Search Results (124)

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disorder characterized by excessive scarring of lung tissue, predominantly affecting middle-aged and elderly populations. Oxidative stress plays a pivotal role in the pathogenesis of pulmonary fibrosis, disrupting redox homeostasis and driving fibrotic progression. Glutathione reductase (GSR), a key antioxidant enzyme, is essential for maintaining cellular glutathione (GSH) levels and mitigating oxidative damage. However, the specific involvement of GSR in IPF remains poorly understood. This study found that GSR levels were downregulated in IPF patients and mice treated with bleomycin (BLM). GSR knockdown enhanced epithelial-to-mesenchymal transition (EMT) in A549 cells and promoted the activation of MRC5 cells. Additionally, GSR depletion promoted cellular migration and senescence in both A549 and MRC5 cells. Mechanistically, silencing GSR in A549 and MRC5 cells led to a marked reduction in intracellular GSH levels, resulting in elevated reactive oxygen species (ROS) accumulation, thereby promoting the activation of the TGF-β/Smad2 signaling pathway. In conclusion, our findings demonstrate that GSR deficiency aggravates pulmonary fibrosis by impairing antioxidant defense mechanisms, promoting EMT, and activating fibroblasts through the TGF-β/Smad2 signaling. These findings suggest that GSR may be essential in reducing the fibrotic progression of IPF. Full article

This study used Jilin-1 satellite data and unmanned aerial vehicle (UAV)-collected visible-thermal infrared imagery to calculate twelve spectral indices and evaluate their effectiveness in distinguishing post-fire forest areas and identifying human-altered land-cover changes in Jinyun Mountain, Chongqing. The research goals included mapping wildfire impacts with M-statistic separability, measuring land-cover distinguishability through Jeffries–Matusita (JM) distance analysis, classifying land-cover types using the random forest (RF) algorithm, and verifying classification accuracy. Cumulative human disturbances—such as land clearing, replanting, and road construction—significantly blocked the natural recovery of burn scars, and during long-term human-assisted recovery periods over one year, the Red Green Blue Index (RGBI), Green Leaf Index (GLI), and Excess Green Index (EXG) showed high classification accuracy for six land-cover types: road, bare soil, deadwood, bamboo, broadleaf, and grass. Key accuracy measures showed producer accuracy (PA) > 0.8, user accuracy (UA) > 0.8, overall accuracy (OA) > 90%, and a kappa coefficient > 0.85. Validation results confirmed that visible-spectrum indices are good at distinguishing photosynthetic vegetation, thermal bands help identify artificial surfaces, and combined thermal-visible indices solve spectral confusion in deadwood recognition. Spectral indices provide high-precision quantitative evidence for monitoring post-fire land-cover changes, especially under human intervention, thus offering important data support for time-based modeling of post-fire forest recovery and improvement of ecological restoration plans. Full article

Radiation therapy, a highly effective cancer treatment that targets cancer cells, may produce challenging side effects, including radiation-induced skin tissue injuries. The wound healing process involves complex cellular responses, with key phases including hemostasis, inflammation, proliferation, and remodeling. However, radiation-induced injuries disrupt this process, resulting in delayed healing, excessive scarring, and compromised tissue integrity. This review explores innovative approaches related to wound healing in post-radiotherapy defects, focusing on the integration of adipose-derived stem cells (ADSCs) in protein/polysaccharide bioengineered scaffolds. Such scaffolds, like hydrogels, sponges, or 3D-printed/bioprinted materials, provide a biocompatible and biomimetic environment that supports cell-to-cell and cell-to-matrix interactions. Various proteins and polysaccharides are discussed for beneficial properties and limitations, and their compatibility with ADSCs in wound healing applications. The potential of ADSCs-polymeric scaffold combinations in radiation-induced wound healing is investigated, alongside the mechanisms of cell proliferation, inflammation reduction, angiogenesis promotion, collagen formation, integrin binding, growth factor signaling, and activation of signaling pathways. New strategies to improve the therapeutic efficacy of ADSCs by integration in adaptive polymeric materials and designed scaffolds are highlighted, providing solutions for radiation-induced wounded skin, personalized care, faster tissue regeneration, and, ultimately, enhanced quality of the patients’ lives. Full article

