Search Results (616)

Sodium–glucose co-transporter-2 inhibitors (SGLT2is) and GLP-1 receptor agonists (GLP-1 RAs) are now established as cornerstone therapies for patients with type 2 diabetes mellitus (T2DM), given their cardiovascular and renal protective properties. However, their use in patients with peripheral artery disease (PAD) remains controversial due to concerns raised in early trials about potential increases in lower limb complications, particularly amputations. This narrative review examines current evidence on the association between SGLT2is and GLP-1 RAs in PAD-related outcomes, including limb events, amputation risk, and cardiovascular and renal endpoints. Drawing from randomized controlled trials, real-world cohort studies, and systematic reviews, we provide an integrated perspective on the safety and utility of SGLT2is and GLP-1 RAs in individuals with PAD, highlight patient selection considerations, and identify areas for future investigation. Full article

Dibutyl phthalate (DBP) is used as a plasticizer to enhance flexibility in several household products, cosmetics, and food-contact materials. Due to its harmful effects, DBP is restricted or banned in children’s products and food items, particularly in Europe. Due to its endocrine disruptor properties and considering its ability to cross the placental barrier, it is imperative to study DBP’s vascular effects in pregnancy, given the vulnerability of this period. Thus, this study investigated the potential effects of DBP on the cardiovascular system using umbilical arteries from healthy pregnant women. Specifically, the impact of DBP on the vascular reactivity after both rapid and 24 h DBP exposure was analyzed, as well as the contractility and the cell viability of vascular smooth muscle cells (VSMC). DBP did not exhibit overt cytotoxic effects on VSMCs, possibly due to its adsorption onto polystyrene surfaces, potentially limiting bioavailability. Interestingly, DBP induced vasorelaxation in a concentration-dependent manner. Although mechanistic insights remain to be fully elucidated, the results suggest the involvement of pathways associated with nitric oxide signaling and calcium handling. Overall, DBP exposure appears to modulate arterial tone regulation, which may have implications for vascular function during pregnancy. Full article

Central nervous system (CNS) disorders present significant therapeutic challenges due to the limited regenerative capacity of neural tissues, resulting in long-term disability for many patients. Consequently, the development of novel therapeutic strategies is urgently warranted. Stem cell therapies show considerable potential for mitigating brain damage and restoring neural connectivity, owing to their multifaceted properties, including anti-apoptotic, anti-inflammatory, neurogenic, and vasculogenic effects. Recent research has also identified exosomes—small vesicles enclosed by a lipid bilayer, secreted by stem cells—as a key mechanism underlying the therapeutic effects of stem cell therapies, and given their enhanced stability and superior blood–brain barrier permeability compared to the stem cells themselves, exosomes have emerged as a promising alternative treatment for CNS disorders. A key challenge in the application of both stem cell and exosome-based therapies for CNS diseases is the method of delivery. Currently, several routes are being investigated, including intracerebral, intrathecal, intravenous, intranasal, and intra-arterial administration. Intracerebral injection can deliver a substantial quantity of stem cells directly to the brain, but it carries the potential risk of inducing additional brain injury. Conversely, intravenous transplantation is minimally invasive but results in limited delivery of cells and exosomes to the brain, which may compromise the therapeutic efficacy. With advancements in catheter technology, intra-arterial administration of stem cells and exosomes has garnered increasing attention as a promising delivery strategy. This approach offers the advantage of delivering a significant number of stem cells and exosomes to the brain while minimizing the risk of additional brain damage. However, the investigation into the therapeutic potential of intra-arterial transplantation for CNS injury is still in its early stages. In this comprehensive review, we aim to summarize both basic and clinical research exploring the intra-arterial administration of stem cells and exosomes for the treatment of CNS diseases. Additionally, we will elucidate the underlying therapeutic mechanisms and provide insights into the future potential of this approach. Full article

