-β). These findings provide an exploratory process-to-phenotype link between the two-step hydrolysis process, physicochemical characteristics of the resulting LMWCPs, and changes in ECM-related gene expression in BJ fibroblasts. Overall, this study demonstrates that salmon skin LMWCPs were cytocompatible within the tested concentration range and modulated several ECM-related genes, providing a preliminary basis for future protein-level, functional, and translational evaluation. Full article

Background: Transforming growth factor beta 1 (TGF-β1) is a master regulator of fibrogenesis and extracellular matrix (ECM) remodeling. Among molecules involved in profibrotic signaling, periostin (POSTN) and the Snail family transcriptional repressor 2 (SLUG, SNAI2) have emerged as potential regulators of tissue remodeling and fibroblast activation. However, the temporal relationship between TGF-β1-induced expression of SLUG and periostin in human dermal fibroblasts remains poorly understood. Objectives: This study aimed to evaluate the effect of TGF-β1 stimulation on SNAI2/SLUG and POSTN/periostin expression dynamics in normal human dermal fibroblasts (NHDFs) and characterize their association with profibrotic responses. Methods: NHDFs were stimulated with recombinant human TGF-β1 (20 ng/mL) for 24, 48, and 72 h. SNAI2 and POSTN mRNA expression was quantified by RT-qPCR, intracellular SLUG protein levels were assessed by Western blotting, and periostin accumulation in the culture medium was measured by enzyme-linked immunosorbent assay (ELISA). The RT-qPCR and ELISA data were analyzed using two-way ANOVA with Bonferroni correction; because of the small number of replicates (n = 2), the Western blot data are presented descriptively. Results: TGF-β1 significantly increased POSTN mRNA expression after 24 and 48 h (both p < 0.001); at 72 h, POSTN mRNA levels remained numerically elevated relative to the control, although this difference did not reach statistical significance. Periostin accumulation in the culture medium increased progressively and was significantly higher than in the control group after 48 and 72 h (p < 0.001). In contrast, SNAI2/SLUG exhibited transient expression kinetics, with increased SNAI2 mRNA at 48 h (p < 0.05) and the highest SLUG protein levels also observed after 48 h of stimulation, followed by a decline at 72 h. Conclusions: TGF-β1 induced time-dependent changes in SNAI2/SLUG and POSTN/periostin expression in human dermal fibroblasts. As fibroblast activation and ECM remodeling were not directly assessed, the present conclusions are restricted to the expression changes in the two investigated molecules, whose concurrent yet temporally distinct regulation may indicate potential relevance in the fibroblast response to profibrotic signaling. Further studies are required to determine whether they participate in common regulatory mechanisms or independently contribute to fibrotic processes. Full article

Periodontitis is a chronic inflammatory disease initiated by dysbiotic subgingival biofilms and characterized by local tissue destruction, epithelial ulceration, immune-cell activation, and extracellular-matrix remodeling. Increasing evidence suggests that periodontal inflammation may extend beyond the oral cavity through recurrent bacteremia, dissemination of microbial products, systemic cytokine activation, endothelial dysfunction, oxidative stress, and thrombo-inflammatory signaling. These mechanisms are also implicated in atrial structural remodeling and atrial fibrillation (AF), but the molecular bridge between periodontal lesions, systemic inflammatory–fibrotic activity, and the atrial substrate remains incompletely defined. This structured narrative review synthesizes mechanistic, translational, biomarker-based, observational, and interventional evidence linking periodontal inflammation with cardiovascular remodeling and AF. Literature was identified through searches of PubMed/MEDLINE, Scopus, and Web of Science, complemented by reference-list screening. Particular attention was given to thrombospondin-1 (TSP-1), transforming growth factor-β (TGF-β)-related signaling, galectin-3 (Gal-3), and SGLT2-related cardiometabolic pathways. Because of heterogeneity in study populations, periodontal definitions, biomarker measurements, interventions, and cardiovascular endpoints, findings were synthesized thematically rather than quantitatively. Periodontitis is associated with systemic inflammatory activation, endothelial dysfunction, oxidative stress, and cardiovascular phenotypes, including atherosclerotic disease, hypertension, heart failure, and AF. Epidemiological studies support an association between periodontitis and incident AF, while human tissue data link periodontal inflammatory burden with atrial fibrosis, non-paroxysmal AF, and left atrial appendage thrombosis in selected AF populations. The strength of evidence differs across the proposed pathways: Gal-3 has the most consistent clinical evidence in AF and cardiac fibrosis; TSP-1/TGF-ß signaling is supported mainly by mechanistic periodontal-tissue and selected cardiovascular studies; and SGLT2-related pathways remain indirect systemic modifiers of the cardiometabolic and inflammatory milieu. Evidence regarding periodontal therapy and AF-related outcomes remains promising but limited and does not establish a direct antiarrhythmic effect. The available evidence supports a biologically plausible inflammatory–fibrotic continuum linking periodontitis, systemic immune activation, endothelial dysfunction, atrial remodeling, and AF susceptibility. However, causality, temporal sequence, tissue-level concordance, and biomarker-based clinical utility remain insufficiently established. Future studies integrating standardized periodontal assessment, circulating biomarkers, tissue-level inflammatory–fibrotic markers, cardiac imaging, and rhythm monitoring are needed to clarify whether local periodontal molecular signatures reflect systemic or cardiac remodeling relevant to AF vulnerability. Full article

