CD2AP promotes the progression of glioblastoma multiforme via TRIM5-mediated NF-kB signaling.

CD2-associated protein (CD2AP) is a scaffolding/adaptive protein that regulates intercellular adhesion and multiple signaling pathways. Although emerging evidence suggests that CD2AP is associated with several malignant tumors, there is no study investigating the expression and biological significance of CD2AP in glioblastoma multiforme (GBM). Here by studying public datasets, we found that CD2AP expression was significantly elevated in GBM and that glioma patients with increased CD2AP expression had a worse prognosis. We also confirmed the increase of CD2AP expression in clinical GBM samples and GBM cell lines. CD2AP overexpression in GBM cells promoted their proliferation, colony formation, migration, and invasion in vitro and their tumorigenesis in vivo, and reduced cell apoptosis both at basal levels and in response to temozolomide. While CD2AP knockdown had the opposite effects. Mechanistically, we revealed that CD2AP interacted with TRIM5, an NF-κB modulator. CD2AP overexpression and knockdown increased and decreased TRIM5 levels as well as the NF-κB activity, respectively. Moreover, downregulation of TRIM5 reversed elevated NF-κB activity in GBM cells with CD2AP overexpression; and inhibition of the NF-κB activity attenuated malignant features of GBM cells with CD2AP overexpression. Our findings demonstrate that CD2AP promotes GBM progression through activating TRIM5-mediated NF-κB signaling and that downregulation of CD2AP can attenuate GBM malignancy, suggesting that CD2AP may become a biomarker and the CD2AP-TRIM5-NF-κB axis may become a therapeutic target for GBM.

Prebiotic Functions of Konjac Root Powder in Chocolate Milk Enriched with Free and Encapsulated Lactic Acid Bacteria.

This study investigated the prebiotic functions of Konjac root powder (KRP) when added to chocolate milk (ChM) enriched with 2% of free or microencapsulated lactic acid bacteria (FLAB or ELAB). The effects of different concentrations of KRP (0%, 2% and 4%) and refrigerated storage time on the physical, chemical and microbiological characteristics of this chocolate milk were examined. The results show that pH significantly declined (p < 0.05), while titratable acidity increased in all ChM samples with KRP and FLAB or ELAB during refrigerated storage. The pH values ranged from 6.0 ± 0.03 in samples enriched ELAB and 4% KRP to 6.33 ± 0.03 in ChM enriched with FLAB and 2% KRP. Viscosity of ChM was affected mainly by the added amounts of KRP and storage time. The largest viscosity (5500 cP) was observed in all samples containing 4% KPR on day zero and decreased significantly (p < 0.05) over storage time to reach 2800 cP in ChM samples containing 0% LAB and 4% KRP after 21 days of storage. Changes in LAB counts proved the initial hypothesis that KRP could act as prebiotics in the presence of LAB using chocolate milk as a carrier. The initial LAB counts in inoculated samples on day zero of refrigeration storage were not significantly different (p > 0.05) among all treatments. However, ChM enriched with 2% and 4% KRP and ELAB revealed significantly (p < 0.05) larger LAB counts (4.91 ± 0.78 and 5.0 ± 0.57 log CFU/mL, respectively) than the control (3.85 ± 0.55 log CFU/mL) after 21 days of storage.

Novel compound heterozygous mutations in the CHST6 gene cause macular corneal dystrophy in a Han Chinese family.

BACKGROUND: Macular corneal dystrophy (MCD), a rare autosomal recessive disorder, is caused by pathogenic mutations in the carbohydrate sulfotransferase 6 gene (CHST6) and is characterized by bilateral progressive stromal clouding and vision loss. Corneal transplantation is often necessary. This study aimed to identify disease-causing mutations in a Han-Chinese MCD patient. METHODS: A 37-year-old female diagnosed with MCD was recruited. The clinical materials were observed and described, and peripheral blood sample was extracted. Whole exome sequencing (WES) and Sanger sequencing were used to reveal genetic defects. The pathogenicity of identified mutations was assessed using in silico analysis. RESULTS: The patient had typical features of MCD, including decreased vision, multiple irregular gray-white corneal opacities, and corneal thinning. A novel nonsense mutation c.544C>T (p.Gln182Ter) and a validated missense mutation c.631C>G (p.Arg211Gly) were identified in the CHST6 gene coding region, both classified as "pathogenic" following the American College of Medical Genetics and Genomics standards and guidelines. CONCLUSIONS: This study reports a Han-Chinese MCD patient with a novel nonsense mutation c.544C>T (p.Gln182Ter) and a recurrent missense mutation c.631C>G (p.Arg211Gly), which expand the spectrum of genetic mutations. The results of this study extend genotype-phenotype correlations between the CHST6 gene mutations and MCD clinical findings, contributing to a more accurate diagnosis and the development of potential gene-targeted MCD therapies. KEYWORDS: Carbohydrate sulfotransferase 6 gene (CHST6); compound heterozygous mutations; Han Chinese family; macular corneal dystrophy (MCD).

pH-triggered morphological change in a self-assembling amphiphilic peptide used as an antitumor drug carrier.

The geometry of nanoparticles plays an important role in the process of drug encapsulation and release. In this study, an acid-responsive amphiphilic polypeptide consisting of lysine and leucine was prepared. In neutral media, the amphiphilic peptide L6K4 self-assembled to form spherical nanoparticles and encapsulated fat-soluble antitumor drugs. The intratumoral accumulation of the drug-loaded nanoparticles was improved in HeLa cells compared with normal cells. Compared to a neutral environment, increasingly acidic solutions changed the secondary structure of the peptide. In addition, the drug-loaded nanoparticles expanded and decomposed, rapidly releasing the poorly soluble antitumor drug doxorubicin (DOX). In addition, the amphiphilic peptide L6K4 had antitumor properties, and the antitumor performance of the combination of L6K4 and DOX was better than that of free DOX. Our results indicate that the use of acid responsiveness to induce geometric changes in drug-loaded peptide nanoparticles could be a promising strategy for antitumor drug delivery.

CO2 Absorption in the Ionic Liquids Immobilized on Solid Surface by Molecular Dynamics Simulation.

Based on our previous experimental research, we studied the absorption of CO2 in the ionic liquid, 1-hexyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([hmim][Tf2N]), immobilized on TiO2 [rutile (110) ] with different thickness by molecular dynamics simulation. The effects of the properties (hydrophobicity and hydrophilicity) of solid interfaces were also studied with IL immobilized on graphite and TiO2, respectively. We studied the influence of the thickness of IL immobilized on TiO2 on the absorption of CO2 via structural and dynamical properties. The results show that the self-diffusion coefficients of IL and CO2 increase as the thickness of immobilized IL decreases. And the CO2 absorption capacity increases as the thickness of immobilized IL decreases as well. Additionally, more CO2 molecules are absorbed in the region near the solid interface as the thickness of IL decreases. For IL immobilized on graphite, the self-diffusion coefficients of cations and anions are larger than that of IL immobilized on TiO2 with the same thickness. They are also larger than nonimmobilized cations and anions.Besides, the CO2 absorption capacity of IL immobilized on TiO2 is the largest compared with IL immobilized on graphite and nonimmobilized IL with the same thickness. From our simulation work, we try to explore the microscopic mechanism that is unexplored by experimental work, and we found the important role of IL/solid interface for CO2 absorption in immobilized ILs.