Coronary artery disease (CAD) constitutes a major contributor to morbidity, mortality and healthcare burden worldwide. Recent innovations in imaging modalities, pharmaceuticals and interventional techniques have revolutionized diagnostic and treatment options, necessitating the reevaluation of established drug protocols or the consideration of newer alternatives. The utilization of beta blockers (BBs) in the setting of acute myocardial infarction (AMI), shifting from the pre-reperfusion to the thrombolytic and finally the primary percutaneous coronary intervention (pPCI) era, has become increasingly more selective and contentious. Nonetheless, the extent of myocardial necrosis remains a key predictor of outcomes in this patient population, with large trials establishing the beneficial use of beta blockers. Computed tomography coronary angiography (CTCA) has emerged as a highly effective diagnostic tool for delineating the coronary anatomy and atheromatous plaque characteristics, with the added capability of MESH-3D model generation. Induction and preservation of a low heart rate (HR), regardless of the underlying sequence, is of critical importance for high-quality results. Landiolol is an intravenous beta blocker with an ultra-short duration of action (t1/2 = 4 min) and remarkable β1-receptor specificity (β1/β2 = 255) and pharmacokinetics that support its potential for systematic integration into clinical practice. It has been increasingly recognized for its importance in both acute (primarily studied in STEMI and, to a lesser extent, NSTEMI pPCI) and chronic (mainly studied in elective PCI) CAD settings. Given the limited literature focusing specifically on landiolol, the aim of this narrative review is to examine its pharmacological properties and evaluate its current and future role in enhancing both diagnostic imaging quality and therapeutic outcomes in patients with CAD. Full article

HMG-CoA reductase inhibitors, statins, are extensively used to treat hyperlipidemia, coronary artery disease, and other atherosclerotic disorders. However, one of the common side effects of statin therapy is a mild elevation in liver aminotransferases, observed in less than 3% of patients. Atorvastatin and simvastatin, in particular, are most frequently associated with statin-induced liver injury, leading to treatment discontinuation. Recent research has highlighted the antioxidant and anti-inflammatory properties of glucagon-like peptide-1 receptor (GLP-1R) activation in protecting against liver injury. Nonetheless, the potential protective effects of liraglutide (LIRA), a GLP-1R agonist, against atorvastatin (ATO)-induced liver dysfunction have not been fully elucidated. In this context, the present study aimed to investigate the protective role of LIRA in mitigating ATO-induced liver injury in rats, offering new insights into managing statin-associated hepatotoxicity. Indeed, LIRA treatment improved liver function enzymes and attenuated histopathological alterations. LIRA treatment enhanced antioxidant defenses by increasing Nrf2 content and superoxide dismutase (SOD) activity, while reducing NADPH oxidase. Additionally, LIRA suppressed inflammation by downregulating the HMGB1/TLR-4/RAGE axis and inhibiting the protein expression of pY323-MAPK p38 and pS635-NFκB p65 content resulting in decreased proinflammatory cytokines (TNF-α and IL-1β). Furthermore, LIRA upregulated GLP-1R gene expression and promoted autophagic influx via the activation of the pS473-Akt/pS486-AMPK/pS758-ULK1/Beclin-1 signaling cascade, along with inhibiting apoptosis by reducing caspase-3 content. In conclusion, LIRA attenuated ATO-induced oxidative stress and inflammation via activation of the Nrf-2/SOD cascade and inhibition of the HMGB1/TLR-4/RAGE /MAPK p38/NFκB p65 axis. In parallel, LIRA stimulated autophagy via the AMPK/ULK1/Beclin-1 axis and suppressed apoptosis, thus restoring the balance between autophagy and apoptosis. Full article

Arterial aneurysms are vascular conditions associated with life-threatening consequences in patients, such as dissection and rupture. Understanding their genetic basis is an evolving field, driven by the robust reporting of genetic variants associated with aneurysms in patients. In this study, we present clinical and genetic data from nine unrelated subjects with arterial aneurysms who were identified to harbor rare variants in the TNXB gene, mainly affecting fibronectin type III (FNIII) domains. The cohort included three female and six male subjects with a mean age of 53.5 years (SD = 14.4). The most frequently affected vascular territory was the thoracic ascending aorta (n = 7). A range of pathogenic impacts was predicted via multiple in silico tools that analyze evolutionary conservation and biochemical properties. Computational protein structure modeling with AlphaFold 3 predicted domain-specific alterations across multiple FNIII regions for four unique missense variants and one in-frame deletion, and premature protein truncation resulting from two frameshift variants. To our knowledge, this study is one of the first and largest to associate TNXB variants with arterial aneurysmal disease. Our findings demonstrate the potential of computational genomics and structural modeling to advance the understanding of extracellular matrix gene alterations in aneurysm pathogenesis. Full article

