Chronic coronary syndromes represent one of the principle causes of death and disability all over the world. ESC guidelines suggest the use of clinical risk scores such as the Risk Factor-Weighted Clinical Likelihood to estimate the probability of obstructive coronary artery disease, and underline the role of functional imaging tests, such as stress echocardiography. This article offers a comprehensive overview of the main applications of stress test, including indications, stress protocols, differences between stressors, and comparison with exercise stress test. This article also highlights emerging applications of traditional stress tests.

α-Amylase and α-glucosidase are complementary therapeutic targets in type 2 diabetes; simultaneous inhibition provides a dual-blockade strategy to suppress postprandial hyperglycemia. Dipyridamole, a conventional antiplatelet drug with proven anti-inflammatory, antioxidant, and antiproliferative effects and a favorable safety profile, is a candidate for repurposing. This study assessed in vitro antioxidant activity and inhibitory actions against both enzymes, and employed molecular docking, molecular dynamics simulations to elucidate mechanisms. Dipyridamole showed EC50 values of 589.7 μM (ABTS+·), 652.2 μM (·OH), and 1607.1 μM (DPPH·), and IC50 values of 257.6 μM (α-amylase) and 348.8 μM (α-glucosidase). Molecular docking yielded binding free energies of -6.5 and -6.0 kcal/mol for α-amylase and α-glucosidase, respectively, with binding mediated mainly by hydrogen bonds and hydrophobic interactions. Molecular dynamics simulations revealed that, under the present simulation conditions, both the apo forms of α-amylase and α-glucosidase and their respective dipyridamole complexes exhibited relatively stable dynamical behavior throughout the course of the trajectories. Overall, dipyridamole showed not only moderate free radical scavenging capacity but also inhibitory activity against α-amylase and α-glucosidase, suggesting that this molecule may serve as a promising lead compound for further relevant drug development and functional exploration.

Craniomaxillofacial and cranial vault reconstruction remain limited by donor-site morbidity, infection, inadequate vascularization, incomplete osseointegration, and poor adaptation of conventional grafts to complex patient-specific anatomy. Nanomaterial-based therapies offer a translationally attractive strategy. Nanoscale hydroxyapatite, calcium phosphates, mesoporous silica, metallic nanoparticles, bioactive glasses, polymeric carriers, injectable nanocomposite hydrogels, extracellular vesicle-inspired systems, and nanostructured coatings can act on several targets at once, including osteogenesis, angiogenesis, immune response, antimicrobial activity, mechanical reinforcement, and controlled release. This review synthesizes recent evidence on nanomaterial-enabled bone regeneration for craniomaxillofacial and cranial vault reconstruction, placing emphasis on the pathway from in vitro mechanisms to animal models, additive manufacturing, patient-specific implants, and early clinical translation. 3D-printed calcium phosphate or hydroxyapatite-based patient-specific scaffolds are currently supported by the strongest near-clinical evidence, whilst immunomodulatory, bioprinted, injectable, and drug-delivering nanocomposites remain largely preclinical. Growth-factor-independent strategies based on ionic signaling, dipyridamole-enhanced adenosine signaling, nanosilicate-mediated osteogenesis, Wnt/beta-catenin mechanotransduction, and nanoparticle-mediated osteoimmunomodulation may reduce reliance on recombinant bone morphogenetic proteins. However, large-animal validation, long-term biodistribution, nanotoxicology, sterilization, manufacturing reproducibility, and regulatory classification remain major barriers. Future clinical translation will require rational scaffold design, anatomical indication-specific testing, antimicrobial integration, and harmonized regulatory evidence packages.

Coronary microvascular dysfunction (CMD) is a common but often underdiagnosed cause of ischemia and angina in patients with angina and no obstructive coronary artery disease (ANOCA). The reliance on invasive testing contributes to delayed or missed diagnosis. Exercise-induced ST-segment abnormalities in ANOCA patients may serve as a non-invasive marker, particularly reflecting impaired endothelium-dependent vasodilation. We report the case of a middle-aged man undergoing a treadmill exercise test for competitive sports eligibility. The patient developed atypical chest pain with significant (>2 mm) down-sloping ST depression in precordial and inferior leads during exertion. Coronary computed tomography angiography revealed normal coronary arteries, raising suspicion for CMD. Further assessment with dipyridamole stress echocardiography demonstrated normal coronary flow velocity reserve (CFVR) in the left anterior descending artery = 3.2, indicating preserved endothelium-independent vasodilation. However, contrast myocardial perfusion imaging revealed patchy areas of delayed replenishment-indicative of CMD and suggestive of impaired endothelium-dependent function. Exercise-induced ST depression was reproducible during stress echocardiography. In patients with ANOCA, patchy perfusion abnormalities during vasodilator stress and preserved CFVR may reflect CMD due to endothelium-dependent dysfunction. Ecostress may offer valuable diagnostic insights and support early identification and management of CMD.

