Search Results (7,981)

Calcium deposition in vascular smooth muscle cells (VSMCs), a form of ectopic ossification in blood vessels, can result in rigidity of the vasculature and an increase in cardiac events. Here, we report that CCAAT/enhancer-binding protein beta (C/EBPβ) potentiates calcium deposition in VSMCs and mouse aorta induced by inorganic phosphate (Pi) or vitamin D₃. Based on cDNA microarray and RNA sequencing data of Pi-treated rat VSMCs, C/EBPβ was found to be upregulated and thus selected for further evaluation. Quantitative RT-PCR and Western blot analysis confirmed that C/EBPβ was upregulated in Pi-treated A10 cells, a rat VSMC line, as well as vitamin D₃-treated mouse aorta. The overexpression of C/EBPβ in A10 cells increased bone runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), and osteopontin (OPN) mRNA in the presence of Pi, as well as potentiating the Pi-induced increase in calcium contents. The Runx2 expression was increased by C/EBPβ through Runx2 P2 promotor. Our results suggest that a Pi-induced increase in C/EBPβ is a critical step in vascular calcification. Full article

The mammalian Apolipoprotein-L families (APOLs) contain several isoforms of membrane-interacting proteins, some of which are involved in the control of membrane dynamics (traffic, fission and fusion). Specifically, human APOL1 and APOL3 appear to control membrane remodeling linked to pathogen infection. Through its association with Non-Muscular Myosin-2A (NM2A), APOL1 controls Golgi-derived trafficking of vesicles carrying the lipid scramblase Autophagy-9A (ATG9A). These vesicles deliver APOL3 together with phosphatidylinositol-4-kinase-B (PI4KB) and activated Stimulator of Interferon Genes (STING) to mitochondrion–endoplasmic reticulum (ER) contact sites (MERCSs) for the induction and completion of mitophagy and apoptosis. Through direct interactions with PI4KB and PI4KB activity controllers (Neuronal Calcium Sensor-1, or NCS1, Calneuron-1, or CALN1, and ADP-Ribosylation Factor-1, or ARF1), APOL3 controls PI(4)P synthesis. PI(4)P is required for different processes linked to infection-induced inflammation: (i) STING activation at the Golgi and subsequent lysosomal degradation for inflammation termination; (ii) mitochondrion fission at MERCSs for induction of mitophagy and apoptosis; and (iii) phagolysosome formation for antigen processing. In addition, APOL3 governs mitophagosome fusion with endolysosomes for mitophagy completion, and the APOL3-like murine APOL7C is involved in phagosome permeabilization linked to antigen cross-presentation in dendritic cells. Similarly, APOL3 can induce the fusion of intracellular bacterial membranes, and a role in membrane fusion can also be proposed for endothelial APOLd1 and adipocyte mAPOL6, which promote angiogenesis and adipogenesis, respectively, under inflammatory conditions. Thus, different APOL isoforms play distinct roles in membrane remodeling associated with inflammation. Full article

The placenta is a vital organ that supports fetal development by mediating nutrient and gas exchange, regulating immune tolerance, and maintaining hormonal balance. Its formation and function are tightly linked to the processes of embryo implantation and the establishment of a robust placental-uterine interface. Recent advances in molecular biology and histopathology have shed light on the key regulatory factors governing these processes, including trophoblast invasion, spiral artery remodeling, and the development of chorionic villi. This review integrates morphological and molecular perspectives on placental development, emphasizing the roles of cytokines, growth factors, and signaling pathways, such as VEGF and Notch signaling, in orchestrating implantation and placental formation. The intricate interplay between molecular regulation and morphological adaptations highlights the placenta’s critical role as a dynamic interface in pregnancy. This review synthesizes current findings to offer clinicians and researchers a comprehensive understanding of the placenta’s role in implantation, emphasizing its importance in maternal-fetal medicine. By integrating these insights, the review lays the groundwork for advancing diagnostic and therapeutic approaches that can enhance pregnancy outcomes and address related complications effectively. Full article

