Black and Green Tea as Well as Specialty Teas Increase Osteoblast Mineralization with Varying Effectiveness

Michael D. McAlpine,William Gittings,Adam J. MacNeil,Wendy E. Ward 한국식품영양과학회 2021 Journal of medicinal food Vol.24 No.8

Many human studies suggest a benefit of tea consumption on bone health. The study objective was to compare the ability of different tea types to promote mineralization. Saos-2 cells underwent mineralization (5 days) in the presence of tea (white: WT, green: GT, black: BT, green rooibos: GR, or red rooibos: RR; 1 μg/mL of polyphenols) or control. Total polyphenol content (TPC, Folin-Ciocalteu's reagent), antioxidant capacity (2,2-diphenyl-1-picrylhydrazyl [DPPH] scavenging), mineralization (Alizarin Red staining), gene expression quantitative reverse transcription PCR (RT-qPCR), and cell activity (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay) were determined. TPC was highest in GT and BT. The ability of each tea to inhibit DPPH also differed (WT, GT > RR) after normalizing for polyphenol quantity. Each tea increased mineralization and differences were observed among types (GT/BT/GR/RR > WT, GT = BT = GR, RR > BT/GT). mRNA expression of alkaline phosphatase (ALP) and ectonucleotide pyrophosphatase/phosphodiesterase (NPP1) remained unchanged, whereas osteopontin (OPN) and sclerostin (SOST) were reduced in cells treated with tea, regardless of type. At 24- and 48-h postexposure to tea, cell activity was greater in cells receiving any of the teas compared with vehicle control. Supplementation increased mineralization regardless of tea type with both rooibos teas and black tea stimulating greater mineralization than WT, whereas green tea is similar to the others. While future study is needed to confirm in vivo effects, the results suggest that consuming any of the teas studied may benefit bone health.

Black Tea Exhibits a Dose-Dependent Response in Saos-2 Cell Mineralization

Riley E. Cleverdon,Michael D. McAlpine,Wendy E. Ward 한국식품영양과학회 2020 Journal of medicinal food Vol.23 No.9

Higher bone mineral density (BMD) is often associated with greater consumption of black tea (BT). However, the dose–response of BT on mineralization in an osteoblast cell model has not yet been studied. The study objective was to determine the dose-dependent response of BT in Saos-2 cells and investigate changes to several proteins involved in the mineralization process. Mineralization was induced in the presence of BT at concentrations that represent levels likely achieved through daily consumption (0.1, 0.5, 0.75, 1 μg gallic acid equivalents [GAE]/mL) or through supplementation (2, 5, or 10 μg GAE/mL). BT exerted a positive dose–response on bone mineralization, peaking at 1 μg GAE/mL of BT (P < .05). Cellular activity was significantly greater than control with exposure to 2–10 μg GAE/mL of BT (at 24 h) (P < .05) and 1–10 μg GAE/mL (at 48 h) (P < .05), with a peak at 5 μg GAE/mL at 24 and 48 h (P < .05). Protein expression of alkaline phosphatase and ectonucleotide pyrophosphatase/phosphodiesterase-1 were unchanged, whereas a moderate dose of BT (0.75 μg GAE/mL) resulted in greater expression of osteopontin compared with the highest dose (10 μg GAE/mL) (P < .05). Doses of BT from 0.5 to 10 μg GAE/mL resulted in higher antioxidant capacity compared with control (P < .05). In summary, the higher antioxidant capacity, enhanced cell viability, and upregulated mineralization suggest that consumption of BT may have a positive effect on BMD at levels obtained through consumption of tea.

