Polystyrene nanoplastics induce vascular stenosis via regulation of the PIWI-interacting RNA expression profile.

Nanoplastics (NPs) have become common worldwide and attracted increasing attention due to their serious toxic effects. Owing to their higher surface area and volume ratios and ability to easily enter tissues, NPs impose more serious toxic effects than microplastics. However, the effect of NP exposure on vascular stenosis remains unclear.

N6-methyladenosine methylation mediates non-coding RNAs modification in microplastic-induced cardiac injury.

Owing to their potential adverse health effects, global contamination by microplastics (MPs) has attracted increased scientific and societal concerns. However, in vivo studies on MP toxicity, along with its effects and underlying mechanisms, remain limited. We recently found that non-coding RNA (ncRNAs) contribute to MP-mediated vascular toxicity.

circ_0086296 induced atherosclerotic lesions via the IFIT1/STAT1 feedback loop by sponging miR-576-3p.

Extensive inflammation of endothelial cells (ECs) facilitates atherosclerotic lesion formation. Circular RNA (circRNA) participates in atherosclerosis (AS)-related inflammation responses; however, whether and how circ_0086296 regulates atherosclerotic inflammation and lesions have not been investigated. Microarray analysis, quantitative real-time polymerase chain reaction, and fluorescence in situ hybridization assay were performed to detect the expression and location of hsa_circ_0086296 in human carotid artery plaques, aorta of atherosclerotic mice, and human umbilical vein endothelial cells (HUVECs).

Monoclonal antibodies: new chance in the management of B-cell acute lymphoblastic leukemia.

Objectives: This review aims to see the progress of several clinically-used monoclonal antibodies in treating ALL patients and how they improved patients' outcomes.

Methods: We searched Web of Science, Elsevier and PubMed for relevant published studies, and summarized eligible evidence on the management of newly-diagnosed and relapsed or refractory ALL with monoclonal antibodies. Ongoing trials were identified from ClinicalTrials.

Differentiation of Neural Crest Stem Cells in Response to Matrix Stiffness and TGF-β1 in Vascular Regeneration.

The neural crest stem cells derived from human induced pluripotent stem cells (iPSC-NCSCs) are a valuable autologous cell source for tissue engineering and regenerative medicine. In this study, we investigated how iPSC-NCSCs could be regulated to regenerate arteries by microenvironmental factors, including the physical factor of matrix stiffness, and the chemical factor of transforming growth factor beta-1 (TGF-β1). We found that, compared to soft substrate, stiff substrate drove iPSC-NCSCs differentiation into smooth muscle cells, which was further enhanced by TGF-β1.

Consciousness: New Concepts and Neural Networks.

The definition of consciousness remains a difficult issue that requires urgent understanding and resolution. Currently, consciousness research is an intensely focused area of neuroscience. However, to establish a greater understanding of the concept of consciousness, more detailed, intrinsic neurobiological research is needed.

Matrix stiffness modulates the differentiation of neural crest stem cells in vivo.

Stem cells are often transplanted with scaffolds for tissue regeneration; however, how the mechanical property of a scaffold modulates stem cell fate in vivo is not well understood. Here we investigated how matrix stiffness modulates stem cell differentiation in a model of vascular graft transplantation. Multipotent neural crest stem cells (NCSCs) were differentiated from induced pluripotent stem cells, embedded in the hydrogel on the outer surface of nanofibrous polymer grafts, and implanted into rat carotid arteries by anastomosis.

Mucin covalently bonded to microfibers improves the patency of vascular grafts.

Due to high incidence of vascular bypass procedures, an unmet need for suitable vessel replacements exists, especially for small-diameter (<6 mm) vascular grafts. Here, we developed a novel, bilayered, synthetic vascular graft of 1-mm diameter that consisted of a microfibrous luminal layer and a nanofibrous outer layer, which was tailored to possess the same mechanical property as native arteries. We then chemically modified the scaffold with mucin, a glycoprotein lubricant on the surface of epithelial tissues, by either passive adsorption or covalent bonding using the di-amino-poly(ethylene glycol) linker to microfibers.

The effect of stromal cell-derived factor-1α/heparin coating of biodegradable vascular grafts on the recruitment of both endothelial and smooth muscle progenitor cells for accelerated regeneration.

