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Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries, with incidence rising in parallel with obesity, insulin resistance, and type 2 diabetes (T2DM). EC exhibits characteristic metabolic vulnerabilities, including hyperactive glycolysis, mitochondrial dysfunction, and PI3K/AKT/mTOR pathway activation, driven by unopposed estrogen stimulation and systemic metabolic dysregulation. Metformin, a first-line antidiabetic agent and mitochondrial complex I inhibitor, has emerged as a promising repurposed drug for EC prevention and treatment through dual mechanisms: direct tumor suppression via AMPK/mTOR, PI3K/Akt, Wnt/β-catenin, and endoplasmic reticulum stress pathways; and indirect metabolic microenvironment improvement via insulin sensitization, sex hormone-binding globulin upregulation, and immune microenvironment remodeling. This narrative review comprehensively summarizes available preclinical mechanistic insights and published clinical evidence across EC disease spectrum: chemoprevention in high-risk populations (obesity, PCOS), fertility-preserving treatment for early-stage disease, and combination strategies for advanced/recurrent EC. We synthesize existing data rather than adopting formal systematic review methodology with predefined database retrieval and PRISMA-compliant screening criteria. We critically analyze survival outcomes, response heterogeneity contingent upon diabetic status and molecular subtypes, and current bottlenecks in biomarker-guided patient selection. Furthermore, we propose translational strategies for precision application: LKB1/PTEN status-based patient stratification, innovative combinations with CDK4/6 inhibitors, mTOR inhibitors, and immune checkpoint inhibitors, and clinical pathway optimization. By bridging metabolic endocrinology and gynecologic oncology, the available data provide preliminary theoretical basis to explore future shift of metformin from empirical off-label reuse toward biomarker-guided individualized medication, which still needs large-scale prospective validation.
Inflammatory diseases represent a major global health burden, and current therapies frequently fail to achieve sustained control of inflammation or prevent progressive tissue damage. Cortistatin (CST), an endogenous neuropeptide structurally related to somatostatin, has emerged as a multifunctional regulator of neuroimmune and immunometabolic pathways. This scoping review was conducted in accordance with PRISMA-ScR guidelines and maps and synthesizes preclinical evidence on the biological roles and therapeutic potential of CST across experimental disease models. A comprehensive literature search identified 31 preclinical studies published between 2006 and 2025 that evaluated CST administration or cortistatin deficiency. Despite substantial heterogeneity in disease models, including neurodegenerative, autoimmune, cardiovascular, fibrotic, and musculoskeletal conditions, CST consistently demonstrated protective effects. Across studies, CST reduced pro-inflammatory cytokine production, attenuated tissue damage, and improved functional outcomes and survival. Mechanistically, CST modulated key inflammatory pathways such as NF-κB signaling and NLRP3 inflammasome activation, suppressed Th1 and Th17 responses, and promoted regulatory T cell expansion through interactions with somatostatin receptors, GHSR1a, and MrgX2. Emerging translational strategies, including peptide analogues, protease-activated prodrugs, and nanoparticle-based delivery systems, have improved pharmacokinetic stability and therapeutic efficacy in experimental models. Collectively, these findings establish cortistatin as a consistent endogenous regulator of neuroimmune responses across diverse experimental conditions, highlighting its potential as a promising therapeutic target for immunomodulation in complex inflammatory diseases.
The human ether-à-go-go-related gene type 1 (hERG1) channel is a voltage-gated potassium channel encoded by the KCNH2 gene. hERG1 channels are essential to the repolarization of cardiac action potentials, and reduced function of the potassium current conducted by hERG1 channels (IKr) is pathogenic, leading to type 2 long QT syndrome (LQT2). LQT2 results from congenital mutation(s) of KCNH2 and affects approximately 1 in 6000 people. A mutation-induced decrease in IKr can be caused by altered channel gating but is most often caused by misfolding and early degradation of hERG1 protein, resulting in reduced trafficking of channels to the plasma membrane. Prolongation of the QT interval can also be drug induced, and many drugs fail preclinical safety assessments due to their inhibition of hERG1 channels. In this review we assess the molecular and structural bases of hERG1 channel function. Furthermore we examine the pharmacology of hERG1 inhibitors and hERG1 channel trafficking mediators, the pathogenesis of LQT2 that can be triggered through these mechanisms and translational and clinical perspectives that may be useful in the prevention and treatment of LQT2. By understanding the molecular mechanisms that lead to the pathophysiological development of LQT2 new therapeutics can be developed to treat this disorder.
