Search Results (147)

Accurate delineation of infarct core and ischemic penumbra in acute ischemic stroke primarily relies on computed tomography perfusion (CTP), where the arterial input function (AIF) is essential for reliable perfusion quantification. However, reliable and fast AIF selection remains challenging in clinical practice due to noise, vascular heterogeneity, and inter-patient variability in bolus dynamics. In this study, we propose TriAIF-RWKV, a three-stage framework for robust and automated AIF extraction. Specifically, ACSANet is first employed for spatial vascular localization using axial and channel-aware attention mechanisms, thereby narrowing the candidate arterial region and reducing the AIF search space. Then, a Dilated-RWKV network is introduced to model temporal intensity dynamics from a global sequence perspective, allowing robust identification of AIF-consistent patterns. Finally, a physiology-informed scoring strategy is used to select the optimal AIF by evaluating baseline stability, peak enhancement, and washout characteristics. Extensive experiments on CTP datasets were conducted from multiple perspectives, including AIF waveform fidelity, perfusion parameter estimation, and lesion-level analysis. The results demonstrate that the proposed method achieved high agreement with expert-selected AIFs, with a global waveform PCC of 0.973, peak correlation of 0.942, and TTP correlation of 0.973 with a mean error of 0.923 s. Furthermore, the proposed method provides more consistent downstream perfusion quantification, achieving higher consistency of CTP-derived parameters and improved lesion-to-normal tissue discrimination compared with existing approaches. These results highlight its potential for reliable clinical perfusion assessment. Full article

Background/Objective: The management of acute ischemic stroke (AIS) has evolved from rigid time-based treatment paradigms toward tissue-based selection guided by advanced neuroimaging, thereby expanding eligibility for reperfusion therapies. To provide an updated narrative review of acute ischemic stroke (AIS) classification and management, with emphasis on extended therapeutic windows for intravenous thrombolysis (IVT) and endovascular therapy (EVT), bridging strategies, posterior circulation stroke, and implementation challenges in Latin America and other resource-constrained settings. Methods: A structured narrative review was conducted using the PubMed/MEDLINE, Embase, Scopus, and LILACS databases, covering the period from 2013 to 2025. Results: Sixty-three studies were selected from 412 records and categorized into etiologic classification, extended-window thrombolysis, EVT and bridging therapy, and posterior circulation stroke. Current evidence supports imaging-guided IVT beyond 4.5 h and EVT up to 24 h in selected patients with salvageable brain tissue, including some individuals with large infarct cores. Recent trials also support EVT for basilar artery occlusion. Tenecteplase offers practical workflow advantages in many centers, particularly where transfer delays and limited access to advanced imaging constrain timely reperfusion decisions. Conclusions: Contemporary AIS management is increasingly guided by pathophysiology and imaging rather than strict time thresholds. However, improving outcomes in middle- and low-income settings requires the implementation of adapted clinical algorithms, strengthening of stroke care networks, and optimization of referral pathways. Full article

Background/Objectives: Oral small-molecule inhibitors of activated factor XI (FXIa) are intended to attenuate thrombosis with less disruption of hemostasis than established anticoagulants, but clinical outcomes have not consistently paralleled pharmacodynamic target engagement. This systematic review integrated molecular design, preclinical pharmacology, human pharmacokinetics/pharmacodynamics (PK/PD), and clinical outcomes to identify where translation is maintained or lost. Methods: The review followed PRISMA 2020 and PRISMA-S and was registered in PROSPERO (CRD420261356169). PubMed/MEDLINE, Scopus, and Web of Science Core Collection were searched from inception through 30 March 2026 and rerun on 11 August 2026, with a final publication-eligibility cut-off of 30 June 2026. Owing to heterogeneity, evidence was synthesized narratively. Results: Sixty-eight eligible reports were included, comprising seven randomized parent outcome trials and nine reports with in vivo thrombosis or bleeding experiments. In the OCEANIC-STROKE trial, ischemic stroke occurred in 6.2% with asundexian versus 8.4% with placebo (HR 0.74, 95% CI 0.65–0.84), while major bleeding was 1.9% versus 1.7% (HR 1.10, 95% CI 0.85–1.44). In OCEANIC-AF, stroke or systemic embolism occurred in 1.3% with asundexian versus 0.4% with apixaban (HR 3.79, 95% CI 2.46–5.83), despite less major bleeding (0.2% vs. 0.7%; HR 0.32, 95% CI 0.18–0.55). Conclusions: Oral small-molecule FXIa inhibition is pharmacologically coherent, but clinical benefit is indication-, comparator-, and background-therapy-dependent. PD markers confirm target engagement but are not validated efficacy surrogates; hard clinical outcomes remain decisive. Full article

