Search Results (1,581)

Coronary endothelial dysfunction is an early and critical vascular abnormality in cardiometabolic syndrome, intensified by irregular sleep patterns and excess adiposity. Disruption of circadian rhythm and accumulation of visceral fat impair nitric oxide signaling and promote arterial stiffness through endothelial injury. The gut vascular axis further contributes via microbial imbalance and endotoxin translocation, elevating systemic inflammation and vascular stress. Clinical evidence indicates that probiotics restore microbial equilibrium and attenuate vascular damage. Phytoantioxidants such as curcumin, berberine, and epigallocatechin gallate exert endothelial protective effects by enhancing nitric oxide synthase activity and suppressing inflammatory mediators. These compounds also activate the nuclear factor erythroid two related factor two (Nrf2) pathway, which regulates oxidative balance and promotes vascular resilience. Together, probiotics and phytoantioxidants represent a promising integrative approach to mitigate coronary endothelial dysfunction in populations affected by sleep disturbance and obesity. This review narratively integrates current molecular and clinical findings to delineate precision-guided pathways for endothelial recovery and cardiometabolic risk reduction. Full article

Gunshot injuries are challenging conditions because of the unique characteristics of the wounding agents producing soft tissue damage that may be compounded by the formation of an expanding temporary cavity (cavitation). Variations in ballistic performance leading to higher energy transfer by the projectile, including bullet tumbling, deformation, and fragmentation, cause increased soft tissue injury and may also lead to more extensive bone comminution compromising local blood supply. Once life-threatening injuries have been excluded or properly addressed, the emergency management of localized trauma from bullets and shotgun pellets may be complicated due to progressive tissue necrosis within the zone of injury. Additionally, the risk of infection should be tackled, especially in high energy bone injuries. War experience suggests a baseline separation between wounds with limited tissue destruction which can routinely be managed as simple penetrating injuries and those resulting from high energy transfer to the tissues involving a substantial amount of necrotic elements surrounding the wound channel which call for a more aggressive surgical approach. A further justification for such a distinction is the need for antibiotic therapy, which varies according to most studies depending on the wounding mechanism, the nature of the wound, and the extent of tissue injury. The emergency physician should also be aware of the possibility of “bizarre” bullet paths resulting in occult injuries of important anatomic structures. Full article

Alzheimer’s disease (AD), epilepsy, and vascular dementia (VaD) are highly prevalent neurological diseases and lead global drivers of morbidity. While these conditions have been historically treated as distinct entities, they now appear to share convergent molecular and cellular processes that drive disease initiation and progression. This narrative review collates evidence from studies published from 2000 to 2025 to investigate overlapping mechanisms and therapeutic opportunities for the three conditions. Five interconnected mechanisms, excitotoxicity, neuroinflammation, oxidative stress, mitochondrial dysfunction, and vascular impairment, were identified as key driving processes resulting in self-sustaining cycles leading to neuronal injury, cognitive impairment, and seizure susceptibility. Clinically, this is represented by shared cognitive, behavioral, and functional impairments, and often, seizures can be overlooked during the dementia process. Therapeutic strategies which may be useful across diseases could include anti-inflammatory treatments, mitochondrial stabilizers, vascular health treatments, and protein aggregation changes. Important translational gaps also exist for practice particularly in the biomarker space and trials that allow intervention across diseases. Each of these conditions, in essence, represent the same inter-relationships at the level of pathophysiology and provides opportunities for multi-targeted treatment approaches and integrated research trajectories to ease the worldwide burden of neurodegenerative disorder. Full article

Background and Clinical Significance: Moyamoya disease is a rare, progressive cerebrovascular disease characterized by steno-occlusion of the terminal internal carotid arteries and the arteries around the circle of Willis, with the formation of abnormal collateral vessels. Early clinical manifestations include recurrent hemodynamic transient ischemic attacks (TIAs), especially in young subjects. Multimodality imaging, including computed tomography, magnetic resonance, and digital subtraction angiography, is necessary to reach a correct diagnosis in young patients with stroke-like symptoms. Various radiological findings are crucial for early diagnosis, staging, and management of moyamoya disease. Case Presentation: We describe the case of a 31-year-old male presenting with acute focal neurological deficits and a history of recurrent TIAs. Neuroimaging was performed to assess vascular pathology, parenchymal injury, and collateral circulation and to provide critical information on vascular anatomy and the extent of ischemic damage. Conclusions: The purpose of this case report is to illustrate the main specific radiological signs and the diagnostic value of multimodality neuroimaging in the evaluation of moyamoya disease, providing a practical imaging-based diagnostic approach for neuroradiologists. Full article

