Effect of endothelium mimicking self-assembled nanomatrices on cell adhesion and spreading of human endothelial cells and smooth muscle cells

The goal of this study is to develop unique native endothelium mimicking nanomatrices and evaluate their effects on adhesion and spreading of human umbilical vein endothelial cells (HUVECs) and aortic smooth muscle cells (AoSMCs). These nanomatrices were developed by self-assembly of peptide amphiphiles (PAs) through a solvent evaporation technique. Three PAs, one containing the Tyr-Ile-Gly-Ser-Arg (YIGSR) ligand, the second containing the Val-Ala-Pro-Gly (VAPG) ligand, and a third without cell adhesive ligands, were developed. Cell adhesion and spreading were evaluated by a PicoGreen-DNA assay and live/dead assay, respectively. Our results show that PA-YIGSR significantly enhances HUVEC adhesion (26,704 ± 2708), spreading (84 ± 8%), and proliferation (50 ± 2%) compared with that of other PAs. PA-VAPG and PA-YIGSR showed significantly greater AoSMC adhesion compared with that of PA-S. PA-VAPG also showed significantly greater spreading of AoSMCs (63 ± 11%) compared with that of other PAs. Also, all the PAs showed significantly reduced platelet adhesion compared with that of collagen I (control). These findings would facilitate the development of novel vascular grafts, heart valves, and cell-based therapies for cardiovascular diseases.From the Clinical EditorThe goal of this study was to develop unique native endothelium mimicking nanomatrices and evaluate their effects on adhesion and spreading of human umbilical vein endothelial cells (HUVECs) and aortic smooth muscle cells (AoSMCs). These nanomatrices were developed by self-assembly of peptide amphiphiles through a solvent evaporation technique. The findings are expected to facilitate the development of novel vascular grafts, heart valves, and cell based therapies for cardiovascular diseases.     

Correction: Seeking potent anti-tubercular agents: design and synthesis of substituted-N-(6-(4-(pyrazine-2-carbonyl)piperazine/homopiperazine-1-yl)pyridin-3-yl)benzamide derivatives as anti-tubercular agents

Correction for ‘Seeking potent anti-tubercular agents: design and synthesis of substituted-N-(6-(4-(pyrazine-2-carbonyl)piperazine/homopiperazine-1-yl)pyridin-3-yl)benzamide derivatives as anti-tubercular agents’ by Singireddi Srinivasarao et al., RSC Adv., 2020, 10, 12272–12288, DOI: 10.1039/D0RA01348J.

The authors regret that the name of one of the authors (Linda De Vooght) was shown incorrectly in the original article. The corrected author list is as shown above.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

Bioactive actinomycetes from Krishna River sediments of Andhra Pradesh

Sediment samples from Krishna River at Nagayalanka of Andhra Pradesh, India were investigated as a source of actinomycetes to screen for the production of novel bioactive compounds. During our investigation on fresh water actinomycetes from 5 different river sediment samples, a total of 80 actinomycetes were isolated. Out of these 80 isolates, 30 isolates which showed distinct macromorphological characteristics were selected. The antimicrobial and enzymatic activities were studied for all the 30 isolates. The preliminary study for antimicrobial activity by cross streak method indicated that 16 isolates (53.3%) have excellent antagonistic properties. All these 16 isolates were subjected to detailed submerged fermentation studies. It was observed that 12 isolates (40.0%) exhibited antibacterial activity, 9 isolates (30.0%) showed antifungal activity while 5 isolates (16.6%) showed both antibacterial and antifungal activities. All the 30 isolates were also subjected for the determination of enzymatic activities 25 isolates (83.3%) exhibited amylolytic activity while 27 isolates (90.0%) showed proteolytic activity. Among these isolates, six promising isolates were selected for detailed morphological, cultural, physiological and biochemical studies. It was established that these isolates belong to the Streptomyces genus by virtue of their cell wall composition pattern and were identified as strains of different Streptomyces species like S. rochei, S. alanosinicus, S. erumpens, S. griseoplanus, S. gancidicus and S. nigrogriseolus.     