Background/Objectives: Acute myocardial infarction (AMI) is a critical medical condition that requires immediate attention to minimise heart damage and improve survival rates. Early identification and prompt treatment are essential to save the patient’s life. Currently, the treatment strategy focuses on restoring blood flow to the myocardium as quickly as possible. However, reperfusion activates several cellular cascades that contribute to organ dysfunction, resulting in the ischaemia/reperfusion (I/R) injury. The search for treatments against AMI and I/R injury is urgent due to the shortage of effective treatments at present. In this regard, histone deacetylase (HDAC) inhibitors emerge as a promising treatment against myocardial infarction. The objective of this systematic review is to analyse the effects of HDAC inhibitors on ventricular function, cardiac remodelling and infarct size, among other parameters, focusing on the signalling pathways that may mediate these cardiovascular effects and protect against AMI. Methods: Original experimental studies examining the effects of HDAC inhibitors on AMI were included in the review using the PubMed and Scopus databases. Non-experimental papers were excluded. The SYRCLE RoB tool was used to assess risk of bias and the results were summarised in a table and presented in sections according to the type of HDAC inhibitor used. Results: A total of 18 studies were included, 10 of them using trichostatin A (TSA) as an HDAC inhibitor and concluding that the treatment improved ventricular function, reduced infarct size, and inhibited myocardial hypertrophy and remodelling after AMI. Other HDAC inhibitors, such as suberoylanilide hydroxamic acid (SAHA), valproic acid (VPA), mocetinostat, givinostat, entinostat, apicidin, and RGFP966, were also analysed, showing antioxidant and anti-inflammatory effects, an improvement in cardiac function and remodelling, and a decrease in apoptosis, among other effects. Conclusions: HDAC inhibitors constitute a significant promise for the treatment of AMI due to their diverse cardioprotective effects. However, high risk of selection, performance, and detection bias in the in vivo studies means that their application in the clinical setting is still a long way off and more research is needed to better understand their benefits and possible side effects. Full article

Background: Small conductance Ca²⁺ activated K⁺ channels (K_Ca2.3) are important regulators of vascular function. They provide Ca²⁺-dependent hyperpolarization of the endothelial membrane potential, promoting agonist-induced vasodilation. Another important mechanism of influence may occur through positive feedback regulation of endothelial Ca²⁺ signals, likely via amplification of influx through membrane cation channels. K_Ca2.3 channels have recently been implicated in flow-mediated dilation of the arterial vasculature and may contribute to the crucial homeostatic role of shear stress in preventing vascular wall remodeling and progressive vascular disease (i.e., atherosclerosis). The impact of K_Ca2.3 channels on endothelial Ca²⁺ signaling under physiologically relevant shear stress conditions remains unknown. Methods: In the current study, we employ mice expressing an endothelium-specific Ca²⁺ fluorophore (cdh5-GCaMP8) to characterize the K_Ca2.3 channel influence on the dynamic Ca²⁺ signaling profile along the arterial endothelium in the presence and absence of shear-stress. Results: Our data indicate K_Ca2.3 channels have a minimal influence on basal Ca²⁺ signaling in the carotid artery endothelium in the absence of flow, but they contribute substantially to amplification of Ca²⁺ dynamics in the presence of flow and their influence can be augmented through exogenous positive modulation. Conclusions: The findings suggest a pivotal role for K_Ca2.3 channels in adjusting the profile of homeostatic dynamic Ca²⁺ signals along the arterial intima under flow. Full article

Background: Bariatric surgery is a safe and effective procedure for treating obesity and metabolic conditions such as type 2 diabetes mellitus (T2DM). Remodeling of the extracellular matrix (ECM) supports adipose tissue expansion and its metabolic activity, where matrix metalloproteinases (MMPs) play a key role in ECM regulation. The MMPs, particularly MMP-2 and MMP-9, are elevated in patients with morbid obesity, metabolic syndrome, and T2DM. Objectives: To evaluate the effect of weight loss in bariatric surgery patients using oxidative stress markers and to compare MMP levels in patients undergoing bariatric surgery. Methods: This was a prospective, controlled study including 45 morbidly obese patients with T2DM (BMI > 35 kg/m²) who underwent RYGB (n = 24) or VG (n = 21). Weight loss was assessed through anthropometric measurements (weight, height, BMI). MMP-2 and MMP-9 levels were measured preoperatively and at 3 and 12 months postoperatively. Results: Significant and sustained weight loss was observed after surgery in both groups, with reductions in BMI. MMP-2 and MMP-9 levels decreased significantly after one year of follow-up. Conclusions: Bariatric surgery is an effective long-term intervention for weight loss and associated comorbidities, including T2DM. MMP-2 and MMP-9 proved to be effective markers of extracellular matrix remodeling, with significant reductions following surgery. Full article

