Search Results (10,966)

Background: Disruption of the corneal epithelial (CE) cell layer is a pathological feature of several ocular disorders including the potentially severe condition, neurotrophic keratitis (NK). The drug, Oxervate™, whose active principle is recombinant human nerve growth factor (NGF), has been shown to promote healing of the corneal epithelial layer in NK. This effect could result from NGF stimulating the repair and regeneration of corneal nerves so that they provide better trophic support for CE healing and general health. Another mechanism of NGF in promoting CE layer healing may be through direct stimulation of the division and migration of CE cells. Fetal bovine serum (FBS) has also been found to promote CE layer healing in experimental studies. Like Oxervate™, FBS contains NGF, but it also contains several other bioactive components including other growth factors. The present study compares the effects of FBS to those of NGF to examine whether the combination of bioactive components in FBS might be more effective than NGF alone in producing corneal wound healing. Methods: CE cells of the HCE-S line were grown in 96-well plates fitted with a silicon plug that occluded a 1 mm circular area in the center of each well. When the cells reached confluence, the plugs were removed, resulting in the cell layers each containing a similar central defect. Different amounts of NGF, FBS, and a combination of the two were then added to each well. The effect of these treatments on the amount of closure of the defect after 24 h was measured and compared. Results: NGF increased the amount of closure of the defect after 24 h. At a concentration of 250 nM, NGF produced a significant, 25 ± 9% increase in closure. No further increase in effect was seen when the NGF concentration was increased to 500 nM. FBS also produced an increase in the closure. At an FBS concentration of 10%, this increase was 118 ± 27%, which was significantly greater than the percentage increase produced by NGF. The addition of both 250 nM NGF and 10% FBS together produced no greater amount of closure than that produced by FBS alone. Conclusions: These findings are consistent with earlier data suggesting that NGF can promote corneal healing through a direct effect on CE cells. They also show that FBS is more effective than NGF alone in producing this effect. Since the therapeutic activity of NGF in NK may be partly mediated through a direct action on corneal epithelial cells, identifying the factors in FBS that promote corneal healing might lead to more effective treatments for NK. Full article

Vascular stents are crucial devices in the treatment of cardiovascular diseases, and their structural design and function critically affect therapeutic efficacy and patient prognosis. Conventional stents can effectively restore vascular patency by providing mechanical support to blood vessels. However, they still face significant challenges including restenosis, thrombosis, and limited adaptability to complex patient-specific lesion characteristics. To address these limitations, drug delivery offers an important strategy to modulate the pathological microenvironment, enhance long-term vascular healing, and reduce systemic side effects. Meanwhile, advances in computational simulations have provided powerful tools for optimizing stent design through structural mechanics, hemodynamics, and drug release modeling. Computational approaches enable the rational design of stent architectures with improved mechanical stability, vascular compatibility, and therapeutic regulation. Consequently, the development of vascular stents is evolving toward the synergistic integration of drug delivery, structural optimization, and intelligent design. This review summarizes the latest advances in functional vascular stents, clinical applications and computational design. This work aims to provide valuable insights for the engineering of efficient, precise, and intelligent vascular stents for cardiovascular therapies. Full article

The ZFP36 family proteins (TTP, ZFP36L1, and ZFP36L2) are RNA-binding proteins that function as key post-transcriptional regulators of gene expression. They bind AU-rich elements (AREs) in target mRNA 3′UTRs, recruit the CCR4-NOT deadenylation complex to trigger mRNA decay, and maintain homeostasis in immunity, barrier function, and stem cell fate. Rather than acting on single targets, all family members share a conserved mRNA destabilization mechanism, with outcomes determined by member-specific expression, kinase-mediated regulation, and cell-type-dependent target availability. Dysregulation of this network stabilizes mRNAs encoding pro-inflammatory cytokines, immune checkpoints, and oncogenes, driving pathogenesis of inflammation, autoimmunity, cancer, cardiovascular and neurodegenerative diseases. Individual family members exert context-dependent and sometimes opposing effects, so their net function depends on the specific cellular and disease context. Therapeutic strategies targeting ZFP36 activity, including phosphatase agonism and epigenetic modulation, have shown promising preclinical results, but clinical translation remains early. This review summarizes the molecular regulatory networks of the ZFP36 family and their physiological and pathological roles, emphasizing the mechanistic principles that unify family-member function and the contextual factors that diversify it, to provide a foundation for future therapeutic development. Full article

