Search Results (182)

The abnormal growth of smooth muscle cells (SMCs) contributes to the vascular remodeling associated with coronary artery disease, a leading cause of death in women. Estradiol (E2) mediates cardiovascular protective actions, in part, by inhibiting the abnormal growth (proliferation and migration) of SMCs through various mechanism. Since microRNAs (miRNAs) play a major role in regulating cell growth and vascular remodeling, we hypothesize that miRNAs may mediate the protective actions of E2. Following preliminary leads from E2-regulated miRNAs, we found that platelet-derived growth factor (PDGF)-BB-induced miR-193a in SMCs is downregulated by E2 via estrogen receptor (ER)α, but not the ERβ or G-protein-coupled estrogen receptor (GPER). Importantly, miR-193a is actively involved in regulating SMC functions. The ectopic expression of miR-193a induced vascular SMC proliferation and migration, while its suppression with antimir abrogated PDGF-BB-induced growth, effects that were similar to E2. Importantly, the restoration of miR-193a abrogated the anti-mitogenic actions of E2 on PDGF-BB-induced growth, suggesting a key role of miR-193a in mediating the growth inhibitory actions of E2 in vascular SMCs. E2-abrogated PDGF-BB, but not miR-193a, induced SMC growth, suggesting that E2 blocks the PDGF-BB-induced miR-193a formation to mediate its anti-mitogenic actions. Interestingly, the PDGF-BB-induced miR-193a formation in SMCs was also abrogated by 2-methoxyestradiol (2ME), an endogenous E2 metabolite that inhibits SMC growth via an ER-independent mechanism. Furthermore, we found that miR-193a induces SMC growth by activating the phosphatidylinositol 3-kinases (PI3K)/Akt signaling pathway and promoting the G1 to S phase progression of the cell cycle, by inducing Cyclin D1, Cyclin Dependent Kinase 4 (CDK4), Cyclin E, and proliferating-cell-nuclear-antigen (PCNA) expression and Retinoblastoma-protein (RB) phosphorylation. Importantly, in mice, treatment with miR-193a antimir, but not its control, prevented cuff-induced vascular remodeling and significantly reducing the vessel-wall-to-lumen ratio in animal models. Taken together, our findings provide the first evidence that miR-193a promotes SMC proliferation and migration and may play a key role in PDGF-BB-induced vascular remodeling/occlusion. Importantly, E2 prevents PDGF-BB-induced SMC growth by downregulating miR-193a formation in SMCs. Since, miR-193a antimir prevents SMC growth as well as cuff-induced vascular remodeling, it may represent a promising therapeutic molecule against cardiovascular disease. Full article

This work explores the morphogenesis of the skeletal mineral component, with a specific emphasis on hydroxyapatite (HAp) crystal assembly. Bone is fundamentally a triphasic biomaterial, consisting of an inorganic mineral phase, an organic matrix, and an aqueous component. The inorganic phase (hydroxyapatite), is characterized by its hexagonal prismatic nanocrystalline structure. We leverage a cellular automata (CA) paradigm to computationally simulate the mineralization process, leading to the formation of the bone’s hydroxyapatite framework. This model exclusively considers the physicochemical aspects of bone formation, intentionally excluding the biological interactions that govern in vivo skeletal development. To optimize computational efficiency, a simplified anatomical segment of a long bone (e.g., the femur) is modeled. This geometric simplification encompasses an outer ellipsoidal cylindrical boundary (periosteal envelope), an inner ellipsoidal surface defining the interface between cortical and cancellous bone, and a central circular cylindrical lumen representing the medullary cavity, which accommodates the bone marrow and primary vasculature. The CA methodology is applied to generate the internal bone microarchitecture, while deliberately omitting the design of smaller, secondary vascular channels. Full article

This case series presents four pediatric patients who developed tracheal complications after prolonged invasive mechanical ventilation. The first case involved an 11-year-old girl with severe hypoxic encephalopathy who developed extensive ulcerative granulation tissue obstructing 60% of the tracheal lumen. The second case was that of a 6-year-old boy with ACTA1-related nemaline myopathy who experienced recurrent tracheal obstruction due to granulomatous tissue formation. The third case involved a 9-year-old boy with hydroxyglutaric aciduria and a large plug obstructing his trachea. The last case involved a 19-year-old female with lissencephaly who developed a tracheoesophageal fistula. These cases highlight the importance of regular surveillance and early intervention in managing tracheal complications in pediatric patients with complex chronic conditions requiring long-term mechanical ventilation. The authors emphasize the need for specialized care and routine endoscopic examinations in order to prevent and address potentially life-threatening complications in this vulnerable patient population. Full article

