Role of high-mobility group box-1 protein in disruption of vascular barriers and regulation of leukocyte–endothelial interactions

Abstract

High-mobility group box-1 protein (HMGB1) is a highly conserved non-histone DNA-binding protein present in the nuclei and cytoplasm of nearly all cell types. The results from recent research provide evidence that HMGB1 is secreted into the extracellular milieu and acts as a pro-inflammatory cytokine and exhibits angiogenic effects to fire the immunological response against the pathological effects. Recently, a great deal of evidence has indicated the critical importance of HMGB1 in mediating vascular barriers dysfunction by modulating the expression of adhesion molecules, such as intercellular adhesion molecule-1, vascular cell adhesion protein 1 and E-selectin on the surface of endothelial cells. Such process promotes the adhesion and migration of leukocytes across the endothelium, leading to breakdown of vascular barriers (blood–brain barrier and blood–retinal barrier) via modulating the expression, content, phosphorylation, and distribution of tight junction proteins. Therefore, here we give an abridged review to understand the mechanistic link between HMGB1 and vascular barriers dysfunction, including interaction with cell-surface receptors and intracellular signaling pathways.     

Effects of fragmentation phenomena on the genetic structure and gene flow in Centaurea cineraria group (Asteraceae) in the Mediterranean Basin

The complex history of the Mediterranean region illustrates how ancient and recent phenomena are closely associated with species distribution and the creation of phylogeographic divisions within Mediterranean flora. A good model to explore the genetic consequences of fragmentation can be found in Centaurea cineraria and its close relatives. We applied simple sequence repeat molecular markers to a dense population sampling throughout the distribution area of all C. cineraria taxa to study how fragmentation has altered the genetic structure and distribution of C. cineraria. The average gene diversity (H_e) was 0.286, and the average allelic richness (A_r) was 3.65 and ranged from 2.15 (C. gymnocarpa) to 5.25 (C. busambarensis). The F_IS averaged a relatively high 0.223, ranging from ? 0.724 in C. aeolica subsp. aeolica to 0.589 in C. leucadea. Our results indicate that habitat fragmentation over several generations reduced heterozygosity due to random genetic drift in populations of C. cineraria. This heterozygosity erosion becomes more severe when the inbreeding coefficient is positive and the outcrossing rates show a significant increase. The results observed for outcrossing rates and inbreeding coefficient could also indirectly support the possibility of disrupted gene flow or mating pattern changes in fragmented C. cineraria populations.     

Synthesis of D‐Altritol Nucleosides with a 3′‐O‐Tert‐Butyldimethylsilyl Protecting Group

Four D‐altritol nucleosides with a 3′‐O‐tert‐butyldimethylsilyl protecting group are synthesized (base moieties are adenine, guanine, thymine and 5‐methylcytosine). The nucleosides are obtained by ring opening reaction of 1,5:2,3‐dianhydro‐4,6‐O‐benzylidene‐D‐allitol. Optimal reaction circumstances (NaH, LiH, DBU, phase transfer, microwave irridation) for the introduction of the heterocycles are base‐specific. For the introduction of the 3′‐O‐silyl protecting group, long reaction times and several equivalents of tert‐butyldimethylsilyl chloride are needed.     

Diastereomeric Process Control in the Synthesis of 2′-O-(2-Methoxyethyl) Oligoribonucleotide Phosphorothioates as Antisense Drugs

Abstract

Coupling of 2′-O-methoxyethylsubstituted nucleoside phosphoramidites to 5′-hydroxyl group of a nucleoside or nucleotide on solid support is under stereochemical process control and is independent of scale, concentration, synthesizer, ratio of amidite diastereomers, solid support etc. However, activators and phosphate protecting groups do play a role in influencing the ratio of phosphorothioate diesters obtained by sulfurization of phosphite triesters.     

