Search Results (1,717)

Hemodynamics significantly impact the biology of endothelial cells (ECs) lining the blood vessels. ECs are exposed to various hemodynamic forces, particularly frictional shear stress from flowing blood. While physiological flows are critical for the normal functioning of ECs, abnormal flow dynamics, known as disturbed flows, may trigger endothelial dysfunction leading to atherosclerosis and other vascular conditions. Such flows can occur due to sudden geometrical variations and vascular abnormalities in the cardiovascular system. In the current study, a microfluidic system was used to investigate the impact of different flow conditions (i.e, normal vs. disturbed) on ECs in vitro. We particularly explored the relationship between specific flow patterns and cellular pathways linked to oxidative stress and inflammation related to atherosclerosis. Here, we utilized a 2D cell culture perfusion system featuring an immortalized human vascular endothelial cell line (EA.hy926) connected to a modified peristaltic pump system to generate either steady laminar flows, representing healthy conditions, or disturbed oscillatory flows, representing diseased conditions. EA.hy926 were exposed to an oscillatory flow shear stress of 0.5 dynes/cm² or a laminar flow shear stress of 2 dynes/cm² up to 24 h. Following flow exposure, cells were harvested from the perfusion chamber for quantitative PCR analysis of gene expression. Reactive oxygen species (ROS) generation under various shear stress conditions was also measured using DCFDA/H2DCFDA fluorescent assays. Under oscillatory shear stress flow conditions (0.5 dynes/cm²), EA.hy926 ECs showed a 3.5-fold increase in the transcription factor nuclear factor (NFκ-B) and a remarkable 28.6-fold increase in cyclooxygenase-2 (COX-2) mRNA expression, which are both proinflammatory markers, compared to static culture. Transforming growth factor-beta (TGFβ) mRNA expression was downregulated in oscillatory and laminar flow conditions compared to the static culture. Apoptosis marker transcription factor Jun (C-Jun) mRNA expression increased in both flow conditions. Apoptosis marker C/EBP homologous protein (CHOP) mRNA levels increased significantly in oscillatory flow, with no difference in laminar flow. Endothelial nitric oxide synthase (eNOS) mRNA expression was significantly decreased in cells exposed to oscillatory flow, whereas there was no change in laminar flow. Endothelin-1 (ET-1) mRNA expression levels dropped significantly by 0.5- and 0.8-fold in cells exposed to oscillatory and laminar flow, respectively. ECs subjected to oscillatory flow exhibited a significant increase in ROS at both 4 and 24 h compared to the control and laminar flow. Laminar flow-treated cells exhibited a ROS generation pattern similar to that of static culture, but at a significantly lower level. Overall, by exposing ECs to disturbed and normal flows with varying shear stresses, significant changes in gene expression related to inflammation, endothelial function, and oxidative stress were observed. In this study, we present a practical, optimized system as an in vitro model that can be employed to investigate flow-associated diseases, such as atherosclerosis and aortic aneurysm, thereby supporting the understanding of the underlying molecular mechanisms. 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

Background/Objectives: Menopause, marked by permanent cessation of menstruation, is a universal transition associated with vasomotor, genitourinary, psychological, and metabolic changes. These conditions significantly affect health-related quality of life (HRQoL) and increase the risk of chronic diseases. Despite their impact, timely diagnosis and individualized management are often limited by delayed care, fragmented health systems, and cultural barriers. Methods: This review summarizes current applications of artificial intelligence (AI) in postmenopausal health, focusing on risk prediction, early detection, and personalized treatment. Evidence was compiled from studies using biomarkers, imaging, wearable sensors, electronic health records, natural language processing, and digital health platforms. Results: AI enhances disease prediction and diagnosis, including improved accuracy in breast cancer and osteoporosis screening through imaging analysis, and cardiovascular risk stratification via machine learning models. Wearable devices and natural language processing enable real-time monitoring of underreported symptoms such as hot flushes and mood disorders. Digital technologies further support individualized interventions, including lifestyle modification and optimized medication regimens. By improving access to telemedicine and reducing bias, AI also has the potential to narrow healthcare disparities. Conclusions: AI can transform postmenopausal care from reactive to proactive, offering personalized strategies that improve outcomes and quality of life. However, challenges remain, including algorithmic bias, data privacy, and clinical implementation. Ethical frameworks and interdisciplinary collaboration among clinicians, data scientists, and policymakers are essential for safe and equitable adoption. Full article

