Search Results (300)

Mechanical loading generated during physical activity and exercise is a fundamental determinant of musculoskeletal development, adaptation, and regeneration. Exercise-based mechanotherapy, encompassing structured movement, resistance training, stretching, and device-assisted loading, has evolved from empirical rehabilitation toward mechanism-driven and precision-oriented therapeutic strategies. At the macroscopic level, biomechanical principles governing load distribution, stress–strain relationships, and tissue-specific adaptation provide the physiological basis for exercise-induced tissue remodeling. At the molecular level, mechanical cues are transduced into biochemical signals through conserved mechanotransduction pathways, including integrin–FAK–RhoA/ROCK signaling, mechanosensitive ion channels such as Piezo, YAP/TAZ-mediated transcriptional regulation, and cytoskeleton–nucleoskeleton coupling. These mechanisms orchestrate extracellular matrix (ECM) remodeling, cellular metabolism, and regenerative responses across bone, cartilage, muscle, and tendon. Recent advances in mechanotherapy leverage these biological insights to promote musculoskeletal tissue repair and regeneration, while emerging engineering innovations, including mechanoresponsive biomaterials, 4D-printed dynamic scaffolds, and artificial intelligence-enabled wearable systems, enable mechanical loading to be quantified, programmable, and increasingly standardized for individualized application. Together, these developments position exercise-informed precision mechanotherapy as a central strategy for prescription-based regenerative rehabilitation and long-term musculoskeletal health. Full article

Liver function plays a pivotal role in the management of hepatocellular carcinoma (HCC). Consequently, managing HCC requires a dual focus on both tumour staging and liver function assessment to guide therapeutic decisions. Comprehensive liver function evaluation involves clinical tools such as the Child–Pugh classification and the Model for End-Stage Liver Disease (MELD) score. This is supplemented by newer metrics, including the MELD-Na score, the albumin–bilirubin (ALBI) grade and liver stiffness measurements. These assessments are integral to tailoring treatments, ranging from curative approaches such as surgical resection and liver transplantation to locoregional options (percutaneous ablation, transarterial chemoembolisation and radioembolisation), and systemic therapies. This review explores strategies for balancing the aggressiveness of cancer therapy with the need to preserve hepatic function, particularly in patients with advanced liver dysfunction. A multidisciplinary approach, incorporating expertise from hepatology, oncology, radiology and surgery, is essential for optimising outcomes. Advanced imaging techniques and biochemical markers also improve decision-making and ensure individualised care. Full article

Ocular allergy (OA) is a subtype of seasonal allergy that causes symptoms of itchiness, redness, swelling and irritation of the ocular surface and eyelids, often triggering allergy-induced eye rubbing and sustained inflammation for up to six months of the year during peak allergy season. These symptoms, coupled with reduced sleep quality, impaired daily productivity and decreased mood, highlight a significant yet underrepresented disease burden. Recent advances in tear-based multi-omics have enabled detailed characterisation of OA-associated biochemical changes on the ocular surface, highlighting human tears as a promising biospecimen for diagnostic biomarker and therapeutic target research. This review discusses emerging proteomic, lipidomic, metabolomic and miRNA findings comparing OA sufferers with healthy controls, and, where relevant, with comorbid conditions such as dry eye disease and keratoconus. Differential expression patterns across these analytes implicate key pathways involved in immune response, wound healing, angiogenesis, inflammation, oxidative stress and return to homeostasis on the ocular surface. By integrating these data into a stepwise model of OA biopathway activation, this review outlines candidate biomarkers and highlights methodological advances that may support translation of tear multi-omics into clinical tools for OA management. Full article

