Search Results (3,480)

The cardiovascular risk imposed by chronic kidney disease is significantly enhanced, and carotid atherosclerosis is an early indicator of systemic vascular damage. In this review, we summarize available data relative to primary prevention strategies for carotid atherosclerosis in chronic kidney disease (CKD) with a focus on risk-adapted and stage-specific management. We conducted a narrative review of the literature. A structured literature search was performed in major databases (PubMed, Scopus, Web of Science and Google Scholar), focusing on studies published between 2012 and 2025, including observational studies, randomized controlled trials, and international guideline recommendations. The review focuses on blood pressure management, lipid-lowering therapy, glycemic control, antiplatelet therapy, as well as lifestyle interventions and screening strategies in patients with CKD without a history of cerebrovascular events. CKD-specific processes, such as inflammation, endothelial dysfunction and vascular calcification, may influence the progression of carotid plaques, highlighting the need to improve traditional and non-traditional risk factor management. The focus of prevention continues to emphasize blood pressure (BP) and lipid control as well. At the same time, routine carotid screening and systematically implemented antiplatelet therapy have no known benefit, but the potential for elevated bleeding risk, especially in advanced CKD. Primary prevention should therefore focus on optimal medical treatment, as well as disease-specific strategies according to CKD stage. Additional CKD-specific studies with carotid endpoints are necessary. Full article

Background and Objectives: Pericoronary adipose tissue (PCAT) attenuation measured on coronary CT angiography is a promising imaging biomarker of coronary inflammation; however, absolute values may be influenced by technical and inter-individual variability, and a standardized methodology for measurement has not been established. Our study aimed to evaluate the association between PCAT attenuation and CAC burden while comparing absolute attenuation values with normalized values to minimize these sources of variability. Materials and Methods: Two hundred patients undergoing cardiac CT were included and stratified into four CAC categories (0, 1–99, 100–299, ≥300). PCAT attenuation was measured at multiple locations on two main levels: aortic root level and four-chamber view level. Relative PCAT attenuation was calculated by subtracting subcutaneous fat attenuation from raw PCAT values. Group comparisons were performed using ANOVA or Kruskal–Wallis tests, and multivariable linear regression models were adjusted for age, sex, and body mass index. Results: In univariate analysis, relative PCAT attenuation differed significantly across CAC categories at the aortic-level right coronary artery (RCA) site (p = 0.007). In multivariable analysis, higher CAC categories were associated with increased relative PCAT attenuation at the aortic RCA (β = 8.56, p = 0.015 for CAC 100–299; β = 10.68, p = 0.005 for CAC ≥300), while associations at the left main coronary artery (LMCA) showed significance in low and moderate CAC categories (β = 6.91, p = 0.047 for CAC 1–99 and β = 8.57, p = 0.016 for CAC 100–299). No significant associations were observed between CAC and raw PCAT attenuation at the aortic level, while isolated and inconsistent findings were observed in other territories. Conclusions: Relative PCAT attenuation is independently associated with CAC severity and normalized values may reduce technical and biological variability, potentially enhancing the sensitivity and robustness of this CT-based biomarker. Full article

Atherosclerosis (AS) is a chronic inflammatory disease of large arteries. It underlies many cardiovascular disorders, including coronary artery disease, myocardial infarction, stroke, and peripheral arterial disease. Current therapies have improved outcomes, especially lipid-lowering, antithrombotic, and anti-inflammatory treatments. Yet residual cardiovascular risk remains, and new molecular targets are still needed. Leucine-rich α-2-glycoprotein 1 (LRG1) is an inflammation-inducible secreted glycoprotein. It has drawn attention because it is linked to pathological angiogenesis, vascular dysfunction, tissue remodeling, and fibrosis. Recent studies indicate that LRG1 is related to AS at several levels. These include circulating clinical associations, plaque localization, and experimental models. In AS, LRG1 may not simply act as a biomarker. It may promote macrophage pro-inflammatory polarization, disturb endothelial homeostasis, support abnormal angiogenesis, and influence extracellular matrix remodeling and plaque structural change. This review examines the biological features of LRG1 and the current evidence connecting it with AS. It also discusses possible mechanisms, therapeutic feasibility, and current limitations. Overall, LRG1 appears to be a promising but still incompletely validated candidate target in AS. Full article

