• Title/Summary/Keyword: Biophysics

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DNA-Binding and Thermodynamic Parameters, Structure and Cytotoxicity of Newly Designed Platinum(II) and Palladium(II) Anti-Tumor Complexes

  • Mansouri-Torshizi, Hassan;Saeidifar, Maryam;Khosravi, Fatemeh;Divsalar, Adeleh;Saboury, Ali.Akbar;Ghasemi, Zahra Yekke
    • Bulletin of the Korean Chemical Society
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    • v.32 no.3
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    • pp.947-955
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    • 2011
  • The complexes [Pd(bpy)(Hex-dtc)]$NO_3$ and [Pt(bpy)(Hex-dtc)]$NO_3$ (bpy is 2,2'-bipyridine and Hex-dtc is hexyldithiocarbamato ligands) were synthesized and characterized by elemental analysis and spectroscopic studies. The cytotoxicity assay of the complexes has been performed on chronic myelogenous leukemia cell line, K562, at micromolar concentration. Both complexes showed cytotoxic activity far better than that of cisplatin under the same experimental conditions. The binding parameters of the complexes with calf thymus DNA (CT-DNA) was investigated using UV-visible and fluorescence techniques. They show the ability of cooperatively intercalating in CT-DNA. Gel filtration studies demonstrated that platinum complex could cleave the DNA. In the interaction studies between the Pd(II) and Pt(II) complexes with CT-DNA, several binding and thermodynamic parameters have been determined, which may provide deeper insights into the mechanism of action of these types of complexes with nucleic acids.

Development of a Magnetic-field Stimulation System for Cell Cultures in situ: Simulation by Finite Element Analysis

  • Dominguez, G.;Arias, S.;Reyes, Jose L.;Rogeli, Pablo
    • Journal of Magnetics
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    • v.22 no.2
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    • pp.326-332
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    • 2017
  • The effects of exposure to an extremely low-frequency magnetic field (25 Hz 20G) on animal cells have been studied. In some reports, stimulation was performed for fixed frequency and variations in magnitude; however, animal-cell experiments have established that both parameters play an important role. The present work undertook the modeling, simulation, and development of a uniform-magnetic-field generation system with variable frequency and stimulation intensity (0-60 Hz, 1-25G) for experimentation with cell cultures in situ. The results showed a coefficient of variation less than 1 % of the magnetic-field dispersion at the working volume, which is consistent with the corresponding simulation results demonstrating a uniform magnetic field. On the other hand, long-term tests during the characterization process indicated that increments of only $0.4^{\circ}C$ in the working volume temperature will not be an interfering factor when experiments are carried out in in situ cell cultures.

Mulberry Silkworm, Bombyx mori L., as a Host for Neurotoxic Braconidae I. Insect-toxic Properties of Bracon Venom Gland Extract and Its Fractions

  • Madyarov, S.R.;Mirzaeva, G.S.;Otarbaev, D.O.;Khamidi, K.S.;Kamilova, S.I.;Akhmerov, R.N.;Khamraev, A.S.
    • International Journal of Industrial Entomology and Biomaterials
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    • v.7 no.2
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    • pp.235-239
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    • 2003
  • The silkworm Bombyx mori L. was studied as the potential “host” of popular in Uzbekistan biocontrol ectoparasite, entomophagous Bracon hebetor Say. Being one of representatives of economic-beneficial insects, the silkworm (larvae, pupae and imago) can be used as highly sensitive test organism for revealing of neuro toxic effects of insects venom as well as of their purified components in screening assays. In comparative aspect, except a mulberry silkworm, representatives of Uzbekistan pests cotton-boll worm Helycoverpa armigera Hbn., lesser mulberry pyralid Glyphodes pyloalis Wlk., codling moth Corpocapsa pomonella L., malaria mosquito Anopheles claviger and Colorado potato beetle Leptinotarsa decemlineata Say have been subjected to insect toxic test of bracon venom gland extract (VGE) and its fractions which were obtained by gel-chromatography on Sephadex G-100. The paralyzing effect of the VGE and its fractions was shown in a various degree on the pests.