Supported Pd-based catalysts have been widely applied in the hydrogenation of specific functional groups. Recent trends have focused on employing Pd-based heterogeneous catalysts supported on inorganic nanotubes, wherein inner surface functionalization modulates both palladium nanoparticle (Pd-NP) dispersion and the interaction between reactants and the catalyst surface, thereby influencing catalytic properties. This study aims to develop a catalytic system using amine-lumened halloysite nanotubes immobilizing Pd-NPs (Pd/HNTA) as catalysts for hydrogenation reactions. The formation of Pd-NPs within the organo-functionalized lumen—modified by 3-aminopropyltrimethoxysilane—is confirmed by transmission electron microscopy (TEM) imaging, which reveals a particle size of 2.2 ± 0.4 nm. For comparison, Pd-NPs supported on pristine halloysite (Pd/HNTP) were used as control catalysts, displaying a metal particle size of 2.8 ± 0.8 nm and thereby demonstrating the effect of organic functionalization on the halloysite nanotubes. Both catalysts were employed in the hydrogenation of furfural (FUR) and nitrobenzene (NB) as model reactions. Pd/HNTA demonstrated superior catalytic performance for both substrates, with TOF values of 880 h⁻¹ for FUR and 946 h⁻¹ for NB, and selectivities exceeding 98% for tetrahydrofurfuryl alcohol (THFOH) and aniline (AN), respectively. However, recyclability studies displayed that Pd/HNTA was deactivated at the 10 catalytic cycles during the hydrogenation of FUR, whereas, in the hydrogenation of NB, 5 catalytic cycles were achieved with maximum conversion and selectivity at 360 min. These results revealed that the liquid-phase environment plays a pivotal role in catalyst stability. In the hydrogenation of NB, the coproduction of H₂O adversely affects the interaction between the Pd particles and the inner amine-modified surface, increasing the deactivation of the catalyst with reuse. Thus, the Pd/HNTA catalyst holds significant promise for the development of noble-metal-based catalysts and their application in the transformation of other reducible organic functional groups via hydrogenation reaction. Full article

Background/Objectives: The aim of the present study was to explore the histopathological effects and tissue Vascular Endothelial Growth Factor (VEGF) levels of filgrastim and hyaluronic acid treatment in a rat model with experimentally induced Asherman syndrome. Methods: In this study, 26 female Sprague Dawley rats were used. First, a rat model of Asherman syndrome was established in two rats, and the remaining rats were randomly divided into three groups. A total of 0.1 mL trichloroacetic acid was applied to the right uterine horns of all groups to induce adhesion formation.Group I received no treatment, Group II received intrauterine hyaluronic acid treatment (0.01), Group III received subcutaneous Filgrastim treatment (50 μg/kg/day), and Group IV received both intrauterine hyaluronic acid and subcutaneous Filgrastim treatment. Histopathological analysis of uterine horns in the rats with and without Asherman syndrome, inflammation, glandular count, and fibrosis levels were examined. Tissue VEGF levels were investigated immunohistochemically. Results: Hyaluronic acid treatment resulted in an increase only in uterine lumen diameter and VEGF levels, while Filgrastim treatment led to an increase in uterine wall diameter, lumen diameter, gland count, and VEGF levels, as well as a decrease in fibrosis and inflammation scores. Combined treatment with filgrastim and hyaluronic acid showed an increase in lumen diameter, gland count, and VEGF levels, along with a decrease in inflammation and fibrosis scores (p < 0.05). Filgrastim treatment resulted in better effects for Asherman syndrome compared to hyaluronic acid treatment. There were no beneficial effects seen with the combined therapy. Conclusions: Filgrastim treatment resulted in better outcomes for Asherman syndrome compared to hyaluronic acid treatment. The combined therapy did not show additional benefits beyond what was achieved with Filgrastim treatment alone. Full article