Background: Major cardiac surgery with cardiopulmonary bypass (CPB) induces a systemic inflammatory response that contributes to postoperative organ dysfunction and hemodynamic instability. While C-reactive protein (CRP) is a well-established downstream marker of postoperative inflammation, the upstream determinants of interindividual variability in inflammatory burden are not fully understood. Platelet-activating factor (PAF) is a potent inflammatory mediator implicated in platelet activation, endothelial dysfunction, and vascular dysregulation, but its role in modulating postoperative inflammation and clinical outcomes after cardiac surgery has not been fully characterized. Methods: We conducted a retrospective observational study of 87 patients undergoing major cardiac surgery with CPB. Preoperative plasma PAF levels and postoperative CRP concentrations were measured, and patients were stratified according to postoperative CRP severity. Associations between PAF, inflammatory response, postoperative vasoactive–inotropic requirements, recovery parameters, acute kidney injury, and mortality were assessed using correlation analyses, multivariable regression models, and receiver operating characteristic curve analyses. Results: Preoperative PAF levels increased progressively across postoperative CRP strata (p < 0.001) and were strongly associated with postoperative CRP concentrations in both univariate and multivariable analyses. Specifically, each 1000 pg/mL increase in preoperative PAF was associated with an adjusted increase of 36.0 mg/L in postoperative CRP (β = 36.0; p < 0.001). Each 1000 pg/mL increase in preoperative PAF was associated with an adjusted increase of approximately 36 mg/L in postoperative CRP. Elevated PAF was also associated with increased intermediate postoperative vasoactive–inotropic requirements and a modest increase in hospital length of stay (r = 0.25, p = 0.023). However, neither PAF nor CRP independently predicted AKI or mortality after adjustment for clinical variables. Discriminative performance for mortality was modest for both biomarkers. Conclusions: Preoperative platelet-activating factor was strongly associated with postoperative inflammatory burden and early hemodynamic instability following major cardiac surgery. Although PAF and CRP were not independent predictors of adverse outcomes, they may help identify a biologically vulnerable phenotype characterized by exaggerated inflammatory and vascular responses to surgical stress. These findings support further investigation of platelet-mediated inflammatory pathways as targets for perioperative risk stratification and mechanistic research. Full article

Background/Objectives: Radiotherapy is a cornerstone of head and neck cancer treatment, but it can adversely affect periodontal tissues by impairing vascularity, cellularity, and healing capacity. The present study aimed to histologically and immunohistochemically evaluate radiotherapy-induced changes in periodontal tissues in a rat model of experimental periodontitis, with particular focus on periodontal ligament width (PerioW) and the RANK/RANKL/OPG axis at different healing stages. Methods: Seventy-two male Sprague–Dawley rats were allocated to three groups: irradiation only (Rt), ligature-induced periodontitis only (Pt), and ligature-induced periodontitis followed by irradiation (PtRt). Experimental periodontitis was induced by placing ligatures around the maxillary first molars for two weeks. On the day of ligature removal, the irradiated groups received a single 20 Gy dose to the head and neck region. Animals were euthanized on days 1, 15, and 30 after ligature removal (n = 8/group/time point). Histomorphometric analysis of PerioW was performed on H&E-stained sections, and immunohistochemical staining was used to quantify RANK, RANKL, and OPG expression. Results: On day 1, PerioW did not differ significantly among groups, although the PtRt group had the highest mean. A significant intergroup difference was observed for RANKL, with higher expression in PtRt than in Pt. On day 15, PerioW differed significantly among groups, with the lowest value in Rt and the highest in PtRt; the Rt–PtRt comparison was significant. At this time point, RANK, RANKL, OPG, and the RANKL/OPG ratio showed no significant intergroup differences. On day 30, no significant intergroup differences were found for PerioW or immunohistochemical parameters; however, PtRt continued to show the highest PerioW and OPG values and the lowest RANKL/OPG ratio. Conclusions: Radiotherapy superimposed on periodontitis enhanced early pro-resorptive signaling and delayed structural normalization of periodontal tissues. Although late increases in OPG suggested a compensatory response, this appeared insufficient to fully reverse radiation-associated periodontal alterations. These findings support the importance of controlling periodontal inflammation before radiotherapy to reduce subsequent periodontal tissue damage. Full article

