Thalassospiramide G, a New γ-Amino-Acid-Bearing Peptide from the Marine Bacterium Thalassospira sp.

Abstract: In the chemical investigation of marine unicellular bacteria, a new peptide, thalassospiramide G (1), along with thalassospiramides A and D (2–3), was discovered from a large culture of Thalassospira sp. The structure of thalassospiramide G, bearing γ-amino acids, such as 4-amino-5-hydroxy-penta-2-enoic acid (AHPEA), 4-amino-3,5-dihydroxy-pentanoic acid (ADPA), and unique 2-amino-1-(1H-indol-3-yl) ethanone (AIEN), was determined via extensive spectroscopic analysis. The absolute configuration of thalassospiramide D (3), including 4-amino-3-hydroxy-5-phenylpentanoic acid (AHPPA), was rigorously determined by 1 H – 1 H coupling constant analysis and chemical derivatization. Thalassospiramides A and D (2–3) inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated mouse macrophage RAW 264.7 cells, with IC50 values of 16.4 and 4.8 μM, respectively

Effects of intra-articular SHINBARO treatment on monosodium iodoacetate-induced osteoarthritis in rats

Background SHINBARO is a refined herbal formulation used to treat inflamed lesions and bone diseases. This study aimed to investigate the anti-osteoarthritic activities of intra-articular administration of SHINBARO and determine its underlying molecular mechanism in a monosodium iodoacetate (MIA)-induced osteoarthritis rat model. Methods Male Sprague–Dawley rats received a single intra-articular injection of MIA into the infrapatellar ligament of the right knee. Subsequently, the rats were treated with normal saline, SHINBARO, and diclofenac once daily for 21 days. Rats treated with normal saline, but not MIA, comprised the control group. Histological changes in the femur of the MIA-induced osteoarthritis rat model were observed by micro-computed tomography scanning and staining with hematoxylin and eosin, and safranin-O fast green. Serum levels of PGE2 and anti-type II collagen antibodies in the MIA-induced osteoarthritis rat model were measured using commercial kits. Protein levels of inflammatory enzymes (iNOS, COX-2), pro-inflammatory cytokines (TNF-α, IL-1β), and inflammatory mediators (NF-κB, IκB) in cartilaginous tissues were determined by western blot analysis. Results Intra-articular administration of SHINBARO (IAS) at 20 mg/kg remarkably restrained the decrease in bone volume/total volume, being 28 % (P = 0.0001) higher than that in the vehicle-treated MIA group. IAS (2, 10, and 20 mg/kg) treatment significantly recovered the mean number of objects values with increased percentage changes of 13.5 % (P = 0.147), 27.5 % (P = 0.028), and 44.5 % (P = 0.031), respectively, compared with the vehicle-treated MIA group. The serum level of PGE2 in the IAS group at 20 mg/kg was markedly inhibited by 60.6 % (P = 0.0007) compared with the vehicle-treated MIA group, and the anti-collagen type II antibody level in the IAS group was reduced in a dose-dependent manner. IAS (20 mg/kg) effectively suppressed the induction of inflammation-mediated enzymes (iNOS and COX-2) and pro-inflammatory cytokines (TNF-α and IL-1β). IAS treatment also downregulated the NF-κB level and increased the IκB-α level in the MIA- induced osteoarthritis rat model. Conclusion SHINBARO inhibited PGE2 and anti-type II collagen antibody production and modulated the balance of inflammatory enzymes, mediators, and cytokines in the MIA-induced osteoarthritis rat model

The image of woman in Lenka Reinerova's memoirs

The thesis deals with the image of a woman in Lenka Reinerova's memoirs published in Czech. The topic is first showed partially, which means separately for each single memorial prose, chronologically according to a year of their publishing, and afterwards coherently by means of general features included at the beginning of the work. The image of a woman is showed by way of both direct and indirect characterization and comparison. Introductory part of the work is connected wih the Prague Circle and its last member Lenka Reinerová, the last Prague author writing in German. The topic of the Prague Circle and Lenka Reinerova's place in Prague literature written in German as well are envisaged problematically. The aim of the first part of the work is to specify some characterizations which are common for all members of the Prague Circle and to specify Lenka Reinerova's place in Prague German literature more accurately by quoting the contemporary authors writing in German and at the same time related to Prague in the broad sense of the word

Structure–Activity Relationships of Truncated C2- or C8-Substituted Adenosine Derivatives as Dual Acting A_2A and A₃ Adenosine Receptor Ligands

Truncated <i>N</i>⁶-substituted-4′-oxo- and 4′-thioadenosine derivatives with C2 or C8 substitution were studied as dual acting A_2A and A₃ adenosine receptor (AR) ligands. The lithiation-mediated stannyl transfer and palladium-catalyzed cross-coupling reactions were utilized for functionalization of the C2 position of 6-chloropurine nucleosides. An unsubstituted 6-amino group and a hydrophobic C2 substituent were required for high affinity at the hA_2AAR, but hydrophobic C8 substitution abolished binding at the hA_2AAR. However, most of synthesized compounds displayed medium to high binding affinity at the hA₃AR, regardless of C2 or C8 substitution, and low efficacy in a functional cAMP assay. Several compounds tended to be full hA_2AAR agonists. C2 substitution probed geometrically through hA_2AAR docking was important for binding in order of hexynyl > hexenyl > hexanyl. Compound <b>4g</b> was the most potent ligand acting dually as hA_2AAR agonist and hA₃AR antagonist, which might be useful for treatment of asthma or other inflammatory diseases