Compartment boundaries divide the embryo into segments with distinct fates and functions. In the vascular system, compartment boundaries organize endothelial cells into arteries, capillaries, and veins that are the fundamental units of a circulatory network. For vascular smooth muscle cells (SMCs), such boundaries produce mosaic patterns of investment based on embryonic origins with important implications for the non-uniform distribution of vascular disease later in life. The morphogenesis of blood vessels requires vascular cell movements within compartments as highly-sensitive responses to changes in fluid flow shear stress and wall strain. These movements underline the remodeling of primitive plexuses, expansion of lumen diameters, regression of unused vessels, and building of multilayered artery walls. Although the loss of endothelial compartment boundaries can produce arterial–venous malformations, little is known about the consequences of mislocalization or the failure to form SMC-origin-specific boundaries during vascular development. We propose that the failure to establish a normal compartment boundary between cardiac neural-crest-derived SMCs of the 6th pharyngeal arch artery (future ductus arteriosus) and paraxial-mesoderm-derived SMCs of the dorsal aorta in mid-gestation embryos leads to aortic coarctation observed at birth. This model raises new questions about the effects of fluid flow dynamics on SMC investment and the formation of SMC compartment borders during pharyngeal arch artery remodeling and vascular development. Full article

Acute aortic dissection (AAD) is a critical cardiovascular emergency marked by the rupture of the aortic intima, resulting in blood infiltration into the media and the formation of a false lumen. AAD incidence varies by area, emphasizing the need for better diagnostics and epidemiological investigations. Bucharest University Emergency Hospital’s Emergency Department conducted this retrospective cohort analysis from May 2021 to May 2023. We examined 26 Stanford Type A aortic dissection patients to establish in-hospital mortality and one-year survival rates. The primary objective was to analyze demographic, clinical, and paraclinical factors and their impact on patient outcomes. A total of 57.7% of the study group was male and had a mean age of 58.2 years, and 69.2% of patients had hypertension, indicating its importance as a risk factor. Acute chest discomfort was reported by 53.8%, neurological problems by 30.8%, and syncope or hypotension by 42.3%. CT angiography and transthoracic echocardiogram (TTE) confirmed the diagnosis and assessed dissection severity. Pericardial effusion (19.2%) and moderate to severe aortic regurgitation (26.9%) were notable. Management varied by dissection intensity and location. Emergency surgery was performed in 61.5% of patients within 24 h of diagnosis, resulting in a 12.5% in-hospital death rate. Conservatively managed patients had a 60.0% in-hospital death rate. Timely intervention is crucial, since the surgical cohort had an 87.5% one-year survival rate compared to 30% for the conservatively managed cohort. Acute renal damage (25%), protracted mechanical ventilation (31.3%), and advanced supportive care infections were postoperative sequelae. Conservative care exacerbated visceral ischemia (20%) and heart failure (10%). Advanced age and hypotension upon admission were independent mortality predictors, emphasizing the need for early risk assessment and personalized treatment. Multimodal imaging, timely surgical referral, and excellent postoperative care improve AAD outcomes, according to this study. Full article

Background and Objectives: The current study was designed as a prospective laboratory investigation to evaluate the histopathological effects and VEGF (vascular endothelial growth factor) expression in uterine tissue following treatment with a combination of methylprednisolone and hyaluronic acid in a rat model of experimentally induced Asherman Syndrome. Materials and Methods: Twenty-six female Sprague-Dawley rats were used. Trichloroacetic acid was applied to the right uterine horns of all the groups to induce adhesion formation. First, we induced the Asherman model in two rats (Group 1). The remaining rats were divided into the following three groups: Group 2 received intrauterine hyaluronic acid treatment, Group 3 received oral methylprednisolone treatment, and Group 4 received both treatments. Inflammation, gland count, and fibrosis levels were assessed histopathologically. VEGF levels were analyzed immunohistochemically. Results: Hyaluronic acid treatment increased the uterine lumen diameter and vascularization. Methylprednisolone treatment increased the gland count and uterine wall thickness while decreasing the inflammation and fibrosis scores. Combined treatment provided a statistically significant advantage over single treatments. In particular, the combined treatment group exhibited significantly lower fibrosis (p = 0.184) and inflammation scores (p = 0.071), as well as higher gland counts (p = 0.849) and VEGF expression (p = 0.114), compared to the groups receiving only methylprednisolone or hyaluronic acid. These differences indicate that the synergistic effect of the two agents results in more effective endometrial healing than when either treatment is applied alone. Conclusions: Methylprednisolone treatment significantly prevented adhesion formation and reduced the inflammation and fibrosis scores compared to hyaluronic acid treatment alone. The combined treatment adds to the effects of the hyaluronic acid treatment alone and provides better healing. Full article