This study aimed to systematically characterize the global research landscape, collaboration patterns, knowledge structure, and emerging hotspots of glucagon-like peptide-1 receptor agonists in neurodegenerative diseases using bibliometric methods. Publications related to glucagon-like peptide-1 receptor agonists and neurodegenerative diseases were retrieved from the Web of Science Core Collection from 2006 to 2025. Only English-language articles and reviews were included. Bibliometric analyses were performed using Bibliometrix, VOSviewer, and CiteSpace to evaluate annual publication trends, country and institutional contributions, author collaborations, journal distribution, citation structures, keyword co-occurrence, thematic evolution, and citation bursts. A Scopus-based sensitivity analysis was conducted to assess the robustness of the main bibliometric findings. A total of 1,202 publications were included, with annual output increasing from 2 in 2006 to 241 in 2025, particularly after 2020. China, the USA, and England were the leading contributors and major collaboration hubs. Shanxi Medical University, Lancaster University, and the National Institute on Aging were among the most productive institutions, while major journals included International Journal of Molecular Sciences, Neuropharmacology, European Journal of Pharmacology, Frontiers in Endocrinology, Frontiers in Pharmacology, and Journal of Alzheimer's Disease. Keyword and citation analyses indicated a thematic shift from exendin-4, Alzheimer's disease, Parkinson's disease, and neuroprotection toward semaglutide, neuroinflammation, cognitive impairment, clinical efficacy, evidence synthesis, and combination therapy. Research on glucagon-like peptide-1 receptor agonists in neurodegenerative diseases has expanded rapidly over the past two decades. Current bibliometric evidence suggests that this field has evolved from preclinical exploration toward broader translational and clinical research, with increasing attention to neuroinflammation, metabolic dysfunction, cognitive outcomes, and newer incretin-based therapies. However, the therapeutic implications of glucagon-like peptide-1 receptor agonists for neurodegenerative diseases remain to be further validated by high-quality mechanistic studies and well-designed clinical trials.
We show that all existing methods quantifying rotational motion in molecular fluids eventually have severe limitations in systems undergoing complex rotational motion characterized by slow, heterogeneous, or intermittent dynamics. This impacts, in particular, the study of rotational dynamics in molecular supercooled liquids near their glass transition, as well as discussions of the decoupling between rotational and translational motion and violations of the Debye-Stokes-Einstein relation. We present a brief overview of existing methods and explain why none of them can accurately capture the evolution of rotational dynamics from a diffusive fluid to an arrested solid, thus resolving inconsistent literature results. We then introduce an empirical method that efficiently solves all issues. We benchmark our method by devising a family of continuous-time random walk models for rotational dynamics. Our method correctly quantifies the statistics of free and caged rotational motion, as well as non-Gaussian and non-Fickian rotational dynamics, and should allow a better characterization of dynamic heterogeneity in the rotational motion of supercooled molecular fluids.
