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https://www.readbyqxmd.com/read/29458213/selective-targeting-and-degradation-of-doxorubicin-loaded-folate-functionalized-dna-nanocages
#1
Sofia Raniolo, Giulia Vindigni, Alessio Ottaviani, Valeria Unida, Federico Iacovelli, Antonio Manetto, Mariangela Figini, Lorenzo Stella, Alessandro Desideri, Silvia Biocca
Selective targeting is a crucial property of nanocarriers used for drug delivery in cancer therapy. We generated biotinylated octahedral DNA nanocages functionalized with folic acid through bio-orthogonal conjugation chemistry. Molecular modelling indicated that a distance of about 2.5 nm between folic acid and DNA nanocage avoids steric hindrance with the folate receptor. HeLa cells, a folate receptor positive tumour cell line, internalize folate-DNA nanocages with efficiency greater than 40 times compared to cells not expressing the folate receptors...
February 16, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29458212/programmed-drug-delivery-system-based-on-optimized-size-decrease-and-hydrophilicity-hydrophobicity-transformation-for-enhanced-hepatocellular-carcinoma-therapy-of-doxorubicin
#2
Yuanyuan Liu, Lian Li, Lijia Li, Zhou Zhou, Fengling Wang, Xiaofeng Xiong, Rui Zhou, Yuan Huang
Requirements on drug delivery systems to surmount a complex series of pathophysiological barriers bear "cascading contradictions", especially size and hydrophilicity/hydrophobicity contradiction. Herein, a programmed drug delivery system (GNPs-Dox-Lac) based on optimized "size decrease and hydrophilicity/hydrophobicity transformation" was developed by combination the gelatin nanoparticle (GNPs) and prodrug Doxorubicin-Lactose (Dox-Lac). The results showed that GNPs-Dox-Lac (133.3 nm) were kinetically stable in blood circulation and inclined to accumulate at the tumor site...
February 16, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29458193/attenuation-of-neuro-inflammation-improves-survival-and-neurodegeneration-in-a-mouse-model-of-severe-neonatal-hyperbilirubinemia
#3
Simone Vodret, Giulia Bortolussi, Alessandra Iaconcig, Elena Martinelli, Claudio Tiribelli, Andrés F Muro
All pre-term newborns and a high proportion of term newborns develop neonatal jaundice. Neonatal jaundice is usually a benign condition and self-resolves within few days after birth. However, a combination of unfavorable complications may lead to acute hyperbilirubinemia. Excessive hyperbilirubinemia may be toxic for the developing nervous system leading to severe neurological damage and death by kernicterus. Survivors show irreversible neurological deficits such as motor, sensitive and cognitive abnormalities...
February 16, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29458169/inhibition-of-microsomal-prostaglandin-e-synthase-1-facilitates-liver-repair-after-hepatic-injury-in-mice
#4
Nobuyuki Nishizawa, Yoshiya Ito, Koji Eshima, Hirotoki Ohkubo, Ken Kojo, Tomoyoshi Inoue, Joan Raouf, Per-Johan Jakobsson, Satoshi Uematsu, Shizuo Akira, Shuh Narumiya, Masahiko Watanabe, Masataka Majima
BACKGROUND & AIMS: Liver repair following hepatic ischemia/reperfusion (I/R) injury is crucial to survival. This study aims to examine the role of endogenous prostaglandin E2 (PGE2 ) produced by inducible microsomal PGE synthase-1 (mPGES-1), a terminal enzyme of PGE2 generation, in liver injury and repair following hepatic I/R. METHODS: mPGES-1 deficient (mPGES-1-/- ) mice or their wild counterparts (WT) were subjected to partial hepatic ischemia followed by reperfusion...
February 16, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29458133/artesunate-derived-monomeric-dimeric-and-trimeric-experimental-drugs-their-unique-mechanistic-basis-and-pronounced-antiherpesviral-activity
#5
Friedrich Hahn, Tony Fröhlich, Theresa Frank, Luca D Bertzbach, Stephan Kohrt, Benedikt B Kaufer, Thomas Stamminger, Svetlana B Tsogoeva, Manfred Marschall
Human cytomegalovirus (HCMV) is a major human pathogen and is associated with severe pathology, such as life-threatening courses of infection in immunocompromised individuals and neonates. Currently, antiviral therapy is still hampered by a considerable toxicity of the available drugs and induction of viral resistance. Recently, we and others reported the very potent antiviral activity of the broad antiinfective drug artesunate in vitro and in vivo. Here, we investigated further optimized analogs including monomeric, dimeric and trimeric derivatives belonging to this highly interesting chemical group of experimental drugs (sesquiterpenes/trioxanes) and compared these to the previously identified trimeric artesunate compound TF27...
