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Lei Hu, Ying Wen, Junji Xu, Tingting Wu, Chunmei Zhang, Jinsong Wang, Jie Du, Songlin Wang
Mesenchymal stem cell (MSC)-mediated bone regeneration is used to replace lost bone. However, methods to accelerate the process and stabilize regenerated bone remain limited. Therefore, we investigated the effect of bisphosphonates (BPs) on the function of bone marrow mesenchymal stem cells (BMMSCs) to determine if they might enhance MSC-mediated bone regeneration. We isolated and cultured BMMSCs from BALB/c mice and treated the cells with 0.1, 0.5, 1, 5, or 10 μM zoledronic acid (ZA; Zometa, a commercially available BP)...
October 13, 2016: Stem Cells and Development
Daniel Załuski, Helena D Smolarz
The chemical composition and pharmacological activity of E. senticosus cultivated in Poland were investigated. Studies included the assay of TPC and TFC, 2D-TLC identification of phenolic acids, HPTLC-detection of antioxidants, and antioxidative, antileukemic, anti-MMPs properties of E. senticosus. The ethanolic extracts from the roots, spring leaves, fruits, and the chloroform extract from the roots were tested. The richest in polyphenols are the fresh fruits (57.5 mg/g), while in flavonoids the spring leaves (27...
September 2016: Pakistan Journal of Pharmaceutical Sciences
Jean-Rémy Marchand, Graziano Lolli, Amedeo Caflisch
The 3-amino-2-methylpyridine derivative 1 was identified as ligand of the BAZ2B bromodomain by automatic docking of nearly 500 compounds, selected on the basis of previous fragment hits. Hit expansion by two in silico approaches, pharmacophore search followed by docking, and substructure search resulted in five additional ligands. The predicted binding mode of the six 3-amino-2-methylpyridine derivatives was validated by protein crystallography. A small displacement of residues 1894-1899 of the ZA loop is observed for two of the six ligands...
October 12, 2016: Journal of Medicinal Chemistry
Shin Saeng Lim, Beomseok Lee, In Sook Kim, Soon Jung Hwang
OBJECTIVES: Osteonecrosis of the jaw has been increasing after dentoalveolar surgery in patients treated with an antiresorptive bisphosphonate (BP), especially strong zoledronate (ZA). The pathophysiology underlying why osteonecrosis occurs exclusively in the jaw bone remains unclear. This study investigated skeletal site-specific bone healing during the use of BPs to explore the preferential incidence of osteonecrosis of the jaw bone. STUDY DESIGN: Extraction of mandibular molar and creation of a tibia defect were performed in rats 2 weeks after weekly intravenous injections with the potent ZA and the weaker BP etidronate...
August 18, 2016: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Philipp Kauffmann, Wolfram Hahn, Niklas Sievers, Markus Troeltzsch, Karin Hohloch, Phillipp Brockmeyer, Robert Cordesmeyer, Henning Schliephake, Rudolf Matthias Gruber
OBJECTIVE: We compared the intraindividual effects of increasing zoledronic acid (ZA) concentrations on osteoblast-like cells with different embryologic origins. STUDY DESIGN: Cultured osteoblast-like cells from mandible and iliac crest bone samples of domestic pigs were exposed to increasing concentrations of ZA (0, 10(-8), 10(-6), and 10(-4) M). Proliferation was assessed by cell counting. Receptor activator of nuclear factor kB ligand and osteoprotegerin (OPG) messenger RNA expression were assessed at 0, 1, 4, 7, and 10 days...
August 18, 2016: Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Dominika Załubiniak, Maciej Zakrzewski, Piotr Piątek
Compounds 2 and 3 were designed and prepared as heteroditopic ion-pair receptors. The design features a 2,2-bis(aminomethyl)propionic acid core to connect and pre-organize binding groups. The cation binding is provided by a sodium selective N-acyl aza-18-crown-6 subunit whereas for anion complexation, two urea groups (receptor 2) or two squaramide groups (receptor 3) were introduced. Beyond acting as anion binding sites, the urea and squaramide groups were used to support sodium cation complexation through metal carbonyl oxygen lone pair interactions...
