Search Results (3,405)

Background: Atherosclerosis is a progressive and complex vascular pathology characterized by cellular heterogeneity, metabolic dysregulation, and chronic inflammation. Despite extensive research, the intricate molecular mechanisms underlying its development and progression remain incompletely understood. Methods: Single-cell RNA sequencing (scRNA-seq) was employed to conduct a comprehensive mapping of immune cell enrichment and interactions within atherosclerotic plaques, aiming to investigate the cellular and molecular complexities of these structures. This approach facilitated a deeper understanding of the heterogeneities present in smooth muscle cells, which were subsequently analyzed using pseudotime trajectory analysis to monitor the developmental trajectories of smooth muscle cell (SMC) subpopulations. An integrative bioinformatics approach, primarily utilizing Weighted Gene Co-expression Network Analysis (WGCNA) and machine learning techniques, identified Cathepsin C (CTSC), transforming growth factor beta-induced protein (TGFBI), and glia maturation factor-γ (GMFG) as critical biomarkers. A diagnostic risk score model was developed and rigorously tested through Receiver Operating Characteristic analysis. To illustrate the functional impact of CTSC on the regulation of plaque formation and SMC viability, both in vitro and in vivo experimental investigations were conducted. Results: An analysis revealed SMCs identified as the most prominent cellular type, exhibiting the highest density of disulfidptosis. Pseudotime trajectory analysis illuminated the dynamic activation pathways in SMCs, highlighting their significant role in plaque development and instability. Further characterization of macrophage subtypes demonstrated intercellular communication with SMCs, which exhibited specific signaling pathways, particularly between the proximal and core areas of plaques. The integrated diagnostic risk score model, which incorporates CTSC, TGFBI, and GMFG, proved to be highly accurate in distinguishing high-risk patients with elevated immune responses and systemic inflammation. Knockdown experiments of CTSC conducted in vitro revealed enhanced SMC survival rates, reduced oxidative stress, and inhibited apoptosis, while in vivo experiments confirmed a decrease in plaque burden and improvement in lipid profiles. Conclusion: This study emphasizes the significance of disulfidptosis in the development of atherosclerosis and identifies CTSC as a potential therapeutic target for stabilizing plaques by inhibiting SMC apoptosis and oxidative damage. Additionally, the risk score model serves as a valuable diagnostic tool for identifying high-risk patients and guiding precision treatment strategies. Full article

Background: Glioblastoma (GB) is a particularly malignant brain tumour which carries a poor prognosis and presents limited treatment options. MRI is standard practice for differential diagnosis at initial presentation of GB and can assist in both treatment planning and response assessment. MRI radiomics allows for discerning GB features of clinical importance that are not evident by visual analysis, augmenting the morphological and functional tumour characterisation beyond traditional imaging techniques. Given that radiotherapy is part of the standard of care for GB patients, establishing a platform for phenotyping radiation treatment responses using non-invasive methods is of high relevance. Methods: In this study, we modelled the responses to ionising radiation across four orthotopic mouse models of GB using diffusion and perfusion radiomics. We have identified the optimal set of radiomic features that reflect tumour cellularity, microvascularity, and blood flow changes brought about by radiation treatment in these murine orthotopic models of GB, and directly compared them with endpoint histopathological analysis. Results: We showed that the selected radiomic features can quantify textural information and pixel interrelationships of tumour response to radiation therapy, revealing subtle image patterns that may reflect intra-tumoural spatial heterogeneity. When compared to GB patients, similarities in selected radiomic features were noted between orthotopic murine tumours and non-enhancing central tumour areas in patients, along with several discrepancies in tumour cellularity and vascularization, denoted by distinct grey level intensities and nonuniformity metrics. Conclusion: As the field evolves, radiomic profiling of GB may enhance the evaluation of targeted therapeutic strategies, accelerate the development of new therapies, and act as a potential virtual biopsy tool. Full article