February 16, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29458110/investigation-of-adhesive-interactions-in-the-specific-targeting-of-triptorelin-conjugated-peg-coated-magnetite-nanoparticles-to-breast-cancer-cells
#6
Jingjie Hu, Sina Youssefian, John Obayemi, Karen Malatesta, Nima Rahbar, Winston Soboyejo
The understanding of adhesive interaction at the nanoscale between functionalized nanoparticles and biological cells is of great importance to develop effective theranostic nanocarriers for targeted cancer therapy. Here, we report a combination of experimental and computational approaches to evaluate the adhesion between Triptorelin (a Luteinizing Hormone-Releasing Hormone (LHRH) agonist)-conjugated poly-(ethylene glycol) (PEG)-coated magnetite nanoparticles (Triptorelin-MNPs) and breast cells. The adhesion forces between Triptorelin-MNPs and normal/cancerous breast cells are obtained using atomic force microscopy...
February 16, 2018: Acta Biomaterialia
https://www.readbyqxmd.com/read/29458089/structural-and-biophysical-insight-into-dual-site-binding-of-the-protoberberine-alkaloid-palmatine-to-parallel-g-quadruplex-dna-using-nmr-fluorescence-and-circular-dichroism-spectroscopy
#7
Kumar Padmapriya, Ritu Barthwal
Plant derived small molecules, which interact with and stabilize G-quadruplex DNA, act as inhibitors of telomere elongation and oncogene expression in humans. The inhibition of telomerase enzyme has immense potential since it is over expressed in most cancer cells. Interaction of palmatine, an antitumor alkaloid, to parallel G-quadruplex DNA, [d(TTGGGGT)]4 and [d(TTAGGGT)]4 , has been investigated using Nuclear Magnetic Resonance (NMR), fluorescence and Circular Dichroism (CD) spectroscopy. Titrations were monitored by1 H and31 P NMR spectra and solution structure of palmatine-[d(TTGGGGT)]4 complex was obtained by restrained Molecular Dynamics (rMD) simulations using distance restraints from 2D NOESY spectra...
February 16, 2018: Biochimie
https://www.readbyqxmd.com/read/29458087/ngf-fak-signal-pathway-is-implicated-in-angiogenesis-after-acute-cerebral-ischemia-in-rats
#8
Hai-Ting Zhao, Yu-Hu Zhang, Ying-Hui Zhang, Yue Shen, Yi-Dan Zhang, Fang-Fang Bi, Bo Xiao, Hao Zhang, Wen Ye, Hong-Hai Zhang, Yi-Wei Liao
Neurogenesis in the cerebral infarction after an ischemic event is important to the rehabilitation of patients. However, the mechanism of angiogenesis around cerebral ischemia is not clear. Our study designed to test whether the nerve growth factor (NGF)-P-focal adhesion kinase (FAK) signaling pathway for associations with angiogenesis plays a key role in post-acute cerebral ischemia of rats. Firstly, we implanted the Matrigel, a carrier of basement membrane matrix, into the abdominal skin of rats to identify the relevant components of the NGF-P-FAK signaling pathway related to angiogenesis...
February 16, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29458076/bone-marrow-mesenchymal-stem-cells-bmscs-improved-functional-recovery-of-spinal-cord-injury-partly-by-promoting-axonal-regeneration
#9
REVIEW
Liya Lin, Hefeng Lin, Shi Bai, Lianshun Zheng, Xiaoming Zhang
Spinal cord injury (SCI) disrupts the spinal cord and results in the loss of sensory and motor function below the lesion site. The treatment of SCI became a challenge because the injured neurons fail to axon regenerate and repair after injury. Promoting axonal regeneration plays a key role in the treatment strategies for SCI. It would meet the goal of reconstruction the injured spinal cord and improving the functional recovery. Bone marrow mesenchymal stem cells (BMSCs) are attractive therapeutic potential cell sources for SCI, and it could rebuild the injured spinal cord through neuroprotection, neural regeneration and remyelinating...
February 16, 2018: Neurochemistry International
https://www.readbyqxmd.com/read/29458071/b-cells-in-operational-tolerance
#10
REVIEW
M Chesneau, R Danger, J-P Soulillou, S Brouard
Transplantation is currently the therapy of choice for endstage organ failure even though it requires long-term immunossuppresive therapy, with its numerous side effects, for acceptance of the transplanted organ. In rare cases however, patients develop operational tolerance, that is, graft survival without immunosuppression. Studies conducted on these patients reveal genetic, phenotypic, and functional signatures. They provide a better understanding of the immunological mechanisms involved in operational tolerance and define biomarkers that could be used to adapt immunosuppressive treatment to the individual, safely reduce immunosuppression doses, and ideally and safely guide immunosuppression withdrawal...
