Search Results (3,542)

As the leading cause of global mortality, cardiovascular diseases demand improved and innovative strategies for early detection and risk assessment to enhance prevention and timely treatment. This comprehensive review examines the potential of combining high-sensitivity cardiac troponins (hs-cTns) and homocysteine (Hcy) as complementary biomarkers for enhanced cardiovascular risk prediction. hs-cTn assays have revolutionized cardiovascular diagnostics by enabling the detection of minimal myocardial injury, improving early diagnosis of acute coronary syndrome, and providing robust prognostic information in both symptomatic and asymptomatic populations. Hcy, while established as a marker of vascular dysfunction, presents an interpretative challenge due to multiple confounding factors and inconsistent therapeutic responses. Emerging evidence demonstrates significant correlations between elevated Hcy and troponins across various clinical conditions, suggesting that their combined assessment—reflecting both myocardial injury and vascular dysfunction—may improve cardiovascular risk stratification. While initial findings are promising, additional studies are required to validate the clinical value of the combined marker approach. Future development of personalized interpretation algorithms, and multi-marker panels incorporating these biomarkers, may significantly advance cardiovascular medicine and enable more effective population-specific risk management strategies. Full article

The integration of organoids with biosensors serves as a miniaturized model of human physiology and diseases, significantly transforming the research frameworks surrounding drug development, toxicity testing, and personalized medicine. This review aims to provide a comprehensive framework for researchers to identify suitable technical approaches and to promote the advancement of organoid sensing towards enhanced biomimicry and intelligence. To this end, several primary methods for technology integration are systematically outlined and compared, which include microfluidic integrated systems, microelectrode array (MEA)-based electrophysiological recording systems, optical sensing systems, mechanical force sensing technologies, field-effect transistor (FET)-based sensing techniques, biohybrid systems based on synthetic biology tools, and label-free technologies, including impedance, surface plasmon resonance (SPR), and mass spectrometry imaging. Through multimodal collaboration such as the combination of MEA for recording electrical signals from cardiac organoids with micropillar arrays for monitoring contractile force, these technologies can overcome the limitations inherent in singular sensing modalities and enable a comprehensive analysis of the dynamic responses of organoids. Furthermore, this review discusses strategies for integrating strategies of multimodal sensing approaches (e.g., the combination of microfluidics with MEA and optical methods) and highlights future challenges related to sensor implantation in vascularized organoids, signal stability during long-term culture, and the standardization of clinical translation. Full article

Sepsis is a complex condition characterized by an uncontrolled inflammatory response to infection, which can trigger multi-organ dysfunction and is associated with high mortality rates. In this context, oxidative stress plays a key role in the progression of tissue damage. Reduced glutathione (GSH), the primary non-enzymatic intracellular antioxidant, serves as a fundamental pillar in redox defense, acting as a key modulator of immune response, endothelial barrier integrity, and mitochondrial metabolism. This review explores the multifaceted role of GSH in the pathophysiology of sepsis, with emphasis on its biphasic effect on both innate and adaptive immunity, as well as its involvement in vascular alterations and mitochondrial dysfunction. The molecular mechanisms of GSH depletion during sepsis are analyzed, including excessive consumption by reactive species, disruption of its synthesis, and its intracellular compartmentalization. Additionally, the available clinical evidence in humans regarding the functional consequences of GSH loss is reviewed, particularly concerning organ failure—understood more as a bioenergetic and functional disruption than a structural one—and mortality, highlighting the methodological limitations and heterogeneity of the reported findings. Altogether, this analysis intends to provide a comprehensive view of the role of glutathione in redox dysregulation and the pathophysiological mechanisms underlying sepsis. Furthermore, it seeks to consolidate current pathophysiological and clinical knowledge to emphasize the potential role of glutathione as a prognostic marker and possible target for future therapeutic strategies in addressing this complex condition. Full article