Myostatin (MSTN), a member of the transforming growth factor-β (TGF-β) superfamily, is a conserved negative regulator of muscle growth in vertebrates. In this study, nine MSTN-related genes were identified in Trachinotus ovatus, including two MSTN ligand genes (ToMSTNa and ToMSTNb) and seven putative receptor genes (ToACVR1A, ToACVR1Ba, ToACVR1Bb, ToACVR2Aa, ToACVR2Ab, ToACVR2Ba, and ToACVR2Bb). Comprehensive evolutionary and expression analyses revealed the conservation and potential functional diversification of MSTN-related genes in T. ovatus. The two MSTN ligands showed relatively conserved gene structures and motif compositions, whereas the receptor genes displayed greater structural diversity. Tissue expression analysis showed that ToMSTNa was relatively highly expressed in muscle, while ToMSTNb was relatively highly expressed in brain, suggesting potential tissue-specific functional divergence between the two MSTN paralogs. In addition, expression analysis between large and small individuals showed that ToMSTNa was more highly expressed in the brain and intestine of small individuals than in large individuals, whereas ToACVR1A and ToACVR2Bb showed higher expression levels in the liver of small individuals, suggesting their potential association with growth variation. The homology-based predicted protein association network suggested potential associations of ACVR1B- and ACVR2A-type receptors with components of MSTN-related signaling. Overall, this study provides new insights into the evolutionary conservation, tissue-specific functional divergence, and potential growth-associated roles of the MSTN ligand–receptor system in T. ovatus, providing a foundation for further functional studies of MSTN-related signaling and the identification of candidate molecular targets associated with growth traits in teleost fish. Full article

Endocrine disorders and inherent flaws in oocyte quality are traditional causes of female infertility. Increasing research indicates that structural and biomechanical alterations in the ovarian microenvironment may significantly contribute to reproductive decline. Progressive extracellular matrix remodeling, stromal fibrosis, chronic inflammation, and heightened tissue stiffness seem to affect follicular homeostasis, granulosa–oocyte communication, and ovarian function. Fibro-inflammatory pathways, including transforming growth factor-β (TGF-β), Hippo/YAP-TAZ signaling, oxidative stress, macrophage activation, and mechanotransduction, are increasingly associated with ovarian ageing, polycystic ovary syndrome, reduced ovarian reserve, and unfavourable reproductive outcomes. Here, the term ‘fibro-inflammatory ovary’ is used descriptively to unify these mechanisms rather than as an established clinical entity. Mechanical alterations of the ovarian stroma may affect follicular activation, vascularization, and oocyte competence by altering cellular tension and extracellular matrix dynamics. Our review examines growing findings about ovarian fibrosis and stromal remodeling in female infertility, focusing on molecular causes, mechanobiology, and translational implications for assisted reproduction. Potential diagnostic uses, such as ovarian elastography, and prospective anti-fibrotic therapy techniques are also examined. Full article

