Search results for "Macromolecular Substance"
showing 10 items of 882 documents
Structural Heteropolysaccharide Adhesion to the Glycocalyx of Visceral Mesothelium
2018
Bioadhesives are biopolymers with potential applications in wound healing, drug delivery, and tissue engineering. Pectin, a plant-based heteropolysaccharide, has recently demonstrated potential as a mucoadhesive in the gut. Since mucoadhesion is a process likely involving the interpenetration of the pectin polymer with mucin chains, we hypothesized that pectin may also be effective at targeting the glycocalyx of the visceral mesothelium. To explore the potential role of pectin as a mesothelial bioadhesive, we studied the interaction of various pectin formulations with the mesothelium of the lung, liver, bowel, and heart. Tensile strength, peel strength, and shear resistance of the bioadhesi…
Cyclophosphamide plus vincristine and prednisone in the treatment of severe pemphigus vulgaris refractory to conventional therapy
1992
Five patients with severe pemphigus vulgaris refractory to conventional therapy with azathioprine and corticosteroids were treated with cyclophosphamide, vincristine and prednisone. One patient was not evaluable, while the remaining four patients showed a complete response. Duration of response was in the range of 13-94 months. Toxicity was mainly represented by alopecia, myelosuppression and gastrointestinal side-effects such as nausea/vomiting. Although cyclophosphamide and vincristine may induce severe side-effects, this association may be useful in controlling severe disease resistant to previous conventional therapies.
Oncogenic Deregulation of EZH2 as an Opportunity for Targeted Therapy in Lung Cancer.
2016
Abstract As a master regulator of chromatin function, the lysine methyltransferase EZH2 orchestrates transcriptional silencing of developmental gene networks. Overexpression of EZH2 is commonly observed in human epithelial cancers, such as non–small cell lung carcinoma (NSCLC), yet definitive demonstration of malignant transformation by deregulated EZH2 remains elusive. Here, we demonstrate the causal role of EZH2 overexpression in NSCLC with new genetically engineered mouse models of lung adenocarcinoma. Deregulated EZH2 silences normal developmental pathways, leading to epigenetic transformation independent of canonical growth factor pathway activation. As such, tumors feature a transcrip…
Beyond protein-coding genes
2019
A long non-coding RNA called lnc-NR2F1 regulates several neuronal genes, including some involved in autism and intellectual disabilities.
Septin/anillin filaments scaffold central nervous system myelin to accelerate nerve conduction
2016
Myelination of axons facilitates rapid impulse propagation in the nervous system. The axon/myelin-unit becomes impaired in myelin-related disorders and upon normal aging. However, the molecular cause of many pathological features, including the frequently observed myelin outfoldings, remained unknown. Using label-free quantitative proteomics, we find that the presence of myelin outfoldings correlates with a loss of cytoskeletal septins in myelin. Regulated by phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P2)-levels, myelin septins (SEPT2/SEPT4/SEPT7/SEPT8) and the PI(4,5)P2-adaptor anillin form previously unrecognized filaments that extend longitudinally along myelinated axons. By confoca…
Profilin 1 delivery tunes cytoskeletal dynamics toward CNS axon regeneration
2020
After trauma, regeneration of adult CNS axons is abortive, causing devastating neurologic deficits. Despite progress in rehabilitative care, there is no effective treatment that stimulates axonal growth following injury. Using models with different regenerative capacities, followed by gain- and loss-of-function analysis, we identified profilin 1 (Pfn1) as a coordinator of actin and microtubules (MTs), powering axonal growth and regeneration. In growth cones, Pfn1 increased actin retrograde flow, MT growth speed, and invasion of filopodia by MTs, orchestrating cytoskeletal dynamics toward axonal growth. In vitro, active Pfn1 promoted MT growth in a formin-dependent manner, whereas localizati…
Pivotal roles of glycogen synthase-3 in hepatocellular carcinoma
2017
Hepatocellular carcinoma (HCC) is one of the most common cancers in the world, and represents the second most frequently cancer and third most common cause of death from cancer worldwide. At advanced stage, HCC is a highly aggressive tumor with a poor prognosis and with very limited response to common therapies. Therefore, there is still the need for new effective and well-tolerated therapeutic strategies. Molecular-targeted therapies hold promise for HCC treatment. One promising molecular target is the multifunctional serine/threonine kinase glycogen synthase kinase 3 (GSK-3). The roles of GSK-3β in HCC remain controversial, several studies suggested a possible role of GSK-3β as a tumor …
Parasites Dampen Dendritic Cell Activation to Ensure Their Survival
2017
Dendritic cells (DCs) are critical for induction of protective immunity against Leishmania major. However, DC activation occurs only several weeks after parasite transmission. Parasites synthesize a macrophage-inducible C-type lectin (Mincle) ligand. Engagement of Mincle by the parasite ligand dampens DC activation, thus delaying induction of interferon-γ-producing T cells responsible for parasite eradication.
Asthmatics with high levels of serum surfactant protein D have more severe disease.
2016
Pulmonary surfactant is a mixture of lipids and surfactant-specific proteins that covers the alveolar surface, as well as the terminal conducting airways, lowering the surface tension at the air–liquid interface during breathing. The involvement of pulmonary surfactant in the pathophysiology of asthma has been suggested. An interesting working hypothesis is that the surface tension of the peripheral airways is altered in asthma, because the inflammatory process affects the structure and function of surfactant, leading to excessive airway narrowing and features of air trapping. We explored whether serum levels of surfactant protein D (SP-D) in asthmatics are related to the severity of the di…
The actin remodeling protein cofilin is crucial for thymic αβ but not γδ T-cell development
2018
Cofilin is an essential actin remodeling protein promoting depolymerization and severing of actin filaments. To address the relevance of cofilin for the development and function of T cells in vivo, we generated knock-in mice in which T-cell–specific nonfunctional (nf) cofilin was expressed instead of wild-type (WT) cofilin. Nf cofilin mice lacked peripheral αβ T cells and showed a severe thymus atrophy. This was caused by an early developmental arrest of thymocytes at the double negative (DN) stage. Importantly, even though DN thymocytes expressed the TCRβ chain intracellularly, they completely lacked TCRβ surface expression. In contrast, nf cofilin mice possessed normal numbers of γδ T cel…