Taxonomic revision of the genus Callimerus Gorham s. l. (Coleoptera,Cleridae). Part I. latifrons species-group

The latifrons species-group (=Brachycallimerus sensu Chapin 1924, Corporaal 1950; = flavofasciatus-group sensu Kolibáč 1998) of Callimerus Gorham is redefined and revised. Five species are recognized including one new species Callimerus cacuminis Yang & Yang sp. n. (type locality: Yunnan, China). Callimerus flavofasciatus Schenkling, 1902 is newly synonymized with Callimerus latifrons Gorham, 1876. Callimerus trifasciatus Schenkling, 1899a is transferred to the genus Corynommadius Schenkling, 1899a. Callimerus gorhami Corporaal, 1949 and Callimerus pallidus Gorham, 1892 are excluded from the latifrons species-group (their assignment to a species-group will be dealt with in a subsequent paper). A key to species of the latifrons species-group is given and habitus of each type specimen, male terminalia, and other diagnostic characters are illustrated.     

Key for European species of the Cheilosia proxima group (Diptera,Syrphidae) with a description of a new species

A new hoverfly species, Cheilosia barbafacies Vujić & Radenković sp. n. (Diptera, Syrphidae), is described and distinguished from the closely related species Cheilosia pascuorum Becker, 1894, based on material collected from the mountains of the Balkan Peninsula. Diagnostic characteristics and an identification key for the members of the proxima group of Cheilosia s. str., including the new taxon, are provided.     

Two newly recognized species of Hemidactylus (Squamata,Gekkonidae) from the Arabian Peninsula?and Sinai,Egypt

A recent molecular phylogeny of the Arid clade of the genus Hemidactylus revealed that the recently described H. saba and two unnamed Hemidactylus species from Sinai, Saudi Arabia and Yemen form a well-supported monophyletic group within the Arabian radiation of the genus. The name ‘Hemidactylus saba species group’ is suggested for this clade. According to the results of morphological comparisons and the molecular analyses using two mitochondrial (12S and cytb) and four nuclear (cmos, mc1r, rag1, rag2) genes, the name Hemidactylus granosus Heyden, 1827 is resurrected from the synonymy of H. turcicus for the Sinai and Saudi Arabian species. The third species of this group from Yemen is described formally as a new species H. ulii sp. n. The phylogenetic relationships of the members of ‘Hemidactylus saba species group’ are evaluated and the distribution and ecology of individual species are discussed.     

Capsaicin as an inducer of damage-associated molecular patterns (DAMPs) of immunogenic cell death (ICD) in human bladder cancer cells

Few conventional cytotoxic anticancer therapeutics induce immunogenic cell death (ICD). This means that they induce tumor cells to undergo apoptosis while eliciting the emission of a spatiotemporal-defined combination of damage-associated molecular patterns (DAMPs) decoded by the immune system to activate antitumor immunity effective for long-term therapeutic success. The neurotoxin capsaicin (CPS) can induce both cancer cell apoptosis and immune-mediated tumor regression. In the present study, we investigated whether CPS is capable of eliciting the emission of ICD hallmarks in human bladder cancer cell lines undergoing apoptosis. We demonstrated that CPS induces pre- and early apoptotic cell surface exposure of calreticulin (CRT), HSP90, and HSP70 as well as ATP release. Moreover, CRT exposure was prevented by inhibition of endoplasmic reticulum–Golgi traffic by brefeldin A. Furthermore, high-mobility group box 1, HSP90, and HSP70 were passively released at late apoptotic stages. We provide the first evidence that CPS is an inducer of ICD hallmarks, suggesting CPS as a novel potential immunogenic cytotoxic agent.     

Lysoglycerophospholipids in chronic inflammatory disorders: The PLA2/LPC and ATX/LPA axes

Lysophosphatidylcholine (LPC) and lysophosphatidic acid (LPA), the most prominent lysoglycerophospholipids, are emerging as a novel class of inflammatory lipids, joining thromboxanes, leukotrienes and prostaglandins with which they share metabolic pathways and regulatory mechanisms. Enzymes that participate in LPC and LPA metabolism, such as the phospholipase A₂ superfamily (PLA₂) and autotaxin (ATX, ENPP2), play central roles in regulating LPC and LPA levels and consequently their actions. LPC/LPA biosynthetic pathways will be briefly presented and LPC/LPA signaling properties and their possible functions in the regulation of the immune system and chronic inflammation will be reviewed. Furthermore, implications of exacerbated LPC and/or LPA signaling in the context of chronic inflammatory diseases, namely rheumatoid arthritis, multiple sclerosis, pulmonary fibrosis and hepatitis, will be discussed. This article is part of a Special Issue entitled Advances in Lysophospholipid Research.