Search Results (558)

The development of advanced wound dressings that integrate favorable physico-mechanical properties with the ability to support physiological healing processes remains a critical challenge in biomaterials science. An ideal dressing should modulate the wound microenvironment, prevent infection, maintain hydration, and possess adequate strength and elasticity. This study aimed to fabricate and characterize electrospun chitosan (CS)-based 3D scaffolds dual-reinforced with halloysite nanotubes (HNTs) and cerium oxide nanoparticles (CeONPs) to enhance material properties and biological performance. HNTs were incorporated to improve electrospinnability and provide mechanical reinforcement, while CeONPs were added for their redox-modulating and anti-inflammatory activities. Composite mats were fabricated via non-capillary electrospinning. The individual and synergistic effects of HNTs and CeONPs were systematically evaluated using physico-chemical methods (SEM, EDX, WAXS, TGA, mechanical testing) and biological assays (in vitro cytocompatibility with mesenchymal stem cells, in vivo biocompatibility, and wound healing efficacy in a rat model). Scaffolds containing only HNTs exhibited defect-free nanofibers with an average diameter of 151 nm, whereas the dual-filler (CS-PEO-HNT-CeONP) composites showed less uniform fibers with a rough surface and a larger average diameter of 233 nm. The dual-filler system demonstrated significantly enhanced mechanical properties, with a Young’s modulus nearly double that of pure CS mats (881 MPa vs. 455 MPa), attributed to strong interfacial interactions. In vivo, the CS-PEO-HNT-CeONP scaffolds degraded more slowly, promoted earlier formation of a connective tissue capsule, and elicited a reduced inflammatory response compared to single-filler systems. Although epithelialization was temporarily delayed, the dual-filler composite ultimately facilitated superior tissue regeneration, characterized by a more organized, native-like collagen architecture. The synergistic combination of HNTs and CeONPs within a CS matrix yields a highly promising scaffold for wound management, offering a unique blend of tailored biodegradability, enhanced mechanical strength, and the ability to guide healing towards a regenerative rather than a fibrotic outcome, particularly for burns and traumatic injuries. Full article

Diabetic nephropathy (DN) remains the leading cause of end-stage renal disease worldwide, with proximal tubular epithelial cells (PTECs) playing a central role in its pathogenesis. Under hyperglycemic conditions, PTECs drive a pathological triad of inflammation, apoptosis, and fibrosis. Recent advances reveal that these processes interact synergistically to form a self-perpetuating vicious cycle, rather than operating in isolation. This review systematically elucidates the molecular mechanisms underlying this crosstalk in PTECs. Hyperglycemia induces reactive oxygen species (ROS) overproduction, advanced glycation end products (AGEs) accumulation, and endoplasmic reticulum stress (ERS), which collectively activate key inflammatory pathways (NF-κB, NLRP3, cGAS-STING). The resulting inflammatory milieu triggers apoptosis via death receptor and mitochondrial pathways, while apoptotic cells release damage-associated molecular patterns (DAMPs) that further amplify inflammation. Concurrently, fibrogenic signaling (TGF-β1/Smad, Hippo-YAP/TAZ) promotes epithelial–mesenchymal transition (EMT) and extracellular matrix (ECM) deposition. Crucially, the resulting fibrotic microenvironment reciprocally exacerbates inflammation and apoptosis through mechanical stress and hypoxia. Quantitative data from preclinical and clinical studies are integrated to underscore the magnitude of these effects. Current therapeutic strategies are evolving toward multi-target interventions against this pathological network. We contrast the paradigm of monotargeted agents (e.g., Finerenone, SGLT2 inhibitors), which offer high specificity, with that of multi-targeted natural product-based formulations (e.g., Huangkui capsule, Astragaloside IV), which provide synergistic multi-pathway modulation. Emerging approaches (metabolic reprogramming, epigenetic regulation, mechanobiological signaling) hold promise for reversing fibrosis. Future directions include leveraging single-cell technologies to decipher PTEC heterogeneity and developing kidney-targeted drug delivery systems. We conclude that disrupting the inflammation–apoptosis–fibrosis vicious cycle in PTECs is central to developing next-generation therapies for DN. Full article