This commentary provides a critical appraisal of the recent study by Chen and colleagues, which demonstrated that cutaneous palmitic acid (PA) aggravates atopic dermatitis (AD) by driving S-palmitoylation of transient receptor potential vanilloid 1 (TRPV1) in sensory neurons and Mas-related G protein-coupled receptor B2 (MRGPRB2) in mast cells, with the serum/glucocorticoid regulated kinase 1 (SGK1)/neural precursor cell expressed developmentally downregulated protein 4-like (NEDD4L) axis serving as a critical contextual regulator. While the original study offers compelling in vivo genetic validation, several mechanistic and translational questions remain unresolved. Here, we prioritize three areas for future investigation: first, the upstream sources of elevated cutaneous PA-whether derived from keratinocyte lipogenesis, systemic circulation, or microbial production-remain undefined and warrant cell-type-specific genetic interrogation complemented by stable-isotope tracing, spatial lipidomics, and germ-free models. Second, the functional divergence of S-palmitoylation on TRPV1 (promoting degradation) versus MRGPRB2 (conferring stabilization) suggests involvement of distinct palmitoyl acyltransferases (PATs) or context-dependent effects; we propose testable hypotheses including the candidate PAT zDHHC4 for TRPV1 and advocate for cell-based reconstitution, cysteine-mutant rescue, and PAT screening approaches. Third, the anatomical divergence in spinal inflammation between nape and ear models raises questions about the generalizability of central neuroimmune engagement across AD phenotypes, with implications for preclinical model selection and clinical subset stratification. Addressing these questions will clarify whether the PA-palmitoylation-neuroimmune axis represents a tractable therapeutic target and will inform the development of precision interventions that interrupt this pathway without disrupting broader homeostatic palmitoylation, while recognizing that current lack of cell-type-specific palmitoylation inhibitors remains a major hurdle.
Soil salinization severely threatens global agricultural sustainability. A key physiological mechanism underpinning plant salt tolerance is the maintenance of Na+/K+ homeostasis. The HAK/KUP/KT family of high-affinity potassium transporters plays a central role in plant responses to both potassium deficiency and salinity stress. This review systematically outlines the classification, evolutionary relationships, and functional specialization of this transporter family across diverse plant species. We focus on the multi-layered regulatory network that sustains Na+/K+ balance under salt stress, including calcium signaling transduced through the CBL-CIPK module, transcriptional control by transcription factors and epigenetic modifications, and post-translational regulation via phosphorylation, ubiquitination, and dynamic trafficking. Recent functional analyses in crops and woody plants highlight functional diversity and adaptive evolution. Notably, certain transporters from halophytes exhibit specialized roles that, when expressed in glycophytes, can paradoxically reduce salt tolerance, underscoring species-specific functional divergence. As a central hub integrating potassium nutrition and stress signaling, the HAK/KUP/KT family represents a promising target for genetic improvement. Future strategies employing gene editing, synthetic promoters, and synthetic biology hold promise for developing salt-tolerant, high-yielding crop varieties.
A common pathological process associated with acute organ injury, which is closely connected to metabolic reprogramming, is ischemia-reperfusion injury (IRI). Ischemia leads to decreased oxygen and substrate availability, with rapid activation of energy-sensing pathways, increased dependence on glycolysis, and predisposition of mitochondria to later oxidative injury. Reperfusion involves the rapid restoration of blood supply, with oxidative stress, inflammatory responses and remodeling of metabolic networks. Here, we summarize current evidence for the bidirectional interaction between IRI and metabolic reprogramming by organizing conceptual topics around glucose metabolism, lipid remodeling, amino acid metabolism and tricarboxylic acid cycle (TCA)-centered substrate convergence. Here, we focus on metabolic events according to the ischemic and reperfusion stages, from the early to the delayed phase, including succinate accumulation, reactive oxygen species (ROS) generation via reverse electron transport, mitochondrial quality control, immunometabolic remodeling, as well as apoptosis, ferroptosis, pyroptosis and post-translational modifications. In addition, recent advances in metabolic biomarkers, experimental models and novel therapeutic strategies are highlighted. Recent evidence suggests that metabolic reprogramming is not simply a passive response to IRI, but an active regulatory process that controls the initiation and amplification of injury, as well as its resolution. A metabolomic framework within a time-staged and cell death-centered context may inform more clinically useful biomarkers and intervention windows for IRI.