Historically, the study of oral fungal species was limited by the inability to cultivate most of them. However, advances in metagenomic techniques have enabled the direct identification of microbial genomes from human samples, markedly broadening our understanding of the oral mycobiome. This narrative review aims to analyze the available scientific evidence on the composition and dynamics of the oral mycobiome, as well as its influence on the development of local pathological conditions. The oral mycobiome is highly diverse, with emphasis on genus Candida, followed by Cladosporium, Aureobasidium and Saccharomyces. Candida albicans remains the most frequently identified species in both health and diseases state. However, individuals with oral candidiasis present a higher detection of Candida dubliniensis, Candida parapsilosis, Pichia kudriavzevii, Antrodiella micra and Cladosporium sphaerospermum. In dental caries, C. albicans and C. dubliniensis are associated with advanced lesions, whereas Debaryomyces and Rhodotorula may exert protective effects against Streptococcus mutans, a cariogenic bacterium. In periodontitis, an increase in yeast-bacteria interactions is observed. Additionally, C. albicans has been implicated in oral carcinogenesis through multiple mechanisms. These findings highlight the need for a deeper understanding of the oral mycobiome to enable early detection of oral diseases and the development of therapeutic approaches. Full article

Proanthocyanidin A₂ (PA₂) is a class of bioactive small-molecule natural polyphenols, while selenocysteine (Sec) represents an essential functional selenium-containing amino acid in humans and has emerged as a cutting-edge research hotspot in the field of natural bioactive factors. This review systematically summarizes the natural resource distribution and biological signaling pathways of PA₂, as well as the in vivo metabolic profiles of Sec. It further elaborates on the core physiological and pathological processes co-regulated by PA₂ and Sec, including oxidative stress homeostasis, inflammatory immune responses, and metabolic reprogramming. Malignant tumors, severe diseases triggered by disrupted organismal homeostasis, serve as the primary research model for exploring the synergistic regulatory effects of PA₂ combined with Sec. Accumulating evidence has validated the independent anti-tumor efficacy of PA₂ and Sec in respective research domains; nevertheless, studies investigating their synergistic bioactivities remain scarce. Starting from the natural resource distribution of PA₂ and the respective core biological functions of the two agents, this work systematically dissects their individual roles in modulating oxidative stress, inflammatory responses, tumor malignant proliferation and apoptosis, and proposes putative synergistic regulatory mechanisms with hypothetical mechanistic validation. The findings are expected to provide theoretical references and innovative research strategies for developing combinatorial interventions of natural polyphenols and selenocysteine against tumors and related disorders, as well as for constructing antioxidant damage defense systems. Full article

Diabetic wounds remain a major clinical challenge owing to persistent dysregulation of the wound microenvironment, which substantially limits the effectiveness of conventional therapies. In recent years, multifunctional hydrogels have emerged as promising platforms for diabetic wound management, attributed to their excellent biocompatibility, tunable physicochemical properties, and unique capacity to actively remodel pathological microenvironments through integrated therapeutic functions. This comprehensive narrative review provides an in-depth synthesis of the pathogenesis and current therapeutic strategies for diabetic wounds, with a particular focus on recent advances in multifunctional hydrogels, as well as their classification, design principles, mechanisms of action, and translational potential. Furthermore, emerging directions are discussed as promising approaches for next-generation therapies, including intelligent closed-loop systems, interdisciplinary technological convergence, and the integration of bioactive components derived from traditional Chinese medicine. Collectively, these advances are poised to facilitate the transition from passive wound coverage to active microenvironment remodeling, paving the way for precision and personalized diabetic wound care. Full article

