Search Results (12,116)

Cardiac fibrosis is a pathology induced by various conditions, such as myocardial infarction, or certain cardiomyopathies, and represents one of the most prevalent cardiac abnormalities. This process, defined as the excessive accumulation of extracellular matrix within damaged cardiac tissue, leads to significant complications, including impaired systolic and diastolic function as well as arrhythmias. Conventional therapies focus primarily on slowing down the progression of fibrosis. Recently, there has been a growing research interest in therapies based on stem cells and their derivatives, which hold the potential to greater decrease formation and area of fibrosis. In this review, we aim to systematise the most recent data regarding the application of these approaches. We focus on describing the types of cells employed, methods of their implementation, and strategies for optimising these processes. Particular attention is given to exosomes due to the reports highlighting their use as innovative and potentially effective tools in the treatment of cardiac diseases. Full article

Exosomes (EXs) mediate intercellular communication in the tissue microenvironment. We previously demonstrated that endothelial progenitor cell-derived exosomes (EPC-EXs) from exercised mice protect neurons and cerebral endothelial cells from hypoxia- and hypertension- induced injury ex vivo, suggesting their therapeutic potential in hypertensive ischemic injury. Here, we investigated whether exercise-conditioned EPC-EXs (ET-EPC-EXs) confer protection against acute ischemic injury. Hypertensive transgenic mice were divided into donor and recipient groups. Donor mice underwent treadmill exercise to generate ET-EPC-EXs. Recipient mice was subjected to middle cerebral artery occlusion and received ET-EPC-EXs via tail vein injection (2 × 10⁸/100 μL saline) two hours after stroke onset. Cerebral blood flow (CBF) was assessed, and brains were collected on day two for histological and molecular analyses. Our data showed that ET-EPC-EXs were robustly taken up by cerebral cells, predominantly in the penumbra in the ipsilateral hemisphere. ET-EPC-EXs reduced cell death and microglia activation and restored tight-junction proteins. Moreover, ET-EPC-EX treatment preserved CBF and improved sensorimotor function on day two post-stroke. Mechanistically, ET-EPC-EXs suppressed p38 activation, accompanied by reduced matrix metalloproteinase-3 and cytochrome c levels in the ipsilateral brain. Collectively, these findings demonstrate that EPC-EXs from exercise mice improve sensorimotor functions and confer protection in hypertensive ischemic brain injury, likely through attenuation of neuroinflammation and preservation of vascular integrity via modulation of the p38 signaling. Full article

Background/Objectives: Amelogenesis imperfecta (AI) is a heterogeneous group of rare hereditary conditions mainly affecting the quantity and/or quality of tooth enamel. Its phenotypic expression is diverse, as is the mutational spectrum of the AI-causing genes and mutations. Integrins are cell-surface receptors that mediate adhesion between cells and between cells and the extracellular matrix. Among these, mutations in integrin αvβ6 have been shown to cause AI; however, phenotypic variation exists between the knockout mouse model and human cases, as well as among different human AI families. Methods: We recruited AI families and performed mutational analysis using whole exome sequencing. Results: We identified compound heterozygous ITGB6 mutations in two families. In Family 1, a paternally transmitted nonsense mutation (NM_000888.5: c.1060C>T, p.(Gln354*)) and a maternally transmitted missense mutation (NM_000888.5: c.2312A>G, p.(Asn771Ser)) were identified; in Family 2, a paternal missense mutation (NM_000888.5: c.1693T>C, p.(Cys565Arg)) and a maternal frameshift mutation (NM_000888.5: c.2091delC, p.(Asn698Metfs*13)) were identified, each causing AI in the respective proband. Both probands exhibited generalized hypoplastic and hypomineralized AI, but no other extraoral symptoms. Conclusions: This report will not only expand the known mutational spectrum of the ITGB6 gene but also provide evidence for the genotype–phenotype correlations, thereby improving our understanding of the functional role of ITGB6 during amelogenesis. Full article

