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Nature Communications Oct 2023The broad bioactivities of nonribosomal peptides rely on increasing structural diversity. Genome mining of the Burkholderiales strain Schlegelella brevitalea DSM 7029...
The broad bioactivities of nonribosomal peptides rely on increasing structural diversity. Genome mining of the Burkholderiales strain Schlegelella brevitalea DSM 7029 leads to the identification of a class of dodecapeptides, glidonins, that feature diverse N-terminal modifications and a uniform putrescine moiety at the C-terminus. The N-terminal diversity originates from the wide substrate selectivity of the initiation module. The C-terminal putrescine moiety is introduced by the unusual termination module 13, the condensation domain directly catalyzes the assembly of putrescine into the peptidyl backbone, and other domains are essential for stabilizing the protein structure. Swapping of this module to another two nonribosomal peptide synthetases leads to the addition of a putrescine to the C-terminus of related nonribosomal peptides, improving their hydrophilicity and bioactivity. This study elucidates the mechanism for putrescine addition and provides further insights to generate diverse and improved nonribosomal peptides by introducing a C-terminal putrescine.
Topics: Putrescine; Peptides; Peptide Synthases
PubMed: 37857663
DOI: 10.1038/s41467-023-42387-z -
Ultrasonics Sonochemistry Apr 2019Under mode of ultrasonic vibration, the neutral octahedral mononuclear [trans-CuBr(N ∩ N)]·3HO complex with N ∩ N = 2,2-dimethylpropane-1,3-diamine was... (Review)
Review
Under mode of ultrasonic vibration, the neutral octahedral mononuclear [trans-CuBr(N ∩ N)]·3HO complex with N ∩ N = 2,2-dimethylpropane-1,3-diamine was obtained. The structure of the desired complex was characterized by UV-Vis. spectroscopy, FT-IR, EDX, MS, SEM, TG/DTA and CHN-analysis. The octahedral-structure of the desired Cu(II) complex was proven via XRD single-crystal diffraction and its molecular interactions were computed by Hirschfeld surface analysis. Alcohol (as solvent) and short ultrasonic vibration dose period played a critical role in sonochemistry synthesis of octahedral neutral trans-CuBr(N ∩ N) complex instead of trigonal bi-pyramidal monocation [CuBr(N ∩ N)]Br one. Due to the Jahn-Teller effect, the complex exhibited a trans bonds elongation along Br-Cu-Br axis originating a distorted-octahedral Cu(II), as revealed by the XRD measurements (Br-Cu = 3.04 Å). Therefore, the Solvatochromic behavior of the complex was successfully performed since the trans di-bromide ions are loosely coordinated to Cu(II) center, the change in complex solutions colors by using different solvents which can be detected even by naked-eye supported atypical Jahn-Teller elongation effect formation. TG/DTA and Flynn Wall Ozawa (FWO) isoconversional kinetic methods were applied for the complex to figure out the thermal behavior, kinetic of the ligands de-structured and estimate its Ea/α relation. The complex binding mode to the CT-DNA was examined by UV-vis. spectroscopic, melting curve, CV and viscosity tests. The complex exhibited very strong DNA binding via an intercalation mode of coordination with K = 6.5 × 10 value.
Topics: Animals; Cattle; Chemistry Techniques, Synthetic; Coordination Complexes; Copper; Crystallography, X-Ray; DNA; Diamines; Electrochemistry; Kinetics; Ligands; Models, Molecular; Molecular Conformation; Solvents; Stereoisomerism; Ultrasonic Waves
PubMed: 30573435
DOI: 10.1016/j.ultsonch.2018.12.019 -
Investigative Radiology Apr 2021Mn-PyC3A is an experimental manganese (Mn)-based extracellular fluid magnetic resonance imaging (MRI) contrast agent that is being evaluated as a direct replacement for...