Biochemical and NMR Characterization of MTH1880 Mutant Proteins for Folding-Unfolding Studies

  • Kim, Hee-Youn;Ryu, Soo-Young;Yun, Ji-Hye;Kim, Suhk-Mann;Chang, Ik-Soo;Lee, Weon-Tae
    • Bulletin of the Korean Chemical Society
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    • v.31 no.12
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    • pp.3521-3524
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    • 2010
  • MTH1880 is a hypothetical protein derived from Methanobacterium thermoautotrophicum, thermophilic methanogen. The solution structure determined by NMR spectroscopy showed that it has a novel $\alpha+\beta$-fold with a highly acidic ligand binding pocket. Since MTH1880 maintains its ultra-stable structural characteristics at both high temperature and pressure, it has been considered as an excellent model for studying protein folding. To initiate the structural and folding study of MTH1880 in proving its unusual stability, we performed the site directed mutagenesis and biochemical analysis of MTH1880 mutants. Data from circular dichroism and NMR spectroscopy suggest that the point mutations perturbed the structural stability of protein even though the secondary structure is retained. This study will provide the useful information in understanding the role of participating residues during folding-unfolding process and our result will be used in designing further folding experiments for hyper-thermopile proteins like MTH1880.

Effects of Dimaine, Diacid and Dintitro Derivatives on the Inhibition of Adenosine Deaminase; Experimental, Molecular Docking and QSAR Studies

  • Ajloo, Davood;Najafi, Leila;Saboury, Ali Akbar
    • Bulletin of the Korean Chemical Society
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    • v.30 no.11
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    • pp.2523-2531
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    • 2009
  • Effects of some diacid, diamine and dinitro aromatic compounds on the structure and activity of adenosine deaminase (ADA) were investigated by UV-Vis spectrophotometry in 50 mM phosphate buffer at pH = 7.5 and 27 ${^{\circ}C}$ and molecular docking studies. The results showed that all tested ligands are showing inhibition; five ligands are uncompetitive and other two ligands are mixed of competitive and noncompetetive inhibitors with majority of competitive behavior. For the later case analysis was done based on competitive inhibition. Diacids have larger size and higher inhibition constant ($K_I$) relative to others. A logical correlation between calculated free energy of binding and experimental values was obtained for un-competitive. Experimental and calculated data showed that competitive inhibitors are distributed near the active site of enzyme and form several cluster of ranks, whereas uncompetitive inhibitors bind to the enzyme-substrate complex and distributed far from the active site. Results of structure-activity relationship showed that, larger, more hydrophobe, less spherical and more aromatic ligands have higher inhibition constants.

Characterizations of nano-zinc doped hydroxyapatite to use as bone tissue engineering

  • Abdel-Ghany, Basma E.;Abdel-Hady, Bothaina M.;El-Kady, Abeer M.;Beheiry, Hanan H.;Guirguis, Osiris W.
    • Advances in materials Research
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    • v.4 no.4
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    • pp.193-205
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    • 2015
  • Contamination by bacterial strands is a major problem after bone replacement surgeries, so there is a great need to develop low cost biocompatible antibacterial bioactive scaffolds to be used in bone tissue engineering. For this purpose, nano-zinc doped hydroxyapatite with different zinc-concentrations (5, 10 and 15 mol%) was successfully prepared by the wet chemical precipitation method. The prepared powders were used to form porous scaffolds containing biodegradable Ca-cross-linked alginate (5%) in order to enhance the properties of alginate scaffolds. The scaffolds were prepared using the freeze-gelation method. The prepared powders were tested by X-ray diffraction; transmission electron microscope and Fourier transform infrared analyses, while the prepared scaffolds were investigated by Fourier transform infrared analyses, thermogravimetric analyses and measurement of the antibacterial properties. Best results were obtained from scaffold containing 15% mol zinc-doped hydroxyapatite powders and 5% alginate concentration with ratio of 70:30.

Altered Cardiac $Na^+,K^+$-ATPase Activity in Prehypertensive Spontaneously Hypertensive Rat

  • Lee, Shin-Woong;Lee, Jeung-Soo;Wallick, Earl-T.
    • Archives of Pharmacal Research
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    • v.16 no.4
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    • pp.305-311
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    • 1993
  • $Na^+,K^+$-ATPase activity, $Na^+$-dependent phosphorylation, and $[^3H]$ ouabain binding in sarcolemma prepared from 4 week old spontaneously hypertensive rat(SHR) ventricles were compared to the same parameters in sarcolemma from age matched nomotensive Wister-Kyoto (WKY) rat ventricles to examine whether the reduced myocardial $Na^+$-pump activity in SHR is an inherited enzymatic defect or a second phenomenon due to sustained hypertension. The total body weights, ventricular weights, and blood pressures were the same for SHR and WKY. No significant differences in sarcolemmal protein content and protein recovery were noted between the two groups. Sarcolemma isolated from SHR ventricles showed significantly less $Na^+,K^+$-ATPase activity ande number of phosphorylation sites when compared to sarcolemma from the WKY ventricles. Equilibrium binding of $[^3H]$ouabain and the tumover number of myocardial $Na^+,K^+$-ATPase, however, were the same for both groups. These reults indicate that the low affinity $(\alpha,\;or\;\alpha^1)\;\alpha$ isoform is the same in ventricles of SHR and WKY. The reduced amount of isoform of the $Na^+,K^+$-ATPase inprehypetensive SHR ventricles may play some role in the development of hypertension.