Cardiovascular and cerebrovascular diseases, encompassing cardiac arrhythmias, atherosclerosis, and ischaemic stroke, remain the foremost causes of death and long-term disability globally. Despite improved outcomes with conventional therapy, substantial residual risk persists, providing the impetus for gene-based intervention. KCNQ1/KCNH2 suppression-and-replacement, SCN5A base editing, and structural protein restoration via PKP2 and TMEM43 have each demonstrated capacity to re-establish electrophysiological stability in arrhythmia models. For atherosclerosis, RNA-based agents, notably inclisiran, alongside in vivo editing strategies such as VERVE-101, offer durable lipid reduction and attenuation of vascular inflammation. In ischaemic stroke, cGAS–STING silencing, AAV-NeuroD1-mediated neuronal reprogramming, and delivery of neurotrophic factors, including VEGF and BDNF, extend the therapeutic window well beyond reperfusion. Collectively, these approaches position gene therapy as a meaningful complement to standard care, capable of addressing root molecular pathology rather than downstream consequences. This review synthesises current mechanistic understanding, translational obstacles, and emerging directions across these three disease domains, arguing that, delivery and safety challenges notwithstanding, gene therapy stands to substantially reshape how cardiovascular and cerebrovascular diseases are prevented and treated. Full article

Coronary artery bypass grafting (CABG) using the autologous saphenous vein (SV) remains widely performed for obstructive atherosclerosis; however, vein graft disease drives recurrent ischaemia through early thrombosis and progressive intimal hyperplasia, and accelerated atherosclerosis developing within the grafts. Extracellular vesicles (EVs) are membrane-bound particles that transfer proteins, lipids, and microRNAs between cells. They modulate endothelial dysfunction, vascular smooth muscle cell phenotypic switching, inflammation, and coagulation, which are core processes in vein graft remodelling. Arterialisation exposes the vein to abrupt rises in shear stress, cyclic stretch, and intraluminal pressure. These forces increase EV release and reshape EV cargo in experimental systems, suggesting a potential mechanism for amplifying early graft injury which warrants direct investigation in vein tissue. This review synthesises current evidence for cell-specific EV contributions from ECs, vascular smooth muscle cells, platelets, and macrophages, and appraises EV-associated microRNAs with biomarker potential relevant to graft failure pathways. We also review therapeutic strategies that may modulate EV signalling including antiplatelet therapy, statins, KCa3.1 inhibition, and pro-reparative mesenchymal stromal cell-derived EVs. No published clinical studies evaluate EV-based biomarkers specifically for saphenous vein graft patency, and none prospectively predict saphenous graft failure. CABG provides a well-defined time zero event that enables longitudinal sampling and risk stratification. Prospective studies linking EV phenotypes and miRNA signatures to imaging-defined graft outcomes are needed to support clinical translation. Full article

