scholarly journals Spectroscopic and In Vitro Investigations of Boron(III) Complex with Meso-4-Methoxycarbonylpropylsubstituted Dipyrromethene for Fluorescence Bioimaging Applications

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4541
Author(s):  
Galina Guseva ◽  
Elena Antina ◽  
Mikhail Berezin ◽  
Svetlana Lisovskaya ◽  
Roman Pavelyev ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Structural Changes ◽  
Apoptotic Cell ◽  
High Quantum Yield ◽  
Cell Organelles ◽  
Fluorescent Marker ◽  
X Ray ◽  
Fluorescence Bioimaging ◽  
Mycotic Infections

This study focuses on the behavior of a new fluorescent marker for labeling individual biomolecules and staining cell organelles developed on a meso-substituted BODIPY platform. Boron(III) complex with meso-4-methoxycarbonylpropylsubstituted 3,3’,5,5’-tetramethyl-2,2′-dipyrromethene has been synthesized and identified via visible, UV-, NMR- and MS-spectra X-ray. The behavior of fluorophore in solutions has been studied with various experimental techniques. It has been found that luminophore exhibits a high quantum yield (almost ~100–75%) in the blue-green region (513–520 nm) and has high photostability. In addition, biological analysis indicates that the fluorophore exhibits a tendency to effectively penetrate into cell membranes. On the other hand, the proposed BODIPY can be used to study the significant differences among a large number of pathogens of mycotic infections, as well as to visualize structural changes in the plasma membrane, which is necessary for the clearance of mammalian cells undergoing apoptotic cell death.

scholarly journals Controlled Release of Ropivacaine from Single-Armed (1-PCL) and Four-Armed PCL (4-PCL) Microspheres

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Wei Xiong ◽  
Yue-kun Shen ◽  
Peng Dong ◽  
Ying Xiao ◽  
Xiong-qing Huang ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Cell Proliferation ◽  
Mammalian Cells ◽  
Great Promise ◽  
X Ray Diffraction ◽  
X Ray ◽  
Initial Release ◽  
Release Assay ◽  
Ft Ir

Sustained release of anesthesia has shown great promise in the treatment of chronic pain in patients. In this research, we used neutralized ropivacaine as an anesthesia and poly(ε-caprolactone) (PCL) with different architectures to systematically study how these architectures affect the release of ropivacaine. After optimizing the parameters of the preparation of microspheres, ropivacaine-loaded 1-PCL microspheres and 4-PCL microspheres were obtained. Fourier Transform infrared spectra (FT-IR) and X-ray diffraction spectra (XRD) confirmed that ropivacaine was encapsulated within the microsphere rather than inserted on the surface of the microsphere. Ropivacaine was found to be buried deeper in the 1-PCL microsphere than in the 4-PCL microsphere. In vitro release assay revealed that small crystalline grains interfered with ropivacaine release in 4-PCL microspheres during the initial release period, but then two kinds of microspheres showed a similar ropivacaine release rate. We basically proved that the architecture of PCL has a negligible effect on ropivacaine release. Cell proliferation test revealed that the release of products from the microspheres resulted in insignificant toxicity towards mammalian cells.

scholarly journals Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis

2019 ◽  
Vol 15 ◽  
pp. 2631-2643 ◽  
Author(s):  
Heather J Lacey ◽  
Cameron L M Gilchrist ◽  
Andrew Crombie ◽  
John A Kalaitzis ◽  
Daniel Vuong ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Biosynthetic Pathway ◽  
Spectroscopic Analysis ◽  
Bioinformatics Analysis ◽  
Biosynthetic Gene Cluster ◽  
In Vitro Activity ◽  
X Ray Diffraction ◽  
X Ray ◽  
Drimane Sesquiterpenoids