Endothelial dysfunction underlies several vascular complications, including diabetes and atherosclerosis. However, the underlying role of long non-coding RNAs (lncRNAs) remains poorly understood. This study elucidated the role of lncRNA Gm39822 in regulating endothelial dysfunction under healthy and diabetic conditions. Our data revealed that Gm39822 is enriched and upregulated in non-diabetic endothelial cells when exposed to high glucose or inflammatory cytokines (TNF-α and IL-1β). Gm39822 overexpression promoted the expression of vascular cell adhesion molecule-1 (VCAM-1) and the adhesion of leukocytes in non-diabetic ECs but not in diabetic ECs. Conversely, Gm39822 silencing reduced VCAM1 expression and leukocyte adhesion in non-diabetic ECs and not in diabetic ECs. Gm39822 deficiency reduced the expression of inflammatory mediators (including p-P65, P65, P50, p-P38, P38, P-ERK1/2, and ERK1/2) in non-diabetic ECs. Furthermore, Gm39822 knockdown inhibited the secretion of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-6, suggesting that Gm39822 regulates EC inflammatory responses. Mechanistically, we identified C1D, a nuclear-enriched corepressor, as an interacting partner of Gm39822 that could play an important role in mediating Gm39822 functions in non-diabetic ECs. Collectively, our results identify a novel lncRNA Gm39822 and provide insights into the molecular mechanisms underlying endothelial dysfunction. These findings highlight Gm39822 as a potential therapeutic target for mitigating vascular complications associated with non-diabetic endothelial dysfunction. Full article

Background/Objectives: The Charlotte Large artery occlusion Endovascular therapy Outcome Score (CLEOS) predicts neurological outcomes after endovascular thrombectomy (EVT). Given recent expanded indications for EVT, we evaluated CLEOS in a modern cohort of thrombectomy patients. Methods: We retrospectively analyzed consecutive, anterior circulation EVT patients from January to December 2024 at multiple centers. The primary outcome was a 90-day modified Rankin Scale (mRS) score of 4–6. We compared primary outcome rates between the original CLEOS derivation cohort and the validation cohort. The area under the curve (AUC) was calculated for CLEOS and compared to other prognostic scales. Results: In the 347 included patients, the mean age was 67.6 (14.9) years, the median National Institutes of Health Stroke Scale (NIHSS) was 15 (10–20), and 137 (42.2%) had a 90-day mRS score of 4–6. A similar proportion of patients in the validation cohort and the derivation cohort achieved the primary outcome (39% each, p = 0.957). The AUC for CLEOS (0.7416, 95% confidence interval [CI] 0.688–0.795) was superior to that of the Pittsburgh Response to Endovascular therapy (AUC 0.681, 95% CI 0.624–0.738, p < 0.01) and Stroke Prognostication using Age and NIHSS (AUC 0.5982, 95% CI 0.556–0.640, p < 0.01), while a trend was observed compared to Houston Intra-Arterial Therapy-2 (AUC 0.6999, 95% CI 0.644–0.756, p = 0.0657) and Totaled Health Risk in Vascular Events (AUC 0.7046, 95% CI 0.560–0.759, p = 0.07). CLEOS ≥ 700 predicted the primary outcome in 16/19 (84.2%) patients. Conclusions: CLEOS performed well in our modern cohort of thrombectomy patients. Prognostic scales such as CLEOS may be useful in guiding conversations and setting expectations with family members pre- and post-thrombectomy. Full article

Extracellular vesicles (EVs) are nanoscale, membrane-bound particles secreted by diverse cell types and act as pivotal mediators of intercellular communication during bone regeneration. These vesicles transport bioactive cargo including proteins, lipids, mRNAs, and microRNAs that modulate osteogenesis, angiogenesis, and immune responses within the bone microenvironment. EVs originating from mesenchymal stem cells, osteoblasts, endothelial cells, and macrophages have demonstrated substantial potential to promote bone formation, inhibit bone resorption, and enhance vascularization. This review examines the biogenesis, classification, and cellular uptake mechanisms of EVs, focusing on their roles in osteogenesis and their therapeutic applications in fracture healing, osteoporosis, and bone tissue engineering. Despite their promise, significant challenges remain, including the need for standardization, scalable production, and assessment of long-term safety to enable clinical translation of EV-based therapies. Here, we provide a comprehensive overview of EV biology, elucidate the molecular mechanisms of EVs in bone regeneration, and discuss innovative strategies to optimize their therapeutic efficacy, highlighting their potential as next-generation orthobiologics. Full article