Background: Preservation of renal hypothermia during vascular anastomosis remains a critical yet insufficiently optimized aspect of kidney transplantation. Rewarming during the second warm ischemic period increases metabolic activity and may exacerbate ischemia–reperfusion injury. Maintaining graft temperatures below the 15–18 °C metabolic threshold during implantation is associated with improved graft preservation, yet more than 80% of grafts exceed this threshold within 20 min under standard conditions. This study evaluated the thermal performance of a novel cooling adjunct, the Ice Pillow, in limiting renal rewarming under simulated ex vivo transplant conditions. Methods: Twelve human renal allografts (six donor pairs) were studied in a controlled laboratory setting following hypothermic machine perfusion. Within each donor pair, kidneys were randomly assigned to the Ice Pillow group or the Control group. Core temperature was measured using an intra-pelvic thermocouple probe, while surface temperature was assessed with a handheld infrared thermometer. Kidneys in the Ice Pillow group were positioned on a thin gauze pouch filled with ice slush. Control kidneys were rewarmed in a simulated body cavity at 30–32 °C. Temperature recordings were obtained at one-minute intervals over 40 min. Rewarming slopes were compared using donor-paired analysis. Longitudinal temperature trajectories were analyzed using a linear mixed-effects model accounting for repeated measurements within kidneys. Agreement between core and surface measurements was evaluated using Bland–Altman analysis. Results: The Ice Pillow reduced the rate of renal rewarming by 56.4% compared with donor-paired controls (0.261 ± 0.057 °C/min vs. 0.599 ± 0.066 °C/min; mean donor-paired difference 0.338 °C/min; 95% CI, 0.237–0.440; t(5) = 8.56, p < 0.001). Linear mixed-effects modelling demonstrated progressive thermal separation between groups, with Control kidneys estimated to be 4.28 °C warmer at 10 min (95% CI, 3.35–5.22; p < 0.001) and 10.44 °C warmer at 40 min (95% CI, 7.88–12.99; p < 0.001). Bland–Altman analysis of core–surface agreement demonstrated a mean bias of −0.51 °C with 95% limits of agreement of −6.46 °C to 5.43 °C, indicating that surface thermometry followed the general direction of core temperature change but demonstrated wide limits of agreement, indicating the two methods are not interchangeable. Conclusions: In this ex vivo model, the Ice Pillow substantially attenuated renal rewarming compared with unassisted controls. Whether this thermal effect translates into improved graft function requires prospective clinical evaluation. Full article

Astrocytic function imbalance is a key factor affecting cerebral ischemia rehabilitation. Mesenchymal stem cells have therapeutic potential for cerebral ischemia, but their mechanisms remain unclear. This study explored how placental mesenchymal stem cells pro-mote astrocytes towards the A2 phenotype, which benefits the repair of cerebral ischemia injury. We established the animal model of middle cerebral artery ischemia/reperfusion and an in vitro interleukin-1β-treated astrocyte inflammation model and utilized neuro-logical function assessment, 2,3,5-triphenyltetrazolium chloride staining, immunofluorescence staining, Western blotting and other methods to evaluate the impact and associated mechanisms of transplanting placental mesenchymal stem cells into rats with cerebral ischemia–reperfusion injuries. The results demonstrated that transplantation of placental mesenchymal stem cells ameliorated neurological dysfunction and histopathological damage, alleviated neuroinflammation and enhanced neurotrophic factor levels, promoted the polarization of interleukin-1β-treated astrocytes toward the A2 phenotype, and suppressed the abundance of core mediators within the cerebral TGF β1/Smad signaling cascade in ischemia/reperfusion model. Collectively, placental mesenchymal stem cell grafting facilitates the polarization of cerebral astrocytes toward the protective A2 phenotype, presumably by regulating the TGF β1/Smad signaling cascade in ischemic brain injury. Full article

