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1.
Claudia Giuseppina Fresta Giuseppe Caruso Annamaria Fidilio Chiara Bianca Maria Platania Nicol Musso Filippo Caraci Filippo Drago Claudio Bucolo 《International journal of molecular sciences》2020,21(23)
Activation of P2X7 signaling, due to high glucose levels, leads to blood retinal barrier (BRB) breakdown, which is a hallmark of diabetic retinopathy (DR). Furthermore, several studies report that high glucose (HG) conditions and the related activation of the P2X7 receptor (P2X7R) lead to the over-expression of pro-inflammatory markers. In order to identify novel P2X7R antagonists, we carried out virtual screening on a focused compound dataset, including indole derivatives and natural compounds such as caffeic acid phenethyl ester derivatives, flavonoids, and diterpenoids. Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) rescoring and structural fingerprint clustering of docking poses from virtual screening highlighted that the diterpenoid dihydrotanshinone (DHTS) clustered with the well-known P2X7R antagonist JNJ47965567. A human-based in vitro BRB model made of retinal pericytes, astrocytes, and endothelial cells was used to assess the potential protective effect of DHTS against HG and 2′(3′)-O-(4-Benzoylbenzoyl)adenosine-5′-triphosphate (BzATP), a P2X7R agonist, insult. We found that HG/BzATP exposure generated BRB breakdown by enhancing barrier permeability (trans-endothelial electrical resistance (TEER)) and reducing the levels of ZO-1 and VE-cadherin junction proteins as well as of the Cx-43 mRNA expression levels. Furthermore, HG levels and P2X7R agonist treatment led to increased expression of pro-inflammatory mediators (TLR-4, IL-1β, IL-6, TNF-α, and IL-8) and other molecular markers (P2X7R, VEGF-A, and ICAM-1), along with enhanced production of reactive oxygen species. Treatment with DHTS preserved the BRB integrity from HG/BzATP damage. The protective effects of DHTS were also compared to the validated P2X7R antagonist, JNJ47965567. In conclusion, we provided new findings pointing out the therapeutic potential of DHTS, which is an inhibitor of P2X7R, in terms of preventing and/or counteracting the BRB dysfunctions elicited by HG conditions. 相似文献
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On sorting triangles in a delaunay tessellation 总被引:1,自引:0,他引:1
In a two-dimensional Delaunay-triangulated domain, there exists a partial ordering of the triangles (with respect to a vertex) that is consistent with the two-dimensional visibility of the triangles from that vertex. An equivalent statement is that a polygon that is star-shaped with respect to a given vertex can be extended, one triangle at a time, until it includes the entire domain. Arbitrary planar triangulations do not possess this useful property which allows incremental processing of the triangles.This work was partially supported by the National Science Foundation's US-Italy Collaborative Research Program under Grant INT-8714578 and Information, Robotics, and Intelligent Research Grant IRI-8704781. 相似文献
5.