Introduction: Biological systems inherently exhibit metabolic variability that functions within optimal ranges, as described by the Constrained Disorder Principle (CDP). Deviations from these ranges, whether excessive or insufficient, are linked to adverse health outcomes. This review examines how signatures of metabolic variability can enhance GLP-1 receptor agonist therapy using artificial intelligence platforms. Methods: We conducted a comprehensive literature review examining metabolic variability across various parameters, including heart rate, blood pressure, lipid levels, glucose control, body weight, and metabolic rate. We focused on studies investigating the relationship between variability patterns and treatment responses, particularly in the context of GLP-1 receptor agonist therapy and the use of CDP-based AI systems. Results: Increased variability in metabolic parameters consistently predicts adverse outcomes, such as cardiovascular events, mortality, and disease progression. Heart rate variability shows a U-shaped association with outcomes, while blood pressure, lipid, and glucose variability demonstrate predominantly linear relationships with risk. Body weight variability is associated with cognitive decline and an increased risk of cardiovascular complications. Additionally, genetic polymorphisms and baseline metabolic profiles can influence responses to GLP-1 receptor agonists. CDP-based AI platforms have successfully enhanced therapeutic outcomes in conditions like heart failure, cancer, and multiple sclerosis by leveraging biological variability rather than suppressing it. Summary: The identification of metabolic variability signatures offers valuable predictive insights for personalizing therapy with GLP-1 receptor agonists. Artificial intelligence systems based on clinical data patterns that include these variabilities represent a significant shift toward dynamic and individualized treatment approaches. This can enhance therapeutic efficacy and help counteract drug resistance in chronic metabolic disorders, potentially improving the response to GLP-1-based therapies. Full article

In the context of multi-organ involvement in sepsis, cardiac toxicity is manifested as sepsis-induced cardiomyopathy (SICM). To date, no unified SICM definition exists, though a left ventricular ejection fraction ≤ 50% and/or an absolute drop ≥ 10% from baseline are the most widely accepted components. Several molecular pathways have been associated with SICM, including (i) pro-inflammatory mediator-induced cardiac depression; (ii) sarcolemmal membrane dysfunction; (iii) autonomic nervous system (ANS) imbalance; (iv) blunted cardiovascular response to catecholamines; (v) dysfunctional intracellular calcium handling; (vi) mitochondrial dysfunction; (vii) metabolic reprogramming; and (viii) disturbed endothelial and microcirculatory function. Atrial and ventricular arrhythmias—particularly atrial fibrillation—commonly complicate disease management and are associated with adverse outcomes. Key mechanisms outlining sepsis-induced arrhythmogenesis are (i) inflammation; (ii) electrolyte imbalances; (iii) myocardial ischemia; (iv) QT prolongation/dispersion; (v) adrenergic overactivation; (vi) calcium mishandling; and (vii) fever-induced arrhythmogenesis in Brugada. Established therapeutic approaches include prompt treatment with antibiotics, hemodynamic optimization, and/or selective use of beta-blockers. Furthermore, several molecules are currently being investigated targeting numerous pathways activated in sepsis. Vitamin C, ginsenoside Rc, Schistosoma Japonicum cystatin, and gasmerdin-D inhibitor Y2 exert anti-inflammatory actions, while melatonin and α-ketoglutarate regulate mitochondrial homeostasis. Triiodothyronine targets microcirculatory optimization and regulates protective pathways against stress-related cell death. Engineered exosomes may facilitate targeted drug delivery, inflammatory response modulation, and activation of pathways related to cell survival, while sodium octanoate exhibits anti-inflammatory actions coupled with improved energy metabolism. Finally, gene-regulating therapies aiming at inflammatory response optimization have also been proposed and are currently under development. Future research should aim to standardize the SICM definition, translate emerging therapeutics into clinical practice, identify novel molecular targets, and implement personalized treatment strategies for SICM. Full article

