Search Results (620)

Atherosclerosis begins with endothelial dysfunction, inflammatory activation, and immune-cell recruitment within a spatially organized vascular wall. Conventional static cultures and Transwell systems are advantageous for isolated readouts, but they fail to effectively recapitulate multicellular compartmentalization, extracellular matrix support, and dynamic perfusion within a singular platform. Here, we present a four-channel microfluidic vascular-wall chip designed to reconstitute an endothelial cell-extracellular matrix-smooth muscle cell arrangement and to model early atherosclerosis-related inflammatory endothelial dysfunction. The device comprises a perfusable endothelial channel, a collagen I hydrogel region embedded with human aortic smooth muscle cells, a cell-free matrix region, and a culture-medium supply channel. Under physiological conditions, HUVECs formed a ZO-1-positive endothelial barrier and maintained high cellular viability. Stimulation with TNF-α and IL-1β (10 ng/mL each) elevated IL-6 secretion, promoted the recruitment of THP-1-derived M0-like macrophages, disrupted ZO-1 continuity, and increased FITC-dextran permeability without causing extensive cell death. The chip was subsequently utilized to evaluate metformin and atorvastatin therapies. The combinational treatment produced a more pronounced attenuation of MCP-1 secretion than either monotherapy under the inflammatory background. While this platform does not recapitulate advanced plaque formation, lipid deposition, foam-cell formation, or disturbed arterial shear, it successfully provides a microfluidic model of early inflammatory endothelial dysfunction to facilitate mechanistic studies and preliminary anti-inflammatory drug evaluation. Full article

With the expansion of modern protected agriculture, the amount of post-harvest tomato biomass has increased sharply. Conventional unmanaged disposal practices disrupt carbon flows and cause substantial environmental emissions. Tomato plant residues (TPRs), which are rich in lignocellulose and selected high-value secondary metabolites, have considerable potential as feedstocks for green industrial materials. However, their complex biophysical properties, high physiological moisture content, and recalcitrant cell-wall barriers hinder large-scale processing. This review systematically examines the mechanisms and process architectures for converting TPRs into macromolecular products. First, it analyzes cross-scale anatomical heterogeneity and dynamic rheological properties of TPRs, defining their physicochemical boundaries as industrial precursors. Second, it summarizes the development of physical field-coupled equipment, ranging from anti-tangling harvest-shredding to die-roller densification. Furthermore, it examines the core mechanisms of multi-field-coupled pretreatment technologies, including steam explosion, deep eutectic solvents (DES), and mechanochemistry, in deconstructing vascular skeletons and reducing multiphase mass-transfer resistance. Finally, this review discusses reconstruction pathways for TPR-derived components in advanced polymer materials, including biodegradable nanocellulose films, bio-based composites, aerogels, and lignin-based polyurethane networks. Overall, it links microscopic reaction kinetics with macroscopic equipment engineering, proposes a closed-loop material conversion system from in-field volume reduction to cascaded biorefinery, and provides an engineering framework for future multi-machine intelligent collaboration and continuous production across the industrial chain. Full article

Chronic lung disease of prematurity (CLD) is a common complication of preterm birth with a complex pathology. Recent epidemiologic studies have identified a link between neonatal exposure to di(2-ethylhexyl) phthalate (DEHP), frequently used in medical equipment, and the development of CLD. We hypothesize that DEHP exposure in the early neonatal period contributes to lung injury in newborn rats. Newborn rat pups were raised in one of the following environments: room air (RA), RA + DEHP, hyperoxia (60% oxygen), and hyperoxia + DEHP. Ambient DEHP was inhaled at a dose of 25 mg/m³ for 6 h daily for 14 days. Lung tissue and blood samples were collected on the 14th day of life. Independent exposure to DEHP and hyperoxia resulted in thicker pulmonary septal walls, fewer alveoli, increased pulmonary polymorphonuclear leukocytes and myeloperoxidase (MPO) activity and decreased expression of CD31 on endothelial cells in lung tissue. Additionally, DEHP-exposed rats showed higher serum malondialdehyde (MDA) levels and reduced vascular endothelial growth factor (VEGF) mRNA and protein levels compared to controls. Our experiments demonstrate that inhaled DEHP, with or without hyperoxia, resulted in a similar pattern of morphological lung injury and inflammation characteristic of CLD, suggesting an association with CLD of prematurity. Full article