OBJECTIVES
Mn-PyC3A is an experimental manganese (Mn)-based extracellular fluid magnetic resonance imaging (MRI) contrast agent that is being evaluated as a direct replacement for clinical gadolinium (Gd)-based contrast agents. The goals of this study were to use simultaneous positron emission tomography (PET)-MRI to (1) compare the whole-body pharmacokinetics, biodistribution, and elimination of Mn-PyC3A with the liver-specific contrast agent mangafodipir (Mn-DPDP), (2) determine the pharmacokinetics and fractional excretion of Mn-PyC3A in a rat model of renal impairment, and (3) compare whole-body elimination of Mn-PyC3A to gadoterate (Gd-DOTA) in a rat model of renal impairment.
METHODS
Mn-PyC3A and Mn-DPDP were radiolabeled with the positron emitting isotope Mn-52 via Mn2+ exchange with 52MnCl2. Dynamic simultaneous PET-MRI was used to measure whole-body pharmacokinetics and biodistribution of Mn-52 immediately and out to 7 days after an intravenous 0.2 mmol/kg dose of [52Mn]Mn-PyC3A to normal or to 5/6 nephrectomy rats or a 0.01 mmol/kg dose of [52Mn]Mn-DPDP to normal rats. The fractional excretion and 1- and 7-day biodistribution in rats after the injection of 2.0 mmol/kg [52Mn]Mn-PyC3A (n = 11 per time point) or 2.0 mmol/kg Gd-DOTA (n = 8 per time point) were quantified by gamma counting or Gd elemental analysis, respectively. Comparisons of Mn-PyC3A pharmacokinetics and in vivo biodistribution in normal and 5/6 nephrectomy rats and comparisons of ex vivo Mn versus Gd biodistribution data in 5/6 nephrectomy were made with an unpaired t test.
RESULTS
Dynamic PET-MRI data demonstrate that both [52Mn]Mn-PyC3A and [52Mn]Mn-DPDP were eliminated by mixed renal and hepatobiliary elimination but that a greater fraction of [52Mn]Mn-PyC3A was eliminated by renal filtration. Whole-body PET images show that Mn-52 from [52Mn]Mn-PyC3A was efficiently eliminated from the body, whereas Mn-52 from [52Mn]Mn-DPDP was retained throughout the body. The blood elimination half-life of [52Mn]Mn-PyC3A in normal and 5/6 nephrectomy rats was 13 ± 3.5 minutes and 23 ± 12 minutes, respectively (P = 0.083). Area under the curve between 0 and 60 minutes postinjection (AUC0-60) in the bladder of normal and 5/6 nephrectomy rats was 2600 ± 1700 %ID/cc*min and 750 ± 180 %ID/cc*min, respectively (P = 0.024), whereas AUC0-60 in the liver of normal and 5/6 nephrectomy rats was 33 ± 13 %ID/cc*min and 71 ± 16 %ID/cc*min, respectively (P = 0.011), indicating increased hepatobiliary elimination in 5/6 nephrectomy rats. The %IDs of Mn from [52Mn]Mn-PyC3A and Gd from Gd-DOTA recovered from 5/6 nephrectomy rats 1 day after injection were 2.0 ± 1.1 and 1.3 ± 0.34, respectively (P = 0.10) and 7 days after injection were 0.14 ± 0.11 and 0.41 ± 0.24, respectively (P = 0.0041).
CONCLUSIONS
Mn-PyC3A has different pharmacokinetics and is more efficiently eliminated than Mn-DPDP in normal rats. Mn-PyC3A is efficiently eliminated from both normal and 5/6 nephrectomy rats, with increased fractional hepatobiliary excretion from 5/6 nephrectomy rats. Mn-PyC3A is more completely eliminated than Gd-DOTA from 5/6 nephrectomy rats after 7 days.
Topics: Animals; Contrast Media; Diamines; Magnetic Resonance Imaging; Manganese; Manganese Compounds; Picolinic Acids; Positron-Emission Tomography; Radioisotopes; Rats; Tissue Distribution
PubMed: 33136686
DOI: 10.1097/RLI.0000000000000736 -
MicrobiologyOpen Jun 2023The simultaneous extraction of intracellular DNA (iDNA) and extracellular DNA (eDNA) can help to separate the living in situ community (represented by iDNA) from...