Aging is a predominant risk factor for cardiovascular diseases. There is evidence demonstrating that senescent cells not only play a significant role in organism aging but also contribute to the pathogenesis of cardiovascular diseases in younger ages. Encouraged by recent findings that the elimination of senescent cells by pharmacogenetic tools could slow down and even reverse organism aging in animal models, senolytic drugs have been developed, and the translation of results from basic research to clinical settings has been initiated. Because numerous studies in the literature show beneficial therapeutic effects of targeting senescent cells in cardiomyopathies associated with aging and ischemia/reperfusion and in atherosclerotic vascular disease, senolytic drugs are considered the next generation of therapies for cardiovascular disorders. However, recent studies have reported controversial results or detrimental effects caused by senolytic therapeutic approaches, including worsening of cardiac dysfunction, instability of atherosclerotic plaques, and even an increase in mortality in animal models, which challenges the translation of senolytic therapy into the clinical practice. This brief review article will focus on (1) analyzing and discussing the beneficial and detrimental effects of senolytic therapeutic approaches in cardiovascular diseases and cardiovascular aging and (2) future research directions and questions that are essential to understand the controversies and to translate preclinical results of senolytic therapies into clinical practice. Full article

Background: Diabetes mellitus (DM) is a major determinant of aging-related vascular diseases. The arterial pulsatility index (PI) and resistance index (RI) are biomarkers of vascular aging. The available data regarding DM with arterial PI and RI are limited. The specific aim of this study was to explore the relationships between DM and the segment-specific PI and RI of the extracranial carotid arteries. Methods: We enrolled 402 DM cases and 3416 non-DM controls from a community-based cohort. Each subject’s blood flow velocities in the extracranial common (CCA), internal (ICA), and external (ECA) carotid arteries were measured by color Doppler ultrasonography and used to calculate PIs and RIs. Results: The DM cases had significantly higher age–sex-adjusted means of carotid RIs and PIs than the non-DM controls (all p-values < 0.005). After controlling for the effects of conventional cardio-metabolic risk factors, all carotid RIs and PIs remained significantly correlated with higher odds ratios (ORs) of having DM. The relationships with DM were stronger and more significant for the ECA RI and PI. The multivariable-adjusted ORs were 1.36 (95% confidence interval [CI], 1.21~1.54, p = 3.9 × 10⁻⁷) and 1.30 (95% CI, 1.17~1.45, p = 8.7 × 10⁻⁷) for 1.0 SD increases in the ECA RI and PI, respectively. Compared to the best fit model of conventional cardio-metabolic risk factors, the additions of the ECA RI and PI significantly increased the area under the receiver operating characteristic curve by 0.85% (95% CI, 0.11~1.59%; p = 0.023) and 0.69% (95% CI, 0.01~1.37%; p = 0.046), respectively. Conclusions: This study shows significantly positive associations between DM and carotid RIs and PIs. Carotid RIs and PIs are potential biomarkers for DM-related vascular diseases. Full article

The mechanism of atherosclerosis lesions was investigated based on a fluid–structure interaction method according to the geometric reconstruction of human arteries by medical imaging. Numerical simulation, mechanical analysis, and dynamic simulation were used to establish a model of the mechanical characteristics of arterial blood transport, analyze the fluid properties of arterial blood flow under the influence of vascular lesion process, and study the mechanism of arterial lesion formation and development. The results indicated that the clinically important areas of secondary flow were generated at stenosis and bifurcation sites, which were prone to lesions during a cardiac cycle. The low flow rate and shear stress levels of blood in this region led to the adhesion and precipitation of lesion-inducing factors on the intimal tissue, creating a hydrodynamic environment suitable for lesion development. According to the research reported here in, early clinical detection and follow-up of atherosclerosis can be performed by collecting data on wall shear stress and blood flow pressure difference. Full article