The dynamic field of radiopharmaceuticals is currently experiencing an explosion of growth due in part to excitement over the emerging field of theranostics (therapy and diagnostics). Radiopharmaceuticals use physiological targeting methods to deliver radionuclides with medically relevant decay properties to disease biomarkers for diagnosis and treatment, offering opportunities for early disease imaging and radiation therapy treatment in disease pathologies that are inoperable or refractory to other forms of radiotherapy. Sustaining this rapidly growing field depends heavily on the continued design and production of novel, effective radiopharmaceuticals. Effective therapeutic radiopharmaceuticals cause complex and varied cellular responses, and to choose radionuclides that maximize therapeutic response, researchers must understand radiation biology. Cellular radiation response depends heavily on factors including linear energy transfer (LET), dose, dose rate, targeted location, direct or indirect energy deposition mechanisms, the broader cellular matrix, cellular stress signaling pathways, and endogenous radiation protection mechanisms. Because of the extensive application of low-LET external beam radiation on clinical cancer treatments, biological responses to low-LET form the basis of radiation biology and are generally considered transferable to high-LET radiopharmaceuticals. However, increased focus on high-LET, radiopharmaceutical therapy-specific radiation biology is motivated by differences between low- and high-LET radiation, external beam versus radiopharmaceutical therapy-induced biological response, and the observed varied clinical responses to radiopharmaceutical therapies. This review article summarizes historical understanding of low- and high-LET radiation responses within cells, with emphasis on radiopharmaceutical-specific responses when available, and discusses current gaps in understanding in the radiation biology of radiotheranostic pharmaceuticals. Full article

Open-heart surgery with cardiopulmonary bypass (CPB) is a high-risk procedure with significant morbidity and mortality. CPB, tissue injury, blood loss, endotoxemia and ischemia–reperfusion injury induce a pronounced systemic inflammatory response, leading to endothelial glycocalyx (EG) damage and vascular endothelial dysfunction. Consequently, immune cells, reactive oxygen species, and enzymes gain free access to vascular endothelial cells, resulting in their dysfunction and enhancing inflammation, vascular permeability, and microvascular impairment. EG degradation is most commonly assessed by measuring the circulating levels of its degradation products. Additionally, CPB triggers an early inflammatory response that is characterized by the secretion of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor alpha, and IL-18, which play roles in initiating the process of EG injury. EG damage is further propagated by the sustained release of cytokines, inhibiting the regeneration of the glycocalyx layer. Heparanase and matrix metalloproteinases are enzymatic pathways involved in cytokine-mediated EG degradation after cardiac surgery, and the balance between the pro- and anti-inflammatory cytokines determines the magnitude and duration of the inflammatory response and EG impairment, which correlates with adverse clinical outcomes, including myocardial dysfunction, acute lung and kidney injury, neurological complications, and prolonged need for intensive care. Thus, identifying patients with an exaggerated cytokine response could potentially provide more personalized therapy based on the circulating biomarkers of EG shedding, and cytokine-directed preservation of EG represents a promising therapeutic strategy in vascular dysfunction prevention during and after open-heart surgery. In this review, we summarize the current knowledge on cytokine-mediated EG impairment following open-heart surgery with CPB. Full article

Boron carbide (B₄C)-reinforced metal matrix composites (MMCs) are promising candidates for biomedical implants due to their mechanical properties and potential biological compatibility. In this study, in vitro biocompatibility and cytotoxicity of B₄C-reinforced CoCrMo, Ti, and 17-4 PH alloys were systematically evaluated using human osteoblast (HOB) cells. Composites were fabricated via powder metallurgy with varying B₄C reinforcement ratios (CoCrMo and Ti: 5–10 wt%; 17-4 PH: 3–12 wt%). Extracts prepared according to ISO 10993-12 standards were applied at different concentrations (100%, 50%, 25%, 12.5%) to assess cell viability using the MTT assay over 24, 48, and 72 h. Results demonstrated a clear dose-dependent cytotoxic effect across all composite systems. Ti composites exhibited the highest biocompatibility, with cell viability largely preserved even at higher B₄C ratios. CoCrMo composites showed moderate cytotoxicity, which decreased upon extract dilution, indicating low-concentration compatibility. In contrast, 17-4 PH composites revealed significant cytotoxicity at higher extract concentrations, exacerbated by increasing B₄C content. Literature-supported findings confirm that B₄C incorporation enhances hardness, wear resistance, and elastic modulus, yet excessive reinforcement can induce local stress and particle detachment, affecting cellular tolerance. Diluted extracts of Ti and CoCrMo composites maintained cell viability at a biocompatible level consistent with ISO 10993-5 criteria. These results highlight the promising biocompatibility of B₄C-reinforced Ti and CoCrMo alloys for biomedical applications and provide a biological basis for the design of next-generation composite implants. Full article