Recent advances in sequencing technologies have highlighted long non-coding RNAs (lncRNAs) as key regulators that perform essential biological functions without encoding proteins. Despite growing interest, the molecular mechanisms of most lncRNAs remain poorly understood, with only a few characterized in detail. A promising strategy to elucidate these mechanisms is to explore their structure–function relationships. Such studies require advanced biophysical and biochemical methods due to the large size and structural complexity of lncRNAs. Equally important is the analysis of lncRNA interactomes, which reveal how lncRNAs engage RNA-binding proteins and other biomolecules to drive conformational and functional changes underlying diverse biological pathways. Ultimately, integrative approaches combining structural and interactome analyses will yield deeper insight into lncRNA function and uncover new therapeutic opportunities. This review highlights recent advances in elucidating lncRNA structure–function relationships by integrating biophysical, biochemical, and sequencing-based approaches to overcome challenges of size and heterogeneity, identify functional binding partners, and inform therapeutic target development. Full article

The cardiac extracellular matrix (ECM) is a dynamic, tissue-specific scaffold essential for cardiovascular development, homeostasis, and disease. Once considered a passive structural framework, the ECM is now recognized as an active regulator of mechanical, electrical, and biochemical signaling in the heart. Its composition evolves from embryogenesis through adulthood, coordinating cardiomyocyte maturation, chamber formation, and postnatal remodeling. In pathological states, diverse stimuli—including ischemia, pressure or volume overload, metabolic dysfunction, and aging—disrupt ECM homeostasis, triggering fibroblast activation, myofibroblast transformation, and maladaptive collagen deposition. These processes underpin myocardial fibrosis, a key driver of impaired contractility, diastolic dysfunction, arrhythmogenesis, and heart failure across ischemic and non-ischemic cardiac diseases. ECM alterations also exhibit age- and sex-specific patterns that influence susceptibility to cardiovascular pathology. Advances in imaging and circulating biomarkers have improved fibrosis assessment, though limitations persist. Therapeutic strategies targeting ECM remodeling, including modulation of profibrotic signaling pathways, non-coding RNAs, cellular therapies, and nano-delivery systems, show promise but remain largely experimental. Collectively, expanding knowledge of ECM biology highlights its central role in cardiovascular physiology and pathology and underscores the need for targeted diagnostic and therapeutic innovations. Full article

Background/Objectives: Despite therapeutic advances, managing relapsed/refractory multiple myeloma (RRMM) remains challenging. For patients with frailty, comorbidities, mobility limitations, or when treatment preference and drug accessibility are key considerations, the all-oral ixazomib–lenalidomide–dexamethasone (IRd) regimen offers a practical alternative. Methods: We performed a multicenter retrospective study of RRMM patients treated with IRd in Hungary between 1 January 2020 and 30 June 2025. Results: The median age at treatment initiation was 73.7 years. Treatment was initiated for clinical progression in 38.2%, biochemical progression in 53.3%, and for intolerance or toxicity of prior therapy in 8.6%. Median progression-free survival (PFS) was 18.7 months, and median overall survival (OS) was 34.7 months. Patients treated at biochemical progression had significantly longer PFS than those treated at clinical progression (24.3 vs. 15.6 months; p = 0.004), with additional benefit when IRd was initiated owing to intolerance or toxicity of previous therapy (p = 0.04). In the second-line setting, median PFS was 24.5 months, and median OS was not reached. Adverse events occurred in 68.3% of patients; dose reductions were required in 18.4%, and 21.6% discontinued treatment because of intolerance or toxicity. Most common toxicities were neutropenia (32.9%), thrombocytopenia (27.6%), diarrhoea (25%), peripheral neuropathy (25.3%), and infections (22.4%). Conclusions: IRd initiation at biochemical progression was associated with superior PFS compared with treatment at clinical progression. When compared with a recent Hungarian multicenter cohort treated with second-line daratumumab, lenalidomide, and dexamethasone, outcomes with IRd are not significantly inferior (36-month OS calculated from 2nd line treatment initiation: 65.5% for DRd vs. 60% in our cohort; p = 0.56). These real-world data support IRd as an effective, convenient, all-oral option for appropriately selected RRMM patients. Full article

