Ginsenoside Rb1 relieves glucose fluctuationinduced oxidative stress and apoptosis in Schwann cells

Cultured Schwann cells were treated with 5.6 mM and 50 mM glucose alternating every 8 hours to simulate intermittent high glucose. The present study analyzed the neuroprotective effects of 1, 10 and 100 μM ginsenoside Rbl on oxidative damage and apoptosis in Schwann cells induced by intermittent high glucose. Flow cytometry demonstrated that ginsenoside Rbl reduced intermittent high glucose-mediated reactive oxygen species production. Enzyme linked immunosorbent assay showed that 8-hydroxy-2-deoxy guanosine levels in Schwann cells decreased following ginsenoside Rbl treatment. Quantitative real-time reverse transcription-PCR and western blot assay results revealed that ginsenoside Rbl inhibited intermittent high glucose-upregulated Bax expression, but antagonized intermittent high glucose-downregulated Bcl-2 expression in Schwann cells. These effects were most pronounced with 100 μM ginsenoside Rbl. These results indicate that ginsenoside Rbl inhibits intermittent high glucose-induced oxidative stress and apoptosis in Schwann cells.

Development of proton-conducting membrane based on incorporating a proton conductor 1,2,4-triazolium methanesulfonate into the Nafion membrane

In this paper, 1,2,4-triazolium methanesulfonate （C_2H_4N_3^＋-CH_3SO_3^-, [Tri][MS]）, an ionic conductor, was successfully synthesized. It exhibited high ionic conductivity of 18.60 mS·cm^-1 at 140 ℃ and reached up to 36.51 mS·cm^-1 at 190 ℃. [Tri][MS] was first applied to modify Nation membrane to fabricate [Tri][MS]/Nafion membrane by impregnation method at 150 ℃. The prepared composite membrane showed high thermal stability with decomposed temperature above 200 ℃ in air atmosphere. In addition, the membrane indicated good ionic conductivity with 3.67 mS·cm^-1 at 140 ℃ and reached up to 13.23 mS·cm^-1 at 180 ℃. The structure of the [Tri][MS] and the composite membrane were characterized by FTIR and the compatibility of [Tri][MS] and Pt/C catalyst was studied by a cyclic voltammetry （CV） method. Besides, the [Tri][MS]/Nafion membrane （thickness of 65 μm） was evaluated with single fuel cell at high temperature and without humidification. The highest power density of [Tri][MS]/Nafion membrane was 3.20 mW·cm^-2 at 140 ℃ and 4.90 mW·cm^-2 at 150 ℃, which was much higher than that of Nation membrane.

Puerarin prevents high glucose-induced apoptosis of Schwann cells by inhibiting oxidative stress

Oxidative stress may be the unifying factor for the injury caused by hyperglycemia in diabetic peripheral neuropathy. Puerarin is the major isoflavonoid derived from Radix puerariae and has been shown to be effective in increasing superoxide dismutase activity. This study sought to investigate the neuroprotective effect of puerarin on high glucose-induced oxidative stress and Schwann cell apoptosis in vitro. Intracellular reactive oxygen radicals and mitochondrial transmembrane potential were detected by flow cytometry analysis. Apoptosis was confirmed by TUNEL and oxidative stress was monitored using an enzyme-linked immunosorbent assay for the DNA marker 8-hydroxy-2-deoxyguanosine. The expression levels of bax and bcl-2 were analyzed by quantitative real-time reverse transcriptase-PCR, while protein expression of cleaved caspase-3 and -9 were analyzed by means of western blotting. Results suggested that puerarin treatment inhibited high glucose-induced oxidative stress, mitochondrial depolarization and apoptosis in a dose-dependent manner. Furthermore, puerarin treatment downregulated Bax expression, upregulated bcl-2 expression and attenuated the activation of caspase-3 and -9. Overall, our results indicated that puerarin antagonized high glucose-induced oxidative stress and apoptosis in Schwann cells.

