RNase L contributes to lipid metabolism

Macrophage-derived foam cell formation is a milestone of the atherosclerotic lesion initiation and progression, leading to cardiovascular diseases and stroke. Foam cells are formed from the disruption of a homeostatic mechanism that manipulates the uptake, intracellular metabolism and efflux of cholesterol within macrophages. Although studies have yielded much information about the homeostatic mechanism, the molecular basis of foam cell formation remains to be fully understood. We recently found that deficiency of RNase L attenuated macrophage functions including macrophage migration and its endocytic activity. Furthermore, RNase L markedly impacted the expression of certain pro- and anti-foam cell genes in macrophages. Most interestingly we have revealed that lack of RNase L significantly increased the formation of foam cells from bone marrow derived macrophages (BMMs). The increase of foam cell formation was associated with up-regulation of the expression of scavenger receptors such as CD36, SR-A, and PPAR-g. These studies provide new insights into foam cell formation and novel therapeutic strategies for atherosclerosis may be designed through activation/up-regulation of RNase L.https://engagedscholarship.csuohio.edu/u_poster_2014/1001/thumbnail.jp

Effect of isopropyl myristate on the viscoelasticity and drug release of a drug-in-adhesive transdermal patch containing blonanserin

AbstractThe purpose of this study was to investigate the effect of isopropyl myristate (IPM), a penetration enhancer, on the viscoelasticity and drug release of a drug-in-adhesive transdermal patch containing blonanserin. The patches were prepared with DURO-TAK® 87-2287 as a pressure-sensitive adhesive (PSA) containing 5% (w/w) of blonanserin and different concentrations of IPM. An in vitro release experiment was performed and the adhesive performance of the drug-in-adhesive patches with different concentrations of IPM was evaluated by a rolling ball tack test and a shear-adhesion test. The glass transition temperature (Tg) and rheological parameters of the drug-in-adhesive layers were determined to study the effect of IPM on the mechanical properties of the PSA. The results of the in vitro release experiment showed that the release rate of blonanserin increased with an increasing concentration of IPM. The rolling ball tack test and shear-adhesion test showed decreasing values with increasing IPM concentration. The results were interpreted on the basis of the IPM-induced plasticization of the PSA, as evidenced by a depression of the glass transition temperature and a decrease in the elastic modulus. In conclusion, IPM acted as a plasticizer on DURO-TAK® 87-2287, and it increased the release of blonanserin and affected the adhesive properties of the PSA

hCLP46 Increases Smad3 Protein Stability Via Inhibiting its Ubiquitin-Proteasomal Degradation

hCLP46 (human CAP10-like protein 46 kDa) was initially isolated and identified from human acute myeloid leukemia transformed from myelodysplastic syndrome (MDS-AML) CD34+ cells (Teng et al., 2006) and we demonstrated previously that hCLP46 is abnormally expressed in many hematopoietic malignancies (Wang et al., 2010). Studies fromits Drosophila homolog, Rumi, suggested that Notch is a potential target of hCLP46 (Acar et al., 2008). We also found that overexpression of hCLP46 enhances Notch activation and regulates cell proliferation in a cell type-dependent manner (Ma et al., 2011; Chu et al., 2013). However, hCLP46−/− embryos show more severe phenotypes compared to those displayed by other global regulators of canonical Notch signaling, suggesting that hCLP46 is likely to have additional important targets during mammalian development (Fernandez- Valdivia et al., 2011). Based on the crosstalk between Notch and the transforming growth factor-β (TGF-β) signaling, we proposed that hCLP46 might be involved in TGF-β signal regulation, but the detail mechanism remains unclear

Paeonol ameliorates chronic itch and spinal astrocytic activation via CXCR3 in an experimental dry skin model in mice

Paeonol is a bioactive phenol presents mainly i

Chinese language teachers’ dichotomous identities when teaching ingroup and outgroup students

Research into second language teacher identity has experienced a shift in recent years from a cognitive perspective to social constructionist orientation. The existing research in Chinese language literature in relation to Foreign Language (CFL) teachers’ identity shift is principally in relation to the change of social, cultural, and institutional contexts. Built on the current literature, this research asks: “How might teachers’ self-images or self-conceptualizations be renegotiated when they are located within their own mainstream cultural and educational system, yet comprised of students from various cultural backgrounds?” The data were collected from a group of CFL teachers in a South China university. The research found that students’ backgrounds largely impacted on, and led to, the teachers’ dichotomous relational identities, but did not dramatically change the teachers’ perception on what or how much subject knowledge to be possessed to make an ideal CFL teacher. This attribute of their identity was sustained even though the teaching content was modified at a practical level in response to groups’ differences. Further, the CFL teachers’ pedagogical identity remained stable with only minor modifications when teaching “ingroups” and “outgroups” of students