PFCP-2-1 (polysaccharide-2-1 of Finger Citron-pickled products), a water-soluble polysaccharide enriched in galacturonic acid, was isolated from Laoxianghuang by hot water extraction and purified using DEAE-52 and agarose CL-6B chromatography. Structural analysis showed that PFCP-2-1 had a smooth surface, flakes of varying sizes and shapes, irregular ellipsoidal structures, and cylindrical-like forms, which likely represent aggregated assemblies formed by the association and curling of polysaccharide chains. It was determined to have an average molecular weight of 749.38 kDa and to consist of rhamnose, galactose, glucose, and galacturonic acid (molar ratio 0.147:0.238:0.059:0.556). FT-IR spectroscopy revealed both α- and β-pyranose configurations, while methylation and NMR analyses identified 16 types of glycosidic linkages, of which 9 were the main types, consistent with a pectic-type structure. In an ethanol-induced acute gastric ulcer mouse model, PFCP-2-1 exhibited significant mucosal protection by elevating prostaglandin E2 (PGE2), transforming growth factor-α (TGF-α), and mucin 5AC (MUC5AC) levels and upregulating Occludin and zonula occludens-1 (ZO-1) expression. It also modulated the gut microbiota by increasing the abundance of Bacteroides and Prevotella_UCG-001, and enhanced short-chain fatty acid (acetate and butyrate) levels. These findings suggest that PFCP-2-1 may exhibit a protective effect against ethanol-induced gastric damage under the conditions of this experiment, suggesting its potential for further development as a functional food ingredient. Full article

The dysregulation of immune homeostasis and the persistence of chronic, low-grade inflammation represent core pathophysiological drivers governing the onset and progression of metabolic and cardiovascular disorders. Myeloid-derived suppressor cells (MDSCs) comprise a highly heterogeneous population of immature myeloid cells that are rapidly mobilized from the bone marrow in response to biological stressors, such as sustained tissue injury and chronic inflammatory signaling. Historically evaluated within oncology and infectious disease frameworks, accumulating evidence highlights the pivotal, context-dependent roles of MDSCs in cardiometabolic environments. In conditions of obesity and type 2 diabetes (T2D), MDSCs undergo substantial expansion and accumulation within peripheral tissues, including adipose tissue and the liver. Functionally, MDSCs act as dynamic immunoregulators that can either buffer metabolic inflammation, via the secretion of interleukin-10 (IL-10), transforming growth factor-beta (TGF-β), and nitric oxide (NO) or, conversely, reflect and exacerbate disease progression depending on specific cellular subsets, glycemic control, and tissue localization. Within the vascular system, specific monocytic MDSC subsets demonstrate significant atheroprotective and cardioprotective capabilities by dampening Th1/Th17-mediated arterial wall inflammation, stabilizing atherosclerotic plaques, and preserving cardiac structural architecture during heart failure. However, phenotypic and functional heterogeneity poses a critical clinical challenge, as certain persistent or altered subsets correlate with heightened cardiovascular risk and adverse cerebrovascular outcomes. This review delivers a comprehensive synthesis of contemporary insights into MDSC biology at the intersection of obesity-associated diabetes and cardiovascular disease, characterizing their dualistic mechanisms, distinguishing preclinical causal mechanisms from human observational data. Moreover, we have established a comprehensive framework to reconcile the conflicting protective versus detrimental effects of MDSCs. And finally, we have also evaluated their potential clinical utility as candidate biomarkers, delineating the safety imperatives essential for translating MDSC-targeted therapeutic interventions into clinical practice. Full article

Clear cell renal cell carcinoma (ccRCC) is a highly immune-evasive malignancy that exhibits limited and often transient responses to immune checkpoint inhibitors (ICIs) and remains a major challenge for emerging cellular immunotherapies, including chimeric antigen receptor (CAR)-T cells. A defining feature of ccRCC, largely driven by von Hippel–Lindau (VHL) deficiency, is persistent activation of the transforming growth factor-β1 (TGF-β1) and hypoxia-inducible factor (HIF) signaling network. Acting as a central immunometabolic regulatory axis, TGF-β1/HIF promotes angiogenesis, metabolic reprogramming, epigenetic dysregulation, and immune escape through coordinated induction of immunosuppressive mediators, including PD-L1, VEGF, and CTLA-4, resulting in impaired T-cell infiltration, functional exhaustion, and resistance to immunotherapy. Preclinical studies have demonstrated that pharmacologic-dose Seleno-L-methionine (SLM) and its active metabolite, methylseleninic acid (MSA), suppress TGF-β1 and both HIF-1α and HIF-2α, leading to downregulation of multiple downstream immunosuppressive pathways at pharmacologically achievable, non-toxic concentrations. In addition to enhancing the antitumor activity of chemotherapy and VEGF-targeted agents, accumulating evidence suggests that SLM exerts broad immunologic, metabolic, and epigenetic effects that may overcome key mechanisms of therapeutic resistance. This review synthesizes current mechanistic and translational evidence supporting the repurposing of SLM as a first-in-class pleiotropic immunomodulatory agent. Using ccRCC as a model of TGF-β1/HIF-driven immune resistance, we discuss how simultaneous targeting of this central regulatory axis may restore immune surveillance, improve T-cell fitness and trafficking, enhance responses to ICIs and CAR-T cell therapy, and provide a mechanistically rational strategy for the treatment of advanced solid tumors. Full article