Testicular development is a highly orchestrated process essential for male fertility, but its temporal genetic regulation remains incompletely resolved in many mammalian models. This study re-analyses rat testis transcriptomes across 15 stages from embryonic day 12 to postnatal week 16 using bulk RNA-sequencing data from a multispecies organ development atlas, generating a continuous, testis-focused temporal framework, and pinpointing key developmental transition windows and regulatory modules. Of 23,748 annotated genes, 17,717 were differentially expressed (DEGs), and hierarchical plus co-expression analyses identified four principal expression modules and five clusters capturing spermatogenic, morphogenetic, immune, and neurone-like programs. Four major transcriptional transition windows, embryonic day 14, embryonic day 19, postnatal week 2, and postnatal week 6, were defined, with the largest remodeling between 2 and 6 weeks coinciding with the onset of robust spermatogenesis and marking a particularly vulnerable window for environmental or toxicant-induced perturbation. Stage-specific spermatogenesis-associated gene sets at embryonic day 19 (n = 28), postnatal week 2 (n = 61), and week 6 (n = 735) showed minimal overlap, supporting sequential regulatory waves driving germ cell commitment, early meiosis, and terminal differentiation. Target enrichment analyses highlighted five conserved microRNAs (rno-miR-151-5p, rno-miR-29b-3p, rno-miR-384-5p, rno-miR-500-5p, rno-miR-672-5p) whose predicted and validated targets form modules related to extracellular matrix remodeling, apoptosis and cell-cycle control, ion-channel signaling, and neuronal-like pathways, with high sequence conservation to human homologs. Immune-related genes and blood-testis barrier components displayed coordinated expression dynamics, and a conserved core of 487 spermatogenesis genes showed strong cross-mammalian orthology, indicating a deeply shared transcriptional backbone on which species-specific regulatory nuances are layered. This multistage transcriptomic analysis delineates major developmental transitions, co-expression modules, and regulatory miRNA-mRNA networks that orchestrate rat testis maturation and highlight a critical P2W-P6W transition window. The resource complements existing multiorgan and single-cell datasets by providing a testis-focused temporal framework and identifies conserved gene sets and regulatory candidates of direct relevance to male infertility, toxicology, and cross-species translational studies.
The circadian clock generates ~ 24-hour rhythms in physiology by coordinating gene expression programs, but temporal mRNA profiles often fail to predict their protein function rhythms. This gap reflects regulatory layers beyond transcription, including rhythmic translation, protein stability, subcellular localization, and post-translational modifications (PTMs) that collectively determine the circadian rhythms of protein abundance and activity. Here, we summarize evidence supporting a shift from RNA-level descriptions to protein-level frameworks and readouts of the circadian rhythms. Here, we highlight three topics: (i) protein abundance rhythms as informative but incomplete readouts, (ii) widespread circadian control of nuclear localization and phosphorylation that can occur without changes in total protein levels, and (iii) multi-tissue proteomic comparisons that reveal how circadian rhythms are organized differently across tissues. We then discuss how recent data-independent acquisition (DIA)-based, high-throughput mass spectrometry accelerates cross-study reuse and hypothesis generation, as illustrated by a mouse circadian proteome atlas and an interactive portal enabled by Orbitrap Astral mass spectrometer. Together, these advances motivate 'functional chronobiology,' linking proteome dynamics to mechanism and disease-relevant physiology.
Organisms can use environmental temperature cues to time life-history events and coordinate necessary adaptive physiological adjustments to synchronize with seasonal environmental changes. However, our knowledge about the adaptations that track environmental temperature cues in life-history events remains limited. Hibernation is an important life-history strategy for many animal groups to survive seasonal cold and food scarcity. This study explored the match between physiological adaptations during hibernation and environmental temperature cues by analyzing monthly hepatic transcriptomic profiles in the Chinese three-keeled pond turtle Mauremys reevesii juveniles throughout field hibernation in relation to water temperature change patterns. We illustrated the transcriptomic dynamics indicative of the onset of hibernation, deep hibernation, and the gradual end of hibernation in M. reevesii corresponding to phases of rapid temperature reduction, low temperatures, and temperature rise, respectively. During these stages, in hibernating M. reevesii, we revealed the substantial upregulation of genes involved in protective mechanisms, including anti-apoptotic processes, autophagy, and mRNA stability regulation prior to the coldest period; a coordinated transcriptional suppression of immune-related genes during deep hibernation; and a pre-activation of genes involved in translational processes before emergence when water temperature began to rise. These results suggested active adaptive regulations that track environmental temperature cues in hibernating M. reevesii, rather than merely passive effects of temperature changes. This study provides insights into the adaptations underlying synchronization between life-history events and environmental changes, a process fundamental to phenology, and offers a crucial mechanistic framework for further understanding of the potential effects of climate change on hibernation processes.