Hytramycins V and I, Anti-<i>Mycobacterium tuberculosis</i> Hexapeptides from a <i>Streptomyces hygroscopicus</i> Strain

Cai, Geping,Napolitano, José,G.,McAlpine, James B.,Wang, Yuehong,Jaki, Birgit U.,Suh, Joo-Won,Yang, Seung Hwan,Lee, In-Ae,Franzblau, Scott G.,Pauli, Guido F.,Cho, Sanghyun American Chemical Society and American Society of 2013 Journal of natural products Vol.76 No.11

<P>Thirty-five thousand actinomycete extracts were screened for anti-<I>Mycobacterium tuberculosis</I> (<I>M. tb</I>) activity, followed by C<SUB>18</SUB> cartridge fractionation of 37 prioritized extracts. Based on MICs against replicating and nonreplicating <I>M. tb</I>, and IC<SUB>50</SUB> values against Vero cells to generate selectivity indices, seven fractions from seven different strains were selected for further examination. When cultured in G.S.S. media and extracted with ethyl acetate, the <I>Streptomyces hygroscopicus</I> strain ECUM 14046 yielded an extract with promising anti-<I>M. tb</I> activity and a well-defined chromatographic profile. Fractionation by preparative HPLC and subsequent structure elucidation of two active fractions using 1D- and 2D-NMR and MS methods revealed the presence of two cyclohexapeptides, hytramycins V and I, each containing three unusual piperazic acid moieties. The use of <SUP>1</SUP>H iterative full spin analysis (HiFSA) on both hytramycins confirmed that quantum mechanics-simulated spectra match the experimental data, and all <I>J</I><SUB>H,H</SUB> and δ<SUB>H</SUB> values are consistent with the proposed structures. The absolute configuration of each amino acid moiety was determined by Marfey’s method. The MICs against replicating and, more importantly, nonreplicating <I>M. tb</I> fall into the range of some existing second-line anti-TB drugs, such as streptomycin and capreomycin, respectively. The activities were maintained against <I>M. tb</I> strains that represent the major global clades, as well as H<SUB>37</SUB>Rv-isogenic strains that are resistant to individual clinical anti-TB drugs.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jnprdf/2013/jnprdf.2013.76.issue-11/np400145u/production/images/medium/np-2013-00145u_0005.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/np400145u'>ACS Electronic Supporting Info</A></P>

The VISTA Deep Extragalactic Observations (VIDEO) survey★

Jarvis, Matt J.,Bonfield, D. G.,Bruce, V. A.,Geach, J. E.,McAlpine, K.,McLure, R. J.,Gonzá,lez-Solares, E.,Irwin, M.,Lewis, J.,Yoldas, A. Kupcu,Andreon, S.,Cross, N. J. G.,Emerson, J. P.,Dalton, Oxford University Press 2013 Monthly notices of the Royal Astronomical Society Vol.428 No.2

Fertility-sparing treatment in early endometrial cancer: current state and future strategies

( Andreas Obermair ),( Franzcog ),( Eva Baxter ),( Donal J. Brennan ),( Jessica N. Mcalpine ),( Jennifer J. Mueller ),( Frédéric Amant ),( Mignon D. J. M. Van Gent ),( Robert L. Coleman ),( Shannon N. 대한산부인과학회 2020 Obstetrics & Gynecology Science Vol.63 No.4

Endometrial cancer (EC) is the fifth most common cancer in women worldwide. Global estimates show rising incidence rates in both developed and developing countries. Most women are diagnosed postmenopausal, but 14-25% of patients are premenopausal and 5% are under 40 years of age. Established risk factors include age and hyperestrogenic status associated with nulliparity, obesity, and metabolic syndrome. Standard treatment for EC, which involves total hysterectomy and bilateral salpingo-oophorectomy, has excellent survival outcomes, particularly for low-grade endometrioid tumors. However, it leads to permanent loss of fertility among women who wish to preserve their reproductive potential. With current trends of reproductive-age women delaying childbearing, rising EC incidence rates, and a growing epidemic of obesity, particularly in developed countries, research on conservative non-surgical treatment approaches remains a top priority. Fertility-sparing treatment predominantly involves the use of oral progestins and levonorgestrel-releasing intrauterine devices, which have been shown to be feasible and safe in women with early stage EC and minimal or no myometrial invasion. However, data on the efficacy and safety of conservative management strategies are primarily based on retrospective studies. Randomized clinical trials in younger women and high-risk obese patients are currently underway. Here, we have presented a comprehensive review of the current literature on conservative, fertility-sparing approaches, defining the optimal candidates and evaluating tumor characteristics, reproductive and oncologic outcomes, and ongoing clinical trials. We have also summarized current guidelines and recommendations based on the published literature.