Fragmented thrombolytic actuators address the limited time window of thrombolysis agents and the risk of intimal injury from mechanical thrombectomy, emerging as a crucial method for rapid vascular recanalization. However, occluded vessels are often tortuous and narrow, imposing strict size constraints on the actuator. Moreover, the inability to assess thrombolysis efficacy in real-time during procedures impedes timely adjustments to control strategies for the actuator. To address these challenges, this study designs a conical piezoelectric actuator that employs high-frequency vibration in conjunction with a small dose of thrombolytics to fragment and accelerate thrombus dissolution. Firstly, structural parameters of the actuator are optimized using grey relational analysis combined with an improved entropy-weighting method, and the optimal design is prototyped and tested. Next, a real-time thrombolytic solution concentration detection algorithm based on an Improved Grey Wolf Optimizer–Support Vector Regression (IGWO-SVR) model is proposed. Finally, an experimental platform is constructed for validation and analysis. The results show that compared to the initial design, the optimized actuator has significantly improved kinematic and force performance, with the tip amplitude increasing by 42% and the output energy density reaching 3.3726 × 10⁻² W/mm³. The IGWO-SVR model yields highly accurate, stable concentration estimates, with a coefficient of determination (R²) of 0.9987 and a root-mean-square error (RMSE) of 0.8118. This work provides a pathway toward actuator miniaturization and real-time thrombolysis monitoring, with positive implications for future clinical applications. Full article

Curcuma phaeocaulis, a perennial herb of the ginger family, has been used to treat many diseases in traditional medicine systems. This study aimed to extract, isolate, and purify a homogeneous polysaccharide from C. phaeocaulis, conduct preliminary structural characterization, and evaluate its antioxidant activity at the cellular level. The structure of the purified polysaccharide (CPAP-1) was characterized using size exclusion chromatography (SEC), chemical derivatization analysis (CDA), GC-MS, FT-IR, and NMR. The results showed that CPAP-1 has an apparent molecular weight of 118.122 kDa and is hypothesized to be an arabinogalactan with a backbone composed of →3,6)-β-d-Galp-(1→ and →3)-β-d-Galp-(1→ residues, a structure that is relatively novel in Curcuma longa. In vitro antioxidant assays demonstrated that CPAP-1 possesses potent antioxidative stress activity, effectively scavenging both DPPH and hydroxyl radicals. Furthermore, cellular experiments revealed that at concentrations of 500 and 750 mg/L, CPAP-1 significantly protected human umbilical vein endothelial cells (HUVECs) against H₂O₂-induced oxidative damage. In conclusion, these findings suggest that CPAP-1 could be developed as a natural antioxidant, functional food, or therapeutic agent for preventing and mitigating oxidative stress-related vascular injury, providing a theoretical basis for further development and application. Full article

Ischemic stroke remains one of the most catastrophic diseases in neurology, in which, due to a disturbance in the cerebral blood flow, the brain is acutely deprived of its oxygen and glucose oligomer, which in turn rapidly leads to energetic collapse and progressive cellular death. There is now increasing evidence that this type of stroke is not simply a type of ‘oxidative stress’ but rather a programmable loss-of-redox homeostasis, within which electron flow and the balance of oxidants/reductants are cumulatively displaced at the level of the single molecule and at the level of the cellular area. The advances being made in cryo-electron microscopy, lipidomics, and spatial omics are coupled with the introduction of a redox code produced by the interaction of the couples NADH/NAD⁺, NADPH/NADP⁺, GSH/GSSG, BH₄/BH₂, and NO/SNO, which determine the end results of the fates of the neurons, glia, endothelium, and pericytes. Within the mitochondria, pathophysiological events, including reverse electron transport, succinate overflow, and permeability transition, are found to be the first events after reperfusion, while signals intercommunicating via ER–mitochondria contact, peroxisomes, and nanotunnels control injury propagation. At the level of the tissue, events such as the constriction of the pericytes, the degradation of the glycocalyx, and the formation of neutrophil extracellular traps underlie microvascular failure (at least), despite the effective recanalization of the vessels. Systemic influences such as microbiome products, oxidized lipids, and free mitochondrial DNA in cells determine the redox imbalance, but this generally occurs outside the brain. We aim to synthesize how the progressive stages of ischemic injury evolve from the cessation of flow to the collapse of the cell structure. Within seconds of injury, there is reverse electron transport (RET) through mitochondrial complex I, with bursts of superoxide (O₂•⁻) and hydrogen peroxide (H₂O₂) being produced, which depletes the stores of superoxide dismutase, catalase, and glutathione peroxidase. Accumulated succinate and iron-induced lipid peroxidation trigger ferroptosis, while xanthine oxidase and NOX2/NOX4, as well as uncoupled eNOS/nNOS, lead to oxidative and nitrosative stress. These cascades compromise the function of neuronal mitochondria, the glial antioxidant capacity, and endothelial–pericyte integrity, leading to the degradation of the glycocalyx with microvascular constriction. Stroke, therefore, represents a continuum of redox disequilibrium, a coordinated biochemical failure linking the mitochondrial metabolism with membrane integrity and vascular homeostasis. Full article