Background: Stroke remains a significant cause of persistent long-term disability globally. Post-stroke neuroplasticity is critical for neurological functional recovery and reducing disability. Nevertheless, the existing scoping reviews rarely systematically integrate its intrinsic mechanisms, predictive biomarkers, and actionable intervention strategies. This scoping review aims to map the current research landscape, synthesize the core research findings, and identify existing research gaps in this field. Methods: This scoping review was conducted following the PRISMA-ScR guidelines. Eligible studies published between 31 January 2021, and 31 January 2026, were retrieved from three major mainstream electronic databases: PubMed, Scopus, and Web of Science. All retrieved evidence was synthesized via narrative approach, focusing on core research findings concerning post-stroke neuroplasticity mechanisms, biomarkers, and therapeutic interventions. Results: The existing research on neuroplastic mechanisms following ischemic stroke is predominantly derived from in vitro and animal studies, which have collectively demonstrated multiple core adaptive alterations, including enhanced synaptic plasticity, dendritic and axonal structural remodeling, restored interhemispheric connectivity, endogenous neurogenesis, and functional reorganization of neural networks. In contrast, mechanistic investigations in human stroke patients primarily highlight compensatory activation within peri-infarct tissues and functionally remote brain regions. The relevant clinical biomarkers are mainly imaging and electrophysiological indicators. Research on therapeutic interventions has mainly focused on rehabilitation treatments such as non-pharmacological magnetic stimulation. Conclusions: This scoping review synthesized the current body of evidence on post-ischemic stroke neuroplasticity and identified critical research gaps, particularly regarding multimodal biomarkers and their translational relevance. The present findings confirm that neuroplastic alterations after ischemic stroke are regulated by multiple pathways, among which those involved in synaptic structure, dendrites, and neural network connections exert pivotal effects. Nevertheless, most existing investigations remain confined to in vitro experiments and animal models. The identification of neuroplasticity biomarkers has opened up new avenues for the development of targeted stroke therapies and offers promising prospects for rehabilitative treatment of stroke patients. Full article

Cerebral ischemia–reperfusion injury is a key determinant of a poor outcome after stroke. The mitochondrial uncoupling protein 2 (UCP2) has been implicated in cerebral ischemia-reperfusion injury and in the outcome of ischemic stroke, although its role remains controversial. In C57BL/6J and B6.129S4-Ucp2^tm1Lowl/J (UCP2^−/−) mice, we analyzed cognitive function and lifespan. In an MCAO model induced for one hour, infarct volumes, neurological deficits, and gene expression patterns were determined after 24 h. The UCP2 inhibitor genipin was used in an oxygen-glucose deprivation (OGD) model to investigate synaptic transmission in the hippocampus. Compared to controls, UCP2^−/− mice exhibited a reduced lifespan and displayed impaired cognition. However, in 6-month-old UCP2^−/− mice, the infarct volume was reduced, primarily due to a smaller core size, but not in 18-month-old animals. In both strains, ischemia induced upregulation of antioxidant defense genes, including catalase and SOD1. In the ex vivo ODG model, synaptic transmission was depressed, but pretreatment with genipin prevented the tissue from this impairment. Our findings indicate an infarct-reducing effect of UCP2 deficiency, especially in young-adult mice, and, mechanistically, a neuroprotective effect by genipin in hippocampal slices. Full article