Background: Over the past decade, few echocardiographic investigations have assessed myocardial strain parameters in women with a history of hypertensive disorders of pregnancy (HDP), and their findings have been inconsistent. Moreover, no study has comprehensively evaluated deformation indices of all biventricular and biatrial chambers in women post-HDP. This study aimed to examine the structural and functional myocardial properties of all cardiac chambers in a cohort of women with prior HDP at six years after delivery. Methods: We analyzed a consecutive cohort of women with previous HDP and compared them with a control group of normotensive healthy women matched for age and body mass index (BMI). Both groups underwent standard transthoracic echocardiography (TTE) supplemented by a detailed speckle tracking echocardiography (STE) evaluation of biventricular and biatrial myocardial deformation, along with carotid ultrasound, at six years postpartum. The primary endpoint was subclinical myocardial dysfunction, defined by impaired left ventricular global longitudinal strain (LV-GLS < 20%), while the secondary endpoint was early carotid atherosclerosis, defined by common carotid artery intima-media thickness (CCA-IMT) ≥ 0.7 mm. Results: The study included 31 women with previous HDP (mean age 42.3 ± 5.9 years) and 30 matched controls without HDP history (mean age 40.8 ± 5.0 years). The average follow-up duration was 6.1 ± 1.3 years postpartum. Despite preserved and comparable systolic function on conventional TTE, most myocardial strain and strain rate measures in both ventricles and atria were significantly reduced in the HDP group compared to controls. Subclinical myocardial dysfunction was detected in 58.1% of women with prior HDP, and 67.7% exhibited increased CCA-IMT (≥0.7 mm). A history of pre-eclampsia (PE) was independently associated with subclinical myocardial dysfunction (HR 4.01, 95% CI 1.05–15.3, p = 0.03). Both third-trimester BMI (HR 1.21, 95% CI 1.07–1.38, p = 0.003) and PE (HR 6.38, 95% CI 1.50–27.2, p = 0.01) independently predicted early carotid atherosclerosis. Notably, a third-trimester BMI above 27 kg/m² showed optimal sensitivity and specificity for identifying the secondary outcome. Conclusions: A history of PE is independently associated with a higher risk of subclinical myocardial dysfunction and early carotid atherosclerosis at six years postpartum. Full article

Mesenchymal stem cell (MSC) transplantation has emerged as a potential therapeutic strategy for systemic sclerosis (SSc), a rare autoimmune disease characterized by inflammation, fibrosis, and vasculopathy. Recent evidence suggests that the therapeutic benefits of MSCs do not depend directly on their ability to proliferate but rather on their capacity to release extracellular nanovesicles known as exosomes (MSC-Exos). MSC-Exos are rich in bioactive molecules such as microRNAs, which can modulate gene expression and trigger significant biological responses, playing a central role in modulating immune responses, inhibiting fibrotic pathways and promoting tissue repair and angiogenesis. Preclinical studies have demonstrated that MSC-Exos can attenuate fibrosis, modulate macrophage polarization, suppress autoreactive lymphocyte activity, and even reverse pulmonary arterial hypertension in animal models of SSc. Compared to cell-based therapies, MSC-Exos offer several advantages, including lower immunogenicity and better safety profile. This review provides an overview of the immunomodulatory, antifibrotic, and angiogenic properties of MSC-Exos and explores their potential as novel cell-free therapy for SSc. Full article

Endometrial stromal cells (EnSCs) undergo decidualization in response to progesterone. Decidualization facilitates spiral artery remodeling, immune tolerance in the endometrium, and fetal cell invasion and placentation—all essential for successful embryo implantation. Therefore, we aimed to investigate whether ergothioneine (EGT) plays a role in reproduction, particularly in decidualization and implantation. In this study, we found that solute carrier family 22 member 4 (SLC22A4), a specific transporter of EGT—a functional food ingredient with strong anti-aging properties—is upregulated in decidualized EnSCs. The effects of EGT were examined using uterine tissues from patients, primary cultured EnSCs, EnSC cell lines, and co-cultures with a fetal cell line. We observed a significant increase in SLC22A4 expression in secretory-phase human uterine tissue, decidualized EnSCs, and EnSC cell lines. We also found that EGT regulates insulin-like growth factor binding protein 1 expression, which promotes placentation. In co-cultures of EnSC and fetal cell lines, EGT upregulated ectonucleoside triphosphate diphosphohydrolase 1 and major histocompatibility complex, class I, G expression in fetal cell lines—both critical for placentation. These findings suggest that EGT is crucial to regulating decidualization and its markers, particularly insulin-like growth factor-binding protein 1, which contributes to placentation. Full article