With the growing of the global population aging, the comorbidity of cardiovascular disease (CVD) and Alzheimer’s disease (AD) has gradually become a major contributor to global disease burden, with the two diseases exhibiting interacting pathological characteristics. This review summarizes the mechanisms underlying CVD-AD comorbidity, including cerebral hypoperfusion and protein aggregation, oxidative stress and inflammation, as well as metabolic disorders and genetic factors. We also assess the value of blood biomarkers in this comorbidity, such as p-tau217, NT-proBNP, NfL, GFAP, and miRNAs. We then review the role of exercise in ameliorating this comorbidity, integrating its potential mechanisms into five aspects: repairing cerebral hypoperfusion and endothelial injury, accelerating Aβ clearance and inhibiting Tau protein hyperphosphorylation, reducing inflammation, protecting neuronal structure and the blood–brain barrier, and improving metabolic disorder. We also analyze in detail the relationship between exercise targets and blood biomarkers. Finally, we discussed the impact and application of different exercise modalities in this comorbidity, concluding with suitable exercise prescriptions and relevant safety considerations for each modality, further organized the mainstream pharmacological and nutritional intervention strategies for CVD-AD comorbidity, and objectively explored their potential interactions when combined with exercise interventions. Future research should integrate multi-omics technologies and gradually refine clinical data on comorbidity, with the aim of developing more targeted, personalized exercise prescriptions for patients with comorbidities, thereby providing scientific theoretical guidance for early risk prevention and disease management in patients with co-occurring CVD and AD. Full article

Background & Objectives: Endovascular embolization has matured into a sophisticated, precision-guided discipline that is central to the management of complex neurovascular pathologies. This review synthesizes contemporary treatment strategies, evaluating the advanced material characteristics of conventional inert liquid polymers, specifically non-adhesive ethylene vinyl alcohol (EVOH) copolymers and adhesive cyanoacrylates, alongside their targeted clinical applications in brain arteriovenous malformations (bAVMs), dural arteriovenous fistulas (dAVFs), hypervascular intracranial tumors, and chronic subdural hematomas (CSDHs). Furthermore, it examines the critical material and hemodynamic constraints that limit these agents in cerebral aneurysm repair. Methods: A comprehensive literature synthesis through 3 July 2026 was integrated with peer-reviewed clinical illustrations to evaluate both procedural mechanics and the necessity of post-procedural physiological management. Review Findings: Embolization serves a critical dual role: as a definitive curative therapy and as an essential preoperative or radiosurgical adjunct. As demonstrated by recent clinical validations, technical angiographic success must be closely coupled with vigilant neurocritical oversight to manage profound, localized hemodynamic shifts. While these conventional methods represent established clinical practice, the field is evolving away from inert mechanical occlusion toward a highly integrated approach. The convergence of stimuli-responsive “smart” hydrogels and endovascular robotics is being evaluated for potential roles in transforming these interventions into dynamic, bioactive platforms capable of modulating disease-specific mechanisms, such as Rat Sarcoma-Mitogen-Activated Protein Kinase (RAS-MAPK) and Bone Morphogenetic Protein (BMP) signaling in bAVMs or the Von Hippel-Lindau/Vascular Endothelial Growth Factor (VHL/VEGF) axis in hypervascular tumors. This review further analyzes landmark data, including the Squid Trial For the Embolization of the Middle Meningeal Artery for Treatment of Chronic Subdural Hematoma (STEM) trial for CSDH, providing a synthesis for translating these advanced material sciences into standardized, multidisciplinary neurointerventional care. Full article

