- Purification and identification of an actinomycin D analogue from actinomycetes associated with Ganoderma applanatum via magnetic molecularly imprinted polymers and tandem mass spectrometry. [Journal Article]
- FCFood Chem Toxicol 2018 May 16
- Actinomycetes are main producers of antibiotics and targeted screening could improve the efficiency of discovering new drugs. This study describes, for the first time, the isolation of endophytic act...
Actinomycetes are main producers of antibiotics and targeted screening could improve the efficiency of discovering new drugs. This study describes, for the first time, the isolation of endophytic actinomycetes from the macrofungus Ganoderma applanatum. To increase the efficiency of screening, novel actinomycin D (Act D) molecularly-imprinted polymers were adsorbed to the surface of Fe3O4@SiO2 magnetic microspheres (MMIPs) and using in the isolation. A monolithic column prepared with magnetic molecularly imprinted polymers was employed to adsorb actinomycin D and its analogues for selective analysis and identification via MS/MS spectroscopy. The MMIP-monolithic column was selective for the structural features of Act D and its analogue, and the maximum loading of the MMIPs for Act D was ∼23.5 μg/g. The recognition time of the Act D was 20-30 min and had good discriminative ability. A new analogue was identified from endophytic actinomycetes KLBMP 2541, and it was purified using MMIPs comparison with MMIPs-solid phase extraction. Structural identification analysis confirmed that the new analogue was 2-methyl-actinomycin D, which has better anti-tumor activity than Act D. The presented method combines the advantages of MMIPs and MS with popular solutions to enable high affinity and selectivity screening of specific antibiotics from endophytic actinomycetes.
- Porcine IGF1 synonymous mutation alter gene expression and protein binding affinity with IGF1R. [Journal Article]
- IJInt J Biol Macromol 2018 May 05; 116:23-30
- CONCLUSIONS: Our findings indicated the synonymous mutation altered the IGF1 gene expression and confirmed the synonymous mutation affected the IGF1 folding and the interactions with the IGF1R preliminarily.
- ApoA-1 Mimetic Peptide ELK-2A2K2E Decreases Inflammatory Factor Levels via the ABCA1-JAK2-STAT3-TTP Axis in THP-1-Derived Macrophages. [Journal Article]
- JCJ Cardiovasc Pharmacol 2018 May 03
- CONCLUSIONS: ApoA-I mimetic peptide ELK-2A2K2E increases the degradation of TNF-α, IL-6 and MCP-1 mRNA and reduces the levels of inflammatory cytokines via activating the JAK2-STAT3-TTP signaling pathway which is dependent on the up-regulation of ABCA1.
- Regulation of Camphor Metabolism: Induction and Repression of Relevant Monooxygenases in Pseudomonas putida NCIMB 10007. [Journal Article]
- MMicroorganisms 2018 May 07; 6(2)
- For the first time, the differential rates of synthesis of all the key monooxygenases involved in the catabolism by Pseudomonas putida NCIMB 10007 of bicyclic (rac)-camphor to ∆2,5-3,4,4-trimethylpim...
For the first time, the differential rates of synthesis of all the key monooxygenases involved in the catabolism by Pseudomonas putida NCIMB 10007 of bicyclic (rac)-camphor to ∆2,5-3,4,4-trimethylpimelyl-CoA, the first aliphatic pathway intermediate, have been determined to help establish the relevant induction profile of each of the oxygen-dependent enzymes. The efficacy of both relevant substrates and pathway metabolites as inducers has been established. Further, inhibitors with characterised functionality have been used to indicate that the pertinent regulatory controls operate at the level of transcription of the corresponding genes.
- Anticancer Activity of Bacterial Proteins and Peptides. [Review]
- PPharmaceutics 2018 Apr 30; 10(2)
- Despite much progress in the diagnosis and treatment of cancer, tumour diseases constitute one of the main reasons of deaths worldwide. The side effects of chemotherapy and drug resistance of some ca...
Despite much progress in the diagnosis and treatment of cancer, tumour diseases constitute one of the main reasons of deaths worldwide. The side effects of chemotherapy and drug resistance of some cancer types belong to the significant current therapeutic problems. Hence, searching for new anticancer substances and medicines are very important. Among them, bacterial proteins and peptides are a promising group of bioactive compounds and potential anticancer drugs. Some of them, including anticancer antibiotics (actinomycin D, bleomycin, doxorubicin, mitomycin C) and diphtheria toxin, are already used in the cancer treatment, while other substances are in clinical trials (e.g., p28, arginine deiminase ADI) or tested in in vitro research. This review shows the current literature data regarding the anticancer activity of proteins and peptides originated from bacteria: antibiotics, bacteriocins, enzymes, nonribosomal peptides (NRPs), toxins and others such as azurin, p28, Entap and Pep27anal2. The special attention was paid to the still poorly understood active substances obtained from the marine sediment bacteria. In total, 37 chemical compounds or groups of compounds with antitumor properties have been described in the present article.