Methionine restriction (MetR) is a common adjuvant treatment for cancer. However, studies of MetR have paid little attention to its potential implications for fibrosis. Hypertrophic scarring (HTS) is an abnormal fibrotic response after burn trauma that results from the excessive activation of fibroblasts. Because of the absence of a fully effective pharmacological treatment, HTS frequently causes great annoyance in patients as a common sequela of burns. To date, the effects of MetR on hypertrophic scar fibroblasts (HTSFs) remain unclear. This study aimed to investigate the anti-fibrotic effects of MetR and explore the associated alterations in signaling pathways in HTSFs. We isolated HTSFs from post-burn HTS tissues and cultured them in a specially prepared MetR medium. Cell and immunocytochemical staining images were captured using light and fluorescence microscopes, respectively. Cell proliferation was evaluated using a CellTiter-Glo Luminescent Cell Viability Assay Kit. mRNA and protein expression levels were determined using quantitative reverse transcription polymerase chain reaction and Western blotting, respectively. In HTSFs, MetR reduced cellular inflammation; downregulated multiple signaling pathways, including the TGF-β-SMAD, STAT, and AKT/mTOR pathways; and upregulated MAPKs. Furthermore, MetR arrested the cell cycle, promoted apoptosis, suppressed cell proliferation and migration, and reduced extracellular matrix protein secretion, thereby exerting multifaceted inhibitory effects on HTS. Our results demonstrated that MetR can inhibit scars’ formation and suggest that regulating methionine metabolism in the scar environment may help treat scars. Full article

Background/Objectives: Fibroproliferative disorders (FPDs), such as Dupuytren’s contracture, scleroderma, capsular contracture, rhinophyma, and keloid scars, are characterised by excessive fibroblast activity and collagen deposition. These conditions are frequently encountered in plastic and reconstructive surgery and remain therapeutically challenging. Cyclooxygenase (COX) inhibitors have emerged as a potential adjunct therapy to modulate fibrotic pathways and improve clinical outcomes. This systematic review aims to evaluate the efficacy and safety profile of COX inhibitors in the management of plastic-surgery-related FPDs. In doing so, it explores how phenotype-guided and route-specific COX-inhibitor use may contribute to precision, patient-centred care. Methods: To identify eligible studies, a comprehensive search was conducted in MEDLINE, Embase, and the Cochrane Library. Data were synthesised using both tabular summaries and narrative analysis. The certainty of evidence was appraised according to the GRADE guidelines. Results: Thirteen studies from 1984 to 2024 met inclusion criteria, addressing FPDs such as hypertrophic scarring, Dupuytren’s contracture, and desmoid tumours, representing 491 patients. Of those, five studies were related to Dupuytren contracture, three studies were related to hypertrophic scar, and one study each was on topics related to scleroderma, keloid scar, osteogenesis imperfecta, actinic keloidalis nuchae/dissecting cellulitis of the scalp, and desmoid tumours. Nine studies reported clinical improvements (four demonstrating statistically significant outcomes), three showed no difference, and one did not assess outcomes. The thirteen studies show minor side effects from oral and topical COX inhibitors. The overall certainty of evidence was graded as “low.” Conclusions: COX inhibitors demonstrate promising efficacy with minimal adverse effects in the management of plastic-surgery-related FPDs. Their accessibility, safety, and potential to reduce fibrosis underscore the need for future high-quality, large-scale studies to establish definitive clinical recommendations. Full article

Background: Systemic sclerosis (SSc) is a rare connective tissue disease characterized by vasculopathy, autoimmunity, and fibrosis. Due to its low prevalence and heterogeneous clinical presentation, early diagnosis remains challenging, often delaying appropriate treatment. The disease progresses from microvascular dysfunction, manifesting as Raynaud’s phenomenon, to systemic fibrosis affecting multiple organs, including the lungs, gastrointestinal tract, heart, and kidneys. There have been considerable advancements in understanding the pathophysiology of the disease during the last few years and this has already resulted in the improvement of the therapeutic approaches used to control organ-specific manifestations. However, the underlying cause of the disease still remains incompletely elucidated. Methods: Here, we summarize the current knowledge on the SSc pathogenesis. Results: The pathophysiology involves an interplay of chronic inflammation, impaired vascular function, and excessive extracellular matrix deposition, leading to progressive organ damage. Endothelial dysfunction in SSc is driven by immune-mediated injury, oxidative stress, and the imbalance of vasoconstrictors and vasodilators, leading to capillary loss and chronic hypoxia. Autoantibodies against endothelial cells or other toxic factors induce apoptosis and impair angiogenesis, further exacerbating vascular damage. Despite increased angiogenic factor levels, capillary repair mechanisms are defective, resulting in progressive ischemic damage. Dysregulated immune responses involving Th2 cytokines, B cells, and macrophages contribute to fibroblast activation and excessive collagen deposition. Transforming growth factor-beta (TGF-β) plays a central role in fibrotic progression, while fibroblasts resist apoptosis, perpetuating tissue scarring. The extracellular matrix in SSc is abnormally stiff, reinforcing fibroblast activation and creating a self-perpetuating fibrotic cycle. Conclusions: Advances in molecular and cellular understanding have facilitated targeted therapies, yet effective disease-modifying treatments remain limited. Future research should focus on precision medicine approaches, integrating biomarkers and novel therapeutics to improve patient outcomes. Full article