Background: Diabetic cardiomyopathy (DCM) is characterized by metabolic dysfunction, inflammation, extracellular matrix (ECM) remodeling, and myocardial fibrosis. Increasing evidence suggests that ferroptosis-associated oxidative injury may contribute to cardiac remodeling; however, the interaction between ferroptosis-related pathways and fibrosis-associated molecular networks remains incompletely understood. This study explored the ferroptosis–fibrosis axis using an integrative transcriptomic and systems pharmacology framework. Methods: Differentially expressed genes were identified from the GSE5406 myocardial transcriptomic dataset comparing nonfailing donor hearts with ischemic and idiopathic cardiomyopathy samples and analyzed using functional enrichment, protein–protein interaction, and disease-association approaches. Cross-dataset comparison and exploratory sample-level external evaluation were performed using the independent GSE263297 DCM-related dataset. Candidate genes were further evaluated by receiver operating characteristic (ROC) analysis and machine learning-based feature selection using least absolute shrinkage and selection operator (LASSO), random forest, and support vector machine-recursive feature elimination (SVM-RFE). Representative compounds associated with fibrosis-, oxidative stress-, inflammation-, and ferroptosis-related pathways were subsequently assessed by molecular docking against TGFBR1, STAT3, GPX4, AKT1, SMAD3, and ACSL4. Results: Transcriptomic analyses highlighted ECM organization, collagen-containing ECM, and fibrosis-related pathways as dominant biological themes. Cross-dataset comparison showed partial preservation of transcriptional patterns between independent myocardial cohorts, with 20 of 51 evaluated genes demonstrating concordant expression direction across datasets. ROC analysis identified LUM and ASPN as having the highest area under the curve (AUC) values among candidate genes, whereas COL1A1, COL1A2, and COL3A1 also showed elevated AUC values. Machine learning analyses identified FCN3, HOPX, CNN1, and GLUL as the core signature consistently prioritized across all three algorithms, whereas LUM was additionally identified by two of three algorithms. Internal validation yielded a cross-validated AUC of 0.934 (95% CI: 0.820–1.000), and exploratory sample-level external evaluation of the four-gene signature in GSE263297 yielded an AUC of 0.673 (95% CI: 0.380–0.967). Exploratory docking analyses suggested potential structural compatibility between several candidate compounds and fibrosis-, inflammation-, and ferroptosis-associated targets, with comparatively lower predicted binding-energy values observed for selected ligand–target combinations. Conclusions: The findings are consistent with a fibrosis-dominant remodeling signature and suggest potential network-level links between ferroptosis-associated processes and cardiac fibrosis. These observations should be regarded as exploratory and hypothesis-generating and require validation in independent cohorts and experimental studies. Full article

Background: Acute kidney injury (AKI) remains a condition with limited effective therapeutic options, partly due to challenges in early diagnosis and timely intervention. While lactate accumulation is a hallmark of ischemic and septic AKI, the underlying mechanisms remain unclear. Methods: This study integrated single-cell RNA sequencing data from AKI patients (GEO database) with lactate metabolism-related genes (LMRGs) to identify key therapeutic targets. Results: Collecting duct (CD) cells exhibited the highest LMRG expression. Machine learning algorithms and validation in bilateral ischemia/reperfusion injury (bIRI) and lipopolysaccharide (LPS)-induced AKI mouse models, as well as hypoxia/reoxygenation (H/R)-stimulated renal cells, identified Ldhb as a core gene. Disruption of lactate metabolism via BAY876 (selective GLUT1 inhibitor) or siRNA-mediated Ldhb knockdown significantly attenuated kidney injury, reduced inflammatory cytokines (IL-1β, IL-6, TNF-α), and decreased reactive oxygen species in vitro and in vivo. Conclusions: These findings reveal that lactate metabolism is reprogrammed in AKI, particularly in CD cells, and identify LDHB as a novel potential therapeutic target for this condition, though further mechanistic studies are required to establish causality. Full article