Background: Non-transected and partially transected peripheral nerve injuries (neuromas-in-continuity) are relatively common but understudied. Their optimal surgical management and expected outcomes remain unclear. We conducted a literature review of surgical repairs in such lesions and illustrate a case to guide decision-making. Systematic searches of PubMed and Google Scholar identified 70 eligible reports (Level I = 2, Level II = 5, Level III = 37, Level IV = 20, Level V = 4). Across studies, neurolysis of NAP-positive lesions often restored antigravity strength, while direct repair or grafting of nonconductive segments yielded meaningful recovery in ~75%. After neurolysis or reconstruction, ~77–92% of brachial plexus/axillary neuromas-in-continuity reached LSUHSC Grade ≥3. Median/ulnar lesions treated with neurolysis, biologic/vascularized coverage, or reconstruction showed reliable pain relief but variable sensory/motor recovery. Radial/PIN lesions improved in some series irrespective of NAPs. Earlier intervention, shorter gaps, distal sites, and younger age correlated with superior outcomes. Meanwhile, prolonged observation risking end-organ atrophy degraded results. Adjuncts such as electrical stimulation and wraps may aid reinnervation or reduce scarring, though high-quality evidence is limited. Conclusions: For non-transected and partially transected PNIs, a pragmatic approach emerges: Observe low-grade injuries with serial examinations. Explore early if recovery stalls (≈3–6 months). Use NAP-guided neurolysis for conductive lesions. Perform tension-free repair or grafting for nonconductive segments, adding anti-adhesive coverage when appropriate. Standardized reporting and prospective trials are needed to refine timing, technique selection, and patient-reported outcomes. Full article

Obesity is a significant risk factor for cardiovascular diseases. Although previous studies have shown uncertainty about its role in aortic dissection (AD), our clinical observations showed that most younger patients with acute AD have a significantly higher body mass index. The underlying reasons are yet to be investigated. Recent studies have suggested that obesity is linked to vascular pathophysiology, including endothelial injury, medial remodeling and deficiency, perivascular adipose tissue dysfunction, and systemic dysfunction. Understanding the association between obesity and acute AD can aid in recognizing high-risk populations, providing an earlier chance of diagnosis and intervention, and improving clinical outcomes for acute AD in young obese patients. This review analyzes and integrates current data to explain the potential role of obesity in acute AD pathogenesis. Full article

Background: The sphenoidal emissary foramen (SEF) is an inconstant foramen of the sphenoid bone that facilitates venous communication between the pterygoid venous plexus and the cavernous sinus. Understanding its prevalence and laterality is crucial to preventing vascular injury during skull base procedures. Methods: A cross-sectional observational study was conducted on 133 adult Chilean dried skulls. Each specimen was examined both internally and externally to record SEF presence and laterality. Three independent observers performed the assessments under direct lighting, achieving excellent interobserver agreement (κ = 0.87, 95% CI = 0.81–0.92). Descriptive statistics, Chi-square tests, and Cramer’s V coefficients were calculated to evaluate side dominance and effect size at a significance level of p < 0.05. Results: The SEF was present in 40.17%. Bilateral foramina were observed in 26.79%, and unilateral SEF in 13.38%. Left-sided SEF (9.12%) was more common than right-sided SEF (4.26%), showing a significant difference (p = 0.03; Cramer’s V = 0.19, 95% CI = 0.02–0.33). This mild but significant left-sided prevalence indicates slight directional asymmetry rather than functional lateralization. Conclusions: The Chilean prevalence of the SEF lies within the mid-range of international data and closely aligns with Brazilian osteological reports. Although a minor left-sided predominance was observed, the effect size was weak (Cramer’s V = 0.19), reinforcing the interpretation of the SEF as a normal morphological variability rather than a true anatomical variant. Precise preoperative identification of the SEF is crucial to reduce the risk of venous injury and avoid unintentional penetration. Full article