In this study, a BTG–15kW high-frequency induction heater was utilized to fabricate composite coatings of Ni-WC-CeO₂ with varying CeO₂ content on the surface of ASTM A36 steel substrates via induction cladding. The effects of CeO₂ content on the phase composition, microstructure, elemental distribution, cross-sectional microhardness, surface hardness, Rockwell hardness, wear resistance, and wear scar morphology of the composite coatings were systematically examined using XRD, SEM, EDS, microhardness testers, Rockwell hardness testers, friction and wear testing machines, OM, and stylus profilers. The aim was to identify the optimal CeO₂ content for enhancing coating performance. The results indicated that the incorporation of CeO₂ promotes elemental inter-diffusion both within the coating and between the coating and the substrate, facilitates the dispersion of WC, and enhances the cross-sectional microhardness and wear resistance of the coating. However, excessive CeO₂ content did not lead to further improvement, suggesting the presence of an optimal concentration. Among the compositions studied, the coating with 0.5% CeO₂ exhibited minimal internal defects, pronounced elemental inter-diffusion, uniform WC, the highest cross-sectional microhardness and surface hardness, and the second-highest wear resistance, identifying this composition as the most effective for achieving superior coating performance. Full article

Scarring is a prevalent and often undesirable outcome of the wound healing process, impacting millions worldwide. The complex and dynamic nature of wound healing, including hemostasis, inflammation, proliferation, and remodeling, necessitates precise, making it hard for stage-specific interventions to prevent pathological scarring. This study introduces a double-layer hydrogel system designed for sequential drug release, aligning with the stage-specific need for wound healing. The lower layer, containing curcumin-loaded chitosan nanoparticles, shows early anti-inflammatory and antioxidant effects, while the upper layer, with pirfenidone-encapsulated gelatin microspheres, presents late-stage anti-fibrotic activity. The hydrogel’s unique design, with varying degradation rates and mechanical properties in each layer, facilitates cascade drug release in synchrony with wound healing stages. Rapid release of curcumin from the lower layer promotes proliferation by mitigating inflammation and oxidative stress, while the sustained release of pirfenidone from the upper layer inhibits excessive fibrillation during late proliferation and remodeling. In a rat model of full-thickness skin defect, treatment with a double-layer hydrogel drug delivery system accelerated the wound closure, improved scar quality, and promoted the formation of hair follicles. Therefore, this innovative approach lays a promising foundation for future clinical applications in anti-scar therapies, offering a significant advancement in wound care and regenerative medicine. Full article

Liver Sinusoidal Endothelial Cells (LSECs) play a crucial role in maintaining liver homeostasis, regulating immune responses, and fibrosis in liver diseases. This review explores the unique functions of LSECs in liver pathology, particularly their roles in immune tolerance, antigen presentation, and the modulation of hepatic stellate cells (HSCs) during fibrosis. LSECs act as key regulators of immune balance in the liver by preventing excessive immune activation while also filtering antigens and interacting with immune cells, including Kupffer cells and T cells. Metabolic Dysfunction-Associated Fatty Liver Disease(MAFLD) is significant because it can lead to advanced liver dysfunction, such as cirrhosis and liver cancer. The prevalence of Metabolic Associated Steatohepatitis (MASH) is increasing globally, particularly in the United States, and is closely linked to rising rates of obesity and type 2 diabetes. Early diagnosis and intervention are vital to prevent severe outcomes, highlighting the importance of studying LSECs in liver disease. However, during chronic liver diseases, LSECs undergo dysfunction, leading to their capillarization, loss of fenestrations, and promotion of pro-fibrotic signaling pathways such as Transforming growth factor-beta (TGF-β), which subsequently activates HSCs and contributes to the progression of liver fibrosis. The review also discusses the dynamic interaction between LSECs, HSCs, and other hepatic cells during the progression of liver diseases, emphasizing how changes in LSEC phenotype contribute to liver scarring and fibrosis. Furthermore, it highlights the potential of LSECs as therapeutic targets for modulating immune responses and preventing fibrosis in liver diseases. By restoring LSECs’ function and targeting pathways associated with their dysfunction, novel therapies could be developed to halt or reverse liver disease progression. The findings of this review reinforce the importance of LSECs in liver pathology and suggest that they hold significant promises as targets for future treatment strategies aimed at addressing chronic liver diseases. Full article