- Regulation of the ARE-binding proteins, TTP (tristetraprolin) and HuR (human antigen R), in inflammatory response in astrocytes. [Journal Article]
- NINeurochem Int 2018 Apr 24; 118:82-90
- Control of decay of mRNA containing the adenine-uridine rich elements (AREs) is an important post-transcriptional mechanism involved in the regulation of inflammatory gene expression. Two widely reco...
Control of decay of mRNA containing the adenine-uridine rich elements (AREs) is an important post-transcriptional mechanism involved in the regulation of inflammatory gene expression. Two widely recognized proteins in this machinery are HuR (human antigen R) - a protein that stabilizes ARE-containing mRNA and TTP (tristetraprolin) - a protein that shortens half-lives of ARE-containing mRNA. Although HuR and TTP regulation mechanisms have been well studied in cells of hematopoietic origin, there are no respective data in astrocytes, cells of ectodermal origin which play an important role in neuroinflammation. Therefore we evaluated the existence of TTP and HuR in primary astrocytes and characterized the features of their regulation after stimulation by the proinflammatory stimuli thrombin, ATP, and agonists of TLR4, TLR2. All proinflammatory stimuli increased levels of TTP mRNA, but not HuR mRNA. Transcripts of both HuR and TTP underwent stabilization upon lipopolysaccharide (LPS) treatment, measured with the actinomycin D protocol. This effect was abolished by treatment with SB203580, an inhibitor of р38 МАРК. Both TTP and HuR transcripts were sensitive to modulation by anisomycin and cycloheximide. LPS induced translocation of HuR protein from nucleus to cytoplasm. TTP is localized in the cytosolic fraction and localization is not sensitive to LPS treatment. Our data for the first time reveal specificity of regulation of ARE-binding proteins in astrocytes. We propose possibilities to manipulate brain inflammatory processes via post-transcription regulatory steps in astrocytes.
- IL6 and LIF mRNA expression in skeletal muscle is regulated by AMPK and the transcription factors NFYC, ZBTB14 and SP1. [Journal Article]
- AJAm J Physiol Endocrinol Metab 2018 Apr 24
- AMPK controls glucose- and lipid- metabolism and modulates inflammatory responses to maintain metabolic and inflammatory homeostasis during low cellular energy levels. The AMPK activator 5-aminoimida...
AMPK controls glucose- and lipid- metabolism and modulates inflammatory responses to maintain metabolic and inflammatory homeostasis during low cellular energy levels. The AMPK activator 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside (AICAR) interferes with inflammatory pathways in skeletal muscle, but the mechanisms are undefined. We hypothesized that AMPK activation reduces cytokine mRNA levels by blocking transcription through one or several transcription factors. Three skeletal muscle models were used to study AMPK effects on cytokine mRNA: human skeletal muscle strips obtained from healthy men incubated in vitro, primary human muscle cells and rat L6 cells. In all three skeletal muscle systems, AICAR acutely reduced cytokine mRNA levels. In L6 myotubes treated with the transcriptional blocker actinomycin D, AICAR addition did not further reduce Il6 or Lif mRNA, suggesting that AICAR modulates cytokine expression through regulating transcription rather than mRNA stability. A cross-species bioinformatic approach identified novel transcription factors which may regulate LIF and IL6 mRNA. The involvement of these transcription factors was studied after targeted gene-silencing by siRNA. siRNA silencing of the transcription factors Nfyc, Sp1 and Zbtb14, or AMPK α1/α2 subunits, increased constitutive levels of Il6 and Lif. Our results identify novel candidates in the regulation of skeletal muscle cytokine expression and identify AMPK, Nfyc, Sp1, Zbtb14 and as novel regulators of immunometabolic signals from skeletal muscle.
- Phosphorylated nucleolar Tau protein is related to the neuronal in vitro differentiation. [Journal Article]
- GENEGene 2018 Apr 20
- Tau is a multifunctional protein, originally identified as a cytoplasmic protein associated with microtubules. It is codified by the MAPT gene, and the alternative splicing, in the neuronal cells, re...