Background: Mechanical processing techniques are commonly employed to prepare adipose tissue for clinical applications in reconstructive and aesthetic procedures. However, their histological and immunohistochemical impact on adipose tissue remains incompletely characterized. Purpose: This systematic review aims to investigate the impact of mechanical processing on the histological and immunohistochemical properties of adipose tissue. Methods: A systematic search was conducted using PubMed, Ovid, and Cochrane Library databases, with publications up to December 2024, employing Boolean operators (“mechanically processed” OR “lipoaspirate” OR “fat graft” OR “gauze rolling” OR “decantation” OR “coleman fat” OR “celt” OR “nanofat” OR “lipofilling” OR “human fat”) AND (“histol*”). Included were English-language studies or studies with a recognized English translation which had been subject to peer review and reported quantitative or qualitative markers of mechanically processed human adipose tissue with histology or immunohistochemistry. Risk of Bias was assessed with the OHAT score. Results: A total of 15 studies (n = 15) were included. In 13 of 15 studies (87%), mechanically processed adipose tissue demonstrated an increased stromal vascular fraction (SVF) cell density compared to unprocessed fat. Twelve studies (80%) reported improved preservation of the extracellular matrix (ECM), while 11 studies (73%) observed a reduction in mature adipocytes. Immunohistochemical analyses in 10 studies (67%) revealed elevated expression of vascular markers (CD31, CD34) and perilipin. Adverse histological features such as oil cysts, fibrosis, and inflammatory infiltrates were reduced in 9 studies (60%). Considerable heterogeneity in processing techniques and staining protocols precluded meta-analysis. Conclusions: Mechanical processing of adipose tissue is associated with favorable histological and immunohistochemical profiles, including increased SVF cell density, improved ECM preservation, and reduced inflammatory and fibrotic features. These findings support the potential of mechanical processing to enhance graft quality; however, standardization of techniques and evaluation protocols is needed to strengthen clinical translation. Full article

Pulmonary fibrosis is a progressive interstitial lung disease that involves stimulated growth of fibroblasts, over-deposition of extracellular matrix (ECM), and permanent damage of the lung structure. Among its various forms, idiopathic pulmonary fibrosis (IPF) is the most common and life-threatening type with few treatment options and a poor prognosis. Such obstacles highlight the urgency to find new molecular targets by better understanding the cellular and signaling processes that contribute to the pathogenesis of the disease. Chemerin is an adipokine and chemoattractant protein that has recently come into the limelight as a major controller of immune cell trafficking, inflammation, and tissue remodeling. Its biological activity is mainly mediated by binding to its receptors Chemokine-like receptor 1 (CMKLR1), G protein-coupled receptor 1 (GPR1), and C-C chemokine receptor-like 2 (CCRL2), and has been linked to numerous pathological conditions, such as metabolic diseases, cancer, and inflammatory diseases. Emerging data now indicate that chemerin can also be a key factor in the initiation and progression of pulmonary fibrosis. The aim of the review is to overview the existing evidence regarding regulatory processes of chemerin expression, signaling pathways, and effects of this protein in cells in the fibrotic lung microenvironment. Moreover, we will comment on the findings of in vitro and in vivo experiments supporting the possibility of chemerin as a promising molecular target in basic research on pulmonary fibrosis. Full article

Cardiovascular aging is a multifactorial and systemic process that contributes significantly to the global burden of cardiovascular disease, particularly in older populations. This review explores the molecular and cellular mechanisms underlying cardiovascular remodeling in age-related conditions such as hypertension, atrial fibrillation, atherosclerosis, and heart failure. Central to this process are chronic low-grade inflammation (inflammaging), oxidative stress, cellular senescence, and maladaptive extracellular matrix remodeling. These hallmarks of aging interact to impair endothelial function, promote fibrosis, and compromise cardiac and vascular integrity. Key molecular pathways—including the renin–angiotensin–aldosterone system, NF-κB, NLRP3 inflammasome, IL-6, and TGF-β signaling—contribute to the transdifferentiation of vascular cells, immune dysregulation, and progressive tissue stiffening. We also highlight the role of the senescence-associated secretory phenotype and mitochondrial dysfunction in perpetuating inflammatory and fibrotic cascades. Emerging molecular therapies offer promising strategies to reverse or halt maladaptive remodeling. These include senescence-targeting agents (senolytics), Nrf2 activators, RNA-based drugs, and ECM-modulating compounds such as MMP inhibitors. Additionally, statins and anti-inflammatory biologics (e.g., IL-1β inhibitors) exhibit pleiotropic effects that extend beyond traditional risk factor control. Understanding the molecular basis of remodeling is essential for guiding future research and improving outcomes in older adults at risk of CVD. Full article