Cancer remains a leading cause of morbidity and mortality globally, with current therapies often limited by toxicity, drug resistance, and reduced efficacy in advanced stages. Medicinal plants represent important sources of bioactive compounds (BACs) with anticancer and chemopreventive potential; however, their successful application is strongly influenced by extraction strategies that determine phytochemical recovery and downstream biological activity. This review evaluates solvent-based extraction techniques used to extract BACs from medicinal plants with reported anticancer properties, synthesizing peer-reviewed articles from PubMed and Google Scholar published between 2020 and 2025. Solvent-based methods, including Soxhlet and maceration, were most widely applied due to their operational simplicity and the preservation of structurally diverse metabolites while percolation, decoction, infusion, and hydro-distillation were sparsely utilized. Extraction strategy and solvent polarity emerged as primary factors shaping phytochemical profiles, with phenolics, flavonoids, alkaloids, and terpenoids identified as dominant classes. Reported half maximal inhibitory concentration (IC₅₀) ranged from highly potent (0.12 µg/mL) to weak (30,000 µg/mL), reflecting variability driven by extraction parameters and plant matrix complexity. Anticancer mechanisms commonly involved apoptosis induction, cell-cycle arrest, reactive oxygen species-mediated cytotoxicity, and inhibition of proliferative signaling pathways across breast, cervical, colon, lung, liver, and prostate cancer models. Although solvent-based extraction approaches remain widely used, their context-dependent nature and lack of standardization limit reproducibility. Overall, anticancer and chemotherapeutic efficacy is primarily governed by BAC composition, while extraction methods act as upstream modulators. Future progress requires phytochemical-informed, standardized workflows supported by hybrid extraction systems, AI-assisted optimization, and advanced bioavailability and delivery systems to enable reproducible and clinically relevant translation of plant-derived chemotherapeutics. Full article

The management of complex acute and chronic wounds remains a formidable challenge in modern medicine, underscoring the urgent need for advanced therapeutic strategies that accelerate healing, prevent infection, and promote functional tissue regeneration. Electrospun nanofibers have attracted considerable attention in the biomedical field due to their extracellular matrix-like architecture, high surface area, interconnected porosity, and tunable physicochemical composition, which drive advances in wound regeneration, tissue engineering, and biopolymer-based therapeutics. In wound healing, nanofibrous dressings composed of natural polymers such as chitosan, gelatin, collagen, and cellulose promote cell attachment and proliferation, support angiogenesis, and enable infection control while delivering bioactive agents, thereby addressing significant challenges related to inflammation, biocompatibility, and antimicrobial resistance. In tissue engineering, aligned and hierarchically organized scaffolds fabricated from biopolymers such as collagen, gelatin, chitosan, and cellulose enhance the guided orientation of cells, differentiation, and functional regeneration of neural, musculoskeletal, vascular, and skin tissues. In addition to their conventional regenerative applications, recent studies have demonstrated that electrospun biopolymer nanofibers can be used in multifunctional biomedical platforms, including smart and stimuli-responsive systems for drug delivery, biosensing, regenerative interfaces, and wearable medical technologies. The integrated constructs that incorporate diagnostic or therapeutic functionalities, hybrid fabrication approaches that combine 3D printing with electrospinning, and intelligent biopolymer frameworks that enable telemedicine, real-time physiological monitoring, and personalized regenerative therapies offer new opportunities for developing improved biomedical systems. Overall, these advances position electrospun nanofiber systems as promising biomaterials for next-generation biomedical innovation. This review summarizes recent progress in tissue-engineered scaffolds, wound dressings, fabrication strategies for integrative therapeutics, and wearable devices with transformative potential for biomedical applications. Finally, the review addresses significant challenges related to scalability and clinical translation. It offers perspectives on future directions, including the integration of artificial intelligence and the regeneration of complex skin appendages, which will shape the next generation of nanofiber-based wound-healing therapies. Full article