The simultaneous extraction of intracellular DNA (iDNA) and extracellular DNA (eDNA) can help to separate the living in situ community (represented by iDNA) from background DNA that originated both from past communities and from allochthonous sources. As iDNA and eDNA extraction protocols require separating cells from the sample matrix, their DNA yields are generally lower than direct methods that lyse the cells within the sample matrix. We, therefore, tested different buffers with and without adding a detergent mix (DM) in the extraction protocol to improve the recovery of iDNA from surface and subsurface samples that covered a variety of terrestrial environments. The combination of a highly concentrated sodium phosphate buffer plus DM significantly improved iDNA recovery for almost all tested samples. Additionally, the combination of sodium phosphate and EDTA improved iDNA recovery in most of the samples and even allowed the successful extraction of iDNA from extremely low-biomass iron-bearing rock samples taken from the deep biosphere. Based on our results, we recommend using a protocol with sodium phosphate in combination with either a DM (NaP 300 mM + DM) or EDTA (NaP + EDTA 300 mM). Furthermore, for studies that rely on the eDNA pool, we recommend using buffers solely based on sodium phosphate because the addition of EDTA or a DM resulted in a decrease in eDNA for most of the tested samples. These improvements can help reduce community bias in environmental studies and contribute to better characterizations of both modern and past ecosystems.
Topics: Ecosystem; Edetic Acid; DNA; Phosphates
PubMed: 37379428
DOI: 10.1002/mbo3.1369 -
Pediatrics and Neonatology Feb 2016
Topics: Aminophylline; Humans; Infant, Premature; Infant, Premature, Diseases
PubMed: 26806848
DOI: 10.1016/j.pedneo.2015.12.002 -
Alterations in the gut microbiome and metabolome profiles of septic rats treated with aminophylline.Journal of Translational Medicine Feb 2022The treatment of sepsis remains a major challenge worldwide. Aminophylline has been shown to have anti-inflammatory effects; however, the role of aminophylline in...
The treatment of sepsis remains a major challenge worldwide. Aminophylline has been shown to have anti-inflammatory effects; however, the role of aminophylline in sepsis, a disease characterized by immune dysregulation, is unknown. In this study, we combined microbiome sequencing and metabolomic assays to investigate the effect of aminophylline administration on the intestinal flora and metabolites in septic rats. Sixty SD rats were randomly divided into three groups: a sham-operated (SC) group, a sepsis model (CLP) group and a CLP + aminophylline treatment (Amino) group. The intestinal flora and metabolic profile of rats in the CLP group were significantly different than those of the SC group, while aminophylline administration resulted in a return to a state similar to healthy rats. Differential abundance analysis showed that aminophylline significantly back-regulated the abundance of Firmicutes, unidentified_Bacteria, Proteobacteria, Lactobacillus, Escherichia-Shigella and other dominant bacteria (P < 0.05) and altered chenodeoxycholic acid, isolithocholic acid and a total of 26 metabolites (variable importance in the projection (VIP) > 1, P < 0.05). In addition, we found that there were significant correlations between differential metabolites and bacterial genera of the Amino and CLP groups. For example, Escherichia-Shigella was associated with 12 metabolites, and Lactobacillus was associated with two metabolites (P < 0.05), suggesting that differences in the metabolic profiles caused by aminophylline were partly dependent on its influence on the gutmicrobiome. In conclusion, this study identified a novel protective mechanism whereby aminophylline could regulate disordered intestinal flora and metabolites in septic rats.
Topics: Aminophylline; Animals; Gastrointestinal Microbiome; Metabolome; Rats; Rats, Sprague-Dawley; Sepsis
PubMed: 35115021
DOI: 10.1186/s12967-022-03280-3 -
Journal of Medicinal Chemistry Dec 2023The impact of methoxy and hydroxyl groups at the salicylidene moiety of chlorido[,'-bis(methoxy/hydroxy)salicylidene-1,2-bis(4-methoxyphenyl)ethylenediamine]iron(III)...
Design, Synthesis, Electrochemical, and Biological Evaluation of Fluorescent Chlorido[,'-bis(methoxy/hydroxy)salicylidene-1,2-bis(4-methoxyphenyl)ethylenediamine]iron(III) Complexes as Anticancer Agents.
