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Optimal phototransduction requires separation of the avascular photoreceptor layer from the adjacent vascularized inner retina and choroid. Breakdown of peri-photoreceptor vascular demarcation leads to retinal angiomatous proliferation or choroidal neovascularization, two variants of vascular invasion of the photoreceptor layer in age-related macular degeneration (AMD), the leading cause of irreversible blindness in industrialized nations. Here we show that sFLT-1, an endogenous inhibitor of vascular endothelial growth factor A (VEGF-A), is synthesized by photoreceptors and retinal pigment epithelium (RPE), and is decreased in human AMD. Suppression of sFLT-1 by antibodies, adeno-associated virus-mediated RNA interference, or Cre/lox-mediated gene ablation either in the photoreceptor layer or RPE frees VEGF-A and abolishes photoreceptor avascularity. These findings help explain the vascular zoning of the retina, which is critical for vision, and advance two transgenic murine models of AMD with spontaneous vascular invasion early in life.

Various combination treatments have been considered to attain the effective therapy threshold by combining independent antitumor mechanisms against the heterogeneous characteristics of tumor cells in malignant brain tumors. In this study, the natural killer (NK) cells associated with bevacizumab (Bev) plus irinotecan (Iri) against glioblastoma multiforme (GBM) were investigated. For the experimental design, NK cells were expanded and activated by K562 cells expressing the OX40 ligand and membrane-bound IL-18 and IL-21. The effects of Bev and Iri on the proliferation and NK ligand expression of GBM cells were evaluated through MTT assay and flow cytometry. The cytotoxic effects of NK cells against Bev plus Iri-treated GBM cells were also predicted via the LDH assay in vitro. The therapeutic effect of different injected NK cell routes and numbers combined with the different doses of Bev and Iri was confirmed according to tumor size and survival in the subcutaneous (s.c) and intracranial (i.c) U87 xenograft NOD/SCID IL-12Rγnull mouse model. The presence of injected-NK cells in tumors was detected using flow cytometry and immunohistochemistry ex vivo. As a result, Iri was found to affect the proliferation and NK ligand expression of GBM cells, while Bev did not cause differences in these cellular processes. However, the administration of Bev modulated Iri efficacy in the i.c U87 mouse model. NK cells significantly enhanced the cytotoxic effects against Bev plus Iri-treated GBM cells in vitro. Although the intravenous (IV) injection of NK cells in combination with Bev plus Iri significantly reduced the tumor volume in the s.c U87 mouse model, only the direct intratumorally (IT) injection of NK cells in combination with Bev plus Iri elicited delayed tumor growth in the i.c U87 mouse model. Tumor-infiltrating NK cells were detected after IV injection of NK cells in both s.c and i.c U87 mouse models. In conclusion, the potential therapeutic effect of NK cells combined with Bev plus Iri against GBM cells was limited in this study. Accordingly, further research is required to improve the accessibility and strength of NK cell function in this combination treatment.

Abstract Recently, Ryoo introduced the weighted q-Euler numbers and polynomials which are a slightly different Kim's weighted q-Euler numbers and polynomials(see C. S. Ryoo, A note on the weighted q-Euler numbers and polynomials, 2011]). In this paper, we give some interesting new identities on the weighted q-Euler numbers related to the q-Bernstein polynomials 2000 Mathematics Subject Classification - 11B68, 11S40, 11S80

Abstract In this paper, we consider the twisted Carlitz's q-Bernoulli numbers using p-adic q-integral on ℤ p . From the construction of the twisted Carlitz's q-Bernoulli numbers, we investigate some properties for the twisted Carlitz's q-Bernoulli numbers. Finally, we give some relations between the twisted Carlitz's q-Bernoulli numbers and q-Bernstein polynomials.

We derive the modified -adic -measures related to -Nasybullin's type lemma.

We give a new construction of the -extensions of Euler numbers and polynomials. We present new generating functions which are related to the -Euler numbers and polynomials. We also consider the generalized -Euler polynomials attached to Dirichlet's character and have the generating functions of them. We obtain distribution relations for the -Euler polynomials and have some identities involving -Euler numbers and polynomials. Finally, we derive the -extensions of zeta functions from the Mellin transformation of these generating functions, which interpolate the -Euler polynomials at negative integers.

We investigate several arithmetic properties of -Genocchi polynomials and numbers of higher order.

We derive formulae for the sums of products of the -Euler polynomials and numbers using the multivariate fermionic -adic -Volkenborn integral on .

We study the symmetry for the generalized twisted Bernoulli polynomials and numbers. We give some interesting identities of the power sums and the generalized twisted Bernoulli polynomials using the symmetric properties for the -adic invariant integral.

We investigate properties of identities and some interesting identities of symmetry for the Bernoulli polynomials of higher order using the multivariate -adic invariant integral on .