Initial oxidation behavior of Fe-Cr-Si alloys in 1200 °C steam

Moon, Joonho,Kim, Sungyu,Park, Won Dong,Kim, Tae Yong,McAlpine, Samuel Westcott,Short, Michael P.,Kim, Ji Hyun,Bahn, Chi Bum ELSEVIER 2019 JOURNAL OF NUCLEAR MATERIALS Vol.513 No.-

<P><B>Abstract</B></P> <P>Accident-tolerant fuel (ATF) cladding with high oxidation resistance during severe accidents is of critical importance to light water reactor safety and sustainability. One newly proposed ATF cladding concept, a multi-metallic layered composite (MMLC), hinges upon the oxidation resistance of an outer Fe-Cr-Si layer on top of a Zr-based alloy, separated by barrier layers to avoid Fe-Zr eutectic formation. The initial oxidation resistance of three potential Fe-Cr-Si alloys was evaluated by exposing them to 1200 °C oxidizing steam for up to one hundred seconds, along with a Zr–Nb–Sn alloy as a reference. The oxidation resistance of Fe12Cr2Si and Fe16Cr2Si was poor, exhibiting a porous, incomplete multilayer oxide composed mainly of mixed Fe/Cr/Si spinels. However, Fe20Cr2Si showed excellent oxidation resistance due to a continuous amorphous SiO<SUB>2</SUB> layer formed at the metal–oxide interface, followed by almost fully dense Cr<SUB>2</SUB>O<SUB>3</SUB>. This motivates the consideration of Fe-Cr-Si alloys as an additional ATF design choice, similar to FeCrAl alloys in performance and oxidation resistance mechanism.</P>

Subtle Chemical Shifts Explain the NMR Fingerprints of Oligomeric Proanthocyanidins with High Dentin Biomodification Potency

( Joo Won Nam ),( Rasika S Phansalkar ),( David C Lankin ),( Jonathan Bisson ),( James B Mcalpine ),( Ariene A Leme ),( Cristina M P Vidal ),( Benjamin Ramirez ),( Matthias Niemitz ),( Ana Bedran Russ 영남대학교 약품개발연구소 2016 영남대학교 약품개발연구소 연구업적집 Vol.26 No.-

The ability of certain oligomeric proanthocya-nidins (OPACs) to enhance the biomechanical properties of dentin involves collagen cross-linking of the 1.3-4.5 nm wide space via protein-polyphenol interactions. A systematic interdisciplinary search for the bioactive principles of pine bark has yielded the trimeric PAC, ent-epicatechin-(4β →S)-epicatechin-(2β→0→7,4β→8)-catechin (3), representing the hitherto most potent single chemical entity capable of enhancing dentin stiffness. Building the case from two congeneric PAC dimers, a detailed structural analysis decoded the stereochemistry, spatial arrangement, and chemical properties of three dentin biomodifiers, Quantum-mechanics-driven ¹H iterative full spin analysis (QM-HiFSA) of NMR spectra distinguished previously unrecognized details such as higher order J coupling and provided valuable information about 3D structure. Detection and quantification of H/D-exchange effects by QM-HiFSA identified C-S and C-6 as (re) active sites, explain preferences in biosynthetic linkage, and suggest their involvement in dentin cross-linking activity. Mapping of these molecular properties underscored the significance of high 8 precision in both ¹H and ¹³C NMR spectroscopy. Occurring at low- to subppb levels, these newly characterized chemical shift differences in ppb are small but diagnostic measures of dynamic processes inherent to the OPAC pharmacophores and can help augment our understanding of nanometer-scale intermolecular interactions in biomodified dentin macromolecules.