RNase L Contributes to Experimentally Induced Type 1 Diabetes Onset in Mice

The cause of type 1 diabetes continues to be a focus of investigation. Studies have revealed that interferon α (IFNα) in pancreatic islets after viral infection or treatment with double-stranded RNA (dsRNA), a mimic of viral infection, is associated with the onset of type 1 diabetes. However, how IFNα contributes to the onset of type 1 diabetes is obscure. In this study, we found that 2-5A-dependent RNase L (RNase L), an IFNα-inducible enzyme that functions in the antiviral and antiproliferative activities of IFN, played an important role in dsRNA-induced onset of type 1 diabetes. Using RNase L-deficient, rat insulin promoter-B7.1 transgenic mice, which are more vulnerable to harmful environmental factors such as viral infection, we demonstrated that deficiency of RNase L in mice resulted in a significant delay of diabetes onset induced by polyinosinic:polycytidylic acid (poly I:C), a type of synthetic dsRNA, and streptozotocin, a drug which can artificially induce type 1-like diabetes in experimental animals. Immunohistochemical staining results indicated that the population of infiltrated CD8+T cells was remarkably reduced in the islets of RNase L-deficient mice, indicating that RNase L may contribute to type 1 diabetes onset through regulating immune responses. Furthermore, RNase L was responsible for the expression of certain proinflammatory genes in the pancreas under induced conditions. Our findings provide new insights into the molecular mechanism underlying β-cell destruction and may indicate novel therapeutic strategies for treatment and prevention of the disease based on the selective regulation and inhibition of RNase L

RNase L Contributes to Experimentally Induced Type 1 Diabetes Onset in Mice

The cause of type 1 diabetes continues to be a focus of investigation. Studies have revealed that interferon α (IFNα) in pancreatic islets after viral infection or treatment with double-stranded RNA (dsRNA), a mimic of viral infection, is associated with the onset of type 1 diabetes. However, how IFNα contributes to the onset of type 1 diabetes is obscure. In this study, we found that 2-5A-dependent RNase L (RNase L), an IFNα-inducible enzyme that functions in the antiviral and antiproliferative activities of IFN, played an important role in dsRNA-induced onset of type 1 diabetes. Using RNase L-deficient, rat insulin promoter-B7.1 transgenic mice, which are more vulnerable to harmful environmental factors such as viral infection, we demonstrated that deficiency of RNase L in mice resulted in a significant delay of diabetes onset induced by polyinosinic:polycytidylic acid (poly I:C), a type of synthetic dsRNA, and streptozotocin, a drug which can artificially induce type 1-like diabetes in experimental animals. Immunohistochemical staining results indicated that the population of infiltrated CD8+T cells was remarkably reduced in the islets of RNase L-deficient mice, indicating that RNase L may contribute to type 1 diabetes onset through regulating immune responses. Furthermore, RNase L was responsible for the expression of certain proinflammatory genes in the pancreas under induced conditions. Our findings provide new insights into the molecular mechanism underlying β-cell destruction and may indicate novel therapeutic strategies for treatment and prevention of the disease based on the selective regulation and inhibition of RNase L

Determination of folic acid and its related substances of the ferrous fumarate and folic acid dispersible tablet by HPLC

The aim of the present study was to establish a method for the determination of folic acid and related substances content in dispersible tablets. Method: A Shim-pack VP-ODS C18 reversed phase column (4.6 mm × 250 mm) was used. The mobile phase consisted of methanol-phosphate buffer (20:80) with a pH of 6.3.The flow rate was 1.0 mL/min, and the detection wavelength was 277nm and the column temperature was 30 °C. Results: The calibration curve was linear in the range of 5~150 μg/mL (r = 0.9998) for folic acid. The minimal detection limit was 99.08 %, n = 9 and the related substances were well separated. This method resulted to be convenient, accurate, selective and reliable, and can be applied for the quality control of folic acid.Colegio de Farmacéuticos de la Provincia de Buenos Aire