Oxaliplatin-induced peripheral neurotoxicity (OIPN) represents a major challenge in cancer therapy, characterized by dorsal root ganglia (DRG) inflammation and disruption of neuro-glio-vascular unit function. In this study, we investigated the involvement of the scaffold protein IQ Motif Containing GTPase Activating Protein 1 (IQGAP1) and dehydropeptidase-1 (DPEP1) in the DRG response to oxaliplatin (OxPt) and the modulatory effect of cilastatin. Behavioral assessment showed a robust nocifensive response to cold stimuli in OxPt-treated rats, attenuated by cilastatin co-treatment. Our confocal study revealed different cellular and subcellular expression patterns of IQGAP1 and DPEP1 in neurons, glia, and endothelial cells, where both signals overlap approximately one-third. OxPt enhanced cytosolic aggregation of IQGAP1 in neurons and upregulation of signal in glia, accompanied by co-expression of TNFα and IL-6, indicating involvement in the inflammatory process. DPEP1 showed altered subcellular distribution in OxPt-treated animals, suggesting a potential role in the inflammatory cascade. Notably, IQGAP1 expression was diminished in endothelial membranes under OxPt, while cilastatin preserved endothelial IQGAP1-CD31 colocalization, suggesting partial restoration of blood-nerve barrier integrity. These findings identify IQGAP1 and DPEP1 as key players in DRG inflammation and position cilastatin as a promising modulator of OIPN through neuro-glio-vascular stabilization. Full article

Despite significant advancements, prosthetic hernia repair continues to face unacceptably high complication rates. These likely stem from poor biological responses, such as stiff scar tissue leading to mesh shrinkage. To overcome these issues, the Stenting and Shielding (S&S) Hernia System, a newly designed 3D dynamic device, has been developed for dissection-free laparoscopic placement to permanently obliterate hernia defects. Unlike conventional meshes, this device induces a regenerative biological response, promoting viable tissue growth rather than fibrotic plaque formation. In a porcine experimental model, the S&S device demonstrated the development of a great amount of muscle fibers, alongside nervous and vascular structures, within well-perfused connective tissue. Histological analysis of biopsy specimens excised from the experimental animals revealed progressive muscle fiber maturation from early myocyte development in the short term to fully developed muscle bundles in the long term. The enhanced biological response observed with the S&S device suggests a promising shift in hernia repair, potentially reversing the degenerative processes of hernia formation and promoting tissue regeneration. The S&S Hernia System described here can be classified not merely as a conventional hernia implant, but as part of a new category of hernia devices: the dynamic regenerative scaffold. Full article

Bioinks represent the core of 3D bioprinting, as they are the carrier responsible for enabling the fabrication of anatomically precise, cell-laden constructs that replicate native tissue architecture. Indeed, their role goes beyond structural support, as they must also sustain cellular viability, proliferation, and differentiation functions, which are critical for applications in the field of regenerative medicine and personalized therapies. However, at present, a persistent challenge lies in reconciling the conflicting demands of rheological properties, which are essential for printability and biological functionality. This trade-off limits the clinical translation of bioprinted tissues, particularly for vascularized or mechanically dynamic organs. Despite huge progress during the last decade, challenges persist in standardizing bioink characterization, scaling production, and ensuring long-term biomimetic performance. Based on these challenges, this review explores the inherent trade-off faced by bioink research optimizing rheology to ensure printability, shape fidelity, and structural integrity, while simultaneously maintaining high cell viability, proliferation, and tissue maturation offering insights into designing next-generation bioinks for functional tissue engineering. Full article