February 16, 2018: Human Immunology
https://www.readbyqxmd.com/read/29458052/regulation-of-proliferation-and-functioning-of-transplanted-cells-by-using-herpes-simplex-virus-thymidine-kinase-gene-in-mice
#11
Mari Tsujimura, Kosuke Kusamori, Chihiro Oda, Airi Miyazaki, Hidemasa Katsumi, Toshiyasu Sakane, Makiya Nishikawa, Akira Yamamoto
Though cell transplantation is becoming an attractive therapeutic method, uncontrolled cell proliferation or overexpression of cellular functions could cause adverse effects. These unfavorable outcomes could be avoided by regulating the proliferation or functioning of transplanted cells. In this study, we used a combination of the herpes simplex virus thymidine kinase (HSVtk) gene, a suicide gene, and ganciclovir (GCV) to control the proliferation and functioning of insulin-secreting cells after transplantation in diabetic mice...
February 16, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29458045/aldose-reductase-inhibitor-fidarestat-prevents-doxorubicin-induced-endothelial-cell-death-and-dysfunction
#12
Himangshu Sonowal, Pabitra Pal, Kirtikar Shukla, Ashish Saxena, Satish K Srivastava, Kota V Ramana
Despite doxorubicin (Dox) being one of the most widely used chemotherapy agents for breast, blood and lung cancers, its use in colon cancer is limited due to increased drug resistance and severe cardiotoxic side effects that increase mortality associated with its use at high doses. Therefore, better adjuvant therapies are warranted to improve the chemotherapeutic efficacy and to decrease cardiotoxicity. We have recently shown that aldose reductase inhibitor, fidarestat, increases the Dox-induced colon cancer cell death and reduces cardiomyopathy...
February 16, 2018: Biochemical Pharmacology
https://www.readbyqxmd.com/read/29458017/synergistic-and-additive-effects-of-atra-in-combination-with-different-anti-tumor-compounds
#13
REVIEW
Eduarda Schultze, Tiago Collares, Caroline Lucas, Fabiana K Seixas
All-trans retinoic acid (ATRA), a derivative of vitamin A, has been shown to potentiate cancer chemotherapy due to its ability to induce signals for cell differentiation or death, and inhibit cell proliferation. The combination of ATRA with taxoids, kinase inhibitors, natural compounds, retinoids, ER or HER2 inhibitors, chemotherapeutic drugs, proteasome inhibitors and nanoformulations of tretinoin have demonstrated additive or synergistic effects in anti-cancer activities. The mechanisms by which the compounds exert their synergistic effects depend on the tumor and the cell type...
February 16, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29458007/a-genomically-characterized-collection-of-high-grade-serous-ovarian-cancer-xenografts-for-preclinical-testing
#14
Paulina Cybulska, Jocelyn M Stewart, Azin Sayad, Carl Virtanen, Patricia A Shaw, Blaise Clarke, Natalie Stickle, Marcus Q Bernardini, Benjamin G Neel
High-grade serous ovarian cancer (HGSC) is the leading cause of morbidity and mortality from gynecologic malignancy. Overall survival remains low, due to the nearly ubiquitous emergence of platinum-resistance and the paucity of effective next-line treatments. Current cell culture-based models show limited similarity to HGSC and are therefore unreliable predictive models for pre-clinical evaluation of investigational drugs. This deficiency could help explain the low overall rate of successful drug development and the decades of largely unchanged approaches to HGSC treatment...
February 16, 2018: American Journal of Pathology
https://www.readbyqxmd.com/read/29457982/discovery-of-gdc-0853-a-potent-selective-and-non-covalent-bruton-s-tyrosine-kinase-inhibitor-in-early-clinical-development
#15
James J Crawford, Adam R Johnson, Dinah L Misner, Lisa D Belmont, Georgette M Castanedo, Regina Choy, Melis Coraggio, Liming Dong, Charles Eigenbrot, Rebecca Erickson, Nico Ghilardi, Jonathan Hau, Arna Katewa, Pawan Bir Kohli, Wendy Lee, Joseph W Lubach, Brent S McKenzie, Daniel Fred Ortwine, Leah Schutt, Suzanne Tay, Binqing Wei, Karin Reif, Lichuan Liu, Harvey Wong, Wendy B Young
Btk is a non-receptor cytoplasmic tyrosine kinase involved in B-cell and myeloid cell activation, downstream of B-cell and Fcγ receptors, respectively. Pre-clinical studies have indicated that inhibition of Btk activity might offer a potential therapy in autoimmune diseases such as rheumatoid arthritis and systemic lupus erythematosus. Here we disclose the discovery and pre-clinical characterization of a potent, selective, and non-covalent Btk inhibitor currently in clinical development. GDC-0853 (29) suppresses B cell- and myeloid cell-mediated components of disease, and demonstrates dose-dependent activity in an in vivo rat model of inflammatory arthritis...