Periodontitis, a chronic inflammatory disease that severely compromises oral health and is linked to systemic disorders, has attracted increasing research attention. Kangfuxin (KFX), an ethanol extract derived from Periplaneta americana (L.) with documented anti-inflammatory and tissue-regenerative properties, remains unexplored for localized periodontal therapy. This study investigated whether KFX extended-release gel (KFX-ERG) could inhibit the progression of periodontal disease and provide potential support for the treatment of periodontitis. We selected the optimal concentration from different component ratios of KFX-ERG for subsequent experiments. In vivo, a periodontitis model was established in rats, and pathological changes in periodontal tissue were examined using histological and micro-computed tomography (micro-CT) analyses. Micro-computed tomography revealed that KFX-ERG reduced alveolar bone resorption in experimental periodontitis in rats. Histopathological analysis further revealed markedly reduced inflammatory cell infiltration and concurrently elevated osteoblast density in periodontal tissues of the KFX-ERG group. This study establishes a theoretical foundation for the therapeutic application of KFX-ERG in mitigating periodontitis progression and demonstrates its significant potential to promote periodontal tissue regeneration, thereby offering promising translational prospects for clinical regenerative periodontal therapy.
Transposable elements (TEs) constitute nearly half of the human genome and are increasingly recognized as context-dependent regulators of genome function rather than passive repetitive DNA. This Review synthesizes classical and recent evidence on TE biology, including TE classification, mechanisms of mobilization, host restriction pathways, insertional mutagenesis, and contributions to gene regulation. We emphasize that TE activity operates across a spectrum: controlled TE expression can contribute cis-regulatory modules, non-coding RNAs, chromatin states, and immune enhancers, whereas excessive or misregulated TE activity can promote genome instability, innate immune activation, and inflammatory pathology. To reduce conceptual redundancy, we organize these processes within an integrative framework, the Transposon Circuitry Theory of Immune Regulation (TACTIR), which links TE-derived modules, chromatin control of TE transcription, stress pathways, and immune gene networks. In this model, TE-derived enhancers and transcription factor motifs may shape stimulus-responsive gene expression, while TE transcripts and reverse-transcribed products can engage innate immune sensors under specific states of derepression. We also discuss how TE-linked regulatory states may contribute to trained immunity and T-cell dysfunction, while distinguishing established mechanisms from inferred or hypothetical links. Clinically, we place TE-mediated insertional disease, cancer-associated TE dysregulation, and immune modulation in appropriate context, noting that TE insertions account for a minority of genetic disease cases but provide important mechanistic examples of genome vulnerability. Finally, we consider how genome-editing approaches and transposon-derived tools can clarify TE function and enable translational applications. Together, this Review frames TEs as regulated genomic elements that connect genome plasticity, immune responsiveness, and disease susceptibility.
