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Cold Atmospheric Plasma in the Treatment of Osteosarcoma.

Human osteosarcoma (OS) is the most common primary malignant bone tumor occurring most commonly in adolescents and young adults. Major improvements in disease-free survival have been achieved by implementing a combination therapy consisting of radical surgical resection of the tumor and systemic multi-agent chemotherapy. However, long-term survival remains poor, so novel targeted therapies to improve outcomes for patients with osteosarcoma remains an area of active research. This includes immunotherapy, photodynamic therapy, or treatment with nanoparticles. Cold atmospheric plasma (CAP), a hig

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… Moreover, CAP activated the secretion of Prx-2, but not Prx-1 and Prx-3, into the extracellular space. The cellular functionality of cell-free Prx-2, however, is unclear. …

Myokines in cancer: bridging molecular mechanisms to biomarker discovery and therapeutic innovation.

Exercise can regulate the physiological functions of the body by inducing the secretion of myokines, which are bioactive factors mainly secreted by muscle cells. This review classifies myokines based on their functional characteristics, including metabolic regulation (such as myostatin, interleukin-6), neuroregulation (brain-derived neurotrophic factor), cell proliferation/differentiation regulation (myogenic proteins), immune regulation (tumor necrosis factor- alpha), and factors involved in angiogenesis and extracellular matrix remodeling (such as connective tissue growth factor).Cancer, as

Biomarker Jeopardy.

In the popular Biomarker Jeopardy session, Sandra E. Kurtin, PhD, ANP-C, AOCN®, Alyssa Henglefelt, PharmD, BCOP, and Haleigh Mistry, MS, PA-C, paired biomarkers with tumor types for which their expression is most commonly used to determine targeted therapy, identified key assays used to measure common biomarkers, and discussed guidelines for biomarker testing.

Моделирование и нацеливание враждебной физико-химической ниши в метастазе костей: от экспериментальных платформ до нишевой терапии.

Метастаз рака до костей формируется не только из-за перекрестка опухолей, но и из-за враждебной физико-химической ниши, которая способствует стойкости к болезням и терапевтической недостаточности. Гипоксия, кислотность, минерализированная матричная архитектура, изменённая механика, интерстициальное давление, дисфункция перфузии и ограниченный перенос наркотиков влияют на метастатическое семя, общность, реактивацию, реконструкцию, боль и реакцию на лечение. Обычные two- размерные культуры и многие упрощенные three- размерные системы воспроизводят только отдельные особенности этой среды, часто п

Exosome-Enriched Hub Gene Networks Identify Diagnostic Biomarkers and Repurposable Therapeutic Targets in Endometriosis.

Endometriosis is a heterogeneous chronic inflammatory disorder associated with substantial diagnostic delay and limited therapeutic options, highlighting the need of robust non-invasive biomarkers and actionable molecular targets to complement existing low-sensitivity tests. To identify conserved pathogenic mechanisms with translational potential, here, we uniformly reprocessed three independent the Gene Expression Omnibus (GEO) microarray cohorts (GSE7305, GSE25628, and GSE11691) and applied a strict, directionally consistent intersection strategy to identify conserved transcriptional signals

Nanogel-Based Precision Bone Regeneration: Rational Design, Biological Barrier Penetration, and Osteoporotic Microenvironment Remodeling.

The pathogenesis of osteoporosis is primarily associated with impaired communication between osteoblasts and osteoclasts, leading to disrupted bone homeostasis. Conventional biomaterials mainly rely on macroscopic structural support and are limited in their ability to precisely regulate the complex bone microenvironment and overcome biological barriers. As representative soft matter nanoplatforms, nanogels possess unique viscoelastic mechanical properties and adaptive biointerfacial properties, offering new opportunities to overcome physical barriers within bone tissues. Moving beyond previous

Bridging the Gap in AL and ATTR Cardiac Amyloidosis: Integrating Histopathology, Biomarkers, and Multimodal Imaging for Subtype-Specific Diagnosis.