Background: Marfan syndrome (MFS) is a connective tissue disorder caused by FBN1 mutations, leading to elastic fiber disarray and early thoracic aortic aneurysm (TAA) formation. Currently, pharmacological treatments lack specificity and only delay progression. We previously reported a specific TGFβ-driven miR-632 upregulation in MFS TAA tissues and blood causing smooth muscle cell dedifferentiation and aortic wall degeneration. This study evaluated the effects of three conventional antihypertensive drugs (β-blocker, ACE inhibitor, and sartan) on parietal remodeling, comparing them with a miR-632 inhibitor in an ex vivo TGFβ1-induced model of MFS TAA. Methods and Results: Using an ex vivo paired experimental framework based on independent biological pools of human TAA tissue, gene expression and Western blot analyses demonstrated that only losartan significantly reduced miR-632 and vascular degeneration markers. Notably, combined treatment with ramipril and carvedilol compromised losartan’s efficacy, highlighting the need for careful therapeutic selection. In this ex vivo setting, miR-632 inhibition demonstrated a promising capacity to counteract aortic remodeling, serving as a mechanistic proof-of-concept that warrants further preclinical in vivo validation. Conclusions: Our data emphasize that choosing the right treatment in MFS aortopathy requires understanding its specific impact on cellular pathways. Our findings identify losartan as the most effective standard drug in this model, while suggesting miR-632 as a potential future target to stabilize the aortic wall and, prospectively, delay surgery. Full article

Background and Clinical Significance: Placental site trophoblastic tumour (PSTT) is a malignant tumour of the implantation site intermediate trophoblasts. It has historically been described using terms such as atypical chorioepithelioma, atypical choriocarcinoma, syncytioma, and chorioepitheliosis. It belongs to one of the heterogeneous spectrums of gestational trophoblastic disease. It accounts for about 0.25 to 5% of all gestational trophoblastic neoplasia. The typical clinical presentation is alternating menorrhagia and amenorrhea, mildly elevated β-hCG, and radiological findings of a uterine mass. Case Presentation: A 32-year-old woman presented with a history of intermittent menorrhagia and amenorrhea, with a persistent mildly raised β-hCG level. Ultrasonography showed a hypoechoic lesion on the right side of the posterior wall of the uterus. She was diagnosed with a missed miscarriage, and an evacuation of the products of conception was performed. Histologically, the tissue fragments comprised cords and sheets of atypical intermediate trophoblast cells, with characteristic features of myometrial smooth muscle infiltration, vascular invasion, and vascular wall replaced by the neoplastic cells. Immunohistochemically, these cells are positive for β-hCG and GATA3, while negative for P63. Conclusions: PSTT is a rare form of gestational trophoblastic neoplasia. Early recognition of PSTT is essential because its clinical presentation may mimic benign pregnancy-related conditions, and diagnosis relies heavily on histopathological and immunohistochemical evaluation. Full article

The myocardium possesses one of the highest vascular densities in the body. The outermost wall layer of large and medium-sized vessels, the adventitia, forms a critical interface between the vasculature and the myocardium and serves as a reservoir for stem and progenitor cells capable of differentiating into all vascular wall lineages as well as innate immune cells, including macrophages. Current cardiac organoid models intrinsically develop networks of endothelial cords and small capillary-like structures that resemble cardiac microvessels. However, these microvessels mostly lack an adventitial compartment in vivo. Here, we present a potential alternative assembloid strategy that combines vascular segments from mouse and human origin with either cardiomyocytes or cardiac spheroids derived from human induced pluripotent stem cells, thereby incorporating large diameter vessels and the vascular adventitia into a cardiac tissue model. Within the assembloids, the myocardial component remained contractile and connected to the vascular adventitia, which displayed cellular sprouting toward the hiPSC-derived cardiac tissue. Immunostaining for vascular and immune markers revealed that the adventitia gave rise to endothelial sprouts and macrophage-like cells which integrated into the myocardial tissue. In summary, we present proof of concept for complex assembloids composed of vessel segments and human iPSC-derived cardiomyocytes which contain and maintain an in vivo-like adventitial compartment. We suggest this model may serve as a platform for investigating myocardial–stromal interactions, cardiac tissue repair, and functional remodeling under both physiological and pathological conditions. Furthermore, the incorporation of large-lumen vessel segments may enable future experimental perfusion, rendering the model particularly suitable for drug testing via intravascular delivery. Full article