Small-diameter synthetic vascular grafts have high failure rate and tissue-engineered blood vessels are limited by the scalability. Here we engineered bioactive materials for in situ vascular tissue engineering, which recruits two types of endogenous progenitor cells for the regeneration of blood vessels. Heparin was conjugated to microfibrous vascular grafts to suppress thrombogenic responses, and stromal cell-derived factor-1α (SDF-1α) was immobilized onto heparin to recruit endogenous progenitor cells.

Uniaxial mechanical strain modulates the differentiation of neural crest stem cells into smooth muscle lineage on micropatterned surfaces.

Neural crest stem cells (NCSCs) play an important role in the development and represent a valuable cell source for tissue engineering. However, how mechanical factors in vivo regulate NCSC differentiation is not understood. Here NCSCs were derived from induced pluripotent stem cells and used as a model to determine whether vascular mechanical strain modulates the differentiation of NCSCs into smooth muscle (SM) lineage.

Induced pluripotent stem cells for neural tissue engineering.

Induced pluripotent stem cells (iPSCs) hold great promise for cell therapies and tissue engineering. Neural crest stem cells (NCSCs) are multipotent and represent a valuable system to investigate iPSC differentiation and therapeutic potential. Here we derived NCSCs from human iPSCs and embryonic stem cells (ESCs), and investigated the potential of NCSCs for neural tissue engineering.

Engineering bi-layer nanofibrous conduits for peripheral nerve regeneration.

Trauma injuries often cause peripheral nerve damage and disability. A goal in neural tissue engineering is to develop synthetic nerve conduits for peripheral nerve regeneration having therapeutic efficacy comparable to that of autografts. Nanofibrous conduits with aligned nanofibers have been shown to promote nerve regeneration, but current fabrication methods rely on rolling a fibrous sheet into the shape of a conduit, which results in a graft with inconsistent size and a discontinuous joint or seam.

VEGF Induces More Severe Cerebrovascular Dysplasia in Endoglin than in Alk1 Mice.

Brain arteriovenous malformations (BAVMs) are an important cause of intracranial hemorrhage (ICH) in young adults. A small percent of BAVMs is due to hereditary hemorrhagic telangiectasia 1 and 2 (HHT1 and 2), which are caused by mutations in two genes involved in TGF-β signaling: endoglin (ENG) and activin-like kinase 1 (ALK1). The BAVM phenotype is an incomplete penetrant in HHT patients, and the mechanism is unknown.

Nanofibrous Patches for Spinal Cord Regeneration.

The difficulty in spinal cord regeneration is related to the inhibitory factors for axon growth and the lack of appropriate axon guidance in the lesion region. Here we developed scaffolds with aligned nanofibers for nerve guidance and drug delivery in spinal cord. Blended polymers including Poly (l-lactic acid) (PLLA) and Poly (lactide-co-glycolide) (PLGA) were used to electrospin nanofibrous scaffolds with two-layer structure: aligned nanofibers in the inner layer and random nanofibers in the outer layer.

Preparation and analysis of endothelial progenitor cells associated with angiogenesis.

Endothelial progenitor cell-based therapy offers great potential to reduce morbidity and mortality in patients with vascular diseases. In animal models of ischemia, circulating endothelial progenitor cells (EPCs) have been shown to home to sites of active angiogenesis and differentiate into endothelial cells in response to tissue ischemia, vascular trauma, or tumor growth. These studies indicate a thorough understanding of EPCs function and role in angiogenesis as a potential therapeutic target for vascular diseases.

Nonischemic cerebral venous hypertension promotes a pro-angiogenic stage through HIF-1 downstream genes and leukocyte-derived MMP-9.

Cerebral venous hypertension (VH) and angiogenesis are implicated in the pathogenesis of brain arteriovenous malformation and dural arteriovenous fistulae. We studied the association of VH and angiogenesis using a mouse brain VH model. Sixty mice underwent external jugular vein and common carotid artery (CCA) anastomosis (VH model), CCA ligation, or sham dissection (n=20).

Restoring transcription factor HoxA5 expression inhibits the growth of experimental hemangiomas in the brain.