Lipids are essential biomolecules involved in membrane structure, energy storage, and intracellular signaling. Dysregulation of lipid metabolism (dyslipidemia) plays a central role in a wide spectrum of pediatric metabolic disorders, including both inherited and acquired conditions. Recent and rapid advances in mass spectrometry-based lipidomics have enabled high-resolution profiling of more than one-thousand lipid species, facilitating the discovery of disease-specific lipid signatures that were previously undetectable with conventional biochemical assays. In parallel, the rising prevalence of pediatric obesity, diabetes, asthma, metabolic dysfunction-associated steatotic liver disease (MASLD; formerly referred to as non-alcoholic fatty liver disease or NAFLD) and cancers has accelerated research aimed at uncovering molecular pathways underlying these conditions. Lipidomic approaches have also improved the identification and characterization of rare metabolic disorders. As analytical technologies continue to advance, lipidomics is poised to become a cornerstone of precision medicine in pediatrics, offering new opportunities for early diagnosis, risk stratification, and therapeutic targeting. Full article

Dystocia represents a multifactorial and clinically significant reproductive disorder affecting a broad spectrum of reptilian species. Commonly resulting from prolonged vitellogenesis, endocrine disruption, or hepatic lipidosis, dystocia is often exacerbated by suboptimal husbandry or concurrent disease. This review critically evaluates the etiology, diagnostic criteria, and therapeutic interventions associated with this condition. Emphasis is placed on the interplay between metabolic exhaustion and hepatic compromise, which may lower the threshold for surgical intervention. The efficacy and limitations of oxytocin-based protocols are discussed in the context of hormonal receptor variability and response attenuation. Advanced diagnostic modalities, including ultrasonography, radiography/CT, and biochemical profiling, are reviewed for their utility in case stratification. Finally, surgical management options are considered for cases refractory to medical treatment, with attention paid to timing, anesthetic risk, and post-operative care. Collectively, this synthesis aims to inform evidence-based clinical decision-making and promote improved standards of care in reptile reproductive medicine. Full article

Acute lung injury (ALI) is driven by a complex interplay between immune dysregulation and structural matrix remodeling. Although inflammation, oxidative stress, and disturbances in the coagulation–fibrinolysis system have long been recognized as core pathogenic drivers, growing evidence demonstrates that the extracellular matrix (ECM) functions as an active regulator of lung injury and repair rather than a passive structural scaffold. This review synthesizes current advances in ECM biology and immunopathology to delineate how ECM remodeling influences, and is concurrently shaped by, the inflammatory microenvironment. We outline how biochemical and physical modes of ECM remodeling engage in bidirectional crosstalk with the immune system. Emerging therapeutic strategies targeting this ECM–immune axis are critically evaluated, including modulation of protease activity, interventions that reprogram cell–matrix interactions, and approaches that restore ECM integrity using stem cells or engineered biomaterials. By redefining ALI as a disease of immune–matrix reciprocity, this review underscores the ECM as both a structural framework and a dynamic immunoregulatory hub, providing conceptual and mechanistic insights that may guide the development of precision therapies for ALI and related pulmonary disorders. Full article

Background and Objectives: Urothelial carcinoma (UC) is one of the most prevalent and lethal cancers worldwide. Identifying and understanding the factors that influence treatment outcome is essential for improving therapeutic effectiveness and predicting patient response. The objective of this review is to estimate how clinical, biochemical, molecular and therapeutic factors impact the prognosis of patients with advanced urothelial carcinoma (aUC) and metastatic urothelial carcinoma (mUC) treated with immune checkpoint inhibitors (ICIs). Methods: A review was performed using PubMed, Scopus and Web of Science databases. All articles were published from 2013 to 2025 focusing on prognostic factors in locally advanced and metastatic urothelial carcinoma treated with ICIs. Results: Clinical prognostic factors for patients treated with ICIs include poor Eastern Cooperative Oncology Group (ECOG) performance status and the presence of liver or bone metastases, both associated with poor outcomes. Low hemoglobin levels and several biochemical markers, such as high neutrophil-to-lymphocyte ratio (NLR), elevated systemic immune-inflammation index (SII) and low serum sodium are also associated with reduced survival. Programmed cell death-ligand 1 (PD-L1) expression shows predictive relevance for ICI response. Concomitant use of antibiotics or proton pump inhibitors (PPIs) may diminish immunotherapy effectiveness. Additionally, sarcopenia and high lactate dehydrogenase (LDH) levels correlate with poorer clinical outcomes. Conclusions: Prognostic outcomes in aUC and mUC are influenced by a complex interaction of clinical, biochemical and molecular factors. Integrative prognostic models are essential to the guidance of personalized immunotherapeutic strategies and the improvement of patient outcomes in aUC and mUC. Full article