Coronary artery disease is a highly prevalent disease that constitutes the leading cause of mortality worldwide. Acute coronary syndromes are the most devastating form of presentation of coronary disease, involving the acute formation of a thrombus within the coronary vessel lumen, further leading to flow limitation and diminished myocardial perfusion. Vulnerable plaques, which are characterized by thin-cap fibroatheroma, a large lipid pool, and macrophage infiltration and spotty calcification of the cap, pose a higher risk of coronary events despite not being flow-limiting. Iterations in intravascular imaging and coronary computed tomography have largely increased the ability to detect and define vulnerable plaques, and its clinical impact in early- and mid-term outcomes has been confirmed in several studies. In this review, we aimed to revise the current concept of vulnerable coronary plaque and its repercussion, to summarize the main pharmacological approaches for its management, and to provide an updated overview of the available evidence on preventive percutaneous interventional strategies in this clinical setting. Full article

The membrane-aerated biofilm reactor (MABR) is an emerging technology for the biological treatment of wastewaters. It can achieve simultaneous nitrification and denitrification due to anoxic liquid conditions. The counter diffusion of oxygen and nutrients in the biofilm allows for aerobic and anoxic layers, providing conditions where the formation, accumulation and consumption of nitrous oxide can all occur. The microbial processes involved in the production and consumption of N₂O are complex, and, due to the innovative nature of the MABR, understanding the influence of operational factors helps to minimise N₂O emission. Using a lab-scale 20L MABR system, an investigation was carried out to determine the influence of operational factors on the emission of nitrous oxide from the reactor. A direct link between the nitrous oxide emissions and bulk liquid conditions could not be established with only limited statistical correlation between them. It was found that under both steady loading rates and transient conditions, the emission of nitrous oxide was most influenced by the air flow rate through the membranes. The majority of N₂O emissions occurred via the membrane off-gas and not through the liquid. N₂O flux through the membrane was influenced not only by the accumulation of N₂O in the biofilm side but also by the gas residence time on the lumen side. Therefore, minimising the air flow rate is an effective strategy to mitigate nitrous oxide emissions from the MABR. Full article

The aim of this study was to verify whether the expression of proteins related to the formation of invadopodia, MT1-MMP, cortactin, Tks-4 and Tks-5 is associated with the degree of tumor invasiveness of different types of unicystic ameloblastomas. An immunohistochemical study was performed on 29 unicystic ameloblastoma (UA) samples, 9 conventional ameloblastoma (CAM) samples and 9 dental follicle (DF) samples. The potential for tumor invasiveness was assessed based on the immunoexpression of the following invadopodia-forming proteins: MT1-MMP, cortactin, Tks-4 and Tks5. Mural unicystic ameloblastoma (MUA) showed higher MT1-MMP, cortactin, Tks-4, and Tks-5 immunoexpression than luminal and intra-luminal types. Conventional ameloblastoma exhibited lower MT1-MMP, cortactin, and Tks-5 expression compared to MUA. MUA’s cystic capsule neoplastic cells had significantly higher MT1-MMP, cortactin, Tks-4, and Tks-5 expression than lumen cells. Dental follicles showed minimal expression. Neoplastic cells in the cystic capsule of mural unicystic ameloblastomas showed higher invadopodia-related protein expression than lumen and luminal/intraluminal cells, suggesting that proximity to the bone region influences the aggressive behavior of mural unicystic ameloblastomas more compared to other subtypes. Full article

This study aimed to evaluate the effects of CD146, a surface antigen of mesenchymal stem cells from human exfoliated deciduous teeth (SHEDs), on angiogenic potential. SHEDs were isolated from patients’ deciduous teeth and sorted into CD146-positive (CD146 + SHED) and CD146-negative (CD146 − SHED) populations. Three groups—non-sorted SHED, CD146 + SHED, and CD146 − SHED—were compared. Angiogenic potential was assessed by co-culturing each group with human umbilical vein endothelial cells (HUVECs) and evaluating lumen formation using an endothelial tube formation assay. The gene and protein expression levels of angiogenic markers, including vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2), cluster of differentiation 31 (CD31), and basic fibroblast growth factor (bFGF), were analyzed using a real-time polymerase chain reaction and enzyme-linked immunosorbent assay. The tube formation assay revealed significantly enhanced angiogenic potential in CD146 + SHED and non-sorted SHED compared to CD146 − SHED. The gene and protein expression levels of VEGF, VEGFR2, CD31, and bFGF were significantly upregulated in CD146 + SHED and non-sorted SHED, highlighting superior angiogenic capabilities in CD146 + SHED. CD146 + SHED demonstrated enhanced angiogenic potential compared to CD146 − SHED, supporting their use in regenerative therapies targeting angiogenesis. Full article