To investigate associations between (human leukocyte antigen) HLA alleles and overall lupus nephritis (LN) susceptibility, biopsy-defined histologic classes and reduced renal function in Taiwanese patients with systemic lupus erythematosus (SLE). We conducted a retrospective case-control study using data from the Taiwan Precision Medicine Initiative. The matched cohort included 388 SLE patients with biopsy-confirmed LN and 381 SLE patients without LN. HLA alleles were imputed from single nucleotide polymorphism (SNP) array data using HIBAG. Multivariable logistic regression was employed to evaluate associations of candidate HLA alleles with LN overall, individual LN histologic classes and reduced renal function within LN, adjusting for age, gender, hypertension and diabetes mellitus. The study included 388 biopsy-confirmed LN cases and 381 matched SLE controls without LN. Four alleles were independently associated with overall LN susceptibility, including HLA-B*13:01 (adjusted OR 1.68, 95% CI 1.09-2.59), HLA-B*58:01 (1.69, 1.15-2.49), HLA-C*03:02 (1.75, 1.19-2.58) and HLA-DRB1*03:01 (1.51, 1.01-2.27). Class-specific analyses showed that HLA-B*13:01 was associated with Class I/II LN; HLA-B*58:01 and HLA-C*03:02 with Class III ± V LN; and HLA-B*13:01, HLA-B*58:01, and HLA-C*03:02 with Class IV ± V LN. No allele remained independently associated with Class V LN after full adjustment. Within the LN cohort, HLA-B*13:01 was the only allele associated with reduced renal function (eGFR < 60 mL/min/1.73 m²; adjusted OR 2.24, 95% CI 1.30-3.85). Overall, the strongest associations were observed for HLA class I alleles, particularly HLA-B*13:01 in this study. In Taiwanese patients with SLE, a narrower set of predominantly HLA class I alleles is associated with LN susceptibility and proliferative LN phenotypes. HLA-B*13:01 showed the most consistent association across overall LN susceptibility, histologic severity and reduced renal function.
Soft collagenous tissues inspire material design because of their excellent fracture properties. Their fracture is integral to surgical procedures and unavoidable in many forms of trauma and disease, yet measuring it remains challenging. Sample size limitations and emergent, strain-induced anisotropy increase boundary condition effects within classic test geometries, prohibiting cross-study comparison. Further, classic tests can neither sense internal heterogeneities nor disentangle their energetic contributions to the apparent fracture energy. Leveraging in situ microstructural observations from second harmonic generation imaging, we demonstrate that Y-shaped cutting addresses these limitations in bovine Glisson's capsule (bGC). We show cutting's sensitivity to tissue heterogeneity through characterization of bGC's sawtooth cutting force. We also report a boundary-condition-independent, intrinsic cutting energy for bGC in phosphate buffered solution (PBS). At 276 ± 17 J m-2, it is surprisingly lower than expected. Contextualizing bGC response against commercial silicone, we show that its excellent failure behavior arises primarily from management of stress concentration near the crack tip over a characteristic microscale, rather than from an unusually high intrinsic fracture energy.
The Kirsten rat sarcoma viral oncogene homolog (KRAS) is one of the most frequently mutated oncogenes and is associated with poor prognosis. Long considered an undruggable target, KRAS has recently become actionable with the development of direct inhibitors, particularly against the G12C mutation. Our group previously reported promising efficacy and safety results for glecirasib (JAB-21822), a novel KRASG12C inhibitor, in phase I/II trials involving solid tumors harboring KRASG12C mutations (ClinicalTrials.gov NCT05009329, NCT05194995). Nevertheless, primary (5.61%) and acquired (9.64%) resistance were observed. This study analyzed 18 patients with advanced solid tumors harboring the KRASG12C mutation from the JAB-21822 cohort. Longitudinal blood samples (N = 45) were collected at baseline, during partial response or stable disease, and at disease progression. Circulating tumor cells (CTCs) were isolated via a microfluidics platform (CTC100, Cellomics) and categorized into epithelial (E-CTCs), mesenchymal (M-CTCs), and epithelial/mesenchymal mixed (E/M-CTCs) subtypes. At progression, the proportion of E-CTCs showed a decreased trend, while that of E/M-CTCs increased significantly (p = 0.03). In long-term responders, the inflection points of declining M-CTC levels correlated with clinical progression and were consistent with radiographic outcomes. Baseline CTC counts > 1 were associated with shorter progression-free survival (PFS; p = 0.046). E-CTC ≤ 1 correlated with longer PFS (p = 0.025), and M-CTC ≤ 1 with longer overall survival (OS; p = 0.033). E/M-CTC ≤ 1 showed a trend toward improved OS (p = 0.086). In addition, patients with > 1 CTC who received local radiotherapy for progressive lesions after glecirasib targeted therapy had significantly prolonged PFS and OS compared to those who did not (p < 0.05).