Small extracellular vesicles (sEVs) derived from mesenchymal stem cells (MSCs) are emerging as potent acellular therapeutics; however, their rapid clearance hinders their clinical translation. To address this issue, 3D-bioprinted genipin-crosslinked gelatin (GECL) was engineered for human health. GECL hydrogels were functionalised with human umbilical cord MSC-derived sEVs (hUCMSC-sEVs) to create a bioactive wound-healing platform. These hydrogels demonstrated favourable physicochemical, mechanical, and biodegradable properties while providing an extracellular matrix (ECM)-mimetic environment conducive to tissue regeneration. MSCs were isolated from the umbilical cords, and their small extracellular vesicles (sEVs) were extracted and incorporated into gelatin-based hydrogels via 3D bioprinting. These sEV-loaded scaffolds were embedded in full-thickness wounds in mice, and healing was evaluated through macroscopic observation, histological analysis, collagen deposition, and angiogenesis assessment. Compared with the untreated controls, both the hydrogel-only (B) and sEV-loaded hydrogel (BE) groups significantly accelerated in vivo wound healing. Notably, the BE group achieved complete wound closure within 14 days, restoring the skin architecture, which closely resembled the native tissue with well-organised epidermal and dermal layers, optimal thickness, and skin appendages. Histological and ultrastructural assessments revealed an increased collagen type I deposition, a reduced α-smooth muscle actin (α-SMA) expression, and a robust neovascularisation. The TEM revealed tight junctions and active cellular infiltration, indicating scaffold integration and functional remodelling. Immunohistochemistry further revealed an upregulated CD31 expression with a balanced α-smooth muscle actin (α-SMA) expression, reflecting coordinated angiogenesis and myofibroblast regulation. These results highlight sEV-functionalised GECL hydrogels as robust and clinically translatable acellular therapeutic green products for accelerated wound closure and functional skin regeneration, advancing the fields of regenerative medicine and life expectancy. Full article

The paper presents SFPD, the new open algorithm developed by the University of Padova (PD in the acronym) for computing the steady-state regime due to any number of simultaneous faults (SF at the beginning of the acronym) both short circuits and open conductors. The algorithm does not have simplified hypotheses, since it benefits from the pre-fault regime based on PFPD_MCA (power flow by University of Padova with multiconductor cell analysis), a multiconductor power flow (developed and published by the first author) which takes into account both the active conductors (i.e., the phases subjected to the impressed voltages) and the passive conductors (i.e., the interfered metallic conductors, namely earth wires of overhead lines, metallic screens and armors of land and submarine cables, enclosures of gas insulated lines, return and earth wires of 2 × 25 kV AC high-speed railway supply system, etc.). Different types of faults are considered, and where they occur (also along the lines), by means of a suitable admittance matrix in phase frame of reference and embedded inside the overall network bus admittance matrix. Some comparisons with simplified approaches are presented in order to demonstrate the power of the method. Eventually, application to the real Italian network is comprehensively shown. Full article

Pesticides are a major cause of water contamination, making this issue a major environmental and public health concern. In this context, the development of advanced and effective remediation materials is needed. In this study, a titanium-functionalized magnetic silica aerogel (AG-Ti@Fe₃O₄-SA) was successfully prepared via microfluidics and evaluated for water decontamination. The structural and compositional features of the aerogel were determined using XRD, FT-IR, RAMAN, SEM, TEM, BET, and DLS, confirming the formation of the aerogel with dispersed Fe₃O₄-SA nanoparticles and the successful incorporation of titanium within the aerogel matrix. Regarding decontamination potential, the aerogel was tested against a pesticide mixture, yielding pesticide-dependent removal efficiencies (16–100%). Notably, the aerogel exhibited a high affinity for organophosphorus pesticides and a moderate affinity for polar compounds, whereas bulky hydrophobic pesticides showed lower adsorption. In vitro, the aerogel induced a moderate decrease in HaCaT cell viability after 48 h of exposure, accompanied by a slight increase in lactate dehydrogenase release, while HEK293 cells remained largely unaffected, indicating a cell-type-dependent biological response. Overall, the findings from this screening-level study recommend AG-Ti@Fe₃O₄-SA aerogel as a promising selective adsorbent for pesticide removal. Full article

While natural muds are widely used in traditional balneotherapy and dermatological applications, the cellular basis of their redox-related effects remains insufficiently defined. In this study, we evaluated the effects of a mineral-rich mud extract on L929 fibroblasts and RAW 264.7 macrophages. This study was designed as an initial in vitro exploratory investigation to evaluate the cellular responses induced by a complex mud-derived material containing multiple inorganic components under standardized extract conditions. The mud extract showed no overt cytotoxicity up to 1000 μg/mL under the tested conditions. Intracellular reactive oxygen species (ROS) levels remained near baseline across the measured time points, with limited cell type-dependent variation. In parallel, antioxidant-related responses were observed primarily in RAW 264.7 cells, including a transient early increase in superoxide dismutase (SOD)-associated activity and subsequent increases in catalase (CAT) and glutathione peroxidase (GPx) activities. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis further showed dose-dependent upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) transcripts, particularly in RAW 264.7 cells. Collectively, these findings suggest that the mud extract is associated with coordinated antioxidant-related responses under non-cytotoxic conditions. However, because the present study was conducted in two murine cell lines and relied partly on assay systems potentially susceptible to matrix effects, the results should be interpreted as supportive of redox-associated modulation rather than definitive proof of a therapeutic mechanism. Furthermore, these findings should be interpreted as preliminary evidence obtained from a standardized aqueous extract system and not as definitive proof of component-specific mechanisms or direct applicability. Full article