CT perfusion (CTP) is widely used in acute ischemic stroke imaging, particularly for treatment selection beyond conventional time windows. However, automated perfusion maps are not direct measurements of irreversible tissue injury, but estimates shaped by deconvolution strategy, temporal correction, dispersion handling, and software-specific thresholds. This review provides a clinically oriented explanation of how CTP algorithms influence the estimation of ischemic core and hypoperfused tissue. Particular attention is given to singular value decomposition (SVD) methods, Bayesian approaches, and timing parameters, including time to maximum (Tmax), Delay, time to peak (TTP), and mean transit time (MTT). Differences in residue function estimation and threshold definition may generate variable outputs across software platforms, even from the same source dataset. Perfusion thresholds should therefore not be treated as universally interchangeable. CTP findings should be integrated with clinical status, non-contrast CT, CT angiography (CTA), collateral status, occlusion site, and imaging-to-treatment context, serving as decision-support tools rather than isolated measures of tissue viability. Full article

Intramyocardial hemorrhage (IMH) is a severe form of post-ischemic microvascular injury that may occur after myocardial infarction, particularly in the setting of extensive ischemia and reperfusion. IMH is closely related to microvascular obstruction (MVO), larger infarct size, impaired left-ventricular (LV) function, and adverse clinical outcomes. Cardiovascular magnetic resonance (CMR), especially susceptibility-sensitive techniques such as T2* or R2* mapping, enables in vivo detection of hemorrhagic microvascular injury and may refine post-MI risk stratification. Mechanistic and translational studies suggest that erythrocyte degradation and infarct-core iron deposition may contribute to persistent inflammation, maladaptive healing, adverse remodeling, and possibly arrhythmogenic substrate formation. However, most clinical evidence remains observational, and IMH-guided management has not yet been prospectively validated. This narrative review summarizes current evidence on the pathophysiology, imaging diagnosis, prognostic significance, and emerging therapeutic implications of IMH, while highlighting unresolved questions regarding standardized imaging, clinical implementation, and future phenotype-directed therapies. Full article

Background: Carotid atherosclerosis and plaque instability are major drivers of ischemic stroke. The NLRP3 inflammasome and interleukin-1 (IL-1) pathway are recognized as key upstream regulators of atherogenesis. This systematic review aims to synthesize the available evidence regarding the impact of NLRP3 and IL-1-mediated inflammation on plaque vulnerability and clinical outcomes in patients undergoing carotid endarterectomy (CEA). Materials and Methods: A systematic search was performed relying on MEDLINE, Scopus, and Web of Science for studies assessing NLRP3 inflammasome and IL-1-mediated biomarkers in adult patients undergoing CEA. Data extraction and risk-of-bias evaluation were independently performed using the National Heart, Lung, and Blood Institute (NHLBI) Quality Assessment Tool. Due to substantial methodological heterogeneity, a narrative synthesis was conducted. Results: Sixteen studies involving 1677 participants were included. Evidence demonstrates that NLRP3 inflammasome components (NLRP3, ASC, Caspase-1) and IL-1 family cytokines (IL-1β, IL-18) are consistently elevated in unstable plaques and in symptomatic patients compared to asymptomatic counterparts. These markers were associated with histological features of instability, such as intraplaque haemorrhage, large lipid cores and extensive macrophage infiltration. While some data suggest a link between these biomarkers and Major Adverse Cardiovascular Events (MACE), most studies were limited by a lack of adjusted multivariable modelling and an overall unclear risk of bias. Conclusions: NLRP3/IL-1/-mediated inflammation is a promising biomarker axis for carotid plaque vulnerability and symptomatic disease. However, small, heterogeneous cohorts and limited adjusted analyses highlight the need for larger, well-designed studies to refine risk stratification and guide targeted anti-inflammatory strategies in carotid atherosclerosis. Full article