Background: Despite percutaneous coronary intervention (PCI) for revascularization, patients with acute coronary syndrome (ACS) still face residual risks of adverse outcomes. Insulin resistance (IR) and renal impairment are independent predictors of poor prognosis in these patients, yet their interaction and underlying mechanisms linked to post-PCI outcomes remain incompletely elucidated. Methods: A retrospective cohort study was conducted involving patients with ACS who underwent PCI at the Third People’s Hospital of Chengdu from July 2018 to December 2020. Insulin resistance (IR) was quantified using the triglyceride–glucose (TyG) index, and renal function was evaluated via the estimated glomerular filtration rate (eGFR). The primary endpoint was major adverse cardiovascular events (MACEs), a composite of all-cause death, non-fatal myocardial infarction, non-fatal stroke, and unplanned revascularization. Multivariable Cox proportional hazards regression and mediation analyses were applied to explore the associations of TyG index and eGFR with patient prognosis, and to quantify the mediating effect of eGFR on the relationship between TyG index and prognosis. Results: A total of 1340 patients with ACS were included in the final analysis. Over a median follow-up duration of 31.02 (interquartile range [IQR]: 27.34–35.03) months, 124 patients (9.25%) experienced MACEs. After adjusting for potential confounders, both the TyG index and eGFR were identified as significant independent predictors of MACEs in the overall population and across predefined subgroups. Specifically, each one-unit increase in the TyG index was associated with a 73.8% higher risk of MACEs (HR 1.738; 95% CI 1.273–2.372), whereas each ten-unit decrease in eGFR was linked to a 12.7% increased MACEs risk (HR 1.127; 95% CI 1.032–1.232). Importantly, after further adjustment for confounders, eGFR significantly mediated 9.63% of the total effect of the TyG index on MACEs risk. Conclusions: Renal impairment partially mediates the association between IR and adverse cardiovascular outcomes in ACS patients undergoing PCI. This finding underscores the clinical importance of the metabolic–cardiorenal axis in this population, suggesting that a comprehensive assessment targeting both IR and renal function-related pathways may enhance risk-stratification accuracy and optimize therapeutic strategies for ACS patients. Full article

Diabetes is a major global health problem, with a rapidly increasing prevalence and long-term health complications in both developed and developing countries. If not diagnosed early, it can lead to cardiovascular diseases, kidney failure, vision loss, and nervous system disorders. This study aimed to classify individuals with diabetes or healthy individuals using e-nose sensor data obtained from breath samples taken from 1000 individuals. Six sensor features and one class feature were used in the analysis. Machine learning methods included Artificial Neural Networks (ANN), Decision Trees (DT), Gradient Boosting (GB), Naive Bayes (NB), and AdaBoost (AB). ANOVA and Information Gain analyses were conducted to determine the effectiveness of the sensor data, and the TGS2610 and TGS2611 sensors were found to be critical for classification. Principal Component Analysis (PCA) reduced data size and saved processing time. Experimental results showed that the ANN model provided the most successful classification, with 100% accuracy. AB and GB achieved 99.8% accuracy, while NB achieved 97.6% accuracy. Dimensionality reduction using PCA optimized training and testing times without loss of accuracy. The study presents a data-driven approach to e-nose-based diabetes detection, demonstrates the comparative performance of the models, and highlights the importance of sensor selection and data size optimization. Full article