Platelets express several glycophosphatidylinositol-(GPI-) anchored receptors, mainly involved in protection against lysis by activated complements. Most of these are well-characterised and are expressed on other blood cells. More recently, CD109 with a mass of 175 kDa was also shown to be a GPI-anchored receptor, surface expressed only on activated platelets, with a role as a co-receptor for transforming growth factor-β (TGF-β). CD109 is expressed on a wide range of cells and is a marker for various types of tumors. Activated platelets express an even larger GPI-anchored receptor at about 500 kDa. We have now isolated this and identified it as fibrocystin L, also known as polycystic kidney hepatic disease L1 (PKHD1L1). Fibrocystin L, like other platelet GPI-anchored receptors, is missing or deficient in paroxysmal nocturnal hemoglobinuria. Fibrocystin L is also expressed in activated T-cells and may be involved in immune responses. Recently, there have been additional reports of PKHD1L1 expression and roles as a coat protein of hair-cell stereocilia essential for normal hearing, as well as reports of them in the dentate gyrus in mice involved in susceptibility to seizure. In all these cases, GPI anchors were not reported, but neither were they tested for. During the fluorescence microscopy studies, we used CD109 as a control and observed that it is also a granule protein that had not been previously reported. Full article

Methyl-CpG binding domain protein 3 (MBD3) is a member of the nucleosome remodeling and deacetylase (NuRD) corepressor protein complex, which plays a pivotal role in embryonic development, pluripotent stem cell (PSC) differentiation, and induced pluripotent stem cell (iPSC) reprogramming. However, whether MBD3 is also involved in iPSC differentiation into primordial germ cell-like cells (PGCLCs) is unclear. In this study, bovine iPSCs generated by MBD3 knockdown (MBD3 KD) during reprogramming were subjected to PGCLC differentiation using a monolayer cell culture method. Our results revealed that MBD3 KD enhanced the ability of bovine iPSCs to differentiate into PGCLCs. MBD3-KD bovine iPSC-derived PGCLCs exhibited the characteristics of in vivo primordial germ cells (PGCs) in a migratory state. MBD3 KD increased NODAL signal transduction during the induction of PGCLCs and was associated with increased expression of PRDM1 and SOX15. Moreover, MBD3 KD increased the bivalent modification of transforming growth factor beta (TGF-β)-related genes concomitant with the upregulation of DPPA4 and DNMT3L expression in bovine iPSCs, and this epigenetic change was associated with enhanced NODAL signaling. Our results indicate that MBD3 KD during reprogramming favors the differentiation of bovine iPSCs into PGCLCs, further highlighting the impact of MBD3 on histone modifications during germ cell development. Full article

Objectives: This study focuses on exploring the mechanism by which Schisandrin B (Sch B) regulates metabolic dysfunction-associated steatotic liver disease (MASLD) mice induced by a high-fat methionine–choline-deficient (MCD) diet through the activation of peroxisome proliferator-activated receptor γ (PPARγ). Methods: Male C57BL/6 mice were fed a high-fat MCD diet for 8 weeks to establish a mouse MASLD model, and the effects of Sch B on MASLD and the mechanisms were investigated. PPARγ overexpression (OE) was induced by adeno-associated virus (AAV) administration via intrahepatic portal vein injection in mice, and a negative control (NC-OE) was also established. Body weight; wet liver weight; hepatic index; serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β); and hepatic triglyceride (TG) levels were measured in the mice. The histopathology and lipid deposition were observed by hematoxylin and eosin (H&E) staining and Oil Red O staining, while the fibrosis was assessed using Masson staining. Western blot was employed to detect the expression levels of PPARγ, sterol regulatory element-binding protein 1c (SREBP-1c), carnitine palmitoyltransferase 1A (CPT1A), transforming growth factor β1 (TGF-β1), α-smooth muscle actin (α-SMA), collagen type I (collagen I), Smad family members 2/3 (Smad2/3), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38), and extracellular signal-regulated kinase 1/2 (ERK1/2), along with the phosphorylation activation status of these kinases. Results: It was confirmed that Sch B caused effects similar to those induced by PPARγ overexpression, reducing the hepatic index, AST, and ALT levels while alleviating lipid accumulation and fibrosis; and upregulating PPARγ and CPT1A while inhibiting SREBP-1c; and the phosphorylation of the TGF-β/Smad and MAPK pathways were involved in the mechanisms. Conclusions: Sch B can alleviate high-fat MCD-induced MASLD by activating PPARγ in mice. Full article