The treatment of full-thickness skin defects remains a major challenge in clinical medicine. Accelerating wound healing and promoting the restoration of tissue function are of paramount importance. Stem cell therapy has been applied in clinical practice to facilitate wound repair. However, the low survival rate of transplanted stem cells in an ischemic and hypoxic microenvironment severely limits the effectiveness of their clinical application. Microspheres, owing to their excellent biocompatibility and drug delivery capabilities, can serve as effective carriers for oxygen transport. It is worthwhile to evaluate the timing and process of oxygen release under hypoxic conditions. In this study, core–shell structured oxygen-releasing microspheres were prepared and incorporated with the photosensitizer hypericin (HYP) to enable dynamic tracking of the oxygen release process via fluorescent signals. The effects of the oxygen-releasing microspheres on cells under hypoxic conditions were analyzed, focusing primarily on the characterization of the microspheres, their biocompatibility, luminescent properties, and oxygen-releasing capacity. Furthermore, the efficacy of the oxygen-releasing microspheres in combination with bone marrow mesenchymal stem cells (BMSCs) in promoting wound healing was evaluated in vivo. The results indicate that the addition of the microspheres improved cell survival rates in hypoxic environments; meanwhile, their luminescent properties demonstrated the potential of fluorescence intensity as a visual indicator of oxygen release. Full article

Ischemic stroke is an acute cerebrovascular disease with high disability and morbidity. However, therapeutic approaches are restricted by a narrow time window for reperfusion. Astilbin has various pharmacological activities and good therapeutic potential against ischemic stroke and neurodegenerative diseases. Nevertheless, Astilbin’s mechanism of action remains unclear. Here, we used an integrated strategy that includes network pharmacology, omics validation, and functional verification. Potential targets of Astilbin were predicted using SwissTargetPrediction and PharmMapper, and cross-analyzed with IS-related genes from multiple databases. GO/KEGG enrichment analyses showed that Astilbin synergistically regulates stroke-associated pathways (e.g., MAPK, AGE-RAGE). Combined transcriptomic and metabolomic assays confirmed that Astilbin ameliorates OGD/R-induced oxidative stress and metabolic disorders by modulating the MAPK and ferroptosis pathways. Molecular docking and dynamics simulations revealed that Astilbin has high affinity for core targets (ERK1/2, CREB, p90RSK, MMP9) and binds stably to MMP9. Using an OGD/R-injured neuronal-like PC12 cell line, in vitro assays confirmed that Astilbin alleviates oxidative stress, calcium overload, lipid peroxidation, and intracellular iron levels, while also modulating apoptosis- and inflammation-related genes. Overall, this study has established a comprehensive pharmacological framework for the use of Astilbin against IS, clarified its multi-target, multi-pathway neuroprotective mechanisms of action, and provided evidence for its potential in the treatment of IS. Full article

Background: Isolated Perfusion Chemotherapy (IPC) with balloon occlusion creates transient ischemic tissue compartments while patients remain exposed to significant perioperative heat loss. Active warming during these phases is commonly avoided due to theoretical concerns regarding impaired heat distribution and potential local heat accumulation in ischemic tissue. This study investigated the thermal safety of forced-air warming during IPC under these conditions. Methods: In this prospective observational study, 31 patients undergoing IPC were monitored during balloon-induced vascular occlusion. Convective warming was applied using a forced-air system set to 43 °C. Core temperature was measured rectally, and local temperatures were continuously recorded at gluteal, lumbar, and interscapular sites. Temperature trajectories and maximum values during occlusion were analysed descriptively. Results: Local temperature increases during ischemia were limited, with a maximum increase of 2.3 °C at the lumbar site. Absolute temperatures remained well below the predefined safety threshold of 39.5 °C at all skin measurement sites (maximum observed 37.7 °C). Core temperature remained stable throughout the occlusion phase. No evidence of local heat accumulation, threshold exceedance, or thermal skin reactions was observed. Conclusions: Under conditions of controlled application, close temperature monitoring, and short ischemic intervals, forced-air warming during IPC did not result in local overheating or clinically relevant thermal exposure. These findings challenge the prevailing precautionary approach of avoiding active warming during vascular isolation and provide prospective clinical evidence supporting a reassessment of temperature management strategies toward actively maintained normothermia in isolated perfusion chemotherapy. Full article