February 19, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29457968/in-vitro-and-in-vivo-effects-of-mk2206-and-chloroquine-combination-therapy-on-endometriosis-autophagy-may-be-required-for-regrowth-of-endometriosis
#16
Sachiko Matsuzaki, Jean-Luc Pouly, Michel Canis
BACKGROUND AND PURPOSE: A high recurrence rate after medical treatment is a major clinical problem for patients with endometriosis. In the present study, we evaluated the in vitro effects of combined treatment with MK2206 (an AKT inhibitor) + chloroquine on cell growth and regrowth of endometriotic stromal cells, and the in vivo effects on endometriotic implants in a mouse xenograft model of endometriosis. EXPERIMENTAL APPROACH: We evaluated the effects of autophagy inhibition by knockdown of the ATG13, Beclin-1, and ATG12 genes and pharmacologic agents (chloroquine, bafilomycin A1, or 3-methyalanine) individually and in combination with MK2206 on cell growth and/or cell regrowth of endometriotic stromal cells in vitro...
February 19, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29457930/nano-loaded-human-umbilical-cord-mesenchymal-stem-cells-as-targeted-carriers-of-doxorubicin-for-breast-cancer-therapy
#17
Shunxiu Cao, Jiamin Guo, Yujing He, Murad Alahdal, Shanshan Tang, Yuekui Zhao, Zhaocong Yang, Huashan Gao, Wenjun Hu, Hulin Jiang, Lianju Qin, Liang Jin
The main challenge of anticancer drugs is poor tumor targeting. Now cellular carriers are widely investigated to deliver anticancer agents. As an ideal cellular candidate, human umbilical cord derived mesenchymal stem cells (hUC-MSCs) possess inherent tropism potential to tumor. Here, we constructed hUC-MSCs carrying transferrin-inspired-nanoparticles that contain doxorubicin(hUC-MSCs-Tf-inspired-NPs) to achieve enhanced anti-tumor efficacy and made an evaluation. Results represented that hUC-MSCs-Tf-inspired-NPs not only exhibit the controlled-release property of Tf-inspired-NPs, but also integrate tumor tropism and penetrative abilities of MSCs...
February 19, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29457878/genetic-determinants-of-heart-failure-facts-and-numbers
#18
EDITORIAL
Frauke S Czepluch, Bernd Wollnik, Gerd Hasenfuß
The relevance of gene mutations leading to heart diseases and hence heart failure has become evident. The risk for and the course of heart failure depends on genomic variants and mutations underlying the so-called genetic predisposition. Genetic contribution to heart failure is highly heterogenous and complex. For any patient with a likely inherited heart failure syndrome, genetic counselling is recommended and important. In the last few years, novel sequencing technologies (named next-generation sequencing - NGS) have dramatically improved the availability of molecular testing, the efficiency of genetic analyses, and moreover reduced the cost for genetic testing...
February 19, 2018: ESC Heart Failure
https://www.readbyqxmd.com/read/29457859/post-infectious-acute-glomerulonephritis-with-podocytopathy-induced-by-parvovirus-b19-infection
#19
Satoshi Hara, Masayoshi Hirata, Kiyoaki Ito, Ichiro Mizushima, Hiroshi Fujii, Kazunori Yamada, Michio Nagata, Mitsuhiro Kawano
Human parvovirus B19 infection causes a variety of glomerular diseases such as post-infectious acute glomerulonephritis and collapsing glomerulopathy. Although each of these appears independently, it has not been fully determined why parvovirus B19 provokes such a variety of different glomerular phenotypes. Here, we report a 68-year-old Japanese man who showed endocapillary proliferative glomerulonephritis admixed with podocytopathy in association with parvovirus B19 infection. The patient showed acute onset of heavy proteinuria, microscopic hematuria and kidney dysfunction with arthralgia and oliguria after close contact with a person suffering from erythema infectiosum...
February 19, 2018: Pathology International
https://www.readbyqxmd.com/read/29457830/mirna-124-3p-neuropilin-1-nrp-1-axis-plays-an-important-role-in-mediating-glioblastoma-growth-and-angiogenesis
#20
Guilong Zhang, Lukui Chen, Ahsan Ali Khan, Bingqian Li, Bin Gu, Fan Lin, Xinhui Su, Jianghua Yan
Glioblastoma Multiforme (GBM) is the most lethal brain malignancy which involves multi-gene abnormality. Unfortunately, effective therapy against GBM is still lacking. Previously, we found that NRP-1 and its downstream NRP-1/GIPC1 pathway played an important role in GBM. In this study, we further investigated the upstream signaling of NRP-1 to understand how it is regulated. Firstly, we identified that hsa-miR-124-3p was miRNA differentially expressed in GBM and in normal brain tissues by high-throughput sequencing...
February 19, 2018: International Journal of Cancer. Journal International du Cancer
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