The aim of this study was to summarize current evidence on dust-related diseases of the bronchopulmonary system, medicinal plants, herbal formulations, and their underlying mechanisms of action. A literature review was conducted based on publications indexed in ScienceDirect, Google Scholar, SciFinder, Scopus, and Medline (PubMed), focusing on the mechanisms underlying dust-related diseases of the bronchopulmonary system, pneumoconiosis, and the potential of phytotherapeutic approaches to modulate these processes. The following keywords were used: bronchopulmonary system, pneumoconiosis, dust-related lung diseases, medicinal plants, herbal preparations, pulmonary rehabilitation, and lymphatic sanitation. The pathogenesis of pneumoconiosis involves the deposition of inhaled dust particles in the lung tissue, followed by chronic inflammation, oxidative stress, and progressive fibrosis. In experimental models, flavonoids, alkaloids, terpenoids, glycosides, tannins, and other phytochemical groups have demonstrated therapeutic potential in bronchopulmonary diseases. Among the compounds investigated, emodin, celastrol, kaempferol, sodium tanshinone IIA sulfonate, astragaloside IV, and dioscin have shown promising effects by modulating key signaling pathways and reducing inflammatory responses. Experimental evidence indicates that these phytochemicals can target major pathways involved in inflammation and fibrogenesis, thereby exerting antioxidant, anti-inflammatory, and antifibrotic effects. The lymphatic system also contributes to the pathogenesis of pneumoconiosis by transporting inhaled dust particles to regional lymph nodes, where their accumulation may promote lymph node sclerosis. Therefore, lymphatic sanitation may represent an important therapeutic mechanism of action of herbal formulations in pneumoconiosis. Our proposed lymphotropic herbal formulation enhances physiological lymphatic drainage and may positively influence the motility and functional activity of the tracheobronchial lymph nodes. The therapeutic potential of medicinal plants and herbal formulations in pneumoconiosis is supported by experimental findings for Tripterygium wilfordii (celastrol, through suppression of the EDNRB/Kng1–(endothelin receptor type B/kininogen1), Delphinium, Camellia, and Berberis species (kaempferol, through inhibition of TLR4 (Toll-like receptor 4 signaling), Astragalus membranaceus (astragaloside IV, through antifibrotic activity mediated by inhibition of the TGF-β1 (transforming growth factor beta 1)/Smad3 (SMAD family member 3) pathway), and Reynoutria japonica Houtt., Rheum, and Aloe species (emodin, through inhibition of Smad3 and NF-κB (nuclear factor kappa B) phosphorylation and reduction of TGF-β1, α-SMA (alpha-smooth muscle actin), collagen I, TNF-α (tumor necrosis factor alpha), and IL-1β (interleukin-1 beta) levels in lung tissue). For these and several other medicinal plants and their flavonoids, antifibrotic activity has been demonstrated through inhibition of the Akt/NF-κB (protein kinase B/nuclear factor kappa B) signaling pathway. A promising direction for future research is to evaluate the combined use of herbal formulations with established antifibrotic agents to determine whether synergistic therapeutic effects can be achieved. Full article