Senescence is a dynamic, multifaceted process implicated in tissue aging, organ dysfunction, and intricately associated with numerous chronic diseases. As senescent cells accumulate, they drive inflammation, fibrosis, and metabolic disruption through the senescence-associated secretory phenotype (SASP). Despite its clinical relevance, senescence remains challenging to detect non-invasively due to its heterogeneous nature and the lack of universal biomarkers. Recent advances in the development of specific imaging probes for positron emission tomography (PET) enable in vivo visualization of senescence-associated pathways across key organs, such as the lung, heart, kidney, and metabolic processes. For instance, [¹⁸F]FPyGal, a β-galactosidase-targeted tracer, has demonstrated selective accumulation in senescent cells in both preclinical and early clinical studies, while FAP-targeted radioligands are emerging as tools for imaging fibrotic remodeling in the lung, liver, kidney, and myocardium. This review examines a new generation of PET radioligands targeting hallmark features of senescence, with the potential to track and measure the process, the ability to be translated into clinical interventions for early diagnosis, and longitudinal monitoring of senescence-driven pathologies. By integrating organ-specific imaging biomarkers with molecular insights, PET probes are poised to transform our ability to manage and treat age-related diseases through personalized approaches. Full article

Pulmonary fibrosis (PF) is a progressive and fatal lung disease characterized by irreversible alveolar destruction and pathological extracellular matrix (ECM) deposition. Currently approved agents (pirfenidone and nintedanib) slow functional decline but do not reverse established fibrosis or restore functional alveoli. Multifunctional bioscaffolds present a promising therapeutic strategy through targeted modulation of critical cellular processes, including proliferation, migration, and differentiation. This review synthesizes recent advances in scaffold-based interventions for PF, with a focus on their dual mechano-epigenetic regulatory functions. We delineate how scaffold properties (elastic modulus, stiffness gradients, dynamic mechanical cues) direct cell fate decisions via mechanotransduction pathways, exemplified by focal adhesion–cytoskeleton coupling. Critically, we highlight how pathological mechanical inputs establish and perpetuate self-reinforcing epigenetic barriers to regeneration through aberrant chromatin states. Furthermore, we examine scaffolds as platforms for precision epigenetic drug delivery, particularly controlled release of inhibitors targeting DNA methyltransferases (DNMTi) and histone deacetylases (HDACi) to disrupt this mechano-reinforced barrier. Evidence from PF murine models and ex vivo lung slice cultures demonstrate scaffold-mediated remodeling of the fibrotic niche, with key studies reporting substantial reductions in collagen deposition and significant increases in alveolar epithelial cell markers following intervention. These quantitative outcomes highlight enhanced alveolar epithelial plasticity and upregulating antifibrotic gene networks. Emerging integration of stimuli-responsive biomaterials, CRISPR/dCas9-based epigenetic editors, and AI-driven design to enhance scaffold functionality is discussed. Collectively, multifunctional bioscaffolds hold significant potential for clinical translation by uniquely co-targeting mechanotransduction and epigenetic reprogramming. Future work will need to resolve persistent challenges, including the erasure of pathological mechanical memory and precise spatiotemporal control of epigenetic modifiers in vivo, to unlock their full therapeutic potential. Full article

Systemic Sclerosis (SSc) is a systemic autoimmune disease of unknown etiology characterized by a severe fibroproliferative vasculopathy and frequently progressive cutaneous and internal organ fibrosis. The small-vessel vasculopathy and the tissue fibrotic alterations are responsible for the most serious clinical and pathological manifestations of the disease and for its high mortality. Despite the high severity and frequent mortality, there are currently no optimal therapeutic approaches for SSc, and its complex pathogenesis has not been fully elucidated. Numerous studies have suggested that growth factors and related regulatory macromolecules released from inflammatory and other cells present in the affected tissues play a crucial role in the frequently progressive cutaneous and visceral fibrosis. Here, we will review some of the recent studies describing the role of various growth factors and related macromolecules in the development and progression of the fibrotic process in SSc. Full article