Microfluidic cell culture systems and organ-on-a-chip platforms provide powerful tools for modeling physiological processes, disease progression, and drug responses under controlled microenvironmental conditions. These technologies rely on diverse cell culture methodologies, including 2D and 3D culture formats, spheroids, scaffold-based systems, hydrogels, and organoid models, to recapitulate tissue-level functions and generate rich, multiparametric datasets through high-resolution imaging, integrated sensors, and biochemical assays. The heterogeneity and volume of these data introduce substantial challenges in pre-processing, feature extraction, multimodal integration, and biological interpretation. Artificial intelligence (AI), particularly machine learning and deep learning, offers solutions to these analytical bottlenecks by enabling automated phenotyping, predictive modeling, and real-time control of microfluidic environments. Recent advances also highlight the importance of technical frameworks such as dimensionality reduction, explainable feature selection, spectral pre-processing, lightweight on-chip inference models, and privacy-preserving approaches that support robust and deployable AI–microfluidic workflows. AI-enabled microfluidic and organ-on-a-chip systems now span a broad application spectrum, including cancer biology, drug screening, toxicity testing, microbial and environmental monitoring, pathogen detection, angiogenesis studies, nerve-on-a-chip models, and exosome-based diagnostics. These platforms also hold increasing potential for precision medicine, where AI can support individualized therapeutic prediction using patient-derived cells and organoids. As the field moves toward more interpretable and autonomous systems, explainable AI will be essential for ensuring transparency, regulatory acceptance, and biological insight. Recent AI-enabled applications in cancer modeling, drug screening, etc., highlight how deep learning can enable precise detection of phenotypic shifts, classify therapeutic responses with high accuracy, and support closed-loop regulation of microfluidic environments. These studies demonstrate that AI can transform microfluidic systems from static culture platforms into adaptive, data-driven experimental tools capable of enhancing assay reproducibility, accelerating drug discovery, and supporting personalized therapeutic decision-making. This narrative review synthesizes current progress, technical challenges, and future opportunities at the intersection of AI, microfluidic cell culture platforms, and advanced organ-on-a-chip systems, highlighting their emerging role in precision health and next-generation biomedical research. Full article

BRCC36, a member of the JAB1/MPN/Mov34 metalloenzymes family, exhibits distinct biochemical characteristics compared to other monomeric deubiquitinating enzymes. To function as a deubiquitinating enzyme, BRCC36 must assemble into a complex with other subunits that specifically cleaves K63-linked polyubiquitin chains. In the cytoplasm, BRCC36 forms the BRISC complex, which plays a crucial role in regulating various signaling pathways through modulating the K63-linked ubiquitination of substrate proteins. The BRISC complex can interact with the cytoplasmic SHMT2, thereby influencing diverse biological processes, including inflammation, mitosis, and hematopoiesis. Within the nucleolus, BRCC36 forms the BRCA1-A complex, which contributes to DNA damage repair. Growing evidence underscores the importance of the ubiquitin system, particularly deubiquitinating enzymes, in the initiation and progression of various diseases. In this review, we first provide a comprehensive overview of the localization, assembly, mutations, and functions of BRCC36 and its associated complexes. We then discuss recent advances in research on BRCC36 across various diseases and explore its potential as a therapeutic target. Full article