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease driven by aberrant extracellular matrix deposition, with the activity of transforming growth factor-beta 1 (TGF-β1) orchestrating fibrogenesis. Current therapies are limited by severe adverse effects, highlighting the unmet need for safer treatments. In this study, the therapeutic potential of chlorogenic acid (CGA) in a murine model of pulmonary fibrosis was evaluated. Methods: Pathology was induced on day 0 via subcutaneous osmotic minipumps delivering bleomycin (BLM) for one week, followed by pump removal on day 10. Therapeutic interventions with intragastric CGA (60 mg/kg) were administered daily from days 14 to 20. Lung tissue samples obtained on day 21 were analyzed via histological, immunohistochemical, and RT–PCR methods. Results: Histological analysis via H&E and Masson’s trichrome staining revealed that CGA treatment significantly attenuated alveolar thickening, restored the alveolar space, and reduced the total cell density and Ashcroft fibrosis score. Furthermore, CGA markedly decreased collagen deposition. Quantitative RT–PCR and immunohistochemical assays revealed that CGA effectively decreased the expression of Col1a1, TGF-β1, and the myofibroblast marker alpha-smooth muscle actin (α-SMA). Conclusions: CGA exerts important therapeutic effects by decreasing the expression of TGF-β1 and the activation of myofibroblasts, indicating that this natural polyphenol is a promising candidate for mitigating the progression of pulmonary fibrosis. Full article

Wound healing is a dynamic and highly coordinated process that involves inflammation, cell proliferation, angiogenesis, re-epithelialization, extracellular matrix remodeling, and tissue maturation. The altered expression of important signaling pathways, such as transforming growth factor-β (TGF-β)/Smad, nuclear factor-κB (NF-κB), phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), mitogen-activated protein kinase (MAPK), and Wnt/β-catenin, may be responsible for slower wound healing, chronic inflammation, excessive fibrosis, and impaired tissue regeneration. Multifunctional nanomaterials are a promising strategy for tuning these highly coordinated processes due to their tunable physicochemical properties, high surface area, and the ability to deliver cargo, as well as the integration of antimicrobial, antioxidant, anti-inflammatory, and pro-angiogenic properties. The aim of current review is to summarize the potential of multifunctional nanomaterials to promote wound healing, with a focus on mechanisms of action and modulation of key cellular signaling pathways. A systematic review of the literature was conducted using PubMed, Scopus, Web of Science, and Google Scholar, searching for publications from 1996 to June 2026, and representative experimental, mechanistic, preclinical, and translational studies were critically evaluated. In this review, the authors discuss the role of nanomaterial properties, therapeutic payload, molecular targets, modulation of cellular signaling pathways, and regenerative effects. These platforms have been shown in in vitro and animal studies to influence inflammatory signaling, oxidative stress, angiogenesis, collagen remodeling, re-epithelialization, cellular proliferation, and migration. However, the modulation of these pathways are dose-responsive, time-dependent, and cell- and wound-stage-specific. Despite the promising therapeutic potential of nanomaterial-based wound care strategies, the available evidence remains predominantly preclinical, with relatively limited clinical data supporting their use in humans. Concerns regarding long-term toxicity, biodistribution, batch-to-batch reproducibility, sterilization, scalable manufacturing, regulatory approval, and commercial feasibility further challenge translation into clinical practice. Multifunctional nanomaterials may offer a promising approach for pathway-specific and multimodal wound management; however, comprehensive mechanistic studies, long-term safety and biodistribution assessments, and well-designed clinically relevant investigations are required to establish their efficacy, safety, and true translational potential. Full article

Coronary artery disease is a leading cause of morbidity and mortality in modern medicine. In contrast, surgical myocardial revascularization via coronary artery bypass grafting (CABG) remains the gold standard of treatment for complex multivessel disease. The great saphenous vein remains the most frequently used conduit due to its availability and technical simplicity, but its long-term patency is significantly inferior to that of arterial grafts. The primary pathological process responsible for vein graft failure is intimal hyperplasia, which represents a complex response of the vascular wall to surgical trauma, vein arterialization, inflammation, and hemodynamic stress. This process is characterized by endothelial dysfunction, inflammatory cell activation, proliferation and migration of vascular smooth muscle cells, and extracellular matrix remodeling. Underpinning these alterations are numerous molecular pathways, including NF-κB, MAPK, PI3K/Akt, TGF-β, and mTOR signaling, as well as substantial contributions from oxidative stress, cytokines, growth factors, and microRNAs. Contemporary research indicates that the phenotypic transformation of vascular smooth muscle cells constitutes the central event in the development of intimal hyperplasia. Understanding the cellular and molecular mechanisms underlying this disease’s onset enables the development of novel therapeutic strategies to preserve long-term graft patency. This review paper aims to provide a systematic overview of current knowledge regarding the molecular and cellular mechanisms of intimal hyperplasia development in vein grafts following CABG. Full article