The impact of methoxy and hydroxyl groups at the salicylidene moiety of chlorido[,'-bis(methoxy/hydroxy)salicylidene-1,2-bis(4-methoxyphenyl)ethylenediamine]iron(III) complexes was evaluated on human MDA-MB 231 breast cancer and HL-60 leukemia cells. Methoxylated complexes (-) inhibited proliferation, migration, and metabolic activity in a concentration-dependent manner following the rank order: > > . In particular, was highly cytotoxic with an IC of 4.2 μM which was 6.6-fold lower than that of cisplatin (IC of 27.9 μM). In contrast, hydroxylated complexes - were almost inactive up to the highest concentration tested due to lack of cellular uptake. caused a dual mode of cell death, ferroptosis, and necroptosis, whereby at higher concentrations, ferroptosis was the preferred form. Ferroptotic morphology and the presence of ferrous iron and lipid reactive oxygen species proved the involvement of ferroptosis. was identified as a promising lead compound for the design of drug candidates inducing ferroptosis.
Topics: Humans; Antineoplastic Agents; Cell Death; Cell Line, Tumor; Ethylenediamines; Iron; Coordination Complexes
PubMed: 38013413
DOI: 10.1021/acs.jmedchem.3c01359 -
Journal of Clinical Laboratory Analysis Feb 2021Acute coronary syndrome (ACS) may induce cardiovascular death. The correlation of mast cells related microRNAs (miRs) with risk of ACS has been investigated. We explored...
BACKGROUND
Acute coronary syndrome (ACS) may induce cardiovascular death. The correlation of mast cells related microRNAs (miRs) with risk of ACS has been investigated. We explored regulatory mechanism of miR-335-5p on macrophage innate immune response, atherosclerotic vulnerable plaque formation, and revascularization in ACS in relation to Notch signaling.
METHODS
ACS-related gene microarray was collected from Gene Expression Omnibus database. After different agomir or antagomir, or inhibitor of Notch signaling treatment, IL-6, IL-1β, TNF-α, MCP-1, ICAM-1, and VCAM-1 levels were tested in ACS mice. Additionally, Notch signaling-related genes and matrix metalloproteinases (MMPs) were measured after miR-335-5p interference. Finally, mouse atherosclerosis, lipid accumulation, and the collagen/vessel area ratio of plaque were determined.
RESULTS
miR-335-5p targeted JAG1 and mediated Notch signaling in ACS. miR-335-5p up-regulation and Notch signaling inhibition reduced expression of JAG1, Notch pathway-related genes, IL-6, IL-1β, TNF-α, MCP-1, ICAM-1, VCAM-1, and MMPs, but promote TIMP1 and TIMP2 expression. Additionally, vulnerable plaques were decreased and collagen fiber contents were observed to increase after miR-335-5p overexpression and Notch signaling inhibition.
CONCLUSIONS
Overexpression of miR-335-5p inhibited innate immune response of macrophage, reduced atherosclerotic vulnerable plaque formation, and promoted revascularization in ACS mice targeting JAG1 through Notch signaling.
Topics: 3' Untranslated Regions; Acute Coronary Syndrome; Animals; Antagomirs; Collagen; Diamines; Gene Expression; Humans; Jagged-1 Protein; Lipids; Male; Mice, Inbred C57BL; MicroRNAs; Plaque, Atherosclerotic; Receptors, Notch; Thiazoles; Mice
PubMed: 33277957
DOI: 10.1002/jcla.23608 -
Molecules (Basel, Switzerland) Oct 2022Two macrocyclic Schiff bases derived from o-phenylenediamine and 2-hydroxy-5-methylisophthalaldehyde or 2-hydroxy-5-tert-butyl-1,3-benzenedicarboxaldehyde ,...