Background: Cutaneous radiation injury arises when ionizing radiation disrupts epidermal barrier integrity, triggering persistent DNA damage, oxidative stress, and senescence-associated inflammatory signaling that drive extracellular matrix degradation and impaired regeneration. Clinical burden is rising due to dose-intensified radiotherapy, but also due to an increased use of energy-based aesthetic procedures that elicit radiation-like dermal injury. Dermal fibroblasts exhibit marked sensitivity to ionizing radiation and rapidly acquire senescence-associated secretory phenotypes that suppress collagen biosynthesis and promote chronic inflammation, underpinning the need for regenerative treatments that restore tissue homeostasis and regenerative competence. Mesenchymal stem cell–derived exosomes have emerged as a promising therapeutic strategy in this setting, with increasing preclinical evidence demonstrating their capacity to attenuate oxidative stress, enhance DNA damage-repair pathways, and normalize fibroblast metabolic function. Methods: In this study, we examine the expression profiles for 14 radiation response–associated genes of irradiated human dermal fibroblasts that were treated with bone marrow and umbilical cord MSC-derived exosomes at different timepoints using quantitative RT-PCR analysis. We also explore functional relationships among these genes through interaction network analysis, and outline a framework to organize pathway-level transcriptional responses to irradiation and exosome treatment. Results: MSC-derived exosome treatment was associated with attenuated early damage response signaling at 24 h, followed by increased expression of genes associated with DNA repair and oxidative stress recovery at intermediate timepoints. Exosome-treated cells also exhibited transcriptional changes consistent with modulation of cell-cycle regulatory pathways and reduced expression of pro-inflammatory markers by 5 d. These findings suggest that MSC-derived exosomes influence the temporal organization of the fibroblast transcriptional response to ionizing radiation and may contribute to molecular programs associated with tissue recovery following ionizing radiation exposure. Full article

This work introduces a systematic small-signal modeling framework for a family of non-isolated high step-up dc–dc converters based on the multistate switching cell (MSSC) operating in continuous conduction mode (CCM). By analyzing the current and voltage waveforms associated with the switching cell, an averaged circuit model based on the pulse width modulation (PWM) switch technique is derived. The proposed method relies only on basic circuit principles, avoiding complex matrix manipulations. To validate the theoretical assumptions, a non-isolated dc–dc boost converter with a high voltage gain is evaluated, and its response is compared with that of the derived model. Full article

Bidirectional communication between the oocyte and surrounding follicular cells coordinates follicle growth, meiotic maturation, and the acquisition of competence. We aimed to identify genes related to follicular crosstalk and the secretory pathway as candidate mediators of cumulus–oocyte complex (COC) crosstalk in cattle. Expressed sequence tags (ESTs) from bovine COCs were retrieved from databases and screened for genes related to secretion and the secretory pathway using SignalP and SecretomeP, and transmembrane proteins were removed, yielding 13 candidate genes. Candidate expression was examined in two GEO RNA-seq datasets to assess enrichment in oocytes versus cumulus cells. RT–qPCR profiling across tissues and reproductive cell types enabled principal component analysis and correlation/network analysis, visualized as heatmaps and Cytoscape, revealing an INBHA-SERPINE2-SDF2L1 co-expression pattern. INHBA and SERPINE2 protein products are secreted, whereas SDF2L1 protein is a secretory pathway-associated, endoplasmic reticulum-resident chaperone. Promoter sequences of INHBA, SERPINE2, and SDF2L1 were scanned with FIMO using JASPAR motifs, identifying shared SMAD-associated motifs and FSH/cAMP-related motif families. The data support a co-regulation model in which endocrine FSH/cAMP and activin/TGF-β–SMAD inputs converge on a shared transcriptional program consistent with a putative INHBA–SERPINE2–SDF2L1 co-regulated module, linking cumulus extracellular matrix remodeling/protease control with oocyte ER protein folding capacity during COC maturation. Full article