Background and Objectives: Cardiac injury caused by cancer therapy can be detected early using high-sensitivity cardiac troponins (hs-cTns), and this is crucial for preventing irreversible consequences. Clinically relevant issues regarding hs-cTns in oncologic settings—such as reliable cut-off values, the optimal assessment timeframe, factors influencing their levels, and their prognostic ability in relation to functional echocardiographic parameters—require further investigation. In this study, we aimed to examine the determinants of hs-cTnT variations during cancer therapy and the relationship between the biomarker and functional conventional echocardiographic parameters. Materials and Methods: We prospectively evaluated adult patients scheduled for chemotherapy for either breast or gastrointestinal cancers, excluding those with pulmonary and cardiac disorders. We enrolled 40 patients who underwent a minimum of one cycle of potentially cardiotoxic regimens containing at least one of the following agents: anthracyclines, cyclophosphamide, taxanes, 5-fluorouracil, platinum compounds, trastuzumab, or bevacizumab. We observed two-dimensional and tissue Doppler echocardiographic parameters and hs-cTnT levels for a median of 360 days (IQR 162, 478) following the start of chemotherapy. Results: The generalised estimating equation (GEE) analysis revealed significant elevations in hs-cTnT levels at three months (β = 1.2; p = 0.005) and six months (β = 2.3; p = 0.02) from baseline, influenced by anthracycline treatment (p = 0.009), renal function (p = 0.003), and increased cardiotoxicity risk (high: p = 0.013; medium: p < 0.001). Elevated hs-cTnT levels independently predicted the deterioration of the LV longitudinal myocardial function, measured by the systolic tissue velocities, according to the GEE analysis. The receiver operating characteristic curve-derived hs-cTnT thresholds—of 8.23 ng/L and 8.08 ng/L—had a high negative predictive value for identifying Average and Lateral LVS′ decreases, respectively. Conclusions: Our research supports the use of baseline and continuing hs-cTnT testing in cancer patients, showing the dependence of the biomarker on renal function, cardiovascular toxicity risk level, and anthracycline treatment. The hs-cTnT cut-off value of approximately 8 ng/L may suggest a low probability of longitudinal myocardial function impairment and this observation needs further validation in larger cohorts. Full article

The reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) is a primary electron donor for both antioxidant enzymes, such as glutathione reductase, and pro-oxidant enzymes, such as NADPH oxidases that produce reactive oxygen species (ROS) and nitric oxide synthases that generate nitric oxide which act as signaling molecules. Monitoring NADPH levels, NADPH/NADP⁺ ratio, and especially distinguishing from NADH, provides vital information about cellular redox status, energy generation, survival, lineage specification, and death pathway selection. NADPH detection is key to understanding metabolic reprogramming in cancer, aging, and cardiovascular, hormonal, neurodegenerative, and autoimmune diseases. Liquid chromatography combined with mass spectrometry (LC-MS) is crucial for NADPH detection in redox signaling because it offers the high sensitivity, specificity, and comprehensive profiling needed to quantify this vital but labile redox cofactor in complex biological samples. Using hepatoma cell lines, liver tissues, and primary hepatocytes from mice lacking transaldolase or nicotinamide nucleotide transhydrogenase, or having lupus, this study demonstrates that accurate measurement of NADPH depends on its preservation in reduced form which can be optimally achieved by extraction of metabolites in alkaline solution, such as 0.1 M potassium hydroxide (KOH) in comparison to 80% methanol (MeOH) alone or 40:40:20 methanol/acetonitrile/formic acid solution. While KOH extraction coupled with hydrophilic interaction liquid chromatography (HILIC) and mass spectrometry most reliably detects NADPH, NADP, NADH, NAD, polyamines, and polyols, MeOH extraction is best suited for detection of glutathione and overall discrimination between complex metabolite extracts. This study therefore supports performing parallel KOH and MeOH extractions to enable comprehensive metabolomic analysis of redox signaling. Full article