October 4, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
Marcin Zaniew, Arend Bökenkamp, Marcin Kołbuc, Claudio La Scola, Federico Baronio, Anna Niemirska, Maria Szczepańska, Julia Bürger, Angela La Manna, Monika Miklaszewska, Anna Rogowska-Kalisz, Jutta Gellermann, Argyroula Zampetoglou, Anna Wasilewska, Magdalena Roszak, Jerzy Moczko, Aleksandra Krzemień, Dariusz Runowski, Grzegorz Siteń, Iga Załuska-Leśniewska, Patrizia Fonduli, Franca Zurrida, Fabio Paglialonga, Zoran Gucev, Dusan Paripovic, Rina Rus, Valerie Said-Conti, Lisa Sartz, Woo Yeong Chung, Se Jin Park, Jung Won Lee, Yong Hoon Park, Yo Han Ahn, Przemysław Sikora, Constantinos J Stefanidis, Velibor Tasic, Martin Konrad, Franca Anglani, Maria Addis, Hae Il Cheong, Michael Ludwig, Detlef Bockenhauer
BACKGROUND: Lowe syndrome (LS) and Dent-2 disease (DD2) are disorders associated with mutations in the OCRL gene and characterized by progressive chronic kidney disease (CKD). Here, we aimed to investigate the long-term renal outcome and identify potential determinants of CKD and its progression in children with these tubulopathies. METHODS: Retrospective analyses were conducted of clinical and genetic data in a cohort of 106 boys (LS: 88 and DD2: 18). For genotype-phenotype analysis, we grouped mutations according to their type and localization...
October 5, 2016: Nephrology, Dialysis, Transplantation
(no author information available yet)
The GMR editorial staff was alerted about some manuscripts that were found to be substantially equal. The Publisher and Editor decided to retract these articles in accordance with the recommendations of the Committee on Publication Ethics (COPE). After a thorough investigation, we have strong reason to believe that the peer review process was failure and, after review and contacting the authors, the editors of Genetics and Molecular Research decided to retract these articles. The authors and their institutions were advised of this serious breach of ethics...
September 30, 2016: Genetics and Molecular Research: GMR
Nedim Günes, Serkan Dundar, Arif Saybak, Gökhan Artas, Izzet Acikan, I Hanifi Ozercan, Serhat Atilgan, Ferhan Yaman
In this study, the aim was to compare the relative efficacy of systemic and local zoledronic acid (ZA) on a hydroxyapatite (HA) bone graft in a rat critical-size calvarial bone defect. In total, 84 female rats were divided into four groups: Empty control (EC) group with no treatment applied; HA group, in which only HA bone graft material was used in the calvarium; and HA plus local ZA (HA+LZA) and HA plus systemic ZA (HA+SZA) groups, in which animals received ZA locally or systemically, respectively, with HA bone graft material in the calvarium...
October 2016: Experimental and Therapeutic Medicine
Serkan Dundar, Cem Ozgur, Ferhan Yaman, Omer Cakmak, Arif Saybak, Ibrahim Hanifi Ozercan, Hilal Alan, Gokhan Artas, Onur Nacakgedigi
The aim of this study was to evaluate the effects on new bone formation of autogenous blood alone or in combination with zoledronic acid (ZA), a β-tricalcium phosphate (β-TCP) graft or ZA plus a β-TCP graft placed under titanium barriers. For this purpose, eight adult male New Zealand white rabbits were used in the study, each with four titanium barriers fixed around four sets of nine holes drilled in the calvarial bones. The study included four groups, each containing 2 rabbits. In the autogenous blood (AB group), only autogeneous blood was placed under the titanium barriers...