Flap viability remains a major challenge in reconstructive surgery due to ischemia–reperfusion injury, excessive inflammation, and impaired tissue regeneration. Boron, a trace element with pro-healing and anti-inflammatory properties, has shown therapeutic promise in various wound models; however, its role in flap healing remains unclear. In this study, we aimed to evaluate the therapeutic potential of sodium pentaborate pentahydrate (SPP)-containing hydrogel, a boron compound we developed, for enhancing flap survival and tissue repair. A dorsal random-pattern flap model was established in male Wistar rats, which were treated topically with an SPP-containing formulation twice daily for seven days. Histological changes were evaluated using hematoxylin–eosin and Masson’s trichrome staining, and proteomic alterations were analyzed using label-free nanoLC-MS/MS followed by bioinformatics analysis. The treatment significantly improved flap survival (p < 0.0001), enhanced granulation tissue formation, promoted organized collagen deposition, and reduced inflammatory infiltration. Proteomic profiling identified 179 differentially expressed proteins, with 14 upregulated and 165 downregulated. Upregulated proteins were enriched in pathways related to complement activation, antioxidant defense, and extracellular matrix remodeling, whereas downregulated proteins were associated with immune overactivation, cellular stress, and senescence, indicating a shift toward regulated inflammation and tissue homeostasis. To our knowledge, this is the first study to demonstrate that an SPP-containing hydrogel promotes flap healing by supporting vascularization, modulating immune responses, and enhancing extracellular matrix remodeling. These findings highlight SPP as a promising therapeutic strategy for improving flap viability in reconstructive surgery. Full article

Matrix metalloproteinase-9 (MMP-9) is a zinc-dependent endopeptidase that plays a central role in extracellular matrix (ECM) remodeling, angiogenesis, immune cell trafficking, and cytokine activation. Dysregulated MMP-9 activity has been implicated in the pathogenesis of diverse conditions, including atherosclerosis, aneurysm formation, chronic obstructive pulmonary disease (COPD), asthma, neurodegeneration, and malignancy. Although broad-spectrum synthetic MMP inhibitors were initially developed as therapeutic agents, clinical trials failed due to lack of selectivity, poor tolerability, and impairment with physiological tissue repair. This outcome has shifted attention toward indirect pharmacological modulation of MMP-9 using drugs that are already approved for other indications. In this paper, we review the evidence supporting MMP-9 modulation by established therapeutics and adjunctive strategies. Cardiometabolic agents such as statins, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), metformin, and pioglitazone reduce MMP-9 expression and enzymatic activity, contributing to vascular protection, improved insulin sensitivity, and attenuation of aneurysm progression. Anti-inflammatory and respiratory drugs, including glucocorticoids, phosphodiesterase-4 (PDE4) inhibitors, macrolide antibiotics, montelukast, and nonsteroidal anti-inflammatory drugs (NSAIDs), suppress MMP-9-driven airway inflammation and pathological tissue remodeling in asthma, COPD, and acute lung injury. Tetracycline derivatives, particularly sub-antimicrobial dose doxycycline, directly inhibit MMP-9 activity and are clinically validated in the treatment of periodontal disease and vascular remodeling. Hormone-related therapies such as rapamycin, estradiol, and tamoxifen exert tissue- and disease-specific effects on MMP-9 within endocrine and oncologic pathways. In parallel, nutritional interventions—most notably omega-3 polyunsaturated fatty acids and antioxidant vitamins—provide adjunctive strategies for mitigating MMP-9 activity in chronic inflammatory states. Taken together, these findings position MMP-9 as a modifiable and clinically relevant therapeutic target. The systematic integration of approved pharmacologic agents with lifestyle and nutritional interventions into disease-specific treatment paradigms may facilitate safer, context-specific modulation of MMP-9 activity and unveil novel opportunities for therapeutic repurposing. Full article