SA Morse DL Trees Y Htun F Radebe KA Orle Y Dangor CM Beck-Sague S Schmid G Fehler JB Weiss RC Ballard 《Canadian Metallurgical Quarterly》1997,175(3):583-589
A multiplex polymerase chain reaction (M-PCR) assay for Haemophilus ducreyi, Treponema pallidum, and herpes simplex virus (HSV) was compared with clinical and standard laboratory methods for the diagnosis of genital ulcer disease (GUD) in 105 patients; 36% were human immunodeficiency virus (HIV)-seropositive. Chancroid (80%), syphilis (8%), and genital herpes (8%) were the most frequent diagnoses. H. ducreyi and HSV were isolated from ulcers of 43% and 18% of patients, respectively; in 35%, all cultures were negative and the laboratory diagnosis indeterminate. M-PCR detected H. ducreyi, T. pallidum, and HSV in 56%, 23%, and 26% of patients, respectively; (no definitive diagnosis, 6%). The proportion of patients with more than one agent was 4% by culture and 17% by M-PCR (P = .002). Resolved sensitivities of M-PCR for H. ducreyi and HSV cultures were 95% and 93%, respectively. The sensitivities of H. ducreyi and HSV cultures were 75% and 60%, respectively. HSV, detected in 47% of specimens from HIV-infected versus 16% from HIV-uninfected patients (P < .001), may be emerging as a more frequent cause of GUD. 相似文献
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E Pittenauer ER Schmid G Allmaier B Pfanzagl W L?ffelhardt CQ Fernández MA de Pedro W Stanek 《Canadian Metallurgical Quarterly》1993,22(9):524-536
A strategy for the structural characterization of the four major NaBH4-reduced peptidoglycan monomers derived from muramidase-digested peptidoglycan from the cyanelles of the flagellate Cyanophora paradoxa Korschikoff is described. Initial molecular weight determination of these glycopeptides was performed by positive and negative ion plasma desorption mass spectrometry. Due to the presence of two pairs of disaccharide tripeptide and disaccharide tetrapeptide monomers differing in mass by 112 units, respectively, an as yet unknown peptidoglycan modification either at the carbohydrate or at the peptide moiety was assumed. beta-Elimination of the disaccharide unit from the unreduced peptidoglycan monomers yielded the corresponding (modified) N1-lactyltripeptides and -tetrapeptides, respectively. These peptides, N-terminally blocked with lactic acid, unambiguously showed the modification to be located on the peptide moiety. By positive ion fast atom bombardment/hybrid tandem mass spectrometry of the reduced peptidoglycan monomers as well as of the corresponding deglycosylated monomers (= N1-lactylpeptides) the modification was determined to be linked to the glutamic acid moiety. Based on combined data from plasma desorption mass spectrometry, tandem mass spectrometry, accurate mass measurement and amino acid analysis of the acid hydrolysate after derivatization with o-phthaldialdehyde by high-performance liquid chromatography we could establish the structure of the modification as N-acetylputrescine. Finally, the confirmation of the linkage of the glutamic acid to diaminopimelic acid via the gamma-COOH was based on the presence of a-type peptide backbone fragment ions in the positive ion plasma desorption mass spectra of the modified N1-lactylpeptides. 相似文献
7.
F F?ndrich AM Waaga J Schr?der E Schweizer A Schmid S Jacob HH Wacker P Schroeder 《Canadian Metallurgical Quarterly》1995,27(2):1553-1554
8.
PL Pirie BL Rooney TF Pechacek HA Lando LA Schmid 《Canadian Metallurgical Quarterly》1997,22(1):131-137
Exposure to foreign particles sometimes causes inflammatory reactions through production of cytokines and chemoattractants by phagocytic cells. In this study, we focused on macrophage migration inhibitory factor (MIF) to evaluate its pathophysiological role in the phagocytic process. Immunohistochemical analysis of human pseudosynovial tissues retrieved at revision of total hip arthroplasty showed that infiltrating mononuclear and multinuclear cells were positively stained by both an anti-CD68 antibody and anti-human MIF antibody. For in vitro study, MIF was released from murine macrophage-like cells (RAW 264.7) in response to phagocytosis of fluorescent-latex beads in a particle dose-dependent manner. Northern blot analysis showed marked elevation of the MIF mRNA level in the phagocytic macrophage-like cells. Moreover, pretreatment of RAW 264.7 cells with rat recombinant MIF increased the extent of phagocytosis by 1.6-fold compared with the control. Taken together, these results suggest that MIF plays an important role by activating macrophages in autocrine and paracrine fashion to phagocytose foreign particles. 相似文献
9.
The dynamic interaction, through the underlying or surrounding soil, between three-dimensional structures has been investigated, by coupling finite and boundary elements. The structures are discretized by finite elements, and the infinite soil is represented by boundary elements. A harmonic force is applied on both mass-lumped structures and mass-distributed structures. On the basis of our numerical studies, we further indicate the effects of distance, direction of alignment between two foundations, bedrock, natural frequency of the system and the location of load on the dynamic responses of structure-soil-structure interaction systems. 相似文献
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