October 2016: Experimental and Therapeutic Medicine
Anna Dziubina, Karina Szmyd, Małgorzata Zygmunt, Jacek Sapa, Magdalena Dudek, Barbara Filipek, Anna Drabczyńska, Michał Załuski, Karolina Pytka, Katarzyna Kieć-Kononowicz
BACKGROUND: It has recently been suggested that the adenosine A2A receptor plays a role in several animal models of depression. Additionally, A2A antagonists have reversed behavioral deficits and exhibited a profile similar to classical antidepressants. METHODS: In the present study, imidazo- and pyrimido[2,1-f]purinedione derivatives (KD 66, KD 167, KD 206) with affinity to A2A receptors but poor A1 affinity were evaluated for their antidepressant- and anxiolytic-like activity...
July 25, 2016: Pharmacological Reports: PR
Terry D Crawford, F Anthony Romero, Kwong Wah Lai, Vickie Tsui, Alexander M Taylor, Gladys de Leon Boenig, Cameron L Noland, Jeremy Murray, Justin Ly, Edna F Choo, Thomas L Hunsaker, Emily W Chan, Mark Merchant, Samir Kharbanda, Karen E Gascoigne, Susan Kaufman, Maureen H Beresini, Jiangpeng Liao, Wenfeng Liu, Kevin X Chen, Zhongguo Chen, Andrew R Conery, Alexandre Côté, Hariharan Jayaram, Ying Jiang, James R Kiefer, Tracy Kleinheinz, Yingjie Li, Jonathan Maher, Eneida Pardo, Florence Poy, Kerry L Spillane, Fei Wang, Jian Wang, Xiaocang Wei, Zhaowu Xu, Zhongya Xu, Ivana Yen, Laura Zawadzke, Xiaoyu Zhu, Steven Bellon, Richard Cummings, Andrea G Cochran, Brian K Albrecht, Steven Magnuson
The single bromodomain of the closely related transcriptional regulators CBP/EP300 is a target of much recent interest in cancer and immune system regulation. A co-crystal structure of a ligand-efficient screening hit and the CBP bromodomain guided initial design targeting the LPF shelf, ZA loop, and acetylated lysine binding regions. Structure-activity relationship studies allowed us to identify a more potent analogue. Optimization of permeability and microsomal stability and subsequent improvement of mouse hepatocyte stability afforded 59 (GNE-272, TR-FRET IC50 = 0...
September 28, 2016: Journal of Medicinal Chemistry
Justyna Gatkowska, Henryka Długońska
Zewnątrzkomórkowe pęcherzyki błonowe (EVs, extracellular vesicles), początkowo uważane za elementy zniszczonych komórek, okazały się niezwykle istotnym sposobem przekazywania informacji między komórkami, bez ich bezpośredniego kontaktu. Ze względu na powszechne występowanie EVs w komórkach organizmów zarówno jedno-, jak i wielokomórkowych należących do różnych grup systematycznych oraz ze względu na pełnioną rolę w komunikacji międzykomórkowej stały się przedmiotem licznych badań i dyskusji...
2016: Postȩpy Higieny i Medycyny Doświadczalnej
Rashmi Priya, Kenneth Wee, Srikanth Budnar, Guillermo A Gomez, Alpha S Yap, Magdalene Michael
Non-muscle myosin II (NMII) motor proteins are responsible for generating contractile forces inside eukaryotic cells. There is also a growing interest in the capacity for these motor proteins to influence cell signaling through scaffolding, especially in the context of RhoA GTPase signaling. We previously showed that NMIIA accumulation and stability within specific regions of the cell cortex, such as the zonula adherens (ZA), allows the formation of a stable RhoA signaling zone. Now we demonstrate a key role for Coronin 1B in maintaining this junctional pool of NMIIA, as depletion of Coronin 1B significantly compromised myosin accumulation and stability at junctions...
September 20, 2016: Cell Cycle
Yusuke Sugama, Hiroyuki Kuroda, Hiroto Horiguchi, Natsumi Yamauchi, Ken Sato, Michiko Yamada, Kohta Hamaguchi, Hajime Nakamura, Tomoyuki Abe, Shigeyuki Fujii, Masahiro Maeda, Miri Fujita, Masato Koguma, Tetsuhiko Koguma, Junji Kato
An 80-year-old man received a diagnosis of anemia and a decreased platelet count from his physician in 2008, and was referred to our department where primary myelofibrosis was diagnosed.The patient was classified into the lower risk group according to the International Prognostic Scoring System(IPSS), and was followed up without treatment.In June 2010, pancytopenia progressed, and the patient was reclassified into the higher risk group.Blood count did not increase with metenolone treatment, but increased with zoledronic acid(ZA)that he started receiving from January 2012...