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Crosstalk between Adipocytes and Immune Cells in Adipose Tissue Inflammation and Metabolic Dysregulation in Obesity

  • Huh, Jin Young;Park, Yoon Jeong;Ham, Mira;Kim, Jae Bum
    • Molecules and Cells
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    • v.37 no.5
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    • pp.365-371
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    • 2014
  • Recent findings, notably on adipokines and adipose tissue inflammation, have revised the concept of adipose tissues being a mere storage depot for body energy. Instead, adipose tissues are emerging as endocrine and immunologically active organs with multiple effects on the regulation of systemic energy homeostasis. Notably, compared with other metabolic organs such as liver and muscle, various inflammatory responses are dynamically regulated in adipose tissues and most of the immune cells in adipose tissues are involved in obesity-mediated metabolic complications, including insulin resistance. Here, we summarize recent findings on the key roles of innate (neutrophils, macrophages, mast cells, eosinophils) and adaptive (regulatory T cells, type 1 helper T cells, CD8 T cells, B cells) immune cells in adipose tissue inflammation and metabolic dysregulation in obesity. In particular, the roles of natural killer T cells, one type of innate lymphocyte, in adipose tissue inflammation will be discussed. Finally, a new role of adipocytes as antigen presenting cells to modulate T cell activity and subsequent adipose tissue inflammation will be proposed.

Activation of the cGMP/Protein Kinase G Pathway by Nitric Oxide Can Decrease TRPV1 Activity in Cultured Rat Dorsal Root Ganglion Neurons

  • Jin, Yun-Ju;Kim, Jun;Kwak, Ji-Yeon
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.3
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    • pp.211-217
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    • 2012
  • Recent studies have demonstrated that nitric oxide (NO) activates transient receptor potential vanilloid subtype 1 (TRPV1) via S-nitrosylation of the channel protein. NO also modulates various cellular functions via activation of the soluble guanylyl cyclase (sGC)/protein kinase G (PKG) pathway and the direct modification of proteins. Thus, in the present study, we investigated whether NO could indirectly modulate the activity of TRPV1 via a cGMP/PKG-dependent pathway in cultured rat dorsal root ganglion (DRG) neurons. NO donors, sodium nitroprusside (SNP) and S-nitro-N-acetylpenicillamine (SNAP), decreased capsaicin-evoked currents ($I_{cap}$). NO scavengers, hemoglobin and 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO), prevented the inhibitory effect of SNP on $I_{cap}$. Membrane-permeable cGMP analogs, 8-bromoguanosine 3', 5'-cyclic monophosphate (8bromo-cGMP) and 8-(4chlorophenylthio)-guanosine 3',5'-cyclic monophosphate (8-pCPT-cGMP), and the guanylyl cyclase stimulator YC-1 mimicked the effect of SNP on $I_{cap}$. The PKG inhibitor KT5823 prevented the inhibition of $I_{cap}$ by SNP. These results suggest that NO can downregulate the function of TRPV1 through activation of the cGMP/PKG pathway in peripheral sensory neurons.

Effects of NOS Inhibitors on Arthritis and Arthritic Pain in Rats

  • Min, Sun-Seek
    • The Korean Journal of Physiology and Pharmacology
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    • v.11 no.6
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    • pp.253-257
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    • 2007
  • Among the arthritis symptoms, chronic pain is the most serious, and it can profoundly affect the quality of human life. Unfortunately, the mechanism of development in arthritis and arthritic pain has not yet been precisely elucidated. Accumulating evidence indicates that nitric oxide (NO) plays a pivotal role in nociceptive processing in the spinal cord. However, the modulation mechanism of NO in the peripheral site of arthritis and arthritic pain has not been clarified. Therefore, I determined in the present study which nitric oxide synthase (NOS) was involved in the induction of arthritis and arthritic pain. Monoarthritis was induced by intra-articular injection of carrageenan (2%, $50{\mu}l$) into rats, and resulted in the reduction of weight load on the injected leg, increase of knee joint diameter and inflammatory response. Pre-treatment of rats with L-N6-(1-iminoethyl)-lysine (L-NIL, $500{\mu}g$, in $50{\mu}l$), an inhibitor of inducible NOS (iNOS), partially prevented the induction of pain-related behavior and partially reduced inflammatory response in the synovial membrane in the knee joint. These results suggest that iNOS in the knee joint may play an important role in the induction of pain-related behavior and inflammation, and that NO produced by iNOS may be associated with nociceptive signaling in the peripheral site.