People, in increasing numbers, are seeking orthodontic treatment to correct malocclusion, while some of them are suffering from orthodontically induced inflammatory root resorption (OIIRR). Recent evidence suggests that the immune-inflammatory response occurring during bone remodeling may be responsible for OIIRR. Ferroptosis, a new type of programmed cell death (PCD), has been found to have a close interrelation with inflammation during disease progression. While ferroptosis has been extensively studied in bone-related diseases, its role in OIIRR is poorly understood. Considering that the tooth root shares a lot of similar characteristics with bone, it is reasonable to hypothesize that ferroptosis contributes to the development of OIIRR. Nevertheless, direct evidence supporting this theory is currently lacking. In this review, we introduced ferroptosis and elucidated the mechanisms underlying orthodontic tooth movement (OTM) and OIIRR, with a special focus on the pivotal role inflammation plays in these processes. Additionally, we covered recent research exploring the connections between inflammation and ferroptosis. Lastly, we emphasized the important regulatory function of ferroptosis in bone homeostasis. Further investigations are required to clarify the modulation mechanisms of ferroptosis in OIIRR and to develop novel and potential therapeutic strategies for the management of OIIRR. Full article

G-protein-coupled receptors (GPCRs) have emerged as critical regulators of bone development and remodeling. In this study, we aimed to identify specific GPCR mutations in osteoporotic patients via next-generation sequencing (NGS). We performed NGS sequencing of six genomic DNA samples taken from osteoporotic patients and two genomic DNA samples from healthy donors. Next, we searched for single-nucleotide polymorphisms (SNPs) in GPCR genes that are associated with osteoporosis. For three osteoporotic patients and one healthy donor, bone biopsies were used to generate patient-specific mesenchymal stem cell (MSC) lines, and their ability to undergo osteodifferentiation was analyzed. We found that MSCs derived from osteoporotic patients have a different response to osteoinductive factors and impaired osteogenic differentiation using qPCR and histochemical staining assays. The NGS analysis revealed specific combinations of SNPs in GPCR genes in these patients, where SNPs in ADRB2 (rs1042713), GIPR (rs1800437), CNR2 (rs2501431, rs3003336), and WLS (rs3762371) were associated with impaired osteogenic differentiation capacity. By integrating NGS data with functional assessments of patient-specific cell lines, we linked GPCR mutations to impaired bone formation, providing a foundation for developing personalized therapeutic strategies. SNP analysis is recognized as a proactive approach to osteoporosis management, enabling earlier interventions and targeted preventive measures for individuals at risk. Furthermore, SNP analysis contributes to the development of robust, holistic risk prediction models that enhance the accuracy of risk assessments across the population. This integration of genetic data into public health strategies facilitates healthcare initiatives. This approach could guide treatment decisions tailored to the patient’s genetic profile and provide a foundation for developing personalized therapeutic strategies. Full article

The most time-consuming aspect of dental prosthesis installation is the osseointegration of a metal implant with bone tissue. The acceleration of this process may be achieved through the use of extracorporeal shock wave therapy. The objective of this study is to investigate the conditions for osseointegration of the second premolar implant in the mandibular segment through the use of a poroelastic model implemented in the movable cellular automaton method. The mandibular segment under consideration includes a spongy tissue layer, 600 µm in thickness, covered with a cortical layer, 400 µm in thickness, and a gum layer, 400 µm in thickness. Furthermore, the periodontal layers of the roots of the first premolar and first molar were considered, while the implant of the second premolar was situated within a shell of specific tissue that corresponded to the phase of osseointegration. The model was subjected to both physiological loading and shock wave loading across the three main phases of osseointegration. The resulting fields of hydrostatic pressure and interstitial fluid pressure were then subjected to analysis in accordance with the mechanobiological principles. The results obtained have indicated that low-intensity shock wave therapy can accelerate and promote direct osseointegration: 0.05–0.15 mJ/mm² in the first and second phases and less than 0.05 mJ/mm² in the third phase. In comparison to physiological loads (when bone tissue regeneration conditions are observed only around the implant distal end), shock waves offer the primary advantage of creating conditions conducive to osseointegration along the entire surface of the implant simultaneously. This can significantly influence the rate of implant integration during the initial osteoinduction phase and, most crucially, during the longest final phase of bone remodeling. Full article