Effect of magnetic field on the biosynthesis of neomycin by Streptomyces marinensis

The effect of 30, 70, 90, 100, 110 and 150 gauss permanent magnetic field strength on the growth and neomycin titre of Streptomyces marinensis was studied. Maximum growth was attained in 120 h at all magnetic strengths. Gradual increase in neomycin titre was observed with increase of magnetic field strength up to 110 gauss.     

The nature of extra-chromosomal maintenance of transforming plasmids in the filamentous basidiomycete Phanerochaete chrysosporium

Summary The nature of extra-chromosomal maintenance of the transforming plasmid p12-6 in Phanerochaete chrysosporium was studied. Our results indicate that the plasmid is maintained in the fungal transformants extra-chromosomally as part of a larger endogenous plasmid (designated pME) of P. chrysosporium. Using the total DNA of p12-6 fungal transformants, p12-6, as well as a larger plasmid, p511, were recovered in recA ^– E. coli strains while only p12-6 was recovered in recA ⁺ E. coli strains. The results also showed that the cytosine methylation system has no apparent effect on the strain-dependent recovery of p12-6 and p511 in E. coli from the total DNA of fungal transformants.     

Urokinase-a very popular cardiovascular agent

Urokinase (UK) [EC 3.4.99.26] is a serine protease that activates plasminogen to plasmin, which in turn degrades fibrin clots. Hence, UK finds its value as an important anti-thromboembolic drug. Plasmin has diverse physiological roles apart from its fibrinolytic role in the regulation of blood clotting. It has been implicated in complement activation, cell migration, wound healing, and generation of localized extracellular proteolysis during tissue remodelling, pro-hormone conversion, carcinogenesis and neoplasia. Among the plasminogen activators, UK provides a superior alternative for the simple reasons of its being more potent as compared to tissue-plasminogen activator and non-antigenic by virtue of its human origin unlike streptokinase. Based on these observations, UK is a very popular cardiovascular agent. Hence, UK, as one of the most potent plasminogen activators is attracting a great deal of attention. We will summarize recent patents related to the occurrence, mechanism of action, structure and function, physico-chemical properties, in vitro production, cloning and expression, purification and applications of UK.     

Streptokinase—the drug of choice for thrombolytic therapy

Thrombosis, the blockage of blood vessels with clots, can lead to acute myocardial infarction and ischemic stroke, both leading causes of death. Other than surgical interventions to remove or by pass the blockage, or the generation of collateral vessels to provide a new blood supply, the only treatment available is the administration of thrombolytic agents to dissolve the blood clot. This article describes a comprehensive review of streptokinase (SK). We discuss the biochemistry and molecular biology of SK, describing the mechanism of action, structures, confirmational properties, immunogenecity, chemical modification, and cloning and expression. The production and physico-chemical properties of this SK are also discussed. In this review, considering the properties and characteristics of SK that make it the drug of choice for thrombolytic therapy.     

Synthesis,study of antileishmanial and antitrypanosomal activity of imidazo pyridine fused triazole analogues

Four groups, thirty-five compounds in total, of novel 1,2,3-triazole analogues of imidazo-[1,2-a]-pyridine-3-carboxamides were designed and synthesized using substituted pyridine, propargyl bromide, 2-azidoethyl 4-methyl benzenesulfonate and substituted acetylenes. These compounds were characterized using ¹H NMR, ¹³C NMR, LCMS and elemental analyses and a crystal structure was obtained for one of the significantly active compounds, 8f. All the synthesized and characterized compounds were screened in vitro for antileishmanial and antitrypanosomal activity against Leishmania major and Trypanosoma brucei parasites, respectively. Among the tested analogues, five compounds (8d, 8f, 8j, 10b and 10d) exhibited significant antileishmanial activity while three compounds (10b, 11a and 11b) showed substantial activity against T. brucei parasite. In silico ADME prediction studies depicted that the essential compounds obeyed Lipinski''s rule of five. The predicted in silico toxicity profile suggested that the tested compounds would be non-toxic, which was confirmed experimentally by the lack of cytotoxicity against HeLa cells. Finally, a molecular docking study was also performed, for 10d the most active antileishmanial compound, to study its putative binding pattern at the active site of the selected leishmanial trypanothione reductase target.