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder and a leading cause of dementia worldwide, yet effective disease-modifying therapies remain elusive. Rodent models have been indispensable for elucidating key pathological mechanisms, including amyloid-beta (Aβ) deposition, tau pathology, neuroinflammation, and synaptic dysfunction. However, despite decades of preclinical success, the translation of therapeutic findings from rodent studies to clinical efficacy in humans has been largely unsuccessful, highlighting critical limitations in current modelling approaches. This narrative review provides a comprehensive and critical evaluation of rodent models of AD, encompassing transgenic, chemically induced, metabolic, inflammatory, and lesion-based paradigms. Rather than presenting these models in isolation, we propose a systems-level framework that categorizes them based on their ability to recapitulate distinct domains of AD pathology, including genetic, environmental, and systemic contributors. By synthesising existing research, highlighting critical gaps, and proposing a tiered minimum-criteria framework for the development of next-generation models, we offer a definitive operational roadmap instead of merely a list of deficiencies. We highlight that most existing models predominantly reflect familial and reductionist aspects of the disease, while failing to capture the complexity of sporadic AD, aging processes, vascular dysfunction, and whole-body interactions. Importantly, we emphasize emerging dimensions that are underrepresented in current rodent models, including glymphatic dysfunction, cerebral small vessel disease, and the microbiota–gut–brain axis, all of which play crucial roles in AD pathogenesis. We further discuss how integrating these factors into next-generation models may improve translational relevance and therapeutic predictability. By synthesizing current evidence and identifying key gaps, we provide a strategic roadmap for the development of more physiologically relevant and translationally robust rodent models. Advancing toward integrative, systems-based approaches will be essential for bridging the persistent gap between preclinical discoveries and clinical success in AD. Full article

Ischemia–reperfusion injury (IRI) of the kidney represents a serious medical issue with complex pathological mechanisms that remain poorly elucidated. The development of ischemic acute kidney injury (AKI) may be mediated by NADPH oxidase and angiotensin II type 2 receptors. The aim of our study was to explore the effects of novokinin (NOV), angiotensin II type 2 receptor (AT2R) agonist and apocynin (APO), an NADPH oxidase inhibitor, on kidney structure and function, as well as the level of oxidative stress in spontaneously hypertensive rats (SHR) with induced IRI. Animals were randomly assigned into five experimental groups: the Sham-operated animals (SHAM) group, the AKI group, and AKI groups receiving APO, NOV, or their combination. Slight improvements in renal function were noted across all treated groups; however, only the combined action of APO + NOV led to a significant decrease in kidney injury molecule-1 (KIM-1) levels and markedly reduced oxidative stress compared with the control AKI group. Our results demonstrate that additively targeting NADPH oxidase and AT2R provides new insights in comparison to individual treatments. These findings suggest a potentially promising new therapeutic strategy for managing IRI and improving outcomes in critically ill patients with AKI. Full article

The kynurenine pathway (KP) constitutes the primary route of tryptophan catabolism, generating a spectrum of neuroactive metabolites that profoundly influence central nervous system function. Dysregulation of the KP is increasingly recognized as a critical pathogenic mechanism underlying diverse neuropathological conditions. This review critically evaluates the most widely cited mammalian cellular models currently utilized to delineate the causal role of KP alterations in neurological disease. Specifically, this article examines primary cell cultures, immortalized and tumor-derived cell lines, stem cell-derived systems, and ex vivo organotypic brain slices and tissues, highlighting their distinct methodological advantages, translational limitations, and specific enzymatic profiles. Across the described cellular systems, a recurring mechanistic theme emerges: quinolinic acid-driven mitochondrial dysfunction, oxidative stress, and NAD+ depletion converge in neurodegenerative conditions such as Alzheimer’s disease, Huntington’s disease, and amyotrophic lateral sclerosis. Conversely, kynurenic acid exhibits disorder-dependent—and at times opposing—roles, attenuating dopaminergic neurotoxicity in Parkinson’s disease models while contributing to synaptic pruning deficits in schizophrenia models. Furthermore, cellular models demonstrate that IDO1/TDO induction and downstream metabolite shifts are frequently cell type- and species-dependent, complicating direct extrapolation to human pathology. Because no single experimental system achieves complete physiological fidelity, elucidating the complex dynamics of the KP and identifying novel therapeutic targets requires the integration of data across complementary platforms. Full article

