SDF‐1/CXCR4 signalling is involved in blood vessel growth and remodelling by intussusception

The precise mechanisms of SDF‐1 (CXCL12) in angiogenesis are not fully elucidated. Recently, we showed that Notch inhibition induces extensive intussusceptive angiogenesis by recruitment of mononuclear cells and it was associated with increased levels of SDF‐1 and CXCR4. In the current study, we demonstrated SDF‐1 expression in liver sinusoidal vessels of Notch1 knockout mice with regenerative hyperplasia by means of intussusception, but we did not detect any SDF‐1 expression in wild‐type mice with normal liver vessel structure. In addition, pharmacological inhibition of SDF‐1/CXCR4 signalling by AMD3100 perturbs intussusceptive vascular growth and abolishes mononuclear cell recruitment in the chicken area vasculosa. In contrast, treatment with recombinant SDF‐1 protein increased microvascular density by 34% through augmentation of pillar number compared to controls. The number of extravasating mononuclear cells was four times higher after SDF‐1 application and two times less after blocking this pathway. Bone marrow‐derived mononuclear cells (BMDC) were recruited to vessels in response to elevated expression of SDF‐1 in endothelial cells. They participated in formation and stabilization of pillars. The current study is the first report to implicate SDF‐1/CXCR4 signalling in intussusceptive angiogenesis and further highlights the stabilizing role of BMDC in the formation of pillars during vascular remodelling.     

Characterization and potential antitumor effect of a heteropolysaccharide produced by the red alga Porphyridium sordidum

Taking into account the rising trend of the incidence of cancers of various organs, effective therapies are urgently needed to control human malignancies. However, almost all chemotherapy drugs currently on the market cause serious side effects. Fortunately, several studies have shown that some non‐toxic biological macromolecules, including algal polysaccharides, possess anti‐cancer activities or can increase the efficacy of conventional chemotherapy drugs. Polysaccharides are characteristic secondary metabolites of many algae. The efficacy of polysaccharides on the normal and cancer cells is not well investigated, but our investigations proved a cell specific effect of a newly isolated extracellular polysaccharide from the red microalga Porphyridium sordidum. The investigated substance was composed of xylose:glucose and galactose:manose:rhamnose in a molar ratio of 1:0.52:0.44:0.31. Reversible electroporation has been exploited to increase the transport through the plasma membrane into the tested breast cancer tumor cells MCF‐7 and MDA‐MB231. Application of 75 µg/mL polysaccharide in combination with 200 V/cm electroporation induced 40% decrease in viability of MDA‐MB231 cells and changes in cell morphology while control cells (MCF10A) remained with normal morphology and kept vitality.     

High-quality draft genome sequence of Pseudomonas aeruginosa san ai,an environmental isolate resistant to heavy metals

Extremophiles - The strain Pseudomonas aeruginosa san ai, isolated from an extreme environment (industrial mineral cutting oil, pH 10), is able to survive and persist in the presence of a variety...     

Beta-aspartylpeptides as substrates of L-asparaginases from Escherichia coli and Erwinia chrysanthemi

L-Asparaginase is known to catalyze the hydrolysis of L-asparagine to L-aspartic and ammonia, but little is known about its action on peptides. When we incubated L-asparaginases purified either from Escherichia coli or Erwinia chrysanthemi - commonly used as chemotherapeutic agents because of their antitumour activity - with eight small beta-aspartylpeptides such as beta-aspartylserineamide, beta-aspartylalanineamide, beta-aspartylglycineamide and beta-aspartylglycine, we found that both L-asparaginases could catalyze the hydrolysis of five of them yielding L-aspartic acid and amino acids or peptides. Our data show that L-asparaginases can hydrolyze beta-aspartylpeptides and suggest that L-asparaginase therapy may affect the metabolism of beta-aspartylpeptides present in human body.     

Two new sulfated furostanol saponins from Tribulus terrestris

The known furostanol saponins methylprotodioscin and protodioscin and two new sulfated saponins, sodium salt of 26-O-beta-glucopyranosyl-22alpha-methoxy-(25R)-furost-5-ene-3beta,26-diol-3-O-alpha-rhamnopyranosyl-(1-->2)-beta-4-O-sulfo-glucopyranoside (methylprototribestin) and sodium salt of 26-O-beta-glucopyranosyl-22alpha-hydroxy-(25R)-furost-5-ene-3beta,26-diol-3-O-alpha-rhamnopyranosyl-(1-->2)-beta-4-O-sulfo-glucopyranoside (prototribestin) have been isolated from the aerial parts of Tribulus terrestris L. growing in Bulgaria. The structures of the new compounds were elucidated on the basis of 1D and 2D (DQF-COSY, TOCSY, HSQC-TOCSY, HSQC, HMBC, ROESY) NMR data, ESI mass spectra and chemical transformation.     