Tau is a multifunctional protein, originally identified as a cytoplasmic protein associated with microtubules. It is codified by the MAPT gene, and the alternative splicing, in the neuronal cells, results in six different isoforms. Tau was subsequently observed in the cell nucleus, where its function is not yet clearly understood. Here, we studied the MAPT gene and the cellular localization of the AT8 and Tau-1 epitopes of Tau protein, in the SK-N-BE cell line, which differentiates in neuronal-like cells after retinoic acid treatment. These epitopes correspond to the phosphorylated Ser202/Thr205 and unphosphorylated Pro189/Gly207 amino acid residues, respectively, possibly involved in conformational changes of the protein. Our results demonstrated the presence of the smaller Tau isoform (352 amino acids), whose amount increases in differentiated SK-N-BE cells, with Tau-1/AT8 nuclear distribution related to the differentiation process. Tau-1 showed a spot-like nucleolar localization, in both replicative and differentiated cells, while AT8 was only detected in the differentiated cells, diffusely occupying the entire nucleolar region. Moreover, in the replicative cells exposed to actinomycin-D, AT8 and Tau-1 move to the nucleolar periphery and colocalize, in few spots, with the upstream binding transcription factor (UBTF). Our results, also obtained with lymphocytes exposed to the mitogenic compound phytohaemagglutinin, indicate the AT8 epitope of Tau as a marker of neuronal cell differentiation, whose presence in the nucleolus appears to be related to rDNA transcriptional inactivation.
- Biliary Rhabdomyosarcoma in an Infant Male With Neurofibromatosis Type 1. [Journal Article]
- JPJ Pediatr Hematol Oncol 2018 Apr 20
- Different types of malignancies can be seen in patients with neurofibromatosis type 1 (NF-1). Herein we present a rare combination of NF-1 and biliary rhabdomyosarcoma in a male infant. An 11-month-o...
Different types of malignancies can be seen in patients with neurofibromatosis type 1 (NF-1). Herein we present a rare combination of NF-1 and biliary rhabdomyosarcoma in a male infant. An 11-month-old boy, who was recently diagnosed with NF-1, presented to the outpatient clinic with a 3-month history of prolonged jaundice, and failure to thrive. Clinical examination showed >20 café au let spots distributed mainly over the abdominal trunk. Hepatomegaly (4 cm below the costal margin) was additionally observed. His father was diagnosed with NF-1. Radiologic imaging studies showed a 6×5×5 cm in diameter cystic mass with multiple septations in the segment 4A of the liver. Surgical excision of the left hepatic lobe followed by hepatojejunostomy was further performed. Histopathology examination showed embryonal type rhabdomyosarcoma originating from the biliary duct. Chemotherapy regimen consisting of cyclophosphamide, actinomycin D, and vincristine, and radiotherapy were then initiated. This treatment led to a significant improvement in the patient's clinical status, and radiologic finding portrayed attainment of complete resolution. He is still in complete remission without any sequelae for 8 years.
New Search Next
- DNA in Squid Synaptosomes. [Journal Article]
- MNMol Neurobiol 2018 Apr 19
- The synthesis of brain metabolic DNA (BMD) is modulated by learning and circadian oscillations and is not involved in cell division or DNA repair. Data from rats have highlighted its prevalent associ...
The synthesis of brain metabolic DNA (BMD) is modulated by learning and circadian oscillations and is not involved in cell division or DNA repair. Data from rats have highlighted its prevalent association with the mitochondrial fraction and its lack of identity with mtDNA. These features suggested that BMD could be localized in synaptosomes that are the major contaminants of brain mitochondrial fractions. The hypothesis has been examined by immunochemical analyses of the large synaptosomes of squid optic lobes that are readily prepared and identified. Optic lobe slices were incubated with 5-bromo-2-deoxyuridine (BrdU) and the isolated synaptosomal fraction was exposed to the green fluorescent anti-BrdU antibody. This procedure revealed that newly synthesized BrdU-labeled BMD is present in a significant percent of the large synaptosomes derived from the nerve terminals of retinal photoreceptor neurons and in synaptosomal bodies of smaller size. Synaptosomal BMD synthesis was strongly inhibited by actinomycin D. In addition, treatment of the synaptosomal fraction with Hoechst 33258, a blue fluorescent dye specific for dsDNA, indicated that native DNA was present in all synaptosomes. The possible role of synaptic BMD is briefly discussed.