Fibrosing disorders including idiopathic pulmonary fibrosis (IPF) are progressive irreversible diseases, often with poor prognoses, characterized by the accumulation of excessive scar tissue and extracellular matrix. Translational regulation has emerged as a critical aspect of gene expression control, and the dysregulation of key effectors is associated with disease pathogenesis. This review examines the current literature on translational regulators in IPF, focusing on microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and RNA transcript modifications including alternative polyadenylation and chemical modification. Some of these translational regulators potentiate fibrosis, and some of the regulators inhibit fibrosis. In IPF, some of the profibrotic regulators are upregulated, and some of the antifibrotic regulators are downregulated. Correcting these defects in IPF-associated translational regulators could be an intriguing avenue for therapeutics. Full article

The most common aftereffect of severe burns in patients is hypertrophic scarring. Hypertrophic scars typically form following severe burns; it refers to excessive collagen production in the dermal layer during the healing process, resulting in an abnormal raised scar. Currently, practical treatments for suppressing hypertrophic scars include laser therapy, pressure therapy, and the application of silicone sheets for moisture retention. The most extensively used treatment involves compression therapy using specially designed garments for the affected areas. However, this method has limitations when applied to curved surfaces like the face. To address this issue, three-dimensional (3D) scanning and 3D printing techniques have been actively developed for face masks and have shown promising clinical results. Unfortunately, current facial masks under development lack a sensor system to measure pressure, making it difficult to ensure consistent and appropriate pressures during clinical trials. In this study, we have developed a burn pressure mask capable of real-time pressure monitoring. The facial mask developed in this study utilizes an FSR-type sensor to measure the pressure applied to the skin. We have also embedded electrical wires within the mask to enhance its comfort and wearability. For this study, two patients wore the facial mask with real-time pressure measurement capabilities for 4 weeks in 12 h per day on average. We evaluated whether the mask maintained the appropriate pressure range (15–25 mmHg) throughout the clinical trial and whether it effectively inhibited scar formation. Through the analysis of recorded pressure signal data, we confirmed that the patients consistently maintained the appropriate pressure while wearing the mask during the clinical trial. Additionally, we observed significant differences in skin moisture levels, transepidermal water loss, and scar thickness before and after the experiment. These findings suggest that the facial mask, featuring real-time monitoring capabilities, effectively prevents the formation of hypertrophic scars. Full article

Introduction: After myocardial infarction (MI), the heart undergoes necrosis, inflammation, scar formation, and remodeling. While restoring blood flow is crucial, it can cause ischemia-reperfusion (IR) injury, driven by reactive oxygen species (ROSs), which exacerbate cell death and tissue damage. This study introduces a mathematical model capturing key post-MI dynamics, including inflammatory responses, IR injury, cardiac remodeling, and stem cell therapy. The model uses nonlinear ordinary differential equations to simulate these processes under varying conditions, offering a predictive tool to understand MI pathophysiology better and optimize treatments. Methods: After myocardial infarction (MI), left ventricular remodeling progresses through three distinct yet interconnected phases. The first phase captures the immediate dynamics following MI, prior to any medical intervention. This stage is mathematically modeled using the system of ordinary differential equations: The second and third stages of the remodeling process account for the system dynamics of medical treatments, including oxygen restoration and subsequent stem cell injection at the injury site. Results: We simulate heart tissue and immune cell dynamics over 30 days for mild and severe MI using the novel mathematical model under medical treatment. The treatment involves no intervention until 2 h post-MI, followed by oxygen restoration and stem cell injection at day 7, which is shown experimentallyand numerically to be optimal. The simulation incorporates a baseline ROS threshold ($R_c$) where subcritical ROS levels do not cause cell damage. Conclusion: This study presents a novel mathematical model that extends a previously published framework by incorporating three clinically relevant parameters: oxygen restoration rate ($\omega$), patient risk factors ($\gamma$), and neutrophil recruitment profile ($\delta$). The model accounts for post-MI inflammatory dynamics, ROS-mediated ischemia-reperfusion (IR) injury, cardiac remodeling, and stem cell therapy. The model’s sensitivity highlights critical clinical insights: while oxygen restoration is vital, excessive rates may exacerbate ROS-driven IR injury. Additionally, heightened patient risk factors (e.g., smoking, obesity) and immunodeficiency significantly impact tissue damage and recovery. This predictive tool offers valuable insights into MI pathology and aids in optimizing treatment strategies to mitigate IR injury and improve post-MI outcomes. Full article