The awareness of the importance of monitoring human vital signs has increased recently due to the outbreak of the COVID-19 pandemic. Non-invasive heart rate monitoring devices, in particular, have become some of the most popular tools for health monitoring. However, heart rate data alone are not enough to reflect the health of one’s cardiovascular function or arterial health. This growing interest has spurred research into developing high-fidelity non-invasive pulse waveform sensors. These sensors can provide valuable information such as data on blood pressure, arterial stiffness, and vascular aging from the pulse waveform. Among these sensors, optical fiber sensors (OFSs) stand out due to their remarkable properties, including resistance to electromagnetic interference, capability in monitoring multiple vital signals simultaneously, and biocompatibility. This paper reviews the latest advancements in using OFSs to measure human vital signs, with a focus on pulse waveform analysis. The various working mechanisms of OFSs and their performances in measuring the pulse waveform are discussed. In addition, we also address the challenges faced by OFSs in pulse waveform monitoring and explore the opportunities for future development. This technology shows great potential for both clinical and personal non-invasive pulse waveform monitoring applications. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) has been consistently linked to increased risk of cardiovascular disease (CVD). HDL lipoproteins may serve as a possible link in this association through their hepatic synthesis and atheroprotective properties. Serum samples were collected from 51 MASLD patients (diagnosed by abdominal ultrasound), 40 with coronary artery disease, and 50 healthy controls. HDL lipid profiles were investigated by proton nuclear magnetic resonance (¹H NMR) spectroscopy. Patients with MASLD exhibit an increased percentage of lysophosphatidylcholine and sphingolipid content, mainly due to increased ceramides, and a reduced percentage of phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol compared to controls. The % content of total and individual polyunsaturated fatty acids including linoleic, docosahexaenoic, eicosapentaenoic, and arachidonic acid was found to be reduced in patients with MASLD, while saturated fatty acid content was increased compared to the control group. These alterations in fatty acid composition were observed also in CAD patients compared to controls but were more pronounced in CAD patients. Compared to CAD patients, those with MASLD showed an increased content of sphingolipids, ceramides, and glycerolipids and a reduced content of phosphatidylinositol. Changes observed in the lipid composition of HDL lipoproteins in MASLD patients may impair the protective properties of HDL particles, contributing to increased CVD risk. Full article

Introduction: In the past decade, chimeric antigen receptor T-cell therapy (CAR-T) has revolutionized the treatment of relapsed refractory multiple myeloma (RRMM) and lymphoma, but it is associated with significant cardiovascular adverse effects. We aim to analyze the incidence, patterns, and outcomes of cardiac events in RRMM and lymphoma patients undergoing CAR-T therapy utilizing the FDA Adverse Event Reporting System (FAERS) database, paving the way for future research and being more vigilant in treating high-risk populations. Methods: We conducted a retrospective post-marketing pharmacovigilance inquiry using the FDA Adverse Event Reporting System (FAERS) database and the Medical Dictionary for Regulatory Activities (MEDRA). We examined the adverse effects associated with CAR-T and TCE since their FDA approval in US and non-US populations (accessed 5 January 2024), and we analyzed the incidence of cardiac events related to six CAR-T products: Idecabtagene vicleucel, Ciltacabtagene autoleucel, Axicabtagene ciloleucel, Tisagenlecleucel, Lisocabtagene maraleucel, and Brexucabtagene autoleucel since FDA approval. Cardiotoxicities were assessed, including coronary artery disease (CAD), myocardial infarction (MI), arrhythmia, heart failure, and hypotension. Results: Out of 12,949 adverse events, we identified 675 (5.2%) cardiac events irrespective of severity. Almost 440 (65%) cardiac events were associated with cytokine release syndrome (CRS). The most common cardiotoxic event was atrial fibrillation (122), followed by the development of heart failure (113), ventricular arrhythmia (108), hypotension (87), and bradyarrhythmia (41). The mortality rate was highest among Brexucabtagene autoleucel recipients (n = 26, 2.3%), followed by Tisagenlecleucel (n = 71, 2.1%) and Lisocabtagene maraleucel (n = 10, 2.1%). Conclusions: CAR-T therapy can result in fatal adverse events due to its cardiotoxic properties. Timely monitoring, such as screening echocardiography and electrocardiograms, can help identify the at-risk population and allow for early intervention—particularly in patients with high baseline cardiovascular risk or previous exposure to cardiotoxic agents—thereby improving outcomes by enabling risk stratification and supportive management. Full article