Critical-sized bone defects remain a significant clinical challenge, and dipyridamole (DIPY)-coated 3D-tricalcium phosphate (β-TCP) scaffolds have shown promising osteogenic efficacy in preclinical models. However, the literature on the systematic physicochemical characterization of this scaffold system, including optimization of DIPY loading parameters, release kinetics, and surface properties, is lacking. This study addresses these gaps by characterizing DIPY-loaded 3D-printed β-TCP scaffolds across solid and porous architectures, three coating concentrations (10, 100, and 1000 µM), and three coating volumes (250, 500, and 1000 µL). Under static PBS conditions, drug release over 21 days was quantifiable only at 1000 µM, and release-kinetics modeling (zero-order, Higuchi, and Korsmeyer-Peppas) was therefore restricted to this highest concentration. At 1000 µM, both scaffold types showed biphasic release profiles, with standard empirical models reasonably approximating the overall kinetics, while not fully capturing the biphasic behavior over the entire duration. Porous scaffolds showed significant volume-dependent release (p = 0.002, η[2] = 0.88), attributable to drug penetration into the interconnected macropore network, whereas solid scaffolds displayed volume-independent release confined to external surfaces. Scanning electron microscopy revealed concentration-dependent needle-shaped DIPY crystal deposition while contact angle measurements indicated no significant changes in surface hydrophilicity. MTT assay demonstrated biocompatibility at all concentrations, with viability influenced by coating volume rather than drug concentration. These findings establish a foundational physicochemical framework for DIPY-loaded β-TCP scaffolds, providing the baseline data necessary to guide subsequent biological evaluation and translational efforts toward critical-sized craniofacial and orthopedic bone defect repair.

Tumour cells commonly exhibit aerobic glycolysis and produce lactate despite oxygen availability. Lactate dehydrogenase (LDH) catalyses pyruvate-lactate interconversion and regulates intracellular lactate levels. Endothelial cells also depend on glycolysis for ATP production, which prompted us to investigate LDH in canine hemangiosarcoma (HSA), a malignant endothelial tumour. We inhibited LDH with (R)-GNE-140 or sodium oxamate in two canine HSA cell lines (HU-HSA-2 and HU-HSA-3) and generated HU-HSA-3 clones with knockout of LDHA or LDHB to evaluate the effects of LDH perturbation. (R)-GNE-140 and sodium oxamate suppressed proliferation and reduced global histone lactylation levels in both cell lines. mRNA-sequencing (mRNA-seq) of (R)-GNE-140-treated HU-HSA-2 cells identified cholesterol/lipid metabolism-related gene sets among the top negatively enriched pathways. Representative cholesterol/lipid metabolism genes such as SREBF2, SQLE and LDLR responded differently depending on cell lines and inhibitors. (R)-GNE-140 decreased these genes in HU-HSA-2 but not HU-HSA-3, whereas sodium oxamate decreased them in HU-HSA-3 with limited effects in HU-HSA-2. In HU-HSA-3, LDHA and LDHB knockout clones decreased SREBP2 expression and reduced the number of lipid droplets. Fluvastatin, a cholesterol metabolism inhibitor, inhibited HSA cell growth in vitro but did not significantly suppress tumour growth in two HSA patient-derived xenograft (PDX) models. In contrast, combined fluvastatin and dipyridamole treatment inhibited proliferation in vitro and tumour growth in PDX models. Collectively, these results suggest a context-dependent association between LDH and cholesterol/lipid metabolism in canine HSA cell lines and provide a rationale for further evaluation of combined cholesterol pathway inhibition.

This overview provides a summary of the commonly used vasoactive agents and the various clinical scenarios in which they are used in the neonatal intensive care unit (NICU). The lack of well-designed clinical trials in this vulnerable population means that these agents continue to be administered without sufficient evidence-based knowledge on their dosing, safety, efficacy and long-term effects. The lack of age appropriate cardiotonic formulations remains an ongoing challenge. Future trials of cardiotonic drugs need to incorporate echocardiography and other objective monitoring tools in their design with robust assessments of short and longer-term outcomes.