Disruption of the molecular pathways during physiological wound healing can lead to raised scar formation, characterized by rigid, thick scar tissue with associated symptoms of pain and pruritus. A key mechanical factor in raised scar development is excessive tension at the wound site. Recently, microneedles (MNs) have emerged as promising tools for scar management as they engage with scar tissue and provide them with mechanical off-loading from both internal and external sources. This review explores the mechanisms by which physical intervention of drug-free MNs alleviates mechanical tension on fibroblasts within scar tissue, thereby promoting tissue remodeling and reducing scar severity. Additionally, the role of MNs as an efficient cargo delivery system for the controlled and sustained release of a wide range of therapeutic agents into scar tissue is highlighted. By penetrating scar tissue, MNs facilitate controlled and sustained localized drug administration to modulate inflammation and fibroblastic cell growth. Finally, the remaining challenges and the future perspective of the field have been highlighted. Full article

Background: Wear particle reaction is present in every arthroplasty. Sometimes, this reaction may lead to formation of large pseudotumors. As illustrated in this case, the volume of the reaction may be out of proportion to the volume of the wear scar. This case also is the first description of elimination kinetics of systemic titanium exposure caused by wear of a hip arthroplasty. Methods: Case report. Results: A 85-year-old male required revision after total hip arthroplasty due to aseptic loosening of the cup. A massive local adverse reaction to metal and polyethylene debris developed before revision, much larger than the implant damage would intuitively suggest. In this case, in vivo transition in wear mode from edge loading to impingement wear resulted in excessive titanium and polyethylene wear and subsequently a voluminous macrophage reaction and an excessive systemic titanium exposure, with blood concentrations showing a very long elimination half-life of more than two years. Conclusions: The volume of the wear particle reaction is dictated by the volume of the inflammatory cells, not of the wear particles. To the best of our knowledge, this is the first description of elimination kinetics in case of systemic titanium exposure. While the tissue response is caused by a sudden increase of titanium and polyethylene debris, titanium is detectable through whole blood, not serum, analysis and thus be an indicator for risk of failure due to abnormal articulation of the joint replacement. Such measurement may be useful if changes in implant position are detected radiographically. Major elevations of titanium concentrations may require revision, as for any other metal ions. Full article

Objective: Liver fibrosis, a hallmark of chronic liver diseases, is characterized by excessive extracellular matrix (ECM) deposition and scar tissue formation. Current antifibrotic nanomedicines face significant limitations, including poor penetration into fibrotic tissue, rapid clearance, and suboptimal therapeutic efficacy. The dense fibrotic ECM acts as a major physiological barrier, necessitating the development of a targeted delivery strategy to achieve effective therapeutic outcomes. Methods: We designed a liposomal delivery system functionalized with the GBI-10 aptamer and encapsulating obeticholic acid (OCA lips@Apt) to enhance selective delivery to fibrotic liver tissue while minimizing systemic toxicity. Results: Both in vitro and in vivo studies demonstrated that the aptamer-modified OCA liposomes effectively treated hepatic fibrosis through dual mechanisms: modulation of abnormal bile acid metabolism and attenuation of inflammation. The targeted delivery system leveraged the overexpression of Tenascin-C (TnC), a key ECM component in fibrotic tissues, for precise localization and enhanced endocytosis via the exposed cationic liposome surface. Conclusions: The OCA lips@Apt nanodrug demonstrated superior therapeutic efficacy with minimal off-target effects, offering a promising strategy to overcome critical barriers in liver fibrosis treatment. By precisely targeting the fibrotic ECM and modulating key pathological pathways, this TnC-guided liposomal delivery system provides a significant advancement in antifibrotic nanomedicine. Full article