Background/Objectives. Pulmonary arterial hypertension (PAH) is a rare but severe disease which leads to right ventricular (RV) maladaptation, failure and death. Currently approved drugs have limited impact on disease progression. A multitarget strategy consisting of adenosine A₂B receptor activation and phosphodiesterase-4 (PDE4) inhibition, combined with human mesenchymal stromal cells (hMSCs) therapy, was tested in experimental PAH. The main objective was to determine whether the combination improved pulmonary hemodynamics, vascular remodeling, and RV function, given the limited disease-modifying effects of currently approved vasodilators. Methods. Vascular reactivity was assessed in isolated rat pulmonary artery rings exposed to the dual-target compound (LASSBio-1860) alone or in the presence of either ZM-241385 or MRS-1706. PAH was induced in male Wistar rats with monocrotaline (MCT, 60 mg·kg⁻¹) and confirmed by a decrease in pulmonary artery acceleration time to ejection time ratio (PAAT/TET). Animals were randomized to receive vehicle, hMSC (single i.v. dose, 1 × 10⁵ cells), LASSBio-1860 (62 mg·kg⁻¹·day⁻¹, p.o., 14 days), or their combination. Outcomes included PAAT/TET and RV cardiac output (RV-CO) by echocardiography, RV systolic pressure (RVSP) by direct puncture, Fulton index and RV wall thickness, lung histology (perivascular cell counts and wall thickness), and RV protein expression (TGF-β, CaMKII) by Western blot. Results. LASSBio-1860 produced endothelium-independent vasorelaxation of rat pulmonary arteries, consistent with A₂B agonism and PDE4 inhibition. In MCT-induced PAH, combination of LASSBio-1860 and hMSCs resulted in recovery of PAAT/TET and RV-CO, decrease in RVSP, RV hypertrophy, vascular inflammation and remodeling by downregulation of ventricular TGF-β and CaMKII. Conclusions. Combination of LASSBio-1860 with hMSC improved RV function, attenuated pulmonary hypertension, RV and vascular remodeling, and reduced inflammatory/proliferative signaling in MCT induced-PAH, supporting a promising multitarget therapeutic strategy for PAH. Full article

In recent years, the study of interleukins (ILs), crucial cytokines involved in inflammation, has garnered significant attention within coronary artery disease including atherosclerosis. This review provides a detailed overview of anti-inflammatory ILs, elucidating their functions within the pathogenesis of atherosclerosis. We examine aspects of all the known anti-inflammatory ILs role in atherosclerosis, the direct impact of these ILs on the inflammation; endothelial, smooth vascular cells and macrophage’s function; and their interactions with signaling pathways and molecules. The potential for diagnostic possibilities and targeted drug therapy to modulate anti-inflammatory ILs activity in atherosclerosis was explored. Taken together, findings from recent studies suggest that the main pathways through which ILs exerts its anti-inflammatory effects are: (1) taking part in the regulation of cholesterol transport or oxidised low-density lipoprotein (oxLDL) phagocytosis (IL-1Ra and IL-36Ra—indirectly); (2) affecting different blood cells’ participation in the inflammation (monocytes, lymphocytes, macrophages); (3) taking place in the remodelation of the arterial wall (affecting smooth muscle and endothelium cells). Overall, IL-35, IL-37, and IL-38 appear to be the most promising for modulation of signaling pathways in experimental works and could be investigated as treatment targets. Recombinant IL-10 is investigated in experimental models as therapeutic tool. IL-1Ra is started being translated into clinical practice already. IL-13 and IL-19 are the least studied. It turns out that anti-inflammatory ILs are unlikely to serve as diagnostic markers for atherosclerosis due to their limited specificity and inconsistent associations with disease progression, as well as insufficient validation in large human cohorts. Moreover, key challenges related to delivery, dosing, and safety remain unresolved. Full article