Cardiac amyloidosis (CA) represents an increasingly recognized but historically underdiagnosed cause of restrictive cardiomyopathy and heart failure. CA is now understood to be more prevalent, particularly in older adults, as advancements in imaging and biomarker technologies have improved detection. The disease results from the misfolding of precursor proteins, primarily immunoglobulin light chains (in light chain (AL) amyloidosis) or transthyretin (in transthyretin (ATTR) amyloidosis), into insoluble fibrils that deposit in myocardial tissue. These deposits cause structural and functional ca

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… This enhancement occurs due to expanded extracellular space caused by amyloid deposits. In advanced disease, nulling of the myocardium becomes difficult due to diffuse gadolinium uptake. Sensitivity and specificity of LGE for CA are approximately 93% and 87%, respectively [ 69 , 70 ]. Fig. 2. …

Targeting vascular endothelial growth receptor-2 (VEGFR-2): structural biology, functional insights, and therapeutic resistance.

Angiogenesis, the process of new blood vessel formation, is a fundamental physiological process implicated in several pathological disorders. The vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are crucial for angiogenesis and vasculogenesis. Among them, the tyrosine kinase receptor VEGFR-2 is primarily expressed in endothelial cells (ECs). These cells regulate various physiological responses, including differentiation, cell proliferation, migration, and survival, by binding to VEGF mitogens. Vascular Endothelial Growth Factor Receptor 2 (VEGFR-2) is a key regulator of

Effects of exosomes from different origins on osteoclasts.

Abnormal osteoclast function is closely related to the development of osteolytic diseases such as osteoporosis and tumor bone metastasis, which seriously affects patients' quality of life. The cellular microenvironment is complex and variable, and exosomes, as an important pathway mediating intercellular communication, can be secreted by a variety of cells in the human body, which carry "cargo" that can affect the biological function of recipient cells. Osteoclasts receive a variety of cellular exosomes to regulate and influence the body's bone homeostasis. In this narrative review, we summari

A bibliometric analysis of light chain amyloidosis from 2005 to 2024: research trends and hot spots.

BackgroundLight chain (AL) amyloidosis stands as the most prevalent subtype of systemic amyloidosis, encompassing a group of rare diseases. Here, we evaluated the scientific landscape of AL amyloidosis to investigate research trends and identify hotspots within the field.MethodsRelevant studies on AL amyloidosis published over the past two decades were retrieved from the Web of Science Core Collection. The publications between 2005 and 2024 were subjected to bibliometric analyses, leveraging tools including CiteSpace, VOSviewer, RStudio and MS Excel to analyse and visualize the annual publicat

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… AL amyloidosis is a clonal plasma cell disorder characterized by the systemic deposition of misfolded immunoglobulin light chains as insoluble fibrils or fragments in the extracellular space of various organs ( 4 ). …

Pathogenic Role of FGFR3 Autoantibodies in Small Fiber Neuropathy.

Sensory neuronopathies (SNN) and small fiber neuropathies (SFN) are debilitating disorders associated with neuropathic pain, yet their underlying mechanisms remain poorly understood. Autoantibodies against fibroblast growth factor receptor 3 define a subset of patients with consistent reports of neuropathic pain harboring a distinct clinical phenotype characterized by small-fiber and non-length-dependent neuropathy, suggesting dorsal root ganglia (DRG) dysfunction. FGFR3-autoantibody-positive sera (FGFR3-AbS) bind to sensory neurons within dorsal root ganglia (DRG). The target of autoantibodie

A review on machine learning approaches and trends in drug discovery.

Drug discovery aims at finding new compounds with specific chemical properties for the treatment of diseases. In the last years, the approach used in this search presents an important component in computer science with the skyrocketing of machine learning techniques due to its democratization. With the objectives set by the Precision Medicine initiative and the new challenges generated, it is necessary to establish robust, standard and reproducible computational methodologies to achieve the objectives set. Currently, predictive models based on Machine Learning have gained great importance in t

The evolving global landscape of first-in-class oncology drug innovation.

First-in-class (FIC) oncology drugs-defined by their novel mechanisms of action or targeting of previously unaddressed molecular targets-have emerged as a leading force in cancer therapeutic innovation. In this Review, we delineate the global landscape of FIC oncology drug approvals between 2009 and 2024 and analyze the evolving characteristics of both approved FIC therapies and potential FIC (PFIC) candidates in clinical development. To clarify the underlying dynamics of this evolution, we construct an analytic framework encompassing four distinct archetypes of FIC development: new targets, n

Invited Lectures : Overviews Purinergic signalling: past, present and future.

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… The following feedback control hypothesis is proposed: AMP is dephosphorylated by ecto-5′-nucleotidase, producing adenosine under hypoxic conditions in the extracellular space adjacent to a parenchymal cell (eg, cardiomyocyte, skeletal muscle fiber, hepatocyte, etc.). …

Comprehensive analysis of mRNA-microRNA-lncRNA expression profiles in post-traumatic elbow heterotopic ossification using RNA sequencing and experimental validation.