Phase transition or phase separation occurs in cells and tissues in many physiological events, such as protein granules (P granules) in early C. elegans development. Inappropriate phase transition is often associated with pathologic processes such as RNA–protein complex (RNP) and FUS-mutation-associated diseases. Given its ubiquity, phase transition has been considered a new frontier for comprehending physiological processes and pathological diseases. However, molecular and cellular mechanisms of phase transition in situ remain poorly described. Combining histochemistry with polarization analysis and biochemical thin-layer chromatography, we identified a massive phase transition change during the development of Taihe fowl (Gallus gallus domesticus Brisson). During embryonic day 12 (E12), the livers of these Silkie chicken demonstrated a sudden massive transition from hepatic lipid droplets (HLD) into hepatic liquid crystal droplets (HLCDs). We identified these changes by characterizing the sudden appearance of birefringent Maltese crosses (MCs) typical to liquid crystals (LC) where non-birefringent lipid droplets used to reside within hepatic cells. LC status was confirmed by fluidity with shape-changing and in vitro thermal phase transition tests. These HLCDs were present consistently until the early postnatal days after hatching. Using thin-layer chromatography combined with X-ray diffraction analysis, we determined that these HLCDs were composed of cholesterol, cholesterol ester and lecithin, which are the same as the components of cytoplasmic membrane. There was no change in the quantity of lipid components during liver development to suggest a critical mass of components triggering these changes. However, expressions of membrane-associated autophagy markers LC3A and Beclin 1 increased dramatically during this HLD to HLCD transition. Increases in membrane-associated LC3A and Beclin 1 are localized with massive increases in membrane lipid components of HLCDs. Areas with enhanced LC3A and Beclin 1 signaling have been associated with liquid crystal MCs to the thickness of 69 Å (Bragg d value). These associations indicate the possible regulatory role autophagy plays during liquid crystal phase transition in embryonic liver development. Reactivation of this autophagy pathway may be a possible mechanism behind the development of non-alcoholic fatty liver disease in adulthood. Full article

The Achilles tendon, the largest and strongest tendon in the human body, exhibits dynamic adaptive changes in its structure and function through mechanobiological regulation. This review synthesizes the dual regulatory effects of mechanical loading on Achilles tendon homeostasis and pathology: Moderate mechanical stimulation activates integrin-mediated signaling pathways (including PI3K/Akt and MAPK/ERK cascades), promoting tenocyte proliferation/differentiation, collagen biosynthesis, and orderly remodeling of extracellular matrix (ECM), thereby enhancing tendon stiffness, elastic modulus, and ultimate tensile strength. Conversely, chronic overload or disuse conditions induce collagen disorganization, aberrant matrix metalloproteinase (MMP) expression, and inflammatory cascades, creating a predisposition to tendinopathy and degenerative disorders. Emerging evidence highlights the critical role of mechanotransduction in injury repair, with early-stage progressive loading regimens demonstrating enhanced healing outcomes through optimized ECM metabolism and biomechanical signal propagation. Clinically, individualized load management strategies, including blood flow restriction training and biomaterial-assisted mechanomodulation, show promise in injury prevention and rehabilitation. Future research integrating multi-omics approaches with intelligent load-monitoring technologies may clarify mechanobiological coupling mechanisms and facilitate precision interventions for Achilles tendon disorders. Full article