Pulmonary hypertension (PH) is a progressive disorder characterized by obstructive changes in the pulmonary vasculature, leading to increased pulmonary vascular resistance (PVR), right ventricular (RV) strain, and eventual RV failure (RVF). Despite advancements in medical therapy, PH remains associated with significant morbidity and mortality, particularly in children. RVF is a clinical syndrome resulting from complex structural and functional remodeling of the right heart, leading to inadequate pulmonary circulation, reduced cardiac output, and elevated venous pressure. Management paradigms for pediatric PH diverge significantly from those in adults, particularly due to the predominance of congenital heart disease (CHD) and the dynamic nature of pediatric cardiovascular and pulmonary development. CHD remains a principal driver of PH in children, and its associated pathophysiology demands a nuanced approach. In patients with unrepaired left-to-right shunts, elevated pulmonary blood flow can lead to progressive pulmonary vascular remodeling and increased PVR. The postoperative persistence or progression of PH may occur if irreversible vascular changes have already developed. Current PH treatments primarily focus on reducing PVR, yet distinguishing between therapeutic approaches that target the pulmonary vasculature and those aimed at improving RV function remain challenging. In pediatric patients with progressive PH despite optimal therapy, additional targeted interventions may be necessary to mitigate RV dysfunction and disease progression. This review provides a comprehensive analysis of the mechanisms underlying RVF in PH, incorporating insights from clinical studies in adults and experimental models, while highlighting the unique considerations in children. Furthermore, it explores current pharmacological and interventional treatment strategies, emphasizing the need for novel therapeutic approaches aimed at directly reversing RV remodeling. Given the complexities of RV adaptation in pediatric PH, further research into disease-modifying treatments and innovative interventions is crucial to improving long-term outcomes in affected children. Full article

Background: Rectal cancer represents a major cause of mortality in the United States. Management strategies are highly individualized, depending on patient-specific factors and tumor characteristics. The therapeutic landscape is rapidly evolving, with notable advancements in response rates to both radiotherapy and chemotherapy. For locally advanced rectal cancer (LARC, defined as up to T3–4 N+), the standard of care involves total mesorectal excision (TME) following neoadjuvant chemoradiotherapy (nCRT). Magnetic resonance imaging (MRI) has emerged as the gold standard for local tumor staging and is increasingly pivotal in post-treatment restaging. Aim: In our study, we proposed an MRI-based radiomic model to identify characteristic features of peritumoral mesorectal fat in two patient groups: good responders and poor responders to neoadjuvant therapy. The aim was to assess the potential presence of predictive factors for favorable or unfavorable responses to neoadjuvant chemoradiotherapy, thereby optimizing treatment management and improving personalized clinical decision-making. Methods: We conducted a retrospective analysis of adult patients with LARC who underwent pre- and post-nCRT MRI scans. Patients were classified as good responders (Group 0) or poor responders (Group 1) based on MRI findings, including tumor volume reduction, signal intensity changes on T2-weighted and diffusion-weighted imaging (DWI), and alterations in the circumferential resection margin (CRM) and extramural vascular invasion (EMVI) status. Classification criteria were based on the established literature to ensure consistency. Key clinical and imaging parameters, such as age, TNM stage, CRM involvement, and EMVI presence, were recorded. A radiomic model was developed using the LASSO algorithm for feature selection and regularization from 107 extracted radiomic features. Results: We included 44 patients (26 males and 18 females) who, following nCRT, were categorized into Group 0 (28 patients) and Group 1 (16 patients). The pre-treatment MRI analysis identified significant features (out of 107) for each sequence based on the Mann–Whitney test and t-test. The LASSO algorithm selected three features (shape_Sphericity, shape_Maximum2DDiameterSlice, and glcm_Imc2) for the construction of the radiomic logistic regression model, and ROC curves were subsequently generated for each model (AUC: 0.76). Conclusions: We developed an MRI-based radiomic model capable of differentiating and predicting between two groups of rectal cancer patients: responders and non-responders to neoadjuvant chemoradiotherapy (nCRT). This model has the potential to identify, at an early stage, lesions with a high likelihood of requiring surgery and those that could potentially be managed with medical treatment alone. Full article