Cellular plasticity enables cells to dynamically adapt their phenotype in response to environmental cues, a process central to development, tissue repair, and disease. Among the most studied plasticity programs is epithelial–mesenchymal transition (EMT), a transcriptionally controlled process by which epithelial cells acquire mesenchymal traits. Originally described in embryogenesis, EMT is now recognized as a key driver in both tumor progression and fibrotic remodeling. In cancer, EMT and hybrid epithelial/mesenchymal (E/M) states promote invasion, metastasis, stemness, therapy resistance, and immune evasion. In fibrotic diseases, partial EMT (pEMT) contributes to fibroblast activation and excessive extracellular matrix deposition, sustaining organ dysfunction mainly in the kidney, liver, lung, and heart. This review integrates recent findings on the molecular regulation of EMT, including signaling pathways (TGF-β, WNT, NOTCH, HIPPO), transcription factors (SNAIL, ZEB, TWIST), and regulatory layers involving microRNAs and epigenetic modifications. Moreover, we discuss the emergence of pEMT states as drivers of phenotypic plasticity, functional heterogeneity, and poor prognosis. By comparing EMT in cancer and fibrosis, we reveal shared mechanisms and disease-specific features, emphasizing the translational relevance of targeting EMT plasticity. Finally, we explore how cutting-edge technologies, such as single-cell transcriptomics and lineage tracing, are reshaping our understanding of EMT across pathological contexts. Full article

Obesity, type 2 diabetes mellitus (T2DM), and cardiovascular diseases (CVDs) represent major global health burdens with overlapping pathophysiological mechanisms, including chronic low-grade inflammation, oxidative stress, and gut microbiota dysbiosis. Galectins, a family of β-galactoside-binding lectins, have been implicated in immune regulation, inflammation, and tissue remodeling. Among them, Galectin-4 (Gal-4), primarily expressed in the gastrointestinal tract, has emerged as a potential biomarker due to its roles in epithelial integrity, inflammatory signaling, and metabolic regulation. Despite its established involvement in cancer and inflammatory disease, the relevance of Gal-4 in cardiometabolic disorders remains poorly defined. A comprehensive literature search was conducted via the PubMed and ScienceDirect databases. The association between Gal-4 and obesity has been reported, indicating that elevated Gal-4 levels correlate with obesity, but primarily in individuals with diabetes. Circulating Gal-4 concentrations are consistently elevated in diabetic populations. In CVD, elevated Gal-4 levels are associated with ischemic heart disease, heart failure, aortic stenosis, carotid atherosclerosis, and adverse outcomes following myocardial infarction and stroke. Furthermore, prospective studies link Gal-4 to increased risk of cardiovascular events and mortality, underscoring its potential prognostic relevance. Available evidence regarding the mechanistic role of Gal-4 in the pathogenesis of obesity, diabetes, and cardiovascular disease remains limited; therefore, future studies should address whether Gal-4 actively contributes to cardiometabolic dysfunction or only reflects secondary inflammatory or fibrotic processes. Elucidating the biological functions of Gal-4 may provide insight into its utility in diagnostics and support the development of novel therapeutic strategies for cardiometabolic disorders. Full article

Promising protein targets are observed to play a role in multiple pathways across a variety of diseases, such as the regulation of immune responses, cell cycle, senescence, and DNA repair. The oncoprotein cancerous inhibitor of protein phosphatase 2A (CIP2A) can coordinate all these cell characteristics predominately by inhibiting the activity of the serine threonine protein phosphatase 2A (PP2A). CIP2A directly interacts with PP2A and other proteins, such as the DNA damage protein topoisomerase II-binding protein 1, to regulate signal transduction. CIP2A is overexpressed in many human cancers, including small and non-small cell lung cancers. High CIP2A expression in lung cancer correlates with poor prognosis, increased tumor proliferation, and resistance to targeted therapies or chemotherapy. Interestingly, CIP2A expression or signaling is also observed in several non-cancerous pulmonary diseases, such as chronic obstructive pulmonary disease. CIP2A can determine whether DNA-damaged cells enter mitosis and can mediate whether DNA repair occurs. CIP2A is also a regulator of inflammation and possibly fibrotic responses. Its functions are linked to altered NFκB activation and TNFα, IL-1β, IL-4, IL-6, IL-10, IL-13, and TGFβ signaling. This review outlines the possible impact of CIP2A-mediated signaling in pulmonary diseases, the processes that regulate CIP2A responses, CIP2A-dependent pathways, and potential therapeutic strategies targeting CIP2A. Substantial medicinal chemistry efforts are underway to develop therapeutics aimed at modulating CIP2A activity. The development of specific inhibitors of CIP2A that selectively target its expression or protein stability could improve our understanding of CIP2A’s function in pulmonary diseases. Full article