Historical districts face pressing disaster preparedness challenges due to their special spatial properties—risks compounded by static approaches that overlook dynamic fire–pedestrian interactions. This study employs an agent-based model (ABM) for fire simulations and AnyLogic pedestrian dynamics to address these gaps in Dukezong Ancient Town, Yunnan Province, China, considering diverse ignition points, seasonal temperatures, and wind conditions. Dynamic simulations of 16 scenarios reveal critical spatial impacts: within 30 min, ≥28% of streets became impassable, with central ignition points causing faster obstructions. Static models underestimate evacuation durations by up to 135%, neglecting early stage congestions and detours caused by high-temperature zones. Congestions are concentrated along main east–west arterial roads, worsening with longer warning distances. A mismatch between evacuation flows and shelter capacity is found. Thus, a three-stage interaction simplification is derived: localized detours (0–10 min), congestion-driven delays on critical roads (11–30 min), and prolonged structural damage afterward. This study challenges static approaches by highlighting the “fast alert-fast congestion” paradox, where rapid alerts overwhelm narrow pathways. Solutions prioritize multi-route guidance systems, optimized shelter access points, and real-time information dissemination to reduce bottlenecks without costly infrastructure changes. This study advances disaster modeling by bridging disaster development with dynamic evacuation, offering a replicable framework for similar environments. Full article

The evolution of percutaneous coronary intervention (PCI) has led to significant advances in drug-coated balloon (DCB) technology, offering a stent-free alternative for treating coronary artery disease. While paclitaxel-coated balloons (PCBs) have been the standard, sirolimus-coated balloons (SCBs) are emerging as a viable alternative with distinct pharmacokinetic and clinical benefits. This review explores the mechanisms of action of paclitaxel and sirolimus, their impact on different plaque morphologies, and the clinical implications of DCB selection. Paclitaxel facilitates positive vascular remodeling and is particularly effective in fibrotic and lipid-rich plaques, but its poor penetration in calcified lesions remains a limitation. Sirolimus, with its homogeneous tissue distribution and anti-inflammatory properties, is better suited for unstable, lipid-rich, and inflammatory plaques, where it promotes plaque stabilization. Recent randomized trials and meta-analyses have compared SCBs vs. PCBs in both de novo lesions and in-stent restenosis, showing non-inferior outcomes. Additionally, DCBs demonstrate comparable efficacy to DES in small vessel disease, reducing the need for permanent metallic scaffolds. This review summarizes the current evidence on DCB selection based on plaque characteristics and highlights areas for further investigation in personalized PCI strategies. Given the narrative review design, the authors conducted a comprehensive literature search using databases such as PubMed and MEDLINE. Keywords included “drug-coated balloon”, “paclitaxel-coated balloon”, “sirolimus-coated balloon”, “in-stent restenosis”, and “plaque morphology”. Studies were selected based on relevance, including randomized controlled trials, registries, and meta-analyses. No formal inclusion/exclusion criteria or systematic screening were applied due to the nature of narrative synthesis. Full article

Introduction: Intermittent claudication, an early symptom of peripheral artery disease, can be treated by cilostazol to alleviate symptoms and improve walking distance. Our previous investigation focused on cilostazol-induced alterations in the thermodynamic properties of plasma, utilizing differential scanning calorimetry (DSC) as a potential monitoring tool. The current proof-of-concept study aimed to enhance the interpretation of DSC data through deconvolution techniques, specifically examining protein transitions within the plasma proteome during cilostazol therapy. Results: Notable differences in thermal unfolding profiles were found between cilostazol-treated patients and healthy controls. The fibrinogen-associated transition exhibited a downward shift in denaturation temperature and decreased enthalpy by the third month. The albumin-related transition shifted to higher temperatures, accompanied by lower enthalpy. Transitions associated with globulins showed changes in thermal stability, while the transferrin-related peak demonstrated increased structural rigidity in treated patients compared to controls. Discussion: These observations suggest that cilostazol induces systemic changes in the thermodynamic behavior of plasma proteins. DSC, when combined with deconvolution methods, presents a promising approach for detecting subtle, therapy-related alterations in plasma protein stability. Materials and methods: Ten patients (median age: 58.6 years) received 100 milligrams of cilostazol twice daily. Blood samples were collected at the baseline and after 2 weeks, 1 month, 2 months, and 3 months of therapy. Walking distances were also assessed. The DSC curves were retrieved from the thermal analysis investigated by deconvolution mathematical methods. Conclusions: Although the exact functional consequences remain unclear, the observed biophysical changes may reflect broader molecular adaptations involving protein–protein interactions, post-translational modifications, or acute phase response elements. Full article