Background and Clinical Significance: Susac syndrome is a rare autoimmune-mediated microangiopathy characterized by the triad of encephalopathy, branch retinal artery occlusion (BRAO), and sensorineural hearing loss. Due to its variable onset and protean manifestations, the syndrome is frequently misdiagnosed, potentially leading to delayed treatment and irreversible organ damage. Ocular involvement is common and often provides the first diagnostic clue. Multimodal imaging, particularly fluorescein angiography (FA) and optical coherence tomography (OCT) as well as optical coherence tomography angiography (OCT-A), enables the detection of both acute and chronic ischemic retinal changes. Their complementary application yields critical insights into disease activity, supports monitoring of relapses, and guides therapeutic strategies. Case Presentation: We describe two patients with Susac syndrome presenting with distinct ocular and neurological features. A 43-year-old male developed recurrent BRAOs in both eyes, documented by FA, OCT, and OCT-A, with preserved best-corrected visual acuity (BCVA) of 0.00 logMAR in both eyes (OU). OCT demonstrated progressive thinning of the retinal nerve fiber layer (RNFL) and inner retinal layers, consistent with sequelae of microinfarctions, while FA revealed focal arteriolar wall hyperfluorescence. Immunosuppressive therapy with corticosteroids and mycophenolate mofetil stabilized his condition. A 31-year-old female with a history of migraine and encephalopathy showed thinning of the RNFL and ganglion cell layer (GCL) with macular atrophy on OCT. FA demonstrated peripheral arteriolar wall hyperfluorescence and microaneurysms. Despite these structural alterations, visual acuity remained unaffected. Serial imaging initially demonstrated mild progression on OCT and OCT-A, followed by disease stabilization under systemic immunosuppressive therapy. Conclusions: These cases highlight the pivotal role of multimodal imaging in the early recognition and long-term monitoring of Susac syndrome. OCT provides a detailed assessment of retinal microinfarctions and chronic atrophy, while FA remains indispensable for detecting vascular leakage and disease activity. The complementary use of OCT, OCT-A, and FA enhances diagnostic accuracy, facilitates timely therapeutic interventions, and supports individualized management. Regular ophthalmological monitoring, including advanced imaging modalities, should be considered an essential component of care in Susac syndrome. Full article

Background: Immune dysregulation and clinical immunosuppression are biologically plausible contributors to thoracic aortic wall vulnerability through endothelial injury, protease-mediated extracellular matrix remodeling, vascular smooth muscle cell dysfunction, and impaired vascular repair. Yet, the clinical relevance of immunomodulated states to thoracic aortic aneurysm (TAA) incidence or growth and acute aortic syndromes remains undefined. Methods: This comprehensive review synthesizes clinical and translation evidence linking immunomodulated states in solid organ transplantation, autoimmune disease (predominantly systemic lupus erythematosus), HIV, and oncologic therapies to thoracic aortic dilation, aneurysmal progression, and acute aortic events. Principal Findings: Across transplant, autoimmune, and HIV cohorts, recurring themes include chronic immune dysregulation, endothelial dysfunction, proteolytic matrix remodeling, and impaired vascular repair capacity, although thoracic segment-specific longitudinal growth data remain limited and are often embedded within analyses of multiple vascular beds. In oncologic cohorts, aggregate analyses generally do not demonstrate uniform acceleration of aneurysm growth with malignancy or chemotherapy exposure, although agent-level models suggest that regimen-specific effects may be obscured in pooled estimates. Two studies most directly addressed our question in thoracic-relevant contexts reported (1) very low mean annual ascending aortic aneurysm growth (0.18 ± 0.64 mm/year) with no detectable association with chemotherapy or radiotherapy and (2) prior immunosuppressive/cytostatic chemotherapy exposure to be common in a proximal TAA surgical cohort (39.3%) without a clear difference in thoracic phenotype at presentation or postoperative outcomes. In HIV cohorts, available evidence supports modest but reproducible proximal aortic remodeling and a clinically meaningful aneurysm burden across vascular beds, yet definitive thoracic segment-specific natural history data remain limited. Conclusions: The available literature supports clinical vigilance and exposure-aware surveillance, while suggesting that thoracic aortic risk is unlikely to be uniform across immunosuppressive and cytotoxic therapies. Standardized, segment-specific longitudinal imaging with granular agent-level exposure characterization (dose, duration, sequencing, and combination regimens), consistent definitions of baseline diameter and growth, careful adjustment for key confounders, and prospective ascertainment of dissection/rupture and operative endpoints are needed to translate immunobiology into actionable risk stratification and long-term management strategies. Full article