Patent foramen ovale (PFO) is implicated in cryptogenic stroke and other clinical syndromes, with transcatheter closure demonstrating superiority over medical therapy in selected patients. Most closure devices are composed of nitinol, a nickel–titanium alloy, raising concerns in individuals with nickel hypersensitivity, one of the most prevalent contact allergies worldwide. Although typically manifesting as localized dermatitis, nickel allergy has been associated with systemic reactions after device implantation, including chest pain, palpitations, migraines, dyspnea, and cutaneous eruptions. Recent evidence indicates that nickel-sensitive patients experience a significantly higher incidence of post-procedural device-related symptoms. Nevertheless, severe reactions remain rare, and the benefits of PFO closure generally outweigh the risks. The predictive value of pre-implantation patch testing remains uncertain, and the lack of nickel-free alternatives constrains device selection. Management strategies are empirical, relying on symptomatic treatment with corticosteroids, antihistamines, or device explantation in refractory cases. Future research should focus on elucidating the pathophysiology of nickel-induced hypersensitivity in cardiovascular implants, improving diagnostic algorithms, and developing biocompatible, nickel-free devices. A multidisciplinary approach involving cardiologists, dermatologists, and allergists is essential to optimize outcomes in this complex subset of patients. Full article

Arsenic contamination in water remains a critical global health challenge, affecting millions and causing severe diseases including cancer, skin lesions, and cardiovascular disorders. Adsorption using metal–organic frameworks (MOFs), particularly zirconium-based UiO-66 and its derivatives, offers a promising and sustainable approach for arsenic remediation due to their high surface area, tunable porosity, and strong chemical stability. Functionalized UiO-66 variants (e.g., –NH₂, –SO₃H, –COOH, –SH), metal-doped, or composite forms such as Fe₃O₄@UiO-66 exhibit arsenic adsorption capacities between 20 and 150 mg g⁻¹, depending on synthesis and surface chemistry. Optimal adsorption occurs within pH 4–8, while high salinity or competing anions reduce performance by 15–40%. UiO-66 materials demonstrate excellent regeneration efficiency (70–95%) after multiple cycles, with limited metal leaching (1–3%). Advances through ligand functionalization, modulator-assisted synthesis, and composite integration have significantly improved adsorption capacity, selectivity, and reusability. However, challenges persist in achieving green, water-based synthesis, maintaining long-term stability under realistic water chemistries, and enabling scalable production. Future work should focus on eco-friendly fabrication, defect engineering, and mechanistic optimization to fully harness UiO-66’s potential as a high-performance and sustainable adsorbent for arsenic-contaminated water treatment. Full article

Breast cancer (BC) is the most common malignancy in women worldwide, with incidence projected to rise, particularly among younger patients. In premenopausal women with hormone receptor-positive disease, ovarian suppression is an established component of systemic therapy, most often achieved pharmacologically with gonadotropin-releasing hormone agonists (GnRHas). Bilateral salpingo-oophorectomy (BSO) represents a surgical alternative that ensures definitive suppression, eliminates compliance issues, and is more cost-effective in the long term. Despite these advantages, BSO induces irreversible menopause, associated with vasomotor symptoms, cardiovascular morbidity, bone loss, cognitive decline, and reduced quality of life. Evidence suggests that BSO is most appropriate in selected cases, including women unable to tolerate or adhere to medical suppression, those with inadequate estradiol suppression, patients approaching natural menopause, individuals with metastatic hormone receptor-positive disease, and carriers of BRCA1 mutations, especially with triple-negative tumors. Conversely, data on its benefit in BRCA2 carriers remain limited. Overall, BSO provides oncologic outcomes comparable to medical suppression but at the cost of permanent systemic effects. The decision between surgical and medical ovarian suppression should be individualized, balancing oncologic efficacy, comorbidities, genetic background, and patient preference. Further studies are needed to define the optimal duration of medical suppression and clarify the role of BSO in hereditary breast cancer. Full article