Background: Scald burns are common thermal injuries in clinical settings, yet existing animal models lack standardization in burn size, exposure time, and severity control. Traditional burn induction methods, such as manual immersion or heated metal contact, suffer from high variability, limited reproducibility, and are operator-dependent, reducing their translational relevance. This study presents RAPID-3D (rat printed induction device—3D), a novel 3D-printed system designed to induce uniform and reproducible scald burns in a rat model, ensuring precise exposure control and minimal variability. Methods: RAPID-3D features four burn exposure windows (10 × 20 mm each, 10 mm spacing), allowing for controlled boiling water (100 °C, 8 s) exposure while immobilizing the anesthetized rat’s dorsum. N = 10 female Wistar rats were subjected to eight controlled burns per animal. Internal unburned control areas were used in each rat for intra-animal comparison. Burn evolution was assessed using digital planimetry, histological evaluation, and real-time microvascular perfusion analysis via laser Doppler line scanning (LDLS) at 1 h, which was repeated on day 4, 9 and 21 post-burn. Results: RAPID-3D generated highly consistent burn sizes (198 ± 3.54 mm²) across all rats, with low inter-animal variability. Histological analysis confirmed full-thickness epidermal necrosis and deep partial-thickness dermal damage (600–900 µm depth). Microvascular Trends: Perfusion dropped immediately post-burn, remained low at day 4, and gradually increased from day 9 onward, suggesting progressive neovascularization and vascular remodeling. RAPID-3D provides a standardized, reproducible, and clinically relevant scald burn model, eliminates operator-induced variability, enhances experimental consistency, and offers strong translational relevance for burn treatment development and wound healing research. Full article

Background: The World Health Organization has indicated that airport noise is strongly associated with cardiovascular disease, with vascular inflammation identified as the primary mechanism. Therefore, long-term exposure to airport noise is considered far more harmful than other types of noise. However, there remains a lack of research into the mechanisms underlying long-term exposure to airport noise and harm to the human body. Methods: A mouse model was established and exposed to airport noise at a maximum sound pressure level of 95 dB(A) and an equivalent continuous sound pressure level of 72 dB(A) for 12 h per day over a period of 100 days. Quantitative polymerase chain reaction (qPCR) was used to detect the mRNA expression levels of pro-inflammatory and anti-inflammatory factors. Enzyme-linked immunosorbent assay (ELISA) was used to detect LPS, LTA, TMA, and TMAO levels. Intestinal flora composition was analyzed by 16S rDNA sequencing, and targeted metabolomics was employed to determine the levels of serum short-chain fatty acids. Results: Long-term airport noise exposure significantly increased systolic blood pressure, diastolic blood pressure, and mean blood pressure (p < 0.05); significantly increased the mRNA expression levels of oxidative stress parameters (nuclear matrix protein 2, 3-nitrotyrosine, and monocyte chemoattractant protein-1) (p < 0.05); significantly increased pro-inflammatory factors (interleukin 6 and tumor necrosis factor alpha) (p < 0.05); significantly decreased the mRNA expression level of anti-inflammatory factor interleukin 10 (p < 0.05); and significantly increased the content of LPS and LTA (p < 0.05). The composition of the main flora in the intestinal tract was structurally disordered, and there were significant differences between the noise-exposed and control groups at the levels of the phylum, family, and genus of bacteria. β-diversity of the principal component analysis diagrams was clearly distinguished. Compared with those of the control group, TMA-producing bacteria and levels of TMA and TMAO were significantly reduced, and the serum ethanoic acid and propanoic acid levels of the noise-exposed group were significantly decreased (p < 0.05). Conclusions: Long-term airport noise exposure causes significant elevation of blood pressure and structural disruption in the composition of the intestinal flora in mice, leading to elevated levels of oxidative stress and inflammation, resulting in metabolic disorders that lead to significant changes in the production of metabolites. Full article