The immune effects of TRYCATs (tryptophan catabolites along the IDO pathway): relevance for depression - and other conditions characterized by tryptophan depletion induced by inflammation

Immune activation is accompanied by induction of indoleamine (2,3)-dioxygenase (IDO), an enzyme which degrades tryptophan, a phenomenon which plays a role in the pathophysiology of major depression and post-natal depression and anxiety states. TRYCATs - tryptophan catabolites along the IDO pathway - such as kynurenine, kynurenic acid, xanthurenic acid, and quinolinic acid, have multiple effects, e.g. apoptotic, anti- versus pro-oxidant, neurotoxic versus neuroprotective, and anxiolytic versus anxiogenic effects. The aim of the present study was to study the immune effects of the above TRYCATS. Toward this end we examined the effects of the above TRYCATs on the LPS + PHA-induced production of interferon-gamma (IFNgamma), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNFalpha) in 18 normal volunteers. We found that the production of IFNgamma was significantly decreased by all 4 catabolites. Xanthurenic acid and quinolinic acid decreased the production of IL-10. Kynurenine, kynurenic acid, and xanthurenic acid, decreased the IFNgamma/IL-10 production ratio, whereas quinolinic acid increased this ratio. Kynurenic acid significantly reduced the stimulated production of TNFalpha. It is concluded that kynurenine, kynurenic acid, and xanthurenic acid have anti-inflammatory effects trough a reduction of IFNgamma, whereas quinolinic acid has pro-inflammatory effects in particular via significant decreases in IL-10. Following inflammation-induced IDO activation, some TRYCATs, i.e. kynurenine, kynurenic acid, and xanthurenic acid, exert a negative feedback control over IFNgamma production thus downregulating the initial inflammation, whereas an excess of quinolinic acid further aggravates the initial inflammation.     

Increased serum IgM antibodies directed against phosphatidyl inositol (Pi) in chronic fatigue syndrome (CFS) and major depression: evidence that an IgM-mediated immune response against Pi is one factor underpinning the comorbidity between both CFS and depression

Major depression and chronic fatigue syndrome (CFS) are accompanied by signs of oxidative and nitrosative stress (O&NS) and an inflammatory response. Phosphatidyl inositol (Pi) is thought to play a role in depression. The aim of the present study is to examine whether depression and CFS are characterized by an IgM-mediated immune response directed against Pi. Toward this end, this study examines the serum IgM antibodies directed against Pi in 14 patients with major depression, 14 patients with CFS, 14 subjects with partial CFS, and in 11 normal controls. We found that the prevalence and mean value for the serum IgM levels directed against Pi were significantly greater in patients with major depression and CFS than in normal controls and patients with partial CFS. There were significant and positive correlations between serum IgM levels directed against Pi and two symptoms of the FibroFatigue Scale, i.e. fatigue and depression. The results show that an IgM-related immune response directed against Pi may occur in both depression and CFS and may play a role in the pathophysiology of the key symptom of CFS and major depression. It is suggested that the above disorders in Pi result from increased O&NS in both depression and CFS. Autoanti-Pi antibodies may have biological effects, for example, by changing inositol 1,4,5-triphosphate (IP3), phosphatidylinositol-4,5-bisphosphate (PIP2), diacylglycerol and phosphatidylinositol-3,4,5-triphosphate (PIP3) production, thus interfering with intracellular signalling processes. Future research in major depression and CFS should focus on the functional consequences of the immune responses directed against Pi.     

Phacoemulsification, vitrectomy and the implantation of an intraocular lens in diabetic patients

The purpose of this study was to evaluate results of combined phacoemulsification, intraocular lens implantation and pars plana vitrectomy in patients with advanced diabetic retinopathy. We retrospectively evaluated postoperative outcomes and complications in 102 eyes of 102 patients who underwent a combined procedure. All patients had a visually significant cataract. Forty two patients had vitreous hemorrhage and mild proliferative diabetic retinopathy. Sixty patients had a mild tractional retinal detachment. The median follow up was 14 months (range 6-36 months). 80% of patients had an increase of visual acuity of at least 2 Snellen lines. The most frequent early postoperative complication was elevated intraocular pressure, followed by mild fibrinous reaction. The most frequent late postoperative complication was the presence of posterior synechia, followed by glaucoma. Eleven patients required a repeated pars plana vitrectomy. Combined phacoemulsification, posterior chamber intraocular lens implantation and pars plana vitrectomy can be successfully performed in selected diabetic patients with favorable postoperative outcome.     

Mutational analyses of the recombinant globular regions of human C1q A, B, and C chains suggest an essential role for arginine and histidine residues in the C1q-IgG interaction

The first step in the activation of the classical complement pathway by immune complexes involves the binding of the globular domain (gC1q) of C1q to the Fc regions of aggregated IgG or IgM. Each gC1q domain is a heterotrimer of the C-terminal halves of one A (ghA), one B (ghB), and one C (ghC) chain. Our recent studies have suggested a modular organization of gC1q, consistent with the view that ghA, ghB, and ghC are functionally autonomous modules and have distinct and differential ligand-binding properties. Although C1q binding sites on IgG have been previously identified, the complementary interacting sites on the gC1q domain have not been precisely defined. The availability of the recombinant constructs expressing ghA, ghB, and ghC has allowed us, for the first time, to engineer single-residue substitution mutations and identify residues on the gC1q domain, which are involved in the interaction between C1q and IgG. Because C1q is a charge pattern recognition molecule, we have sequentially targeted arginine and histidine residues in each chain. Consistent with previous chemical modification studies and the recent crystal structure of gC1q, our results support a central role for arginine and histidine residues, especially Arg(114) and Arg(129) of the ghB module, in the C1q-IgG interaction.