Traumatic brain injury (TBI) in childhood is a major global health concern and a leading cause of morbidity and mortality in the pediatric population. Its incidence is rising worldwide, with early childhood and adolescence representing the most vulnerable age groups. Beyond acute neurological injury, post-traumatic endocrine dysfunction has emerged as an underrecognized but clinically significant sequela, with potential long-term consequences for growth, puberty, metabolism, and overall quality of life. The hypothalamic–pituitary axis (HPA) is uniquely vulnerable due to its anatomical and vascular characteristics, making pituitary cells—particularly somatotrophs and gonadotrophs—susceptible to ischemic, traumatic, and inflammatory damage. Reported prevalence of post-TBI pituitary dysfunction in children ranges from 5 to 57%, reflecting a deep heterogeneity in injury severity, diagnostic methods, and timing of evaluations. Growth hormone deficiency (GHD) is the most frequently reported abnormality, with presentations varying from transient to persistent forms. Gonadal axis disturbances, including hypogonadotropic hypogonadism and, less commonly, central precocious puberty, highlight the impact of TBI on pubertal development. Adrenal dysfunctions, though less frequent, may be life-threatening if unrecognized, while posterior pituitary disorders, such as diabetes insipidus, usually revealed acutely, are often transient. Importantly, many endocrine sequelae manifest months to years after the initial trauma, complicating a timely diagnosis. Current evidence underscores the need for structured, longitudinal endocrine surveillance after pediatric TBI, with baseline and follow-up assessments at defined intervals. Early recognition and intervention, including hormone replacement when appropriate, may improve neurocognitive recovery and overall rehabilitation outcomes. Future multicenter studies and standardized screening protocols should be considered essential to clarify incidence, natural history, and optimal management strategies for post-traumatic endocrine dysfunction in children. Full article

A comprehensive understanding of gene-environment interactions is essential for maintaining human cardiac health, and deficiency in the key parkin gene exacerbates cardiac injury. Per- and polyfluoroalkyl substances (PFAS) exposure has been determined cardiotoxicity from the epidemiological perspective but the potential remained unclear. Here, we investigated the co-effects on cardiac pathological structure and function of an emerging PFAS, 6:2 chlorinated polyfluorinated ether sulfonate acid (F-53B), on male parkin^−/− mice at dose of 3 and 3000 μg/kg for 60 d. Mechanism was focused on the activity, phosphorylation of endothelial nitric oxide synthase (eNOS), and the content of nitric oxide (NO), vital vascular function regulating molecule. F-53B significantly increased cardiac fibrosis to 1.58- and 2.80-fold, and cardiac troponin T (cTNT) to 1.17- and 1.32-fold compared with control group, at dose of 3 and 3000 μg/kg, respectively, indicating F-53B can inhibit the normal activities of the heart and cause functional disorders. Content and phosphorylation of eNOS significantly decreased to 0.68-, 0.67-fold, and to 0.65-, 0.54-fold compared with control group, respectively. The subsequent content of NO level was also significantly decreased to 0.47- and 0.33-fold, respectively, indicating that significant co-effects of parkin deficiency and F-53B exposure on cardiac function and structural changes via eNOS/NO signalling. Our work underscores the importance of assessing cardiac risk associated with PFAS at environmentally relevant doses, especially considering environmental exposure and gene co-interaction from the perspective of F-53B and parkin gene. Full article

Cardiogenic shock (CS) is a complex, life-threatening syndrome characterized by inadequate tissue perfusion due to impaired cardiac function. Acute myocardial infarction (AMI) and acute decompensated heart failure are the leading causes, with mortality remaining high despite advances in revascularization and supportive care. The Society for Cardiovascular Angiography and Interventions (SCAI) classification allows risk stratification and guides clinical decision making by capturing the spectrum of shock severity. Percutaneous mechanical circulatory support (pMCS) devices, such as the intra-aortic balloon pump (IABP) and Impella, aim to stabilize hemodynamics by augmenting cardiac output and unloading the left ventricle. However, randomized trials and meta-analyses have not demonstrated a consistent survival advantage of Impella over IABP, while reporting higher rates of bleeding and vascular complications. Landmark trials, including ECLS-SHOCK and DanGer, have provided conflicting results, likely reflecting differences in baseline severity and timing of device implantation. Veno-arterial extracorporeal membrane oxygenator (VA-ECMO) offers full cardiopulmonary support but increases left ventricular afterload, potentially worsening myocardial injury. Combined strategies such as ECPELLA (Impella + VA-ECMO) or ECMO + IABP may mitigate left ventricle (LV) overload and improve bridging to recovery or advanced therapies, although evidence remains largely observational and complication rates are considerable. In right-sided or biventricular failure, tailored options (e.g., Impella RP, Bi-Pella) guided by invasive hemodynamics may be required. Current evidence suggests that pMCS benefits are limited to carefully selected subgroups, underscoring the importance of early diagnosis, prompt referral, and individualized intervention. Robust randomized data are still needed to define the optimal role of pMCS in AMI-related CS. Full article