Hemangiomas are angiogenesis-dependent benign vascular tumors that can rupture and cause intracranial hemorrhages. We previously showed that the transcription factor homeobox A5 (HoxA5), which is absent in activated angiogenic endothelial cells can block angiogenesis. Here, we investigated whether restoring expression of HoxA5 blocks hemangioma growth by transplanting mouse hemangioendothelioma endothelial cells (EOMA) or HoxA5-expressing EOMA cells into the brains of mice.

Del-1 gene transfer induces cerebral angiogenesis in mice.

Developmental endothelial locus-1 (Del-1) is a novel angiomatrix protein that has been shown to stimulate a potent angiogenic response and promote functional recovery in hind-limb and cardiac ischemia in animal models; however, its impact on cerebral angiogenesis is unknown. In this study, we investigated whether Del-1 overexpression via gene transfer induces cerebral angiogenesis in a murine model, and examined Del-1 expression after ischemic stroke. Cerebral Del-1 overexpression was achieved with AAV (adeno-associated virus) transduction system via stereotactic injection.

Matrix metalloproteinase-9 inhibition attenuates vascular endothelial growth factor-induced intracerebral hemorrhage.

Background And Purpose: Human brain arteriovenous malformation tissue displays increased levels of vascular endothelial growth factor (VEGF) as well as matrix metalloproteinase (MMP)-9, a tissue protease associated with various intracerebral hemorrhage (ICH). We hypothesized that increased MMP-9 was associated with ICH induced by vascular endothelial growth factor hyperstimulation and that this effect could be attenuated by nonspecific MMP inhibition.

Methods: We used a mouse model with adenoviral vector-mediated vascular endothelial growth factor transduction in the brain.

Antithrombogenic property of bone marrow mesenchymal stem cells in nanofibrous vascular grafts.

Nanostructured biomaterials have tremendous potential for tissue engineering. However, the performance and integration of the nanomaterials in vivo are not well understood. A challenge in vascular tissue engineering is to develop optimal scaffolds and establish expandable cell sources for the construction of tissue-engineered vascular grafts that are nonthrombogenic and have long-term patency.

Interleukin-6 stimulates circulating blood-derived endothelial progenitor cell angiogenesis in vitro.

Circulating blood endothelial progenitor cells (EPCs) contribute to postnatal vasculogenesis, providing a novel therapeutic target for vascular diseases. However, the molecular mechanism of EPC-induced vasculogenesis is unknown. Interleukin-6 plays multiple functions in angiogenesis and vascular remodeling.

Neutrophil depletion decreases VEGF-induced focal angiogenesis in the mature mouse brain.

To explore the role of neutrophil-derived matrix metalloproteinases (MMPs) during angiogenesis in the brain, we hypothesized that transient neutrophil depletion attenuates the angiogenic response to focal hyperstimulation with vascular endothelial growth factor (VEGF). Brain focal angiogenesis was achieved using an adeno-associated virus delivered VEGF (AAV-VEGF) gene transfer in the mature mouse. Four groups of mice underwent AAV vector injection in the brain parenchyma: (1) AAV-LacZ; (2) AAV-VEGF; (3) AAV-VEGF plus anti-polymorphonuclear (PMN) antibody; and (4) AAV-VEGF plus serum.

Expression of hypoxia-inducible factor-1 and vascular endothelial growth factor in response to venous hypertension.

Objective: Experimentally, a fistula created surgically between the carotid artery and jugular vein, together with occlusion of venous sinuses, generate venous hypertension, which can induce dural arteriovenous fistula formation intracranially in rats. Our aim was to study the effect of nonischemic venous hypertension on the elaboration of the angiogenic signal, hypoxia-inducible factor-1 (HIF-1), and its downstream signal, vascular endothelial growth factor (VEGF).

Methods: Sixty rats were exposed to venous hypertension for periods ranging from 4 hours to 3 weeks.

Adeno-associated viral-vector-mediated hypoxia-inducible vascular endothelial growth factor gene expression attenuates ischemic brain injury after focal cerebral ischemia in mice.

Background And Purpose: Exogenous delivery of vascular endothelial growth factor gene (VEGF) may provide a useful approach to the treatment of brain ischemia. We investigated the use of a hypoxia-responsive element to control VEGF expression given for neuroprotection.

Methods: Three groups (n=36) of mice received AAVH9-VEGF, AAVH9-lacZ, or saline injection.