Background: Segmental arterial mediolysis (SAM) is a rare, non-inflammatory, non-atherosclerotic, non-hereditary arteriopathy of unknown etiology that typically affects medium-sized visceral arteries. The absence of reliable diagnostic criteria poses a significant challenge. Consequently, the diagnosis of SAM should be considered in the setting of a distinctive combination of clinical features, angiographic findings, and histopathology. Renal artery involvement is uncommon, and its occurrence in the donor graft during kidney transplantation (KT) has not previously been reported. Case presentation: We report the case of a kidney graft from a deceased donor in her seventh decade of life, transplanted into a recipient in her seventh decade of life. Donor–recipient ABO compatibility was confirmed, and both complement-dependent cytotoxicity crossmatch and flow cytometry crossmatch were negative. Cold ischemia time was 14 h, and warm ischemia time was 20 min. Immediately after declamping, massive thrombosis of the graft renal artery was observed and confirmed using an intraoperative flowmeter. The arterial anastomosis was taken down, the thrombus was removed, the artery was flushed with heparin, and the anastomosis was reconstructed using interrupted sutures. Despite revision, no arterial flow was detected, and the graft was deemed unsalvageable and explanted. Histopathological examination showed thinning of the tunica media, reduced smooth muscle cells on desmin staining, medial-adventitial dissection, and occlusive thrombosis, findings considered likely attributable to SAM. Conclusions: This case suggests that occult donor arterial wall disease compatible with SAM may present catastrophically during KT and may lead to immediate graft loss despite standard surgical salvage attempts. Although no validated strategy currently exists to screen for or prevent occult SAM in asymptomatic donors, awareness of this entity may assist transplant surgeons and pathologists in the evaluation of unexplained early graft arterial thrombosis, donor-graft vascular pathology, and communication with centres receiving paired organs from the same donor. Full article

Heritable thoracic aortic diseases (HTAD) are inherited conditions that increase the risk of thoracic aortic aneurysms, dissections, and premature aortic rupture. Advances in human genetics and experimental models have transformed our understanding of these disorders from a phenotype-based classification system to a mechanism-based view involving extracellular matrix (ECM) architecture, transforming growth factor-β (TGFβ) signaling, and vascular smooth muscle cell contractility. Marfan syndrome, Loeys–Dietz syndrome, and nonsyndromic HTAD demonstrate how genetic mutations can disrupt the components that stabilize the aortic wall. These pathogenic mechanisms influence matrix organization, intracellular signaling, and the contractile machinery within the mechanically stressed proximal aorta. In this review, we summarize current mechanistic insights into the major forms of HTAD and discuss how new molecular and cellular concepts could influence surveillance, genetic counseling, and genotype-guided therapeutic strategies. Full article

