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https://www.readbyqxmd.com/read/29458219/clinical-endocrine-and-imaging-characteristics-of-patients-with-primary-hypophysitis
#1
Anna Angelousi, Carolina Cohen, Soledad Sosa, Karina Danilowicz, Lina Papanastasiou, Marina Tsoli, Aparna Pal, Georgios Piaditis, Ashley Grossman, Gregory Kaltsas
Primary hypophysitis (PH) is a rare disease with a poorly-defined natural history. Our aim was to characterise patients with PH at presentation and during prolonged follow-up. Observational retrospective study of 22 patients was conducted from 3 centres. In 14 patients, PH was confirmed histologically and in the remaining 8 clinically, after excluding secondary causes of hypophysitis. All patients had hormonal and imaging investigations before any treatment. Median follow up was 48 months (25-75%: 3-60). There was a female predominance with a female/male ratio: 3...
February 19, 2018: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/29458213/selective-targeting-and-degradation-of-doxorubicin-loaded-folate-functionalized-dna-nanocages
#2
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
#3
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/29458203/precision-pharmacology-for-alzheimer-s-disease
#4
REVIEW
Harald Hampel, Andrea Vergallo, Lisi Flores Aguilar, Norbert Benda, Karl Broich, A Claudio Cuello, Jeffrey Cummings, Bruno Dubois, Howard J Federoff, Massimo Fiandaca, Remy Genthon, Marion Haberkamp, Eric Karran, Mark Mapstone, George Perry, Lon S Schneider, Lindsay A Welikovitch, Janet Woodcock, Filippo Baldacci, Simone Lista
The complex multifactorial nature of polygenic Alzheimer's disease (AD) presents significant challenges for drug development. AD pathophysiology is progressing in a non-linear dynamic fashion across multiple systems levels - from molecules to organ systems - and through adaptation, to compensation, and decompensation to systems failure. Adaptation and compensation maintain homeostasis: a dynamic equilibrium resulting from the dynamic non-linear interaction between genome, epigenome, and environment. An individual vulnerability to stressors exists on the basis of individual triggers, drivers, and thresholds accounting for the initiation and failure of adaptive and compensatory responses...
February 16, 2018: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29458193/attenuation-of-neuro-inflammation-improves-survival-and-neurodegeneration-in-a-mouse-model-of-severe-neonatal-hyperbilirubinemia
#5
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
#6
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/29458152/controversies-in-endoscopic-eradication-therapy-for-barrett-s-esophagus
#7
Srinadh Komanduri, V Raman Muthusamy, Sachin Wani
Advances in Endoscopic Eradication Therapy for Barrett's Esophagus associated neoplasia have resulted in a significant paradigm shift in diagnosis and management of this complex disease. A robust body of literature critically evaluating outcomes of resection and ablative strategies has allowed gastroenterologists to make quality, evidence based decisions for their patients. Despite this progress, there are still many unanswered questions and challenges that remain. Ultimately, identification of a cost-effective screening modality, biomarkers for risk stratification, and strides to eliminate post surveillance endoscopy after EET are essential to reach our long term goal for eradication of esophageal adenocarcinoma...
February 16, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29458151/endoscopic-management-of-pancreatobiliary-neoplasms
#8
Andrew Y Wang, Patrick S Yachimski
Endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) are the mainstays of interventional endoscopic practice. EUS occupies a central role in the diagnosis of pancreatobiliary neoplasms and offers a platform for a wide range of direct tumor therapies. Initial steps have demonstrated the feasibility of such applications in animal models and pilot studies. Larger clinical trials and incorporation of EUS-based therapies into cooperative cancer studies might demonstrate an impact in the clinical prognosis of patients with pancreatic cancer...
February 16, 2018: Gastroenterology
https://www.readbyqxmd.com/read/29458142/insufficient-radiofrequency-ablation-promotes-proliferation-of-residual-hepatocellular-carcinoma-via-autophagy
#9
Zizhuo Zhao, Jiayi Wu, Xiaodi Liu, Ming Liang, Xinchuan Zhou, Shi Ouyang, Jiyi Yao, Jinquan Wang, Baoming Luo
Radiofrequency ablation (RFA) is considered to be a potentially curative therapy for hepatocellular carcinoma (HCC). However, insufficient RFA (IRFA) can promote rapid progression of the residual tumor. The mechanisms underlying IRFA-induced tumor promotion remain poorly understood. In the present study, we have established a subcutaneous xenograft mouse model and monitored the location and extent of IRFA by dual monitoring with ultrasonography and a thermal imager. For the first time, we provide evidence of the activation of autophagic pathways in mice exposed to IRFA...
February 16, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29458133/artesunate-derived-monomeric-dimeric-and-trimeric-experimental-drugs-their-unique-mechanistic-basis-and-pronounced-antiherpesviral-activity
#10
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/29458132/therapeutic-drug-monitoring-in-treatment-experienced-hiv-infected-patients-receiving-darunavir-based-salvage-regimens-a-case-series
#11
Sébastien Landry, Chi-Nan Chen, Nimish Patel, Alice Tseng, Richard G Lalonde, Denis Thibeault, Steven Sanche, Nancy L Sheehan
Therapeutic drug monitoring (TDM) constitutes a compelling approach for the optimization of antiretroviral therapy in treatment-experienced HIV-1 patients. While various inhibitory indices have been proposed to predict virologic outcome, there is a lack of consensus on the clinical value of TDM. Here, we report the comparative results of TDM in 14 HIV-1-infected patients who had previously received at least two different PI-based regimens and who initiated darunavir (DRV)-based salvage therapy. Pharmacokinetic/pharmacodynamics (PK/PD) parameters were calculated for each subject...
February 16, 2018: Antiviral Research
https://www.readbyqxmd.com/read/29458129/honeysuckle-encoded-microrna2911-inhibits-enterovirus-71-replication-via-targeting-vp1-gene
#12
Xihan Li, Ying Huang, Menghuai Sun, Hong Ji, Hui Dou, Jia Hu, Yanfeng Yan, Xu Wang, Leiyao Chen
Enterovirus 71 (EV71) is the primary pathogen of hand-foot-and-mouth disease (HFMD) in children and virus infections are associated with severe neurological dysfunctions and even death. MIR2911 is a honeysuckle-encoded atypical microRNA with extremely stability. Here, we report that MIR2911 directly inhibits EV71 replication by targeting the VP1 gene. Bioinformatics prediction and luciferase reporter assay showed that MIR2911 could target the VP1 gene of EV71. Transfection experiments using synthetic MIR2911 and extracted RNA from HS decoction shown that each of these preparations was capable of inhibiting EV71 VP1 protein expression; however, these preparations did not impact EV71 mutants in which the MIR2911-binding sites were mutated...
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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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