Adenosine has emerged as a central metabolic signal linking cellular stress to systemic physiological adaptation. Under conditions such as hypoxia, ischemia, inflammation, and tissue injury, extracellular adenosine triphosphate (eATP) released from stressed cells is sequentially metabolized by the ectonucleotidases CD39 and CD73, generating adenosine that accumulates in the extracellular microenvironment. This stress-responsive nucleoside activates four G-protein-coupled receptors (A1, A2A, A2B, and A3), triggering intracellular signaling networks including the cyclic adenosine monophosphate–protein kinase A (cAMP–PKA), mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase–protein kinase B (PI3K–Akt), and hypoxia-inducible factor-1 alpha (HIF-1α) pathways. Through these integrated mechanisms, adenosine orchestrates diverse physiological processes such as vascular regulation, metabolic adaptation, immune modulation, and cellular survival. In the cardiovascular system, adenosine promotes coronary vasodilation and ischemic preconditioning, limiting reperfusion injury. In pulmonary tissues, it mediates acute anti-inflammatory responses but may also drive chronic fibrotic remodeling. Within the central nervous system, adenosine functions as a neuromodulator regulating neuronal excitability, sleep–wake homeostasis, and neuroprotection. In the tumor microenvironment, hypoxia-driven adenosine accumulation suppresses cytotoxic T cell and natural killer activity, facilitating immune evasion and tumor progression. Collectively, adenosine signaling represents a central integrative network that links metabolic stress sensing to coordinated cellular adaptation while simultaneously emerging as a clinically actionable therapeutic target across cardiovascular, inflammatory, neurological, and oncological diseases. Full article

At present, there is still a lack of effective treatments to slow the progression of Parkinson’s disease. Naturally derived active substances, valued for their safety and multi-target potential, have become an important direction in anti-PD drug development, with marine organisms representing a valuable source of bioactive peptides. This study aimed to isolate and identify anti-PD peptides from Rapana venosa protein hydrolysates. Through bioactivity-guided screening combined with an MPTP-induced zebrafish PD model, three novel active peptides—KSTELLI, FLVKLPMFM, and SDSLSEILIS—were successfully identified. The study showed that these peptides significantly alleviated dopaminergic neuron loss, improved the cerebral vascular system, restored motor and sensory function, and alleviated oxidative stress. Molecular docking confirmed their stable binding to key PD targets (DDC, α-synuclein, and MAO-B). Further transcriptomic and gene expression analyses revealed that their neuroprotective effects involve the regulation of pathways related to metabolism, oxidative stress, inflammation, and apoptosis, with the three peptides exhibiting distinct mechanistic emphases. The research demonstrates that these marine-derived peptides exert neuroprotective effects through a synergistic multi-target mechanism, laying a foundation for the development of novel lead compounds against Parkinson’s disease. Full article

Annually, there are more than two million deaths from liver disease. This is driven by organ inflammation and scarring, leading to a decline in function and regeneration. Frequently, this can develop into decompensated liver disease, resulting in the loss of physiological balance and toxin build-up within the body, with an increased risk of patient mortality. Currently, there are no approved medicines for the long-term treatment of liver cirrhosis. The only successful treatment option for end-stage liver disease patients is donor organ transplantation. However, patient requirement outstrips the number of donated organs. To address this bottleneck, researchers around the world have developed cell-based prototype systems to restore failing liver function, with some in clinical trials. Although significant progress has been made, no mainstream commercial liver assist products are available for routine clinical use. In this study we developed a stem cell-derived vascularized liver tissue implant prototype from pluripotent cells. The liver tissue was produced from a stem cell line that is banked at clinical grade, and displayed stable and mature liver function over a 6-week period in vitro. This included decreasing levels of the fetal marker, alpha-fetoprotein, when the serum albumin increased. This was further supported by stable alpha-1-antitrypsin secretion and cytochrome P450 function. Following the establishment of stable liver tissue, it was delivered as a cell product or attached to an electrospun polycaprolactone scaffold, to form a tissue implant. Next, cellular material was quality-controlled, and subsequently shipped to a contract research organization for external in vivo validation. The transplanted liver tissue functioned when implanted into the kidney capsule and subcutaneously, remaining functional for up to two weeks in vivo. Full article