Behçet’s syndrome (BS) is a chronic, relapsing inflammatory disease with multisystem involvement and prominent neutrophil activation. The neutrophil-to-lymphocyte ratio (NLR) has gained increasing attention as a potential surrogate marker for systemic inflammation. In this review we aimed to summarize and critically review the current evidence regarding the utility of NLR in BS, including its association with overall disease activity and specific organ involvement, as well as to explore its strengths and limitations as a clinical biomarker. NLR seems to be a simple, accessible, and cost-effective biomarker that can be elevated in Behçet’s syndrome and tends to be higher during active disease. Studies have demonstrated its consistent correlation with overall disease activity, as well as with specific manifestations such as mucocutaneous, ocular, vascular, and articular involvement. Moreover, NLR levels have been shown to decrease in response to anti-inflammatory treatments, supporting its potential utility in monitoring treatment effectiveness. Despite its seemingly cost-effective features, its routine integration into daily practice remains largely limited, mainly due to low specificity and the lack of standardized cut-off level. Further prospective studies are needed to assess its use in daily practice before it can be integrated into any disease activity score. Full article

The use of hydrogel and biostimulants holds great potential for plants’ adaptation to stressful urban conditions, increasing their tolerance to drought stress. In this study, we investigated the plant performance and anatomical response of Petunia × hybrida hort. ex E. Wilm., cultivated under different substrate volumes and compositions, hydrogel amendments, and biostimulant treatments, as well as their interactions under drought stress. Namely, the plants were planted in pots with a substrate depth of 7 cm and 10 cm and cultivated under different combinations of organic (peat) and inorganic (perlite) substrates. Moreover, half of the plants were subjected to hydrogel and biostimulant treatments. Different watering intervals (24–96 h) were applied in combination with exposing the plants to direct sunlight for 8–10 h. The results showed that a larger substrate depth, along with hydrogel and biostimulant amendments in a mixture of perlite and peat, helps plants adapt to dry conditions when grown in shallow substrates, providing optimal water availability and thus contributing to the physiological adaptation of plants to water deficit. The study clearly demonstrates that substrate selection and irrigation frequency must be jointly optimized to ensure resilient urban greening. Hydrogels stand out as essential amendments, enabling significant water savings by extending irrigation intervals without compromising vascular growth or drought resilience. These water-efficient substrate strategies are vital for sustainable urban vegetation management, especially as cities face increasing environmental pressures and the imperative of climate adaptation, thereby supporting multiple Sustainable Development Goals. Full article

Emerging evidence suggests that vitamin D and dipeptidyl peptidase-4 (DPP-4) inhibitors exert synergistic immunomodulatory, anti-inflammatory and antioxidant actions. Moreover, intervention studies showed that combination therapy based on the concomitant use of vitamin D and DPP-4 inhibitors (VIDPP-4i) may preserve beta-cell function in patients with type 1 diabetes mellitus (T1D) and latent autoimmune diabetes in adults (LADA). These effects are particularly relevant in the context of beta-cell replacement strategies, whose long-term efficacy can be hampered by various factors, such as immune-mediated graft rejection, inadequate vascularization, hypoxia, trauma-induced cell apoptosis, fibrosis, host immune response, and recurrence of autoimmunity. Based on preclinical and clinical studies conducted in the fields of autoimmune diabetes and solid organ/cell transplantation, the present narrative review aims to describe the rationale behind the investigation of VIDPP-4i combination therapy as an adjuvant treatment strategy to enhance the efficacy of novel beta-cell replacement therapies for T1D. In this regard, we discuss the potential immune and metabolic mechanisms through which vitamin D and DPP-4 inhibitors can promote the long-term function and survival of transplanted islets in patients with T1D receiving various types of beta-cell replacement therapies, including therapeutic approaches using encapsulated stem cell-derived beta cells. Full article

