Differentiation of multipotent vascular stem cells contributes to vascular diseases.

It is generally accepted that the de-differentiation of smooth muscle cells, from the contractile to the proliferative/synthetic phenotype, has an important role during vascular remodelling and diseases. Here we provide evidence that challenges this theory. We identify a new type of stem cell in the blood vessel wall, named multipotent vascular stem cells. Multipotent vascular stem cells express markers, including Sox17, Sox10 and S100β, are cloneable, have telomerase activity, and can differentiate into neural cells and mesenchymal stem cell-like cells that subsequently differentiate into smooth muscle cells. On the other hand, we perform lineage tracing with smooth muscle myosin heavy chain as a marker and find that multipotent vascular stem cells and proliferative or synthetic smooth muscle cells do not arise from the de-differentiation of mature smooth muscle cells. In response to vascular injuries, multipotent vascular stem cells, instead of smooth muscle cells, become proliferative, and differentiate into smooth muscle cells and chondrogenic cells, thus contributing to vascular remodelling and neointimal hyperplasia. These findings support a new hypothesis that the differentiation of multipotent vascular stem cells, rather than the de-differentiation of smooth muscle cells, contributes to vascular remodelling and diseases

Overexpression of long non-coding RNA NORAD promotes invasion and migration in malignant melanoma via regulating the MIR-205-EGLN2 pathway.

Growing evidence suggests that long non-coding RNAs NORAD and miR-205 play a significant role in regulating cancer progression and metastasis. In this study, high expression of NORAD was firstly observed in melanoma tissues and human malignant melanoma cell lines, our aim was to study the interaction of them in the process of invasion and migration of malignant melanoma cells. NORAD, miR-205, and EGLN2 mRNA level in MM cells was detected by qRT-PCR. In situ hybridization (ISH) was performed to detect NORAD expression in MM tissues specimens. Effects of NORAD and miR-205 on Prolyl hydroxylase 2 (EGLN2) expression was explored by western blot in MM cells line. Dual-luciferase reporter assay was performed to verify the interaction relationship between NORAD and miR-205, as well as, miR-205 and EGLN2. Transwell assay was conducted to explore the effects of NORAD and miR-205 in vitro. Xenografts in nude mice experiment were used to confirm the role of NORAD and miR-205 in vivo. In vitro, NORAD knockdown significantly inhibited migration and invasion of malignant melanoma cells and elevated the expression of miR-205, there was an interaction between miR-205 and NORAD in the RNA-induced silencing complex. Upregulation of miR-205 induced significant inhibition of migratory and invasive ability compared with the scrambled control. However, downregulating NORAD largely reversed this effect. Furthermore, the regulatory effects of miR-205 on EGLN2 levels and the induction of endoplasmic reticulum stress were reversed by NORAD. In vivo, deletion of miR-205 induced tumor growth in nude mice. NORAD may play critical roles in tumorigenesis and progression of malignant melanoma by regulating of the miR-205-EGLN2 pathway, and may serve as a new therapeutic target

Placental Mesenchymal Stem Cell-Derived Extracellular Vesicles Promote Myelin Regeneration in an Animal Model of Multiple Sclerosis.

Mesenchymal stem/stromal cells (MSCs) display potent immunomodulatory and regenerative capabilities through the secretion of bioactive factors, such as proteins, cytokines, chemokines as well as the release of extracellular vesicles (EVs). These functional properties of MSCs make them ideal candidates for the treatment of degenerative and inflammatory diseases, including multiple sclerosis (MS). MS is a heterogenous disease that is typically characterized by inflammation, demyelination, gliosis and axonal loss. In the current study, an induced experimental autoimmune encephalomyelitis (EAE) murine model of MS was utilized. At peak disease onset, animals were treated with saline, placenta-derived MSCs (PMSCs), as well as low and high doses of PMSC-EVs. Animals treated with PMSCs and high-dose PMSC-EVs displayed improved motor function outcomes as compared to animals treated with saline. Symptom improvement by PMSCs and PMSC-EVs led to reduced DNA damage in oligodendroglia populations and increased myelination within the spinal cord of treated mice. In vitro data demonstrate that PMSC-EVs promote myelin regeneration by inducing endogenous oligodendrocyte precursor cells to differentiate into mature myelinating oligodendrocytes. These findings support that PMSCs' mechanism of action is mediated by the secretion of EVs. Therefore, PMSC-derived EVs are a feasible alternative to cellular based therapies for MS, as demonstrated in an animal model of the disease

Correlated alterations in prostate basal cell layer and basement membrane

Our recent studies revealed that focal basal cell layer disruption (FBCLD) induced auto-immunoreactions represented a contributing factor for human prostate tumor progression and invasion. As the basement membrane surrounds and attaches to the basal cell layer, our current study assessed whether FBCLD would impact the physical integrity of the associated basement membrane. Paraffin sections from 25-human prostate tumors were subjected to double immunohistochemistry to simultaneously elucidate the basal cell layer and the basement membrane with corresponding biomarkers. The physical integrity of the basement membrane overlying FBCLD was examined to determine the extent of correlated alterations. Of a total of 89 FBCLD encountered, 76 (85 %) showed correlated alterations in the overlying basement membrane, which included distinct focal disruptions or fragmentations. In the remaining 13 (15%) FBCLD, the overlying basement membrane showed significant attenuation or reduction of the immunostaining intensity. The basement membrane in all or nearly all ducts or acini with p63 positive basal cells was substantially thicker and more uniform than that in ducts or acini without p63 positive basal cells, and also, a vast majority of the focal disruptions occurred near basal cells that lack p63 expression. These findings suggest that focal disruptions in the basal cell layer and alterations in the basement membrane are correlated events and that the physical and functional status of the basal cells could significantly impact the physical integrity of the overlying basement membrane. As the degradation of both the basal cell layer and the basement membrane is a pre-requisite for prostate tumor invasion or progression, ducts or acini with focally disrupted basal cell layer and basement membrane are likely at greater risk to develop invasive lesions. Thus, further elucidation of the specific molecules and mechanism associated with these events may lead to the development of a more effective alternative for repeat biopsy to monitor tumor progression and invasion

microRNA-33a-5p increases radiosensitivity by inhibiting glycolysis in melanoma.