Abdominal aortic aneurysm (AAA) is a life-threatening disease for which no definitive medical therapy has been established, partly because its underlying mechanisms remain incompletely understood. Given accumulating evidence suggesting microbial involvement in vascular inflammation, we conducted a detection-based investigation to identify bacterial DNA in aneurysmal tissues. We performed 16S ribosomal RNA (rRNA) gene sequencing of the aneurysmal wall, intraluminal thrombus, feces, saliva, and dental plaque collected from 32 patients undergoing open surgical repair of non-infectious AAA. Based on the sequencing data, diversity analyses were performed for each sample to characterize bacterial composition, and exploratory statistical analyses were conducted to examine associations between patient characteristics and the relative abundance of bacterial taxa. Oral-associated genera were frequently detected in aneurysm-derived samples, including Prevotella in 78%, Leptotrichia in 81%, and Capnocytophaga in 38% of aneurysmal wall or thrombus samples, whereas their detection in fecal samples was limited. Beta diversity analysis demonstrated significant compositional differences between fecal and oral samples (permutational multivariate analysis of variance [PERMANOVA], p < 0.01). These findings demonstrate the presence of bacterial DNA in aneurysmal tissues and provide descriptive evidence of microbial signatures in AAA. Full article

Since the first approval of CTLA-4 blockade for melanoma, immune checkpoint inhibitors (ICIs) have expanded into a major class of cancer therapy, with more than 100 FDA-approved oncological indications across metastatic and earlier-stage disease settings, including use as monotherapy and in combination regimens. Preclinical research has largely focused on myocarditis and atherosclerosis, but a wider set of phenotypes, such as non-inflammatory left ventricular dysfunction (NILVD), arrhythmias, and vasculitis, can be observed, and they are rarely connected within a single mechanistic model. We aim to build a systems-oriented, mechanistic framework of the most widely studied biological processes; it will link the main checkpoint pathways to relevant cardiac and vascular cell types, molecular pathways, immune synapses, and candidate biomarkers. We searched PubMed, Scopus, and Web of Science using combinations of terms for immune checkpoint inhibition and cardiovascular-immune-related adverse events that provide mechanistic insight into cardiac-immune-related adverse reactions (irAEs). An AI-assisted semantic clustering approach was used only to organize the included literature. The integrated framework identifies PD-1/PD-L1 as the dominant mechanistic hub linking T-cell activation, endothelial recruitment, myocardial injury, and vascular inflammation. Across phenotypes, a shared immune core involving checkpoint pathways, cytokine signaling, and leukocyte trafficking coexists with phenotype-restricted mediators that may bias injury toward myocarditis, vascular inflammation, conduction-system disease, or NILVD. KEGG analyses support the enrichment of T-cell receptor signaling, Th17 differentiation, JAK-STAT signaling, cytokine–cytokine receptor interaction, and lipid and atherosclerosis pathways. Candidate biomarkers emerging from the reviewed literature include troponin, IL-6, CXCL9/CXCL10/CXCL13, S100A family proteins, ROCK2, HLA-linked susceptibility signals, and T-cell receptor clonality markers. The AI-assisted clustering broadly recapitulated the expert-defined thematic structure while identifying finer semantic neighborhoods within the literature. This framework provides a support map for further hypotheses about toxicity patterns with current and next-generation checkpoint strategies on the cardiac system, while AI-assisted clustering provides a complementary method for organizing the literature rather than an independent source of biological inference. Full article