Atrial fibrillation (AF) and cancer are increasingly recognized as interrelated conditions, with cancer patients showing elevated incidences of AF, and there is evidence that AF may sometimes precede cancer diagnoses. This comprehensive review investigates the epidemiology, pathophysiology, and management challenges associated with AF in cancer patients. Epidemiologically, several cancers are more closely related to increased rates of AF, including lung, colorectal, gastrointestinal, and hematologic malignancies. Mechanistically, both AF and cancer share pathophysiological pathways centered on inflammation, oxidative stress, and common cardiovascular risk factors, such as hypertension, obesity, and diabetes. The inflammatory microenvironment in tumors, marked by increased cytokines and growth factors, promotes atrial remodeling and AF susceptibility. Elevated reactive oxygen species (ROS) levels, driven by the metabolic demands of cancer, further contribute to atrial fibrosis and structural changes. Moreover, many anticancer treatments exacerbate AF risk. Management of AF in cancer patients presents many unique challenges and requires a multidisciplinary approach. Rate and rhythm control strategies are complicated by potential drug–drug interactions and limited data surrounding early implementation of rhythm control strategies in cancer patients. Interventional approaches such as catheter ablation, though effective in maintaining sinus rhythm, carry significant perioperative risk in patients with malignancy. Stroke prevention with anticoagulants is essential but requires cautious administration to avoid heightened bleeding risks, particularly in patients undergoing chemotherapy. Further, the limited applicability of standard risk stratification tools like CHA2DS2-VASc in this population complicate decisions regarding anticoagulation. This review highlights the bidirectional relationship between AF and cancer, the difficulties in management, and the critical need for further research in this field. Full article

Background/Objectives: A novel patient group with chronic pulmonary fibrosis is emerging post COVID-19. To identify patients at risk of developing post-COVID-19 lung fibrosis, we here aimed to identify systemic proteins that overlap with fibrotic markers identified in patients with idiopathic pulmonary fibrosis (IPF) and may predict COVID-19-induced lung fibrosis. Methods: Ninety-two proteins were measured in plasma samples from hospitalized patients with moderate and severe COVID-19 in Sweden, before the introduction of the vaccination program, as well as from healthy individuals. These measurements were conducted using proximity extension assay (PEA) technology with a panel including inflammatory and remodeling proteins. Histopathological alterations were evaluated in explanted lung tissue. Results: Connecting to IPF pathology, several proteins including decorin (DCN), tumor necrosis factor receptor superfamily member 12A (TNFRSF12A) and chemokine (C-X-C motif) ligand 13 (CXCL13) were elevated in COVID-19 patients compared to healthy subjects. Moreover, we found incrementing expression of monocyte chemotactic protein-3 (MCP-3) and hepatocyte growth factor (HGF) when comparing moderate to severe COVID-19. Conclusions: Both extracellular matrix- and inflammation-associated proteins were identified as overlapping with pulmonary fibrosis, where we found DCN, TNFRSF12A, CXCL13, CXCL9, MCP-3 and HGF to be of particular interest to follow up on for the prediction of disease severity. Full article

Background: Secondary mitral regurgitation (SMR) is characterized by a pathological process impacting the left ventricle (LV) as opposed to the mitral valve (MV). In the absence of structural alterations to the MV, the expansion of the LV or impairment of the papillary muscles (PMs) may ensue. A number of technical procedures are accessible for the purpose of determining the optimal resolution for MR. Nevertheless, there is a dearth of rigorous data to facilitate a comparative analysis of MV replacement, MV repair (including subvalvular repair), and transcatheter mitral valve interventions (TMV-Is). The objective of this investigation is to evaluate and compare the efficacy and clinical outcomes of transcatheter mitral valve repair (TMV-r) utilizing the edge-to-edge mitral valve repair (TEER) procedure in comparison to conventional surgical mitral valve interventions (S-SMVis) in patients with secondary mitral regurgitation. Methods and analysis: A consortium of five cardiac surgery institutions from four European states and Japan have joined forces to establish a multicenter observational registry, designated TEERMISO. Patients who underwent technical procedures for SMR between January 2007 and December 2023 will be enrolled consecutively into the TEERMISO registry. The investigation team evaluated the comparative efficacy of replacement and repair techniques, utilizing both the standard surgical methodology and the transcatheter intervention. The primary clinical outcome will be the degree of left ventricular remodeling, as assessed by the left ventricular end-diastolic volume index, at 10 years. The forthcoming research will assess a variety of secondary endpoints, among which all-cause mortality will be the primary endpoint. Subsequent assessments will be made in the following order: functional status, hospitalization, neurocognition, physiological measures (echocardiographic assessment), occurrence of adverse clinical incidents, and reoperation. Ethics and dissemination: The multicenter design of the database is anticipated to reduce the potential for bias associated with institutional caseload and surgical experience. All participating centers possess an established mitral valve protocol that facilitates comprehensive follow-up and management of any delayed mitral complications following replacement surgery or surgical repair of the secondary mitral regurgitation. The data collected will provide insights into the impact of diverse surgical approaches on standard mitral valve surgery and TEER. This will facilitate the evaluation of LV remodeling over the course of long-term post-procedural follow-up. Trial Registration: ClinicalTrials.gov ID: NCT05090540; IRB ID: 202201143 Full article