BackgroundThis study aimed to profile the molecular signatures of post-traumatic elbow heterotopic ossification (HO) to identify key regulators and potential therapeutic targets.MethodsTotal RNA from post-traumatic elbow HO tissues (n=4) and normal bone tissues (n=6) was subjected to high-throughput sequencing to identify differentially expressed mRNAs (DEGs), microRNAs (DEMs), and lncRNAs (DELs). Bioinformatics analyses included Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein-protein interaction network construction, and transcription factor (TF)

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… Within the CC category, these genes were primarily associated with the ‘extracellular space’ and ‘extracellular region.’ For MF, the most significantly enriched terms were ‘cytokine activity’ and ‘growth factor activity.’ Figure 5. …

Diffusion MRI for Assessment of Bone Quality; A Review of Findings in Healthy Aging and Osteoporosis.

Diffusion MRI (dMRI) is a growing imaging technique with the potential to provide biomarkers of tissue variation, such as cellular density, tissue anisotropy, and microvascular perfusion. However, the role of dMRI in characterizing different aspects of bone quality, especially in aging and osteoporosis, has not yet been fully established, particularly in clinical applications. The reason lies in the complications accompanied with implementation of dMRI in assessment of human bone structure, in terms of acquisition and quantification. Bone is a composite tissue comprising different elements, ea

Research progress in inducing immunogenic cell death of tumor cells.

Immunogenic cell death (ICD) is a regulated cell death (RCD) pathway. In response to physical and chemical signals, tumor cells activate specific signaling pathways that stimulate stress responses in the endoplasmic reticulum (ER) and expose damage-associated molecular patterns (DAMPs), which promote antitumor immune responses. As a result, the tumor microenvironment is altered, and many tumor cells are killed. The ICD response in tumor cells requires inducers. These inducers can be from different sources and contribute to the development of the ICD either indirectly or directly. The combinati

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… Driven by the endoplasmic reticulum stress response, many damage-associated molecular patterns (DAMPs) associated with ICD development are secreted or transported to the extracellular space, expressed on the cell surface, and attracted to dendritic cells (DCs) and macrophages through various pattern … Furthermore, DAMPs associated with ICD development, HSP70 and HSP90, enter the extracellular space and bind to antigen-presenting cell surface receptors, promoting DC activation and maturation and further enhancing tumor-associated immune effects ( 82 , 83 ). …

Mechanisms inducing low bone density in Duchenne muscular dystrophy in mice and humans.

Patients affected by Duchenne muscular dystrophy (DMD) and dystrophic MDX mice were investigated in this study for their bone phenotype and systemic regulators of bone turnover. Micro-computed tomographic (µCT) and histomorphometric analyses showed reduced bone mass and higher osteoclast and bone resorption parameters in MDX mice compared with wild-type mice, whereas osteoblast parameters and mineral apposition rate were lower. In a panel of circulating pro-osteoclastogenic cytokines evaluated in the MDX sera, interleukin 6 (IL-6) was increased compared with wild-type mice. Likewise, DMD patie

Disruption of the microenvironmental ecosystem in subchondral bone marrow lesions: Roles in osteoarthritis pathophysiology, pain and progression.

This narrative review explores the role of subchondral bone in the pathophysiology of osteoarthritis (OA), emphasizing the biomechanical and biochemical contributions that it makes to disease progression. A fresh perspective is presented by the authors in the form of a novel hypothesis that implicates mechano-inflammatory disruption of the bone marrow (BM) microenvironmental ecosystem (BM niche), unresolved inflammation, and fibrosis as key drivers of OA pathogenesis and pain. BMLs, detectable via magnetic resonance imaging (MRI), serve as dynamic imaging biomarkers that correlate with pain se

Guided immunotherapy for residual solid tumor: integrating platelets and CAR T cells to reduce post-surgical recurrence.

Postoperative recurrence remains a major obstacle to durable remission in patients with solid tumors, even after complete macroscopic resection. Growing evidence suggests that surgery creates a transient yet highly permissive biological window characterized by inflammatory signaling, coagulation activation, endothelial disruption, and systemic immune suppression. Together, these processes foster a protective niche that enables microscopic residual disease to evade immune surveillance and initiate metastatic outgrowth. Although modern adjuvant therapies have improved outcomes, their effectivene