Chemical investigation of an undescribed Australian fungus, Aspergillus nanangensis, led to the identification of the nanangenines – a family of seven new and three previously reported drimane sesquiterpenoids. The structures of the nanangenines were elucidated by detailed spectroscopic analysis supported by single crystal X-ray diffraction studies. The compounds were assayed for in vitro activity against bacteria, fungi, mammalian cells and plants. Bioinformatics analysis, including comparative analysis with other acyl drimenol-producing Aspergilli, led to the identification of a putative nanangenine biosynthetic gene cluster that corresponds to the proposed biosynthetic pathway for nanangenines.

scholarly journals Structure of the SAS-6 cartwheel hub from Leishmania major

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Mark van Breugel ◽  
Rainer Wilcken ◽  
Stephen H McLaughlin ◽  
Trevor J Rutherford ◽  
Christopher M Johnson
Keyword(s):  
Small Molecules ◽  
Self Assembly ◽  
Leishmania Major ◽  
Cell Organelles ◽  
Cylindrical Cell ◽  
X Ray ◽  
Cilia And Flagella ◽  
Proof Of Principle

Centrioles are cylindrical cell organelles with a ninefold symmetric peripheral microtubule array that is essential to template cilia and flagella. They are built around a central cartwheel assembly that is organized through homo-oligomerization of the centriolar protein SAS-6, but whether SAS-6 self-assembly can dictate cartwheel and thereby centriole symmetry is unclear. Here we show that Leishmania major SAS-6 crystallizes as a 9-fold symmetric cartwheel and provide the X-ray structure of this assembly at a resolution of 3.5 Å. We furthermore demonstrate that oligomerization of Leishmania SAS-6 can be inhibited by a small molecule in vitro and provide indications for its binding site. Our results firmly establish that SAS-6 can impose cartwheel symmetry on its own and indicate how this process might occur mechanistically in vivo. Importantly, our data also provide a proof-of-principle that inhibition of SAS-6 oligomerization by small molecules is feasible.

scholarly journals Development of Fe3O4 core-TiO2 shell nanocomposites and nanoconjugates as a foundation for neuroblastoma radiosensitization

2020 ◽  
Author(s):  
William Liu ◽  
Salida Mirzoeva ◽  
Ye Yuan ◽  
Junjing Deng ◽  
Si Chen ◽  
...  
Keyword(s):  
Radiation Effects ◽  
Conventional Medicine ◽  
Apoptotic Cell ◽  
Neuroblastoma Cells ◽  
Intracellular Distribution ◽  
Dna Double Strand Breaks ◽  
X Ray ◽  
Solid Malignancy ◽  
Enhanced Sensitivity

Abstract BackgroundNeuroblastoma is the most common extracranial solid malignancy in childhood which, despite the current progress in radiotherapy and chemotherapy protocols, still has a high mortality rate in high risk tumors. Nanomedicine offers exciting and unexploited opportunities to overcome the shortcomings of conventional medicine. The photocatalytic properties of Fe3O4 core-TiO2 shell nanocomposites and their potential for cell specific targeting suggest that nanoconstructs produced using Fe3O4 core-TiO2 shell nanocomposites could be used to enhance radiation effects in neuroblastoma. In this study, we evaluated bare, metaiodobenzylguanidine (MIBG) and 3,4-Dihydroxyphenylacetic acid (DOPAC) coated Fe3O4@TiO2 as potential radiosensitizers for neuroblastoma in vitro.ResultsThe uptake of bare and MIBG coated nanocomposites modestly sensitized neuroblastoma cells to ionizing radiation. Conversely, cells exposed to DOPAC coated nanocomposites exhibited a five-fold enhanced sensitivity to radiation, increased numbers of radiation induced DNA double-strand breaks, and apoptotic cell death. The addition of a peptide mimic of the epidermal growth factor (EGF) to nanoconjugates coated with MIBG altered their intracellular distribution. Cryo X-ray fluorescence microscopy tomography of frozen hydrated cells treated with these nanoconjugates revealed cytoplasmic as well as nuclear distribution of the nanoconstructs.ConclusionsThe intracellular distribution pattern of different nanoconjugates used in this study was different for different nanoconjugate surface molecules. Cells exposed to DOPAC covered nanoconjugates showed the smallest nanoconjugate uptake, with the most prominent pattern of large intracellular aggregates. Interestingly, cells treated with this nanoconjugate also showed the most pronounced radiosensitization effect in combination with the external beam x-ray irradiation. Further studies are necessary to evaluate mechanistic basis for this increased radiosensitization effect. Preliminary studies with the nanoparticles carrying an EGF mimicking peptide showed that this approach to targeting could perhaps be combined with a different approach to radiosensitization – use of nanoconjugates in combination with the radioactive iodine. Much additional work will be necessary in order to evaluate possible benefits of targeted nanoconjugates carrying radionuclides.