The purpose of this study was to demonstrate the first use of a commercially available, CE-marked line-field confocal optical coherence tomography (LC-OCT) in ophthalmology and assess its safety and feasibility for ocular imaging in rabbits, focusing on phototoxicity and tissue integrity. Five 14-week-old New Zealand White rabbits underwent corneal imaging using the DeepLive device (DAMAE Medical, Paris, France), originally developed for dermatologic applications. Imaging sessions lasted 5 to 10 minutes per eye, using illumination at a center wavelength of 820 nm and a power of 13.2 mW. Safety was evaluated in silico according to International Electrotechnical Commission (IEC) 60825-1 standards and in vivo through clinical assessments including slit-lamp examination, retinal imaging, and intraocular pressure (IOP) measurements at baseline, immediately after imaging, and on days 7 and 14. Histological analysis was performed day 14. LC-OCT provided high-resolution three-dimensional imaging of the cornea (1.2 × 0.5 × 0.5 mm) and two-dimensional views of corneal layers, conjunctiva, and the nictitating membrane, revealing cellular details. In silico analysis confirmed that laser exposure remained below IEC safety limits. In vivo evaluations showed no corneal opacity, neovascularization, inflammation, or retinal alterations at any time point. Lens transparency remained normal (Lens Opacities Classification System [LOCS] III grade = 0), and IOP showed no treatment-related differences (P = 0.6713). Histology confirmed preservation of corneal and retinal structures. Ophthalmologic use of CE-marked LC-OCT demonstrated safe, effective imaging in rabbits without phototoxicity, supporting its potential for clinical ophthalmic applications. These findings provide preclinical safety evidence supporting LC-OCT as a noninvasive, high-resolution imaging modality for future clinical ophthalmology applications.
Cardio-oncology has emerged as a pivotal discipline aimed at preserving cardiovascular health in patients undergoing contemporary cancer therapies. Despite growing awareness of treatment-related cardiac injury, the evidence base supporting preventive strategies and standardized safety assessment remains fragmented. This review critically appraises randomized controlled trials evaluating pharmacological and non-pharmacological interventions for the prevention of cancer therapy-related cardiac dysfunction. In parallel, we examine how cardiovascular events are monitored, defined, and reported in major oncology trials, with particular emphasis on patient selection criteria and the use of structured surveillance protocols. Across drug classes repurposed from heart failure (HF) prevention and treatment, including neurohormonal antagonists, angiotensin receptor-neprilysin inhibition, lipid-lowering therapies, as well as exercise-based interventions, randomized evidence has demonstrated modest and inconsistent benefits. Reported effects are largely confined to subclinical alterations, such as changes in left ventricular systolic function, myocardial deformation parameters, or circulating cardiac biomarkers. By contrast, convincing reductions in clinically meaningful outcomes, including overt HF, treatment interruption, or cardiovascular mortality, remain limited. Concurrently, oncology trials frequently exhibit heterogeneous cardiovascular event definitions, incomplete safety reporting, and systematic exclusion of patients with pre-existing cardiac disease, thereby constraining external validity and obscuring the true burden of cardiotoxicity and competing cardiovascular risks. Advancing the field will require a paradigm shift toward individualized, risk-enriched prevention strategies anchored in clinically relevant endpoints. Broader inclusion of patients with stable cardiovascular comorbidities, managed under structured specialist supervision, alongside standardized frameworks for cardiovascular safety monitoring and reporting, is essential. Emerging artificial intelligence, as enabled tools applied to cardiac imaging, electrocardiography, and remote monitoring offer a promising opportunity to harmonize early detection of cardiotoxicity across trial sites and refine phenotyping of treatment-related cardiac injury. Integrating these elements into future trial design will be critical to ensure that therapeutic progress in oncology is not undermined by preventable cardiovascular harm.
This trial within the Danish DAN-RSV adult respiratory syncytial virus vaccine trial assesses whether the sex of the person presenting an informational video for potential trial participants is associated with trial enrollment.