Accurate assessment of haemostasis is essential in both research and clinical practice. Thrombin generation assays (TGA) provide a comprehensive evaluation of coagulation; however, results can be influenced by preanalytical conditions, including the choice of blood collection tubes. Citrate-theophylline-adenosine-dipyridamole (CTAD) tubes are recommended by the manufacturer of the Ceveron[®] alpha TGA system due to their ability to inhibit platelet activation. Nevertheless, CTAD tubes are costly, less widely available, and not manufactured in small volumes suitable for specific patient populations, such as paediatric cohorts. To evaluate whether standard citrate tubes can serve as a viable alternative, we prospectively compared TGA parameters from blood collected in 3.2% sodium citrate tubes versus CTAD tubes in 12 healthy volunteers. Assays were performed using low and high phospholipid micelle concentrations (RC low/RC high). Significant differences between citrate and CTAD were observed for all parameters with the RC low reagent. In contrast, only lag time showed significant differences with the RC high reagent. In conclusion, while citrate tubes may be used for TGA, the type of blood collection tube can influence measurements under specific assay conditions and should be considered a relevant factor when comparing and interpreting TGA results.

A highly sensitive fluorescent lateral flow immunoassay (LFIA) was developed for SARS‑CoV‑2 IgG detection. Polystyrene (PS) microspheres were synthesized via emulsion polymerization, doped with dipyridamole (Dip), and coated with a protective silica (SiO2) shell through a sol-gel process. After amine functionalization, the SARS‑CoV‑2 nucleocapsid (N) protein was covalently immobilized onto the microsphere surface using EDC/NHS chemistry, yielding PS@Dip@SiO2-N fluorescent probes. The LFIA strip enabled one‑step detection within 15 min. Under optimized conditions (N protein conjugation concentration of 40 µg/mL), the strip showed excellent specificity with no cross‑reactivity against other human coronaviruses (NL63, OC43, 229E). Quantitative determination based on the T/C grayscale ratio fitted the Hill equation (R[2] = 0.9782). The detection limit for SARS‑CoV‑2 IgG was 10 ng/mL, approximately two orders of magnitude lower than that of a commercial colloidal gold‑based LFIA strip. This platform provides a rapid, sensitive, and low‑cost solution for point‑of‑care serological screening of COVID‑19.

Intracellular metal dyshomeostasis has emerged as a key regulator of specialized regulated cell death (RCD) programs, challenging classical views that regard necrosis as entirely accidental. This review systematically delineates the molecular architecture and translational trajectories underlying metal-dependent RCD, including iron-driven ferroptosis, copper-mediated cuproptosis, and additional emerging modalities such as calcicoptosis, necrosis by sodium overload (NECSO), and the newly designated zincoptosis, mnoptosis, and coptosis. We examined distinct execution mechanisms, ranging from membrane lipid peroxidation and lipoylation-targeted proteotoxic stress to organelle-specific bioenergetic failure, which arise following disruption of compartmentalized metal-buffering networks. To bridge the persistent knowledge gap between foundational metallobiology and clinical application, we evaluated a bidirectional therapeutic framework: exploiting synthetic lethality and metabolic gating via clinical inducers (e.g., sorafenib, elesclomol) to selectively eliminate therapy-resistant malignancies while deploying targeted pathway inhibitors and systemic agonists (e.g., dipyridamole, omaveloxolone) to limit pathological tissue degeneration in ischemic and neurodegenerative disorders. Recognizing that off-target multiorgan toxicity and complex in vivo crosstalk among interconnected death pathways (e.g., disulfidptosis and PANoptosis) represent major translational challenges, we assessed advanced materials-science strategies designed to overcome these barriers. Specifically, we highlighted the integration of single-atom catalysts, stimuli-responsive nanomedicines, and biomimetic carriers engineered to spatiotemporally confine catalytic oxidative flux. Finally, we examined the systemic immunological consequences of targeted metal dysregulation, detailing how metal-induced immunogenic cell death and cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway hyperactivation reshape immunosuppressive microenvironments and modulate sterile inflammation, thereby enhancing responsiveness to immune checkpoint blockade, providing a definitive molecular blueprint for next-generation precision therapeutics.