Background/Objectives: Periodontal disease is a chronic inflammatory condition associated with systemic vascular dysfunction and elevated cardiovascular risk. This systematic review and meta-analysis aimed to quantitatively evaluate the association between periodontitis and endothelial dysfunction and to assess the effects of periodontal therapy on endothelial function and inflammatory biomarkers. Methods: Conducted per PRISMA 2020 and registered in PROSPERO (CRD420261309247). Electronic databases (PubMed, Scopus, Cochrane Library) were searched for observational and interventional studies assessing endothelial function in patients with periodontitis. Risk of bias was evaluated using RoB 2, ROBINS-I, and the Newcastle–Ottawa Scale; certainty of evidence was assessed with GRADE. Pooled effects on flow-mediated dilation (FMD) and inflammatory markers were estimated using random-effects meta-analysis (DerSimonian–Laird). Results: Fourteen studies were included in qualitative synthesis; six contributed quantitative FMD data. Observational studies consistently demonstrated impaired endothelial function and elevated inflammatory markers in patients with periodontitis versus controls. Meta-analysis showed that periodontal therapy significantly improved endothelial function (pooled FMD: +3.3 percentage points; 95% CI 1.7–4.9; I² = 77%; p < 0.001), though results should be interpreted cautiously given substantial heterogeneity and the limited number of studies (n = 6). Periodontal treatment reduced CRP levels (mean difference −0.38 mg/L; I² = 41%); IL-6 showed a favorable direction but with very low certainty of evidence. Publication bias could not be reliably assessed given the small number of included studies. Conclusions: Periodontitis is associated with impaired endothelial function and systemic inflammation. Periodontal therapy leads to measurable improvements in both, supporting its role as a potentially modifiable contributor to cardiovascular risk. Larger randomized trials with long-term cardiovascular endpoints are warranted. Full article

Medical thermography is a noninvasive, contactless imaging technique that captures spatial temperature distributions across the human body, providing insights into vascular function, inflammation, metabolism, physiological regulation, and aging. Recently, machine learning has been increasingly utilized to analyze thermographic data for disease screening, functional assessment, and biomarker identification. However, the existing literature is fragmented, with varied clinical applications, feature-engineering strategies, and predictive modeling frameworks, often lacking a focus on interpretability and the reliable identification of clinically relevant thermal markers. This review offers a structured overview of explainable machine learning in medical thermography, emphasizing thermal feature representation, model interpretability, and biomarker discovery. It categorizes thermographic features into pixel-based representations, region-wise statistical descriptors, texture measures, and deep latent features. Additionally, it evaluates conventional machine learning and deep learning methods for classification, regression, and risk assessment tasks. The review pays special attention to interpretable learning strategies, such as feature importance analysis, surrogate explanation models, saliency-based visualization, and Shapley-value-based methods, which can enhance transparency and confidence in model outputs. Key challenges are critically discussed, including imaging variability, limited dataset sizes, weak protocol standardization, class imbalance, generalizability, and the gap between predictive performance and clinical trust. Overall, this review synthesizes current advancements, identifies major research gaps, and outlines future directions for developing trustworthy machine learning frameworks in medical thermography and enhancing interpretable thermal biomarker discovery. Full article

Chronic kidney disease (CKD), a progressive disorder leading to renal dysfunction, remains a significant global health issue. This study investigated whether Lactiplantibacillus plantarum HY7718 modulates gut–kidney axis-associated inflammatory, gastrointestinal, and microbial alterations in a mouse model of adenine-induced chronic kidney disease. We examined fibrosis- and inflammation-related gene expression in mouse tissues and analyzed the gut microbiota via next-generation sequencing. HY7718 supplementation was associated with reduced expression of genes related to renal fibrosis (Col1a1, Acta2) and vascular inflammation (Icam-1, Vcam-1). Further, HY7718 suppressed intestinal inflammatory responses, including downregulation of pro-inflammatory cytokines (Tnf, Il-1β, Il-6) and TLR4/MyD88/NF-κB signaling pathway genes in the colon tissues. Gastrointestinal function was also improved, with significant upregulation of gastric motility-related genes and increased digestive enzyme activity. The gut microbiota composition was altered by HY7718, with reduced abundance of pro-inflammatory taxa such as Mucispirillum and Deferribacterota, whereas beneficial genera like Lactiplantibacillus were enriched. These microbial shifts were associated with reduced intestinal inflammatory and renal fibrosis-related markers. Overall, the findings indicate that HY7718 supplementation modulates gut–kidney axis-associated inflammatory, gastrointestinal, and microbial alterations in adenine-induced CKD mice and supports further investigation of this strain in CKD-related settings. Full article