Background: Besides conventional norms that recognize synovial fluid (SF) as a joint lubricant, nutritional channel, and a diagnostic tool in knee osteoarthritis (kOA), based on the authors previous studies, this study aims to define functional role of SF in kOA. Methods: U937, a monocytic, human myeloid cell line, was induced with progressive grades of kOA SF, and the induction response was assessed on various pro-inflammatory parameters. This ‘SF challenge test model’ was further extended to determine the impact of SF on U937 differentiation using macrophage-specific markers and associated transcription factor genes. Mitochondrial membrane potential changes in SF-treated cells were evaluated with fluorescent JC-1 probe. Results: a significant increase in nitric oxide, matrix metalloproteinase (MMP) 1, 13, and vascular endothelial growth factor (VEGF)-1 was noted in the induced cells. A marked increase was seen in CD68, CD86, and the transcription factors –activator protein (AP)-1, interferon regulatory factor (IRF)-1, and signal transducer and activator of transcription (STAT)-6 in the SF-treated cells indicating active monocytes to macrophage differentiation. Reduced mitochondrial membrane potential was reflected by a reduced red-to-green ratio in JC-1 staining. Conclusions: these results underline the active role of OA SF in stimulating and maintaining inflammation in joint cells, fostering monocyte differentiation into pro-inflammatory macrophages. The decline in the membrane potential suggestive of additional inflammatory pathway in OA via the release of pro-apoptotic factors and damaged associated molecular patterns (DAMPs) within the cells. Overall, biochemical modulation of SF warrants a potential approach to intervene inflammatory cascade in OA and mitigate its progression. Full article

Background and Objectives: The pancreas receives blood through a complex network of multiple branches, primarily originating from the celiac trunk (CeT) and the superior mesenteric artery (SMA). This blood supply is structured into three main arterial groups, each serving different regions of the pancreas to effectively support its endocrine and exocrine functions. Materials and Methods: The databases Medline, Scopus, Web of Science, Google Scholar, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Latin American and the Caribbean Literature in Health Sciences (LILACS) were searched until January 2025. Methodological quality was evaluated using an assurance tool for anatomical studies (AQUA). Pooled prevalence was estimated using a random effects model. Results: A total of sixteen studies met the established selection criteria in this study for meta-analysis. Pancreatic irrigation variants presented a prevalence of 11.2% (CI: 7–14%) and a heterogeneity of 88.2%. The other studies were analyzed by subgroups, showing statistically significant differences in the following subgroups: (1) sample type—a larger sample of images analyzed in the included studies (p = 0.312), which did not show statistically significant differences; (2) geographical region (p = 0.041), which showed a greater presence in the Asian population studied, and this was statistically significant; and (3) sex (male or female) (p = 0.12), where there were no statistically significant differences. Conclusions: The discovery of variations in pancreatic irrigation is common due to the numerous blood vessels involved in supplying this vital organ. Understanding different vascular patterns (such as those from the splenic and mesenteric arteries) is crucial for surgical interventions on the pancreas. For transplant patients, a thorough vascular analysis of both the donor and recipient is essential. Variations can impact blood flow and compatibility, potentially leading to transplant rejection if not addressed. To enhance outcomes, it is recommended to develop more accurate imaging tools for pre-surgical analysis, necessitating ongoing research in this area. Full article

Artificial intelligence (AI) has emerged as a transformative tool in placental pathology, offering novel diagnostic methods that promise to improve accuracy, reduce inter-observer variability, and positively impact pregnancy outcomes. The primary objective of this review is to summarize recent developments in AI applications tailored specifically to placental histopathology. Current AI-driven approaches include advanced digital image analysis, three-dimensional placental reconstruction, and deep learning models such as GestAltNet for precise gestational age estimation and automated identification of histological lesions, including decidual vasculopathy and maternal vascular malperfusion. Despite these advancements, significant challenges remain, notably dataset heterogeneity, interpretative limitations of current AI algorithms, and issues regarding model transparency. We critically address these limitations by proposing targeted solutions, such as augmenting training datasets with annotated artifacts, promoting explainable AI methods, and enhancing cross-institutional collaborations. Finally, we outline future research directions, emphasizing the refinement of AI algorithms for routine clinical integration and fostering interdisciplinary cooperation among pathologists, computational researchers, and clinical specialists. Full article