Phenolics in Sphagnum can inhibit its microbial decomposition. Climate warming and drainage have driven vascular plants, such as Ericaceae, to expand into Sphagnum-dominated peatland. However, the impact of fine root invasion by Rhododendron auriculatum Hemsl. on Sphagnum decomposition and changes in phenolic compounds remains unclear. This study compared Sphagnum decomposition in a Sphagnum palustre L.-dominated peatland and an R. auriculatum (Sapling)–S. palustre peatland by examining the microscopic structure of S. palustre and microbial community composition. Decomposition was higher in the R. auriculatum–S. palustre peatland. On this site, bacterial metabolic types such as aerobic chemoheterotrophy and chemoheterotrophy had higher relative abundances, as did fungal trophic modes, including those with combined ectomycorrhizal, ericoid mycorrhizal, and saprotrophic functions. Acid phosphatase, laccase, total nitrogen (TN), C/N ratio (C:N), and pH differed significantly across decomposition stages. Microbial communities are affected by physicochemical factors and enzyme activities. Untargeted metabolomics revealed more downregulated than upregulated phenolics, cinnamic acids, and tannins, indicating loss of phenolic compounds. In summary, R. auriculatum fine root invasion altered enzyme activities and physicochemical properties, driving the restructuring of bacterial and fungal trophic modes and accelerating S. palustre cell wall and hyaline cell decomposition. Full article

Astrocytes are key regulators of neuronal, metabolic, and vascular homeostasis, yet their morphological diversity and involvement in alcohol-related brain pathology remain incompletely characterized. In this study, we investigated astrocytic morphology in the human striatum of control individuals and subjects with short- and long-term alcohol exposure using immunohistochemistry combined with Sholl-based morphometric analysis, and ultrastructural assessment. GFAP immunohistochemistry was used to identify astrocytes, assess their morphology, and manually quantify GFAP⁺ cells in gray and white matter, followed by Sholl-based morphometric analysis to characterize astrocytic branching architecture and spatial organization. The number of GFAP⁺ astrocytes differed between tissue compartments, with a significant increase in white matter in alcohol-exposed individuals and no detectable change in gray matter. Morphometric analysis revealed pronounced astrocytic heterogeneity across all study groups. Sholl-derived metrics supported the distinction of six recurrent astrocytic morphometric profiles in the human striatum, distinguished by soma size, branching complexity, process length, and cell territory size. These profiles were present across gray and white matter, indicating intrinsic astrocytic structural diversity. Ultrastructural analysis further revealed alcohol-associated alterations at the astrocyte–vascular interface, including swelling of perivascular astrocytic endfeet, accumulation of intermediate filaments, and focal reductions in vascular wall coverage. Together, these findings demonstrate substantial astrocytic structural diversity in the human striatum accompanied by alcohol-related gliovascular remodeling. Full article

Mucormycosis, triggered by fungi of the order Mucorales, represents a potentially fatal invasive mycosis, with death rates over 50% despite intensive therapy. The COVID-19 pandemic brought a sharp increase in cases, especially in individuals with diabetes mellitus and those undergoing immunosuppressive treatment, emphasizing significant gaps in our comprehension of disease pathogenesis. Emerging molecular studies have highlighted key virulence factors, such as the CotH family of invasins that facilitate endothelial invasion via interaction with glucose-regulated protein 78 (GRP78), complex iron acquisition systems necessary for fungal growth, and the release of mucoricin, a ricin-like toxin that impairs vascular integrity. Host defense depends mainly on innate immunity, with neutrophils and macrophages working as critical effector cells, while adaptive Th1 and Th17 responses aid in the fungal removal. Mucorales use a variety of immune evasion techniques, such as pathogen-associated molecular pattern (PAMP) masking via cell wall transformations, resistance to phagocytic death, and metabolic utilization of host factors including hyperglycemia and increased free iron in diabetic ketoacidosis (DKA). This review summarizes current evidence of the molecular processes underlying mucormycosis pathogenesis, underscoring host–pathogen interactions at the cellular and molecular levels, immune evasion tactics, and translational potential for new diagnostic and therapeutic approaches. Comprehending these molecular processes is crucial for creating efficient therapies against mucormycosis in an era of growing immunocompromised patients and expanding infectious disease synergies. Full article