We give some interesting relationships between the power sums and the generalized Bernoulli numbers attached to of higher order using multivariate -adic invariant integral on .

We construct the -Euler numbers and polynomials of higher order, which are related to Barnes' type multiple Euler polynomials. We also derive many properties and formulae for our -Euler polynomials of higher order by using the multiple integral equations on .

The main purpose of this paper is to present new -extensions of Apostol's type Euler polynomials using the fermionic -adic integral on . We define the - -Euler polynomials and obtain the interpolation functions and the Hurwitz type zeta functions of these polynomials. We define -extensions of Apostol type's Euler polynomials of higher order using the multivariate fermionic -adic integral on . We have the interpolation functions of these - -Euler polynomials. We also give -extensions of Apostol's type Euler polynomials of higher order and have the multiple Hurwitz type zeta functions of these - -Euler polynomials.

We investigate the properties of the Genocchi functions and the Genocchi polynomials. We obtain the Fourier transform on the Genocchi function. We have the generating function of -Genocchi polynomials. We define the Cangul-Ozden-Simsek's type twisted -Genocchi polynomials and numbers. We also have the generalized twisted -Genocchi numbers attached to the Dirichlet's character . Finally, we define zeta functions related to -Genocchi polynomials and have the generating function of the generalized -Genocchi numbers attached to .

Several species within the genus Phellinus are used as a traditional medicine for various health conditions. A new neo-lignan derivative, phelignan A (1), and a known neo-lignan (2) were isolated from the culture broth of P. linteus. The chemical structures of the isolated compounds were determined using 1D- and 2D-NMR and MS data and by comparisons of the data with those reported in the literature. The anti-viral activity of the isolated compounds against dengue virus-2 (DENV-2) was evaluated. Compounds 1 and 2 exhibited anti-viral activity against DENV-2, with IC 50 values of 1.45 and 2.15 µM, respectively. [Display omitted] • Two neo-lignans, one of them a newly identified neo-lignan, were isolated from the culture broth of Phellinus linteus. • Their chemical structures were determined using NMR and HR-ESI-MS spectroscopy. • Compounds 1–2 exhibited potent anti-viral activities against DENV-2. [ABSTRACT FROM AUTHOR]

Pendrin is a Cl-/HCO3- exchanger expressed in the apical regions of renal intercalated cells. Following pendrin gene ablation, blood pressure falls, in part, from reduced renal NaCl absorption. We asked if pendrin is expressed in vascular tissue and if the lower blood pressure observed in pendrin null mice is accompanied by reduced vascular reactivity. Thus, the contractile responses to KCl and phenylephrine (PE) were examined in isometrically mounted thoracic aortas from wild-type and pendrin null mice. Although pendrin expression was not detected in the aorta, pendrin gene ablation changed contractile protein abundance and increased the maximal contractile response to PE when normalized to cross sectional area (CSA). However, the contractile sensitivity to this agent was unchanged. The increase in contractile force/cross sectional area observed in pendrin null mice was due to reduced cross sectional area of the aorta and not from increased contractile force per vessel. The pendrin-dependent increase in maximal contractile response was endothelium- and nitric oxide-independent and did not occur from changes in Ca2+ sensitivity or chronic changes in catecholamine production. However, application of 100 nM angiotensin II increased force/CSA more in aortas from pendrin null than from wild type mice. Moreover, angiotensin type 1 receptor inhibitor (candesartan) treatment in vivo eliminated the pendrin-dependent changes contractile protein abundance and changes in the contractile force/cross sectional area in response to PE. In conclusion, pendrin gene ablation increases aorta contractile force per cross sectional area in response to angiotensin II and PE due to stimulation of angiotensin type 1 receptor-dependent signaling. The angiotensin type 1 receptor-dependent increase in vascular reactivity may mitigate the fall in blood pressure observed with pendrin gene ablation.

Several members of the genus Phellinus have been used as traditional medicine for treating various diseases. They produce unique yellow pigments composed of a styrylpyrone class of compounds. Styrylpyrones exhibit various biological activities. The styryl group is derived from phenylalanine via cinnamic acid, p -coumaric acid, and caffeoyl-CoA pathways, whereas the pyrone ring is derived from acetate. In a feeding experiment using ferulic acid, a phenylpropanoid, three undescribed dimeric ferulates designated as phellidiferulates A-C were isolated from culture broth of P. linteus. Their structures were determined by spectroscopic methods. These compounds exhibited anti-viral activities against dengue virus type 2 (DENV-2) with IC 50 values ranging from 0.12 to 0.18 µg/mL. [Display omitted] ● Three undescribed dimeric ferulates were isolated from the culture broth of Phellinus linteus. ● Their chemical structures were determined by NMR and HR-ESI-MS spectroscopy. ● Compounds 1 - 3 showed potent anti-viral activities against DENV-2. [ABSTRACT FROM AUTHOR]