Objective: To develop an unsupervised artificial intelligence algorithm for identifying and quantifying the presence of false lumen thrombosis (FL) after Frozen Elephant Trunk (FET) operation in computed tomography angiographic (CTA) images in an interdisciplinary approach. Methods: CTA datasets were retrospectively collected from eight patients after FET operation for aortic dissection from a single center. Of those, five patients had a residual aortic dissection with partial false lumen thrombosis, and three patients had no false lumen or thrombosis. Centerlines of the aortic lumen were defined, and images were calculated perpendicular to the centerline. Lumen and thrombosis were outlined and used as input for a variational autoencoder (VAE) using 2D convolutional neural networks (2D CNN). A 2D latent space was chosen to separate images containing false lumen patency, false lumen thrombosis and no presence of false lumen. Classified images were assigned a thrombus score for the presence or absence of FL thrombosis and an average score for each patient. Results: Images reconstructed by the trained 2D CNN VAE corresponded well to original images with thrombosis. Average thrombus scores for the five patients ranged from 0.05 to 0.36 where the highest thrombus scores coincided with the location of the largest thrombus lesion. In the three patients without large thrombus lesions, average thrombus scores ranged from 0.002 to 0.01. Conclusions: The presence and absence of a FL thrombus can be automatically classified by the 2D CNN VAE for patient-specific CTA image datasets. As FL thrombosis is an indication for positive aortic remodeling, evaluation of FL status is essential in follow-up examinations. The presented proof-of-concept is promising for the automated classification and quantification of FL thrombosis. Full article

The receptor for advanced glycation end-products (RAGE), a member of the immunoglobulin superfamily, is expressed in various cell types and mediates cellular responses to a wide range of ligands. The activation of RAGE triggers complex signaling pathways that drive inflammatory, oxidative, and proliferative responses, which are increasingly implicated in the pathogenesis of skin diseases. Despite its well-established roles in conditions such as diabetes, cancer, and chronic inflammation, the contribution of RAGE to skin pathologies remains underexplored. This review synthesizes current findings on RAGE’s involvement in the pathophysiology of skin diseases, including conditions such as psoriasis, atopic dermatitis, and lichen planus, focusing on its roles in inflammatory signaling, tissue remodeling, and skin cancer progression. Additionally, it examines RAGE-modulating treatments investigated in dermatological contexts, highlighting their potential as therapeutic options. Given RAGE’s significance in a variety of skin conditions, further research into its mediated pathways may uncover new opportunities for targeted interventions in skin-specific RAGE signaling. Full article

This article presents an overview of thermal calculation methods used in boilers powered by fossil fuels (solid, liquid or gas). The analysis was carried out mainly in terms of combustion chamber calculation methods. Changing standards and legal regulations regarding the use of fossil fuels in Europe and the world make it necessary to adapt calculation methods and boiler design to current requirements, and many of them are related to outdated boiler models or for fuels that are no longer so heavily used in industrial solutions. Current research and development trends implemented in the EU and in the world related to the issues of the European Green Deal, the Fit for 55 directive and other ecological trends in the energy sector make it necessary to verify and remodel the calculation methods used so far in terms of the thermal efficiency of the device, fuel consumption or the use of fuels not previously used in their wide range in a wider application. Hence, the knowledge and updating of the state of knowledge in the field of the thermal calculation of boilers in terms of their environmental performance is necessary and strongly sought after by researchers. It is undoubted that in the next few years, boilers will continue to be the main source of thermal energy, especially in the power industry or industry. A reasonable energy transition should be based on the direction of the thermal optimization of already functioning structures and adaptation of their operating parameters to the planned new ecological fuels in the sense of the intensification of energy converted from primary form to thermal energy, and in the last step, it should reorganize the energy and industrial sectors, leaving only these groups of devices treated as a stable and necessary source of energy. Therefore, it should be recognized that activities aimed at improving the thermal parameters of boilers should directly improve the thermal efficiency of the device, and this will translate into fuel savings and reduce their negative impact on the environment. Full article