Sheep are an important livestock species whose gastrointestinal tract is essential for overall health. Feed contaminants such as bacterial toxins and mycotoxins severely damage the sheep intestine, yet the mechanisms remain mostly elusive partially due to the lack of physiologically relevant in vitro models. Here, we investigated molecular mechanisms underlying deoxynivalenol (DON)-induced toxicity by developing intestinal organoids from isolated intestinal crypts of Hu sheep. The organoids had a central lumen and monolayer epithelium, and could be continuously passaged, cryopreserved, and resuscitated. Histological and transcriptomic analysis showed that the intestinal organoids recapitulate the cell lineages and gene expression characteristics of the original intestinal tissues. Statistical analysis indicated that DON exposure significantly inhibited organoid formation efficiency, as well as the proliferation and activity of intestinal organoid cells. RNA-seq and Western blotting analysis further revealed that DON exposure induces intestinal toxicity by inhibiting the PI3K/AKT/GSK3β/β-catenin signaling pathway. Our study provides a novel example of organoid application in toxicity studies and reveals the signaling pathway involved in DON-induced toxicity in sheep, which is of great significance for improving mitigation strategies for DON. Full article

Hemodialysis (HD) is a critical treatment for patients with end-stage kidney disease (ESKD). The effectiveness of conventional dialyzers used there could be compromised during extended use due to limited blood compatibility of synthetic polymeric membranes and sub-optimal dialyzer design. In fact, blood flow in the hollow fiber (HF) membrane could trigger inflammatory responses and thrombus formation, leading to reduced filtration efficiency and limiting therapy duration, a consequence of flowing the patients’ blood through the lumen of each fiber while the dialysate passes along the inter-fiber space (IOF, inside-out filtration). This study investigates the development of HF membranes for “outside-in filtration” (OIF) in HD. In OIF, blood flows through the inter-fiber space while dialysate flows within the fiber lumens, reducing the risk of fiber clogging and potentially extending treatment duration. For the OIF mode, the membrane should have a blood-compatible outer selective layer in contact with the patient’s blood. We develop HFs for OIF via liquid-induced phase separation using PES/PVP (polyethersulphone/polyvinylpyrrolidone) blends. The fibers’ surface morphology (SEM, scanning electron microscopy), chemistry (ATR-FTIR—attenuated total reflection-Fourier transform infrared spectroscopy, XPS—X-ray photoelectron spectroscopy), transport properties, and uremic toxin removal from human plasma are evaluated and compared to commercial HFs. These membranes feature a smooth, hydrophilic outer layer, porous lumen, ultrafiltration coefficient of 13–34 mL m² h⁻¹ mmHg⁻¹, adequate mechanical properties, low albumin leakage, and toxin removal performance on par with commercial membranes in IOF and OIF. They offer potential for more efficient long-term HD by reducing clogging and systemic anticoagulation needs and enhancing treatment time and toxin clearance. Full article

Myocardial ischemia-reperfusion injury increases myocardial microvascular permeability, leading to enhanced microvascular filtration and interstitial fluid accumulation that is associated with greater microvascular obstruction and inadequate myocardial perfusion. A burst of reactive oxygen species and inflammatory mediators during reperfusion causes myosin light chain kinase (MLCK)-dependent endothelial hyperpermeability, which is considered a preventable cause of reperfusion injury. In the present study, a single intravenous injection of MLCK peptide inhibitor PIK7 (2.5 mg/kg or 40 mg/kg) was found to suppress the vascular hyperpermeability caused by ischemia/reperfusion injury in an in vivo rat model. The antiedemic effect of PIK7 is transient and ceases within 90 min of reperfusion. The early no-reflow detected for the first time after 30 min ischemia in this model of myocardial infarction reduces the area accessible for PIK7. Electron microscopy has shown membrane-bound blebs of endotheliocytes, which partially or completely obturate the capillary lumen, and few capillaries with signs of intercellular gap formation in samples obtained from the center of the early no-reflow zone in control and PIK7-injected rats. Co-injection of PIK7 with NO donor sodium nitroprusside (SNP) increases blood flow in the zone of early no-reflow, while reducing the increased vascular permeability caused by SNP. Full article