Diabetic nephropathy (DN) is a consequence of diabetes mellitus (DM), in which hyperglycemia triggers osmotic and oxidative stress and activates inflammatory pathways. These processes damage kidney cells, with mesangial cells (MCs) undergoing mesangial expansion. Antihyperglycemic drugs prevent the progression of renal disease. Although tamsulosin is not conventionally used for the treatment of DN, its previously reported anti-fibrotic and anti-inflammatory effects in liver and lung injury models suggest that it may exert renoprotective actions like those of pioglitazone, which has also been shown to improve cellular carbohydrate and lipid metabolism. MCs were exposed to 20 mM glucose medium and treated with either 50 nM tamsulosin or 100 nM pioglitazone. Subsequently, cell proliferation, inflammatory markers (NF-κB, IL-1β, IL-17), fibrogenic markers (TGF-β, collagen I), oxidative stress parameters (NRF2, superoxide), and indicators of mesangial activation (α-SMA, rhodamine–phalloidin) were assessed in vitro. Both treatments reduced cellular proliferation and hypertrophy, attenuated the release of reactive oxygen species (ROS), decreased IL-17 and α-SMA expression, and reduced mesangial activation and hypertrophy. In an in vivo model of DN in Wistar rats, both treatments decreased mesangial cell activation and expansion. In conclusion, tamsulosin and pioglitazone exert anti-fibrogenic and anti-inflammatory effects in MCs exposed to HG, thereby limiting mesangial activation and expansion. Full article

Fibrosis is a pathological process characterized by the excessive accumulation of extracellular matrix (ECM), particularly collagen, leading to tissue scarring, architectural distortion, and organ dysfunction. While fibrosis is a physiological component of wound healing, its persistence and dysregulation can drive chronic tissue damage and organ dysfunction. In autoimmune diseases, fibrosis arises from prolonged inflammation and immune system dysregulation, creating a vicious cycle that exacerbates tissue injury and promotes disease progression. This review provides a comprehensive overview of the fibrotic processes across a range of immune-mediated and autoimmune conditions, including systemic sclerosis (SSc), morphea, autoimmune hepatitis (AIH), systemic lupus erythematosus (SLE), Sjögren’s syndrome (SS), inflammatory bowel disease (IBD), and rheumatoid arthritis (RA), Finally, we discuss current and emerging antifibrotic strategies aimed at interrupting pathological ECM remodeling and restoring tissue homeostasis. Full article

Adropin is a regulatory peptide hormone involved in metabolic homeostasis, cardiovascular protection, and immune modulation. Recent evidence suggests that adropin plays a role in the pathophysiology of autoimmune rheumatic diseases (ARDs) by influencing key processes such as endothelial function, oxidative stress, tissue fibrosis, and immune cell regulation. This review summarizes current knowledge on adropin’s biological functions and its relevance in conditions including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, primary Sjögren’s syndrome, osteoarthritis, psoriasis, Behçet’s disease, and Kawasaki disease. We discuss how adropin interacts with various signaling pathways and highlight its potential role in macrophage polarization, regulatory T cell activity, and fibrotic remodeling. Although data remain limited and sometimes conflicting, altered adropin levels have been observed across several ARDs, suggesting potential utility as a biomarker or therapeutic target. Further research is needed to clarify its clinical significance and translational potential in immune-mediated diseases. Full article

Alkali burns to the cornea cause severe damage characterized by an intense inflammatory response driven by inflammatory cytokines, which orchestrate pathological processes, including neovascularization, fibrosis, apoptosis, abnormal cell proliferation, and disorganization of the extracellular matrix (ECM), often resulting in permanent vision impairment or loss. Rapamycin (RAPA), a well-known mTOR inhibitor with potent immunosuppressive activity and pleiotropic therapeutic effects, was investigated as a novel restorative modality for promoting corneal wound healing in a mouse model of alkali burn injury. Topical RAPA treatment significantly reduced clinical signs of inflammation and decreased the infiltration of F4/80⁺ macrophages and CD45⁺ leukocytes, along with suppressed expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-17A). RAPA also markedly downregulated angiogenic mediators, such as VEGF, and endothelial markers, like CD31, resulting in significant inhibition of neovascularization. Furthermore, it prevented fibrotic tissue formation and myofibroblast activation, as evidenced by reduced α-SMA levels, and attenuated pathological matrix remodeling through decreased MMP-9 expression. Notably, RAPA preserved epithelial barrier function by maintaining the tight junction protein ZO-1 and reduced both apoptotic cell death (TUNEL) and dysregulated proliferation (Ki67⁺), thereby preserving the functional and structural integrity of the cornea. In conclusion, RAPA represents a promising therapeutic candidate for managing severe corneal alkali burn injuries, with the potential to enhance corneal wound healing, minimize long-term complications, and protect visual function. Full article