Plasma cell myeloma (PCM) is classified as a blood cancer and is characterized by the abnormal proliferation of plasma cells in the bone marrow and the excessive production of monoclonal immunoglobulins, which lead to permanent damage to vital organs. Although treatment strategies have improved with the development of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and monoclonal antibodies (mAbs), PCM remains an incurable disease due to its molecular heterogeneity and the development of drug resistance. In this review, we discuss the biochemical and molecular foundations underlying the diagnosis and treatment of PCM, emphasizing both traditional and advanced approaches. Classical methods such as serum protein electrophoresis (SPEP), immunofixation electrophoresis (IFE), and serum free light chain (sFLC) determination are highlighted alongside their integration with highly sensitive techniques like mass spectrometry (MS) and next-generation sequencing (NGS). Special attention is given to nanotechnology-based systems, including liposomes, polymeric nanoparticles (NPs), dendrimers, and hybrid nanocapsules, which enable controlled drug release, targeted delivery, and the minimization of systemic toxicity. Increasingly, nanomaterials are being shown to greatly enhance the biodistribution and pharmacokinetics of anticancer drugs, leading to improved therapeutic effects and escaping resistance mechanisms by employing multifunctional strategies that include dual drug co-encapsulation, pH-sensitive release and theranostic applications. Furthermore, the integration of nanotechnology with immunotherapy platforms represents a paradigm shift toward precision and personalized medicine for the treatment of PCM. Overall, this review views nanotechnology as an enabling technology to improve therapeutic effectiveness, minimize toxicity and open new avenues toward next-generation smart and personalized therapeutics for the treatment of PCM. Full article

Cell migration plays a central role in physiological processes such as wound healing, tissue regeneration, and immune responses, as well as in pathological conditions like chronic inflammation and tumor metastasis. Among the in vitro approaches to study this phenomenon, the conventional wound healing assay (scratch assay) has been widely used due to its simplicity and low cost. However, its limitations, including poor reproducibility, damage to the extracellular matrix (ECM), and lack of dynamic physiological conditions, have prompted the development of microfluidic alternatives. Scratch-on-a-chip platforms integrate engineering and microtechnology to provide standardized, non-destructive methods for wound generation, preserve ECM integrity, and allow precise control of the cellular microenvironment. These systems also enable miniaturization, reducing reagent and cell consumption, while facilitating the application of biochemical or physical stimuli and real-time monitoring. This review synthesizes advances reported in the literature, addressing the different wound induction strategies (enzymatic depletion, physical depletion, and physical exclusion), the role of ECM composition, and the impact of mechanical forces such as shear stress. Overall, scratch-on-a-chip assays emerge as promising tools that enhance reproducibility, better mimic in vivo conditions, and broaden applications for therapeutic testing and mechanistic studies in cell migration. Full article

Primary biliary cholangitis (PBC) is a heterogeneous autoimmune liver disease in which clinical presentation, disease progression, and response to therapy vary markedly from patient to patient. This heterogeneity reflects its complex, multifactorial, and not-completely elucidated pathogenesis. Currently, serological markers are available to non-invasively diagnose PBC, reserving liver biopsy for selected cases with atypical presentations or diagnostic uncertainty. Anyway, the accurate non-invasive prediction of liver-related and non-liver-related (i.e., extra-hepatic, including pruritus) outcomes remains an open challenge, as well as an urgent need, considering the great variability in clinical course and prognosis reported in PBC patients. Moreover, although ursodeoxycholic acid (UDCA) remains the standard first-line treatment, not all individuals respond equally, either in terms of therapeutic efficacy or timing of biochemical improvement. This further variability in treatment response underscores the inadequacy of uniform management approaches and reinforces the urgent need for personalized medicine, where treatment decisions are guided by patient-specific biological and clinical parameters. In this scenario, the identification and validation of non-invasive predictive biomarkers capable of detecting early therapeutic responsiveness are pivotal for optimizing care pathways. Finally, a growing portion of patients show an insufficient UDCA response or are UDCA intolerant, making the identification of novel strategies of care an urgent need. Concerning this, very recently, new therapeutic options beyond UDCA targeting, among the other pathways, bile acid metabolism (including the modern Peroxisome Proliferator-Activated Receptor agonists), immune regulation, and fibrogenesis, have expanded the treatment landscape. In the Era of Precision Medicine, these diagnostic, prognostic, and therapeutic innovations, by reflecting the complexity of PBC pathogenesis, underline the cruciality of a patient-tailored strategy to improve outcomes and mitigate disease progression. The present review reports recent advances, highlights ongoing challenges, and outlines future perspectives in the management of PBC. Full article