Cyclic X-Ray Responses in Mammalian Cells in Vitro

1968 ◽  
Vol 33 (3) ◽  
pp. 620 ◽  
Author(s):  
Warren K. Sinclair
Keyword(s):  
Mammalian Cells ◽  
X Ray

scholarly journals Structural changes of TasA in biofilm formation ofBacillus subtilis

2018 ◽  
Vol 115 (13) ◽  
pp. 3237-3242 ◽  
Author(s):  
Anne Diehl ◽  
Yvette Roske ◽  
Linda Ball ◽  
Anup Chowdhury ◽  
Matthias Hiller ◽  
...  
Keyword(s):  
Structural Change ◽  
Structural Changes ◽  
Analytical Ultracentrifugation ◽  
Magic Angle Spinning ◽  
Magic Angle ◽  
X Ray ◽  
X Ray Crystallography ◽  
Angle Spinning

Microorganisms form surface-attached communities, termed biofilms, which can serve as protection against host immune reactions or antibiotics.Bacillus subtilisbiofilms contain TasA as major proteinaceous component in addition to exopolysaccharides. In stark contrast to the initially unfolded biofilm proteins of other bacteria, TasA is a soluble, stably folded monomer, whose structure we have determined by X-ray crystallography. Subsequently, we characterized in vitro different oligomeric forms of TasA by NMR, EM, X-ray diffraction, and analytical ultracentrifugation (AUC) experiments. However, by magic-angle spinning (MAS) NMR on live biofilms, a swift structural change toward only one of these forms, consisting of homogeneous and protease-resistant, β-sheet–rich fibrils, was observed in vivo. Thereby, we characterize a structural change from a globular state to a fibrillar form in a functional prokaryotic system on the molecular level.

scholarly journals Max is acetylated by p300 at several nuclear localization residues

2007 ◽  
Vol 403 (3) ◽  
pp. 397-407 ◽  
Author(s):  
Francesco Faiola ◽  
Yi-Ting Wu ◽  
Songqin Pan ◽  
Kangling Zhang ◽  
Anthony Farina ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Dna Binding ◽  
Nuclear Localization ◽  
Mammalian Cells ◽  
Target Genes ◽  
Apoptotic Cell ◽  
Central Component ◽  
Post Translational Modification ◽  
E Box

Max is a ubiquitous transcription factor with a bHLHZip [basic HLH (helix–loop–helix) leucine zipper] DNA-binding/dimerization domain and the central component of the Myc/Max/Mad transcription factor network that controls cell growth, proliferation, differentiation and apoptotic cell death in metazoans. Max is the obligatory DNA-binding and dimerization partner for all the bHLHZip regulators of the Myc/Max/Mad network, including the Myc family of oncoproteins and the Mad family of Myc antagonists, which recognize E-box DNA elements in the regulatory regions of target genes. Max lacks a transcription regulatory domain and is the only member of the network that efficiently homodimerizes. Binding of Max homodimers to E-box elements suppresses the transcription regulatory functions of its network partners and of other non-network E-box-binding regulators. In contrast with its highly regulated partners, Max is a constitutively expressed and phosphorylated protein. Phosphorylation is, however, the only Max post-translational modification identified so far. In the present study, we have analysed Max posttranslational modifications by MS. We have found that Max is acetylated at several lysine residues (Lys-57, Lys-144 and Lys-145) in mammalian cells. Max acetylation is stimulated by inhibitors of histone deacetylases and by overexpression of the p300 co-activator/HAT (histone acetyltransferase). The p300 HAT also directly acetylates Max in vitro at these three residues. Interestingly, the three Max residues acetylated in vivo and in vitro by p300 are important for Max nuclear localization and Max-mediated suppression of Myc transactivation. These results uncover novel post-translational modifications of Max and suggest the potential regulation of specific Max complexes by p300 and reversible acetylation.