Glycolysis was reported to have a positive correlation with radioresistance. Our previous study found that the miR-33a functioned as a tumor suppressor in malignant melanoma by targeting hypoxia-inducible factor1-alpha (HIF-1α), a gene known to promote glycolysis. However, the role of miR-33a-5p in radiosensitivity remains to be elucidated. We found that miR-33a-5p was downregulated in melanoma tissues and cells. Cell proliferation was downregulated after overexpression of miR-33a-5p in WM451 cells, accompanied by a decreased level of glycolysis. In contrast, cell proliferation was upregulated after inhibition of miR-33a-5p in WM35 cells, accompanied by increased glycolysis. Overexpression of miR-33a-5p enhanced the sensitivity of melanoma cells to X-radiation by MTT assay, while downregulation of miR-33a-5p had the opposite effects. Finally, in vivo experiments with xenografts in nude mice confirmed that high expression of miR-33a-5p in tumor cells increased radiosensitivity via inhibiting glycolysis. In conclusions, miR-33a-5p promotes radiosensitivity by negatively regulating glycolysis in melanoma

Behavioral and Antennal Responses of \u3ci\u3eDrosophila suzukii\u3c/i\u3e (Diptera: Drosophilidae) to Volatiles From Fruit Extracts

Native to Southeast Asia, the spotted wing drosophila, Drosophila suzukii Matsumura (Diptera: Drosophilidae), has become a serious pest of soft-skinned fruit crops since its introduction into North America and Europe in 2008. Current monitoring strategies use baits based on fermentation products; however, to date, no fruit-based volatile blends attractive to this fly have been identified. This is particularly important because females are able to cut into the epicarp of ripening fruit for oviposition. Thus, we conducted studies to: 1) investigate the behavioral responses of adult D. suzukii to volatiles from blueberry, cherry, raspberry, and strawberry fruit extracts; 2) identify the antennally active compounds from the most attractive among the tested extracts (raspberry) using gas chromatography (GC)– mass spectrometry and coupled gas chromatography –electroantennographic detection (GC-EAD); and 3) test a synthetic blend containing the EAD-active compounds identified from raspberry extract on adult attraction. In olfactometer studies, both female and male D. suzukii were attracted to all four fruit extracts. The attractiveness of the fruit extracts ranks as: raspberry \u3e/= strawberry \u3e blueberry \u3e/= cherry. GC analyses showed that the fruit extracts emit distinct volatile compounds. In GC-EAD experiments, 11 raspberry extract volatiles consistently elicited antennal responses in D. suzukii. In choice test bioassays, a synthetic EAD-active blend attracted more D. suzukii than a blank control, but was not as attractive as the raspberry extract. To our knowledge, this is the first report of a behaviorally and antennally active blend of host fruit volatiles attractive to D. suzukii, offering promising opportunities for the development of improved monitoring and behaviourally based management tools

Evaluation of attract-and-kill strategy for management of cocoa pod borer, Conopomorpha cramerella, in Malaysia cocoa plantation

In South-East Asia, cocoa production is dramatically affected by cocoa pod borer (CPB) infestations. As an alternative tool to chemical control, the efficacy of attract-and-kill strategy (CPB sex-pheromone as attractant and Delta trap without sticky liner sprayed with cypermethrin solution as killing station) was evaluated and compared with current standard CPB management approach as control treatment during two main cocoa harvest seasons in Malaysia (with 100 mu g and 33.3 mu g CPB-pheromone loading per station, respectively). In both seasons, attract-and-kill strategy was highly effective at reducing male flight activity (p < 0.05) in attract-and-kill plots comparing with standard CPB management plots. For the percentage of CPB-infested pods, the attract-and-kill strategy (100 mu g) was as good as the conventional pesticide spray applications of cypermethrin (p = 0.083) in first season. However, it was significantly (p = 0.021) reduced in the second season with lower pheromone loading (33.3 mu g), indicating that this semiochemical based strategy is far superior to and more feasible than the currently applied conventional synthetic pesticide treatment and is therefore a good alternative in CPB integrated pest management

A Review of Carbon-Composited Materials as Air-Electrode Bifunctional Electrocatalysts for Metal–Air Batteries

AbstractMetal–air batteries (MABs), particularly rechargeable MABs, have gained renewed interests as a potential energy storage/conversion solution due to their high specific energy, low cost, and safety. The development of MABs has, however, been considerably hampered by its relatively low rate capability and its lack of efficient and stable air catalysts in which the former stems mainly from the sluggish kinetics of the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) and the latter stems from the corrosion/oxidation of carbon materials in the presence of oxygen and high electrode potentials. In this review, various carbon-composited bifunctional electrocatalysts are reviewed to summarize progresses in the enhancement of ORR/OER and durability induced by the synergistic effects between carbon and other component(s). Catalyst mechanisms of the reaction processes and associated performance enhancements as well as technical challenges hindering commercialization are also analyzed. To facilitate further research and development, several research directions for overcoming these challenges are also proposed