September 2016: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Tomomi Kamba, Toshiyuki Kamoto, Shinichiro Maruo, Takashi Kikuchi, Yosuke Shimizu, Shunichi Namiki, Kiyohide Fujimoto, Hiroaki Kawanishi, Fuminori Sato, Shintaro Narita, Takefumi Satoh, Hideo Saito, Mikio Sugimoto, Jun Teishima, Naoya Masumori, Shin Egawa, Hideki Sakai, Yusaku Okada, Toshiro Terachi, Osamu Ogawa
OBJECTIVE: To examine the antitumor activity of zoledronic acid (ZA) combined with androgen deprivation therapy (ADT) for men with treatment-naive prostate cancer and bone metastasis. METHODS: We enrolled 227 men with treatment-naive prostate cancer and bone metastasis. Participants were randomly assigned (1:1 ratio) to receive combined androgen blockade alone (CAB group) or ZA with combined androgen blockade (CZ group). Time to treatment failure (TTTF), time to the first skeletal-related event (TTfSRE), and overall survival (OS) rates were estimated using the Kaplan-Meier method...
September 10, 2016: International Journal of Clinical Oncology
Qingping Zhang, Xinhua Bao
The English Title for the above article, as appeared in our June 2015 issue, should be corrected as "Advance in research on MECP2 duplication syndrome".
October 2016: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
Giulia Calenda, Guillermo Villegas, Patrick Barnable, Claudia Litterst, Keith Levendosky, Agegnehu Gettie, Michael L Cooney, James Blanchard, José A Fernández-Romero, Thomas M Zydowsky, Natalia Teleshova
The Population Council's microbicide gel MZC (also known as PC-1005) containing MIV-150 and zinc acetate dihydrate (ZA) in carrageenan (CG) has shown promise as a broad spectrum microbicide against HIV, HSV and HPV. Previous data show antiviral activity against these viruses in cell-based assays, prevention of vaginal and rectal SHIV-RT infection and reduction of vaginal HSV shedding in rhesus macaques and also excellent antiviral activity against HSV and HPV in murine models. Recently we demonstrated that MZC is safe and effective against SHIV-RT in macaque vaginal explants...
August 19, 2016: Journal of Acquired Immune Deficiency Syndromes: JAIDS
Hannah R Wardill, Joanne M Bowen, Ysabella Za Van Sebille, Kate R Secombe, Janet K Coller, Imogen A Ball, Richard M Logan, Rachel J Gibson
We have previously shown increased intestinal permeability, to 4 kDa FITC-dextran, in BALB/c mice treated with irinotecan. Importantly, genetic deletion of Toll-like receptor 4 (TLR4; Tlr4-/-) protected against loss of barrier function indicating, TLR4 is critical in tight junction regulation. The current study aimed to (1) determine the molecular characteristics of intestinal tight junctions in wild-type and Tlr4-/- BALB/c mice, and (2) characterize the secretory profile of the distal colon. Forty-two female wild-type and 42 Tlr4-/- BALB/c mice weighing between 18-25 g received a single 270 mg/kg (i...
August 22, 2016: Molecular Cancer Therapeutics
Michele Casanova, Janelle Herelle, Marcel Thomas, Rowan Softley, Aaron Schindeler, David Little, Philipp Schneider, Ralph Müller
In recent years, great interest in combined treatment of parathyroid hormone (PTH) with anti-resorptive therapy has emerged. PTH has been suggested to aid bridging of atrophic fractures and improve strength in closed fracture models. Bisphosphonate treatments typically result in a larger woven bone callus that is slower to remodel. The combination of both drugs has been demonstrated to be effective for the treatment of osteoporotic bone loss in many preclinical studies. However, the effect of combined treatment on fracture repair is still largely unexplored...
November 2016: Bone
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