The Cyclic Peptide Ecumicin Targeting ClpC1 Is Active against <i>Mycobacterium tuberculosis In Vivo</i>

Gao, Wei,Kim, Jin-Yong,Anderson, Jeffrey R.,Akopian, Tatos,Hong, Seungpyo,Jin, Ying-Yu,Kandror, Olga,Kim, Jong-Woo,Lee, In-Ae,Lee, Sun-Young,McAlpine, James B.,Mulugeta, Surafel,Sunoqrot, Suhair,Wang, American Society for Microbiology 2015 Antimicrobial Agents and Chemotherapy Vol.59 No.2

<P>Drug-resistant tuberculosis (TB) has lent urgency to finding new drug leads with novel modes of action. A high-throughput screening campaign of >65,000 actinomycete extracts for inhibition of <I>Mycobacterium tuberculosis</I> viability identified ecumicin, a macrocyclic tridecapeptide that exerts potent, selective bactericidal activity against <I>M. tuberculosis</I> <I>in vitro</I>, including nonreplicating cells. Ecumicin retains activity against isolated multiple-drug-resistant (MDR) and extensively drug-resistant (XDR) strains of <I>M. tuberculosis</I>. The subcutaneous administration to mice of ecumicin in a micellar formulation at 20 mg/kg body weight resulted in plasma and lung exposures exceeding the MIC. Complete inhibition of <I>M. tuberculosis</I> growth in the lungs of mice was achieved following 12 doses at 20 or 32 mg/kg. Genome mining of lab-generated, spontaneous ecumicin-resistant <I>M. tuberculosis</I> strains identified the ClpC1 ATPase complex as the putative target, and this was confirmed by a drug affinity response test. ClpC1 functions in protein breakdown with the ClpP1P2 protease complex. Ecumicin markedly enhanced the ATPase activity of wild-type (WT) ClpC1 but prevented activation of proteolysis by ClpC1. Less stimulation was observed with ClpC1 from ecumicin-resistant mutants. Thus, ClpC1 is a valid drug target against <I>M. tuberculosis</I>, and ecumicin may serve as a lead compound for anti-TB drug development.</P>

Bioautography with TLC-MS/NMR for Rapid Discovery of Anti-tuberculosis Lead Compounds from Natural Sources

( Edyta M. Grzelak ),( Changhwa Hwang ),( Geping Cai ),( Joo Won Nam ),( Mary P Choules ),( Wei Gao ),( David C Lankin ),( James B Mcalpine ),( Surafel G Mulugeta ),( Jose G Napolitano ),( Joo Won Suh 영남대학교 약품개발연구소 2016 영남대학교 약품개발연구소 연구업적집 Vol.26 No.-

While natural products constitute an established source of lead compounds, the classical iterative bioassay-guided isolation process is both time- and labor-intensive and prone to failing to identify active minor constituents. (HP)TLC.bioautography.MS/NMR, which combines cutting-­edge microbiological, chromatographic, and spectrometric technologies, was developed 10 accelerate anti-tuberculosis (TB) drug discovery from natural sources by acquiring structural information at a very early stage of the isolation process, Using the avirulent, bioluminescent Mtb strain mc²7000 luxABCDE, three variations of bioautography were evaluated and optimized for sensitivity in detecting anti-T``B agent , including established clinical agents and new lead with novel mechanisms of action. Several exemplary applications of this approach to microbial extracts demonstrate its potential as a routine method in anti-TB drug discovery from natural sources.

Discovery and Characterization of the Tuberculosis Drug Lead Ecumicin

Gao, Wei,Kim, Jin-Yong,Chen, Shao-Nong,Cho, Sang-Hyun,Choi, Jongkeun,Jaki, Birgit U.,Jin, Ying-Yu,Lankin, David C.,Lee, Ji-Ean,Lee, Sun-Young,McAlpine, James B.,Napolitano, José,G.,Franzblau, Sc American Chemical Society 2014 ORGANIC LETTERS Vol.16 No.23

<P>The new tuberculosis (TB) lead ecumicin (<B>1</B>), a cyclic tridecapeptide, was isolated from <I>Nonomuraea sp.</I> MJM5123, following a high-throughput campaign for anti-TB activity. The large molecular weight of 1599 amu detected by LC-HR-MS precluded the initial inference of its molecular formula. The individual building blocks were identified by extensive NMR experiments. The resulting two possible planar structures were distinguished by LC-MS<SUP>2</SUP>. Determination of absolute configuration and unambiguous structural confirmation were carried out by X-ray crystallography and Marfey’s analysis.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/orlef7/2014/orlef7.2014.16.issue-23/ol5026603/production/images/medium/ol-2014-026603_0003.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ol5026603'>ACS Electronic Supporting Info</A></P>