scholarly journals Conventional frequency ultrasound detection of tumor response in vivo to cancer treatment administration

2021 ◽  
Author(s):  
Naum Papanicolau
Keyword(s):  
Cell Death ◽  
Cancer Therapy ◽  
Structural Changes ◽  
Apoptotic Cell ◽  
High Frequency Ultrasound ◽  
Patient Response ◽  
Tumor Morphology ◽  
Frequency Ultrasound

Current methods employed to evaluate patient response to cancer therapy are typically invasive requiring examination of excised tissue. The development of a non-invasive method of monitoring patient response to cancer therapy administration would potentiate clinical decisions permitting clinicians to adjust therapy regimens early in a treatment course based upon individual patient responses. It has been previously demonstrated that high frequency ultrasound is capable of reliably quantifying structural changes in tumor morphology in response to cancer therapies. Preliminary work has also indicated that ultrasound employed at clinically relevant frequencies (1-15 MHz) can detect apoptotic cell death using in vitro models. This thesis examines changes in tumor morphology in response to cancer therapy administration employing ultrasound at a clinically applicable frequency in a preclinical in vivo mouse model. The power spectrum of the radiofrequency data obtained from tumors was analyzed via linear regression spectroscopic analysis, as well as evaluating a statistical analysis of the amplitude distribution of the signal envelope. It is demonstrated here for the first time that 7 MHz ultrasound can detect apoptotic and other forms of cell death in vivo. A potential for a parametric imaging technique to visually represent analysis results is also demonstrated.

scholarly journals The mitochondrial protein Bak is pivotal for gliotoxin-induced apoptosis and a critical host factor of Aspergillus fumigatus virulence in mice

2006 ◽  
Vol 174 (4) ◽  
pp. 509-519 ◽  
Author(s):  
Julian Pardo ◽  
Christin Urban ◽  
Eva M. Galvez ◽  
Paul G. Ekert ◽  
Uwe Müller ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Molecular Basis ◽  
Mammalian Cells ◽  
Fungal Infections ◽  
Apoptotic Cell ◽  
Mitochondrial Protein ◽  
Wild Type ◽  
Apoptotic Pathway

Aspergillus fumigatus infections cause high levels of morbidity and mortality in immunocompromised patients. Gliotoxin (GT), a secondary metabolite, is cytotoxic for mammalian cells, but the molecular basis and biological relevance of this toxicity remain speculative. We show that GT induces apoptotic cell death by activating the proapoptotic Bcl-2 family member Bak, but not Bax, to elicit the generation of reactive oxygen species, the mitochondrial release of apoptogenic factors, and caspase-3 activation. Activation of Bak by GT is direct, as GT triggers in vitro a dose-dependent release of cytochrome c from purified mitochondria isolated from wild-type and Bax- but not Bak-deficient cells. Resistance to A. fumigatus of mice lacking Bak compared to wild-type mice demonstrates the in vivo relevance of this GT-induced apoptotic pathway involving Bak and suggests a correlation between GT production and virulence. The elucidation of the molecular basis opens new strategies for the development of therapeutic regimens to combat A. fumigatus and related fungal infections.

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