The transmembrane domain of TACE regulates protein ectodomain shedding

Numerous membrane proteins are cleaved by tumor necrosis factor-α converting enzyme （TACE）, which causes the release of their ectodomains. An ADAM （a disintegrin and metalloprotease domain） family member, TACE contains several noncatalytic domains whose roles in ectodomain shedding have yet to be fully resolved. Here, we have explored the function of the transmembrane domain （TM） of TACE by coupling molecular engineering and functional analysis. A TM-free TACE construct that is anchored to the plasma membrane by a glycosylphosphatidylinositol （GPI）-binding polypeptide failed to restore shedding of transforming growth factor-or （TGF-α）, tumor necrosis factor-α （TNF-α） and L-selectin in cells lacking endogenous TACE activity. Substitution of the TACE TM with that of the prolactin receptor or platelet-derived growth factor receptor （PDGFR） also resulted in severe loss of TGF-α shedding, but had no effects on the cleavage of TNF-α and L-selectin. Replacement of the TM in TGF-α with that of L-selectin enabled TGF-α shedding by the TACE mutants carrying the TM of prolactin receptor and PDGFR. Taken together, our observations suggest that anchorage of TACE to the lipid bilayer through a TM is required for efficient cleavage of a broad spectrum of substrates, and that the amino-acid sequence of TACE TM may play a role in regulatory specificity among TACE substrates.

Dynamic relaxation process of a 3D super crystal structure in a Cu:KTN crystal

In this Letter,we report the existence and relaxation properties of a critical phenomenon on called a 3D super crystal that emerges at T=TC?3.5℃,that is,in the proximity of the Curie temperature of a Cu:KTN sample.The dynamics processes of a 3D super crystal manifest in its formation containing polarized nanometric regions and/or polarized clusters.However,with strong coupling and interaction of microcomponents,the characteristic relaxation time measured by dynamic light scattering demonstrates a fully new relaxation mechanism with a much longer relaxation time.As the relaxation mechanism of a relaxator is so-far undetermined,this research provides a novel perspective.These results can help structure a fundamental theory of ferroelectric relaxation.

Field-induced transformation of ferroelectric domain states in KTN crystal

We report an interesting study of electric-field-induced transformation from a single domain ferroelectric state to the multiple domain ferroelectric state in a KTa_(1-x)Nb_(x)O_(3)(KTN) crystal. Experimental results obtained using the confocalμ-Raman spectroscopy confirm the dynamic change of lattice structures induced by an external electric field.Furthermore, the dependence of relative permittivity on the applied voltage also indicates the transformation of ferroelectric states involving the processes of splintering, inversion, and re-formation of ferroelectric domains.

Targeting the CXCR4/CXCL12 axis with the peptide antagonist E5 to inhibit breast tumor progression

Emerging evidence has demonstrated that stromal cell-derived factor 1(SDF-1)and its cognate receptor CXCR4 have critical roles in tumorigenesis,angiogenesis and metastasis.In this study,we demonstrated the significant inhibitory effects of a novel chemically synthetic peptide(E5)on the CXCR4/CXCL12 axis in breast cancer both in vitro and in vivo.E5 was capable of specifically binding to the murine breast cancer cell line 4T1,remarkably inhibiting CXCL12-or stromal cell(MS-5)-induced migration,and adhesion and sensitizing 4T1 cells to multiple chemotherapeutic drugs.Furthermore,E5 combined with either paclitaxel or cyclophosphamide significantly inhibited tumor growth in a breast cancer model.Mechanistic studies implied that E5 can inhibit the expression of CXCR4 to block the CXCL12-mediated recruitment of endothelial progenitor cells and repress CXCR4 downstream of the Akt and Erk signaling pathway,which are involved in tumor angiogenesis and progression.Further pharmacokinetic evaluation suggested that E5 has an acceptable stability,with a half-life of 10 h in healthy mice.In conclusion,E5 demonstrates a promising anti-tumor effect and could be a potential chemotherapeutic sensitizer to improve current clinical breast cancer therapies.