Two macrocyclic Schiff bases derived from o-phenylenediamine and 2-hydroxy-5-methylisophthalaldehyde or 2-hydroxy-5-tert-butyl-1,3-benzenedicarboxaldehyde , respectively, were obtained and characterized by X-ray crystallography and spectroscopy (UV-vis, fluorescence and IR). X-ray crystal structure determination and DFT calculations for compounds confirmed their geometry in solution and in the solid phase. Moreover, intermolecular interactions in the crystal structure of and were analyzed using 3D Hirshfeld surfaces and the related 2D fingerprint plots. The 3D Hirschfeld analyses show that the most numerous interactions were found between hydrogen atoms. A considerable number of such interactions are justified by the presence of bulk -butyl groups in . The luminescence of and in various solvents and in the solid state was studied. In general, the quantum efficiency between 0.14 and 0.70 was noted. The increase in the quantum efficiency with the solvent polarity in the case of was observed (λ = 350 nm). For , this trend is similar, except for the chloroform. In the solid state, emission was registered at 552 nm and 561 nm (λ = 350 nm) for and , respectively. Thin layers of the studied compounds were deposited on Si(111) by the spin coating method or by thermal vapor deposition and studied by scanning electron microscopy (SEM/EDS), atomic force microscopy (AFM), spectroscopic ellipsometry and fluorescence spectroscopy. The ellipsometric analysis of thin materials obtained by thermal vapor deposition showed that the band-gap energy was 3.45 ± 0.02 eV (359 ± 2 nm) and 3.29 ± 0.02 eV (377 ± 2 nm) for /Si and /Si samples, respectively. Furthermore, the materials of the /Si and /Si exhibited broad emission. This feature can allow for using these compounds in LED diodes.
Topics: Schiff Bases; Phenylenediamines; Crystallography, X-Ray; Models, Theoretical; Solvents
PubMed: 36364223
DOI: 10.3390/molecules27217396 -
Journal of Inorganic Biochemistry Nov 2022The electrochemical oxidation of anodic metal copper in a solution of the ligands N-[(5-tert-butyl-2-hydroxyphenyl)methylidine]-N'-tosylbenzene-1,2-diamine [HL] and...
The electrochemical oxidation of anodic metal copper in a solution of the ligands N-[(5-tert-butyl-2-hydroxyphenyl)methylidine]-N'-tosylbenzene-1,2-diamine [HL] and N-[(3,5-di-tert-butyl-2-hydroxyphenyl)methylidine]-N'-tosylbenzene-1,2-diamine, [HL] afforded homoleptic [CuL] compounds or solvate [CuLS] complexes. The addition to the electrochemical cell of coligands (L') such as 2,2'-bipyridine (2-bpy), 4,4'-bipyridine(4-bpy) or 1,10-phenanthroline (phen) allowed the synthesis, in one step, of heteroleptic [CuLL'] compounds, namely [CuL(HO)] (1), [CuL(2,2'-bpy)]⋅CHCN (2), [CuL(phen)]·HO (3), [CuL(4,4'-bpy)] (4), [CuL(CHOH)] (5), [CuL(2,2'-bpy)] (6), [CuL(phen)] (7) and [CuL(4,4'-bpy)] (8). The crystal structures of both ligands, HL, HL, and those of the complexes (2), (4), (5), (6) and (7) have been determined by X-ray diffraction techniques. Coordination polyhedron around metal atom is square planar for [CuL(CHOH)] (5) and [CuL(4,4'-bpy)] (4) and square pyramid for the other complexes with additional chelating ligands. The cytotoxic activity of this new series of copper(II) complexes against the SH-SY5Y neuroblastoma cell line and U87-MG and U373-MG glioblastoma cell lines has been investigated. Most of the test compounds showed higher activity than cisplatin in the three cell lines. Among this series, compound [CuL(phen)] (3) displayed the highest activity with IC equal to 1.77 μM on SH-SY5Y whereas compound [CuL(4.4'-bpy)] (4) resulted the most potent compounds on U87 MG and U373 MG glioblastoma cell lines. Studies on the cytotoxic activity of these derivatives suggest that these compounds induce cell death by a mechanism other than apoptosis.
Topics: 2,2'-Dipyridyl; Antineoplastic Agents; Cisplatin; Coordination Complexes; Copper; Crystallography, X-Ray; Diamines; Glioblastoma; Humans; Ligands; Neuroblastoma; Phenanthrolines; Schiff Bases
PubMed: 36055108
DOI: 10.1016/j.jinorgbio.2022.111975