Background: Cardiotocography (CTG) represents a cornerstone in modern intrapartum fetal surveillance, allowing continuous assessment of fetal well-being through the analysis of fetal heart rate patterns in relation to uterine contractions. Despite its widespread clinical use, the interpretation of CTG tracings remains complex and is often associated with high interobserver variability and limited specificity in predicting adverse outcomes. In recent years, increasing attention has been directed toward placental pathology as a key determinant in the pathophysiology of adverse perinatal events. The placenta, as a dynamic organ mediating maternal–fetal exchange, plays a crucial role in fetal oxygenation and nutrient supply. Alterations in its structure and function may contribute to both chronic and acute fetal compromise. This retrospective study aimed to investigate the relationship between pathological intrapartum CTG tracings and maternal–fetal outcomes, with a particular focus on correlating these findings with macroscopic and microscopic placental abnormalities, compared to a control group of uncomplicated pregnancies with normal CTG patterns. Material and methods: We evaluated maternal, fetal, and placental histopathological data from 85 patients who exhibited pathological intrapartum cardiotocographic tracings. All deliveries occurred between January 2023 and March 2025 at the Obstetrics and Gynecology Departments of the ‘A. Gemelli’ University Hospital and Careggi University Hospital. A control group consisting of 50 women with normal CTG patterns and uncomplicated term singleton pregnancies, delivered at the same institutions, was used for comparison. Results: Cases with pathological CTG showed poorer neonatal outcomes compared with those with normal CTG. Infants in the pathological CTG group had lower Apgar scores, more frequent NICU admissions, and one case of hypoxic–ischemic encephalopathy. Mode of delivery, Apgar scores, NICU admission, and arterial pH were all significantly associated with CTG classification. A higher birth weight-to-placental weight ratio in the pathological CTG group suggested possible uteroplacental insufficiency. Macroscopic and histological placental findings, including hypercoiled umbilical cords and intervillous thrombosis, were also significantly more frequent in cases with pathological CTG. Conclusions: The findings of this study suggest that pathological CTG reflects not an isolated event but rather a multifactorial dysfunction of the feto-placental unit. Its associations with low Apgar scores, reduced arterial pH, abnormal BW/PW ratio, intervillous thrombi, and umbilical cord hypercoiling are consistent with existing evidence and support the interplay of chronic placental abnormalities and acute mechanical factors in the development of suspected fetal hypoxia. The future development of multivariate predictive models integrating clinical, biochemical, and anatomo-pathological variables may improve the early identification of pregnancies at risk and optimize intrapartum management, thereby reducing adverse perinatal outcomes. Full article

Through multifaceted reprogramming, mitochondria, the fundamental organelles of eukaryotic cells, can drive the malignant growth of malignancies. They also control energy metabolism, redox balance, and cell fate determination. Due to its high heterogeneity and primary/acquired drug resistance, gastric cancer (GC), a highly deadly and common cancer worldwide, continues to present significant clinical treatment challenges. Current targeted and immunotherapy strategies have been unable to significantly improve long-term patient survival. Thus, the pathological roles and molecular mechanisms of mitochondrial dysfunction (including mutations in mitochondrial DNA, imbalances in mitochondrial dynamics, aberrant mitophagy, abnormalities in mitochondrial permeability transition pores, and metabolic disorders) in the development of GC are systematically reviewed in this article. The specific mitochondrial phenotypic remodeling of various molecular subtypes of GC, abnormalities in membrane contact interactions between mitochondria and other organelles, the regulatory roles of mitochondrial dysfunction in tumor microenvironment (TME) immune evasion, maintenance of tumor stemness, and ferroptosis, as well as their major effects on the malignant progression and treatment resistance of GC, are all thoroughly examined. In order to provide important theoretical references and novel research perspectives for identifying therapeutic targets with greater precision, clarifying resistance mechanisms, and developing novel combination strategies in GC, this article summarizes the current research status and translational potential of anti-GC therapeutic strategies targeting mitochondria. It also explores the translational challenges currently faced in this field and the core future research directions. Full article