Background: Load carriage is an activity of daily living, can be an occupational risk, and is a popular method of resistance training. Type of carry could be related to vascular and blood pressure (BP) responses and may be related to cardiovascular risk. As physical activity is recommended by clinicians and exercise physiologists, understanding the vascular responses in relation to type of carry is important to consider in terms of risk. The purpose of this study was to compare the vascular health and BP responses to the farmer’s handle (load at the side of the body) and zercher (load in front of the body) carry and to examine sex differences in the responses. Methods: A total of 38 adults (22 females and 16 males) completed farmer’s handle and zercher load carriage with pre- and post-vascular measurements using pulse wave analysis. Results: We found that load carriage with weight in front of the body (zercher) elicits a larger increase in arterial stiffness (AIx@75), and load carriage with the load on the side of the body (farmer’s handle) elicits a larger increase in peripheral systolic BP. There were no sex differences in the responses to carry. Females exercise (3.1 vs. 4.8) and weight train (1.5 vs. 2.6) fewer times per week and had a lower resting systolic BP (121.5 ± 10.3 vs. 131.3 ± 8.3 mmHg) (p < 0.05). Both types of load carriage increased peripheral systolic BP, central systolic BP, and vascular stiffness (p < 0.05). Conclusions: Location of load carriage is important to consider based on potential cardiac risk of patients. Full article

Blood–brain barrier (BBB) deterioration with increasing age is an important factor contributing to vascular dementia. Previous studies show that endothelial nitric oxide synthase (eNOS) facilitates vascular endothelial growth factor-mediated angiogenesis and increased vascular permeability. In contrast, recent work has shown that aged hemi-deficient hemizygous eNOS^+/− mice manifest BBB disruption in association with increased incidence of thromboembolic events in the brain. To unravel whether eNOS contributes to or protects against hypoxia-induced cerebrovascular damage, we compared chronic mild hypoxia (CMH)-induced cerebrovascular angiogenic remodeling and BBB breakdown in aged (20 months old) eNOS^+/− and wild-type (WT) mice. This revealed that CMH strongly enhanced eNOS expression in cerebral blood vessels with much lower levels in eNOS^+/− mice. eNOS hemi-deficiency resulted in greater CMH-induced BBB disruption, but unexpectedly, had no effect on endothelial proliferation. eNOS^+/− mice also displayed enhanced endothelial expression of the endothelial activation markers MECA-32, VCAM-1, and β3 integrin in cerebral blood vessels, indicating greater vascular inflammation, and this correlated with increased levels of microglial activation and demyelination. Taken together, our results support the concept that eNOS plays an important protective function in the aged brain by suppressing endothelial activation and maintaining cerebrovascular health. Full article

The ring finger protein 213 (RNF213) Arg4810Lys variant has been previously identified as a significant risk factor for Moyamoya disease (MMD), particularly in East Asian populations. This review explores the broader impact of the Arg4810Lys mutation on various cerebrovascular conditions, including Moyamoya syndrome (MMS), intracranial artery stenosis, quasi-Moyamoya syndromes, ischemic stroke, and intracranial atherosclerosis. Beyond the brain, it is also implicated in pulmonary arterial hypertension, coronary artery disease, and renal artery stenosis, emphasizing its systemic effects. Functional studies suggest that RNF213 Arg4810Lys alters angiogenic signaling, endothelial cell function, vascular remodeling, and immune response pathways, especially when influenced by environmental stressors, like hypoxia or inflammation. The gene dosage of Arg4810Lys significantly affects disease phenotypes, with homozygous carriers typically experiencing earlier onset with increased severe symptoms. The variant also exhibits incomplete penetrance and frequently co-occurs with additional genetic alterations, including trisomy, KIF1A, FLNA, and PCSK9 mutations, which complicates its pathogenicity. A comprehensive understanding of RNF213 Arg4810Lys’s systemic impact is essential to developing effective risk assessment strategies, personalized treatments, and targeted therapies for associated vascular diseases. Full article