Tertiary hyperparathyroidism (THPT) arises in patients with chronic kidney disease (CKD) as a consequence of prolonged secondary hyperparathyroidism and is marked by autonomous parathyroid hormone (PTH) secretion. In some cases, parathyroid hyperplasia persists even after successful renal transplantation, resulting in sustained PTH elevation and hypercalcaemia. These alterations contribute to bone loss, vascular calcification, and increased cardiovascular risk. Management includes medical therapy with calcimimetics or vitamin D analogues and surgical intervention via parathyroidectomy. However, optimal timing and treatment strategy remain uncertain. This review examines the pathophysiology, clinical manifestations, and current management paradigms of THPT, with an emphasis on areas that require further research and consensus. Full article

Omega-3 and omega-6 fatty acids play essential roles in human health, being widely used in the prevention and treatment of various conditions, such as cardiovascular diseases, inflammation, and metabolic disorders. However, their oral administration faces significant challenges, including low solubility, rapid oxidation, and low bioavailability, which limit their therapeutic efficacy. This article explores recent advances in oral drug delivery systems designed for polyunsaturated fatty acids, highlighting how innovative technologies, such as nanoemulsions, liposomes, microencapsulation, and solid lipid nanoparticles (SLNs/NLCs), can improve their stability, absorption and clinical performance. In addition, the main natural sources of these compounds, as well as their extraction and purification methods, and the challenges related to their absorption and metabolism are discussed. This narrative review was based mainly on a comprehensive search of peer-reviewed literature published between 2015 and 2025 in PubMed, Scopus, and Web of Science. The therapeutic benefits of these emerging approaches are analyzed by comparing conventional methods with modern delivery strategies to optimize the use of omega-3 and omega-6 in the body. Finally, the article outlines future perspectives and regulatory challenges associated with these technologies, highlighting their potential to revolutionize the administration of essential fatty acids and broaden their applications in medicine and nutrition. Full article

Aim: With the intensification of population aging, the public health challenges posed by multimorbidity have become increasingly severe. This study employs bibliometric analysis to elucidate research hotspots and trends in the field of multimorbidity against the backdrop of global aging. The immediate aim is to systematically map the intellectual landscape and evolving patterns in multimorbidity research. The ultimate long-term aim is to provide a scientific basis for optimizing chronic disease prevention systems and guiding future research directions. Methods: The study adopted the descriptive research method and employed a bibliometric approach, analyzing 8129 publications related to multimorbidity from the Web of Science Core Collection. Using CiteSpace, we constructed and visualized several knowledge structures, including collaboration networks, keyword co-occurrence networks, burst detection maps, and co-citation networks within the multimorbidity research domain. Results: The analysis included 8129 articles from 2004 to 2024, published across 1042 journals, with contributions from 740 countries/regions, 33,931 institutions, and 40,788 authors. The five most frequently occurring keywords were prevalence, health, older adult, mortality, and risk. The top five contributing countries globally were the United States, the United Kingdom, Germany, China, and Spain. Five pivotal research trajectories delineate the intellectual architecture of this field: ① Evolution of Disease Cluster Management: Initial investigations (2013–2014) prioritized disease cluster coordination within general practice settings, particularly cardiovascular comorbidity management through primary care protocols and self-management strategies. ② Paradigm Shifts in Health Impact Assessment: Multimorbidity outcome research demonstrated sequential transitions—from physical disability evaluation (2013) to mental health consequences like depression (2016), culminating in current emphasis on holistic health indicators including frailty syndromes (2015–2019). ③ Expansion of Risk Factor Exploration: Analytical frameworks evolved from singular physical activity metrics (2014) toward comprehensive lifestyle-related determinants encompassing behavioral and environmental dimensions (2021). ④ Emergence of Polypharmacy Scholarship: Medication optimization studies emerged as a distinct research stream since 2016, addressing therapeutic complexities in multimorbidity management. ⑤ Frontier Investigations: Cutting-edge directions (2019–2021) feature cardiometabolic multimorbidity patterns and their dementia correlations, signaling novel interdisciplinary interfaces. Conclusions: The prevalence of multimorbidity is on the rise globally, particularly in older populations. Therefore, it is essential to prioritize the prevention of cardiometabolic conditions in older adults and to provide them with appropriate and effective health services, including disease risk monitoring and community-based chronic disease care. Full article