Isolation and screening of rareActinobacteria, a new insight for finding natural products with antivascular calcification activity

Abstract

Aim: Vascular calcification (VC) is a significant pathological process in some life-threatening diseases. Several pathological mechanisms, including transdifferentiation of vascular smooth muscle cells to osteoblast-like cells and apoptosis are involved in VC. Compounds with an inhibitory effect on these processes are potentially efficient medications. In consideration of the multiple biological activities of Actinobacteria, this research was aimed at finding anti-VC metabolite-producing Actinobacteria. Methods and Results: After the isolation and identification of Actinobacteria, the effect of their fermentation broth extracts on the apoptosis rate was measured using various methods, for example, ethidium bromide/acridine orange staining, DNA laddering and diphenylamine assays. The effect of the most effective fermentation broth extract of Actinobacteria (FBEA) on the mRNA expression of runt-related transcription factor 2 (Runx2) and osteopontin (OPN) was examined. Finally, the most effective FBEA was fractionated and the chemical composition of anti-VC fractions was analysed using GC-MS. Various VC inhibition rates were observed in the tested FBEA (20 lg ml À1 ; 17Á9-60Á15%). The inhibition of DNA fragmentation was 7-48%.The FBE with the greatest anticalcification activity belonged to Kribbella sp. UTMC 267 and, according to 16S rRNA analysis, Kribbella sancticallisti with a similarity of 98Á53% is its nearest neighbour. The FBE of Kribbella sp. UTMC 267 reduced Runx2 mRNA expression by 2Á95-fold and OPN mRNA expression by 28Á57-fold, both of which are considered significant (P < 0Á05). Finally, GC-MS analysis showed the existence of potent anti-oxidative and anti-inflammation agents in FBE of Kribbella sp. UTMC 267. Conclusions: Actinobacterial metabolites can provide a new strategy for treating VC diseases by reducing the expression of osteogenic genes, the apoptosis rate and oxidative stress. Significance and Impact of the Study: This study highlights the therapeutic potential of Kribbella sp. metabolites and Actinobacteria as a new natural source for drug discovery programs in the nonantibiotic bioactivity field.

Simultaneous anti-diabetic and anti-vascular calcification activity of Nocardia sp. UTMC 751

“…In addition, this FBE showed good anti‐VC characteristics in the alizarin red staining and anti‐apoptotic effects in the VSMCs under the calcification condition (Salimi et al . ). Recent studies have indicated that hyperglycaemia induces VC in the human aortic smooth muscle cells by up‐regulation the osteoblastic markers (Giugliano et al .…”

Introduction of marine-derivedStreptomycessp. UTMC 1334 as a source of pyrrole derivatives with anti-acetylcholinesterase activity

“…The metabolic extracts were screened for toxicity against larvae of Artemia salina (brine shrimp) as described before (Salimi et al . ). The test was performed in triplicate with extract concentrations of 10, 50 and 100 μ g ml −1 and the lethal dose of extracts was calculated by enumeration of the dead larvae after 24 h.…”

“…), enzyme inhibitors (Imada ), antivascular calcification activity (Salimi et al . ), antitumour (Salcedo et al . ), anti‐angiogenic and proangiogenic agents (Azarakhsh et al .…”

Pulmonary Nocardia ignorata Infection in Gardener, Iran, 2017

“…ignorata is a rare human pathogen. However, soil samples have been described as a possible reservoir (2,7,8). Accordingly, this patient, who had frequent exposure to soil through his work as a gardener, might have acquired the infection from that source.…”