Background:Sweet Tea (Lithocarpus polystachyus Rehd.), a traditional ethnobotanical medicine, contains phlorizin, a dihydrochalcone compound with antioxidative and anti-inflammatory properties. Given the critical role of oxidative stress and inflammation in age-related macular degeneration (AMD), this study tested the hypothesis that phlorizin mitigates oxidative damage and inflammation in AMD models, thereby offering therapeutic potential. Materials and Methods: Adult retinal pigmented epithelial cells (ARPE-19) were pre-treated with phlorizin (0.01–0.1 μM) and subjected to oxidative stress induced by ultraviolet A (UVA) radiation or sodium iodate (NaIO₃). Cell viability, reactive oxygen species (ROS) production, MAPK/NF-κB signaling, and the level of pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) and pro-angiogenic factors (VEGF, MMP2, MMP9) expression were assessed using MTT assays, fluorescence imaging, Western blotting, and RT-qPCR. In vivo, a laser-induced choroidal neovascularization (CNV) mouse model was used to evaluate phlorizin’s effects on CNV formation and vascular leakage via fundus photography and fluorescence angiography. Result: Phlorizin significantly enhanced cell viability, reduced ROS production, inhibited MAPK/NF-κB activation, and downregulated inflammatory and angiogenic mediators. In vivo studies confirmed the reduced CNV formation and vascular leakage following the phlorizin treatment. Conclusions: Phlorizin demonstrated significant protective effects against oxidative stress and inflammation, highlighting its therapeutic potential for treating AMD. Full article

Background: Fibroblast activation protein (FAP) is a cell surface glycoprotein expressed by myofibroblastic cells in areas of active tissue remodeling, such as wound healing, fibrosis, and certain chronic inflammatory lesions. As FAP is uniquely present in chronic inflammatory lesions and has an important role in extracellular matrix (ECM) turnover, it appears to have all the characteristics necessary for involvement in atherosclerosis and atherosclerotic plaque rupture and has become a potential target in the treatment of myocardial infarction. Methods: To further understand the role of FAP, its expression in atherosclerotic plaques was examined in a genetically modified mouse model of accelerated atherosclerosis (Apobec1 −/− Ldlr −/− double-knockout mice). The immunohistochemical Fap staining of atherosclerotic plaques in a mouse model of atherosclerosis was correlated with quantification of Fap mRNA obtained from the atherosclerotic plaques of the aortic arch. Fap distribution was characterized in mouse atherosclerotic plaques relative to other markers of activated smooth muscle cells, such as alpha smooth muscle actin and myosin heavy chain (Acta2 and Myh2), ECM turnover (Ki-67, procollagen III and Mmp-9), and inflammation in atherosclerosis (Cd-44, Il-12 and Tgf beta) using immunohistochemistry (IH) and RT-PCR analysis. Results: The mouse model of accelerated atherosclerosis showed an increasing presence of Fap with the progression of atherosclerosis and a high expression level in advanced atherosclerotic lesions compared with other markers of ECM turnover and inflammation in atherosclerosis. Conclusions: FAP exhibits a distinct pattern of expression in a mouse model of atherosclerosis as compared to other markers of activated vascular smooth muscle cells, ECM degeneration, and inflammatory cytokines. Full article

Peripheral nerve injury (PNI) remains a significant clinical challenge, often leading to long-term functional impairment. Despite advances in therapies, current repair strategies offer unsatisfactory clinical outcomes. Exosomes derived from induced pluripotent stem cells (iPSC-Exos) have emerged as a promising therapeutic approach in regenerative medicine. This study assesses the efficacy and safety of iPSC-Exos in a rat model of sciatic nerve crush injury. Briefly, iPSCs were generated from peripheral blood mononuclear cells (PBMCs) of healthy donors using Sendai virus vectors and validated for pluripotency. iPSC-Exos were characterized and injected at the injury site. Functional recovery was assessed through gait analysis, grip strength, and pain response. Histological and molecular analyses were used to examine axonal regeneration, myelination, Schwann cell (SC) activation, angiogenesis, and changes in gene expression. iPSC-Exos were efficiently internalized by SC, promoting their proliferation. No adverse effects were observed between groups on body weight, organ histology, or hematological parameters. iPSC-Exos injection significantly enhanced nerve regeneration, muscle preservation, and vascularization, with RNA sequencing revealing activation of PI3K-AKT and focal adhesion pathways. These findings support iPSC-Exos as a safe and effective non-cell-based therapy for PNIs, highlighting their potential for clinical applications in regenerative medicine. Full article