Thirty-five novel 1,2,3-triazole analogues of imidazo-[1,2-a]-pyridine-3-carboxamides were designed, synthesized and evaluated for in vitro antileishmanial and antitrypanosomal activity against L. major and T. brucei parasites, respectively.     

Efficacy of lycopene in the treatment of gingivitis: a randomised, placebo-controlled clinical trial

PURPOSE: The aim of the present study was to compare the effect of systemically administered lycopene (LycoRed) as a monotherapy and as an adjunct to scaling and root planing in gingivitis patients. MATERIALS AND METHODS: Twenty systemically healthy patients showing clinical signs of gingivitis were involved in a randomised, double-blind, parallel, split-mouth study. The subjects were randomly distributed between the two treatment groups: experimental group (n = 10), 8 mg lycopene/day for 2 weeks; and controls (n = 10), placebo for 2 weeks. Quadrant allocation within each group was randomised with two quadrants treated with oral prophylaxis (OP) and two quadrants not receiving any form of treatment (non-OP). Bleeding index (SBI) and non-invasive measures of plaque (PI) and gingivitis (GI) were assessed at baseline, 1 and 2 weeks. Salivary uric acid levels were also measured. RESULTS: All the treatment groups demonstrated statistically significant reductions in the GI, SBI and PI. Treatment with OP-lycopene resulted in a statistically significant decrease in GI when compared with OP-placebo (p < 0.05) and non-OP-placebo (p < 0.01). Treatment with non-OP-lycopene resulted in a statistically significant decrease in GI when compared with non-OP-placebo (p < 0.01). The OP-lycopene group showed a statistically significant reduction in SBI values when compared with the non-OP-lycopene group (p < 0.05) and the non-OP-placebo group (p < 0.001). There was a strong negative correlation between the salivary uric acid levels and the percentage reduction in GI at 1 and 2 weeks in the OP-lycopene group (r = -0.852 and -0.802 respectively) and in the non-OP-lycopene group (r = -0.640 and -0.580 respectively). CONCLUSIONS: The results presented in this study suggest that lycopene shows great promise as a treatment modality in gingivitis. The possibility of obtaining an additive effect by combining routine oral prophylaxis with lycopene is also an exciting possibility, which deserves further study.     

Crystal modifications and dissolution rate of piroxicam

Piroxicam is a nonsteroidal anti-inflammatory drug with low aqueous solubility which exhibits polymorphism. The present study was carried out to develop polymorphs of piroxicam with enhanced solubility and dissolution rate by the crystal modification technique using different solvent mixtures prepared with PEG 4000 and PVP K30. Physicochemical characteristics of the modified crystal forms of piroxicam were investigated by X-ray powder diffractometry, FT-IR spectrophotometry and differential scanning calorimetry. Dissolution and solubility profiles of each modified crystal form were studied and compared with pure piroxicam. Solvent evaporation method (method I) produced both needle and cubic shaped crystals. Slow crystallization from ethanol with addition of PEG 4000 or PVP K30 at room temperature (method II) produced cubic crystal forms. Needle forms produced by method I improved dissolution but not solubility. Cubic crystals produced by method I had a dissolution profile similar to that of untreated piroxicam but showed better solubility than untreated piroxicam. Cubic shaped crystals produced by method II showed improved dissolution, without a significant change in solubility. Based on the XRPD results, modified piroxicam crystals obtained by method I from acetone/benzene were cube shaped, which correlates well with the FTIR spectrum; modified needle forms obtained from ethanol/methanol and ethanol/acetone showed a slight shift of FTIR peak that may be attributed to differences in the internal structure or conformation.