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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/29458146/enhanced-anticancer-effects-of-scutellaria-barbata-d-don-in-combination-with-traditional-chinese-medicine-components-on-non-small-cell-lung-cancer-cells
#3
Qian Wang, Narayan Acharya, Zhongwei Liu, Xianmei Zhou, Meghan Cromie, Jia Zhu, Weimin Gao
ETHNOPHARMACOLOGICAL RELEVANCE: Experience-based herbal medicine as a complementary to modern western medicine has triggered an array of studies in quest of novel anticancer drugs. Scutellaria barbata D. Don (SB) is commonly used to treat different types of cancers, but its molecular mechanism of action is not clearly understood. In this study, we attempted to elucidate the mode of action of a traditional Chinese medicine prescription with a total of 14 components, named Lian-Jia-San-Jie-Fang (LJSJF, in Chinese), where SB works as the "principle" against non-small cell lung cancer (NSCLC) cells...
February 16, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29458119/the-function-of-hla-b-13-01-involved-in-the-pathomechanism-of-dapsone-induced-severe-cutaneous-adverse-reactions
#4
Wei-Ti Chen, Chuang-Wei Wang, Chun-Wei Lu, Chun-Bing Chen, Hua-En Lee, Shuen-Iu Hung, Siew-Eng Choon, Chih-Hsun Yang, Ming-Tsan Liu, Ting Jui Chen, Wen-Lang Fan, Shih-Chi Su, Yang Yu-Wei Lin, Ya-Ching Chang, Wen-Hung Chung
Dapsone-induced hypersensitivity reactions may cause severe cutaneous adverse reactions (SCAR), such as drug reaction with eosinophilia and systemic symptoms (DRESS). It has been reported that HLA-B*13:01 is strongly associated with dapsone-induced hypersensitivity reactions among leprosy patients. However, the phenotype specificity and detailed immune mechanism of HLA-B*13:01 remains unclear. We investigated the genetic predisposition, HLA-B*13:01 function, and cytotoxic T cells (CTLs) involved in pathogenesis of dapsone-SCAR...
February 16, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29458109/modulation-of-cyp1a1-metabolism-from-adverse-health-effects-to-chemoprevention-and-therapeutic-options
#5
Melina Mescher, Thomas Haarmann-Stemmann
The human cytochrome P450 (CYP) 1A1 gene encodes a monooxygenase that metabolizes multiple exogenous and endogenous substrates. CYP1A1 has become infamous for its oxidative metabolism of benzo[a]pyrene and related polycyclic aromatic hydrocarbons, converting these chemicals into very potent human carcinogens. CYP1A1 expression is mainly controlled by the aryl hydrocarbon receptor (AHR), a transcription factor whose activation is induced by binding of persistent organic pollutants, including polycyclic aromatic hydrocarbons and dioxins...
February 16, 2018: Pharmacology & Therapeutics
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
#6
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/29458045/aldose-reductase-inhibitor-fidarestat-prevents-doxorubicin-induced-endothelial-cell-death-and-dysfunction
#7
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/29458018/5-chloro-n4-2-isopropylsulfonyl-phenyl-n2-2-methoxy-4-4-4-methylpiperazin-1-yl-methyl-1h-1-2-3-triazol-1-yl-phenyl-pyrimidine-2-4-diamine-wy-135-a-novel-alk-inhibitor-induces-cell-cycle-arrest-and-apoptosis-through-inhibiting-alk-and-its-downstream-pathways
#8
Mengting Han, Jiwei Shen, Lijing Wang, Yu Wang, Xin Zhai, Yao Li, Meiqiao Liu, Zengqiang Li, Daiying Zuo, Yingliang Wu
Anaplastic lymphoma kinase (ALK)-positive cancers have rising morbidity and mortality in recent years, and novel chemotherapeutic drugs with no drug resistance and high activity for treating ALK-positive cancers are needed urgently. In this study, we investigated the anti-cancer effect of 5-chloro-N4-(2-(isopropylsulfonyl)phenyl)-N2-(2-methoxy-4-(4-((4-methylpiperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)phenyl)pyrimidine-2,4-diamine (WY-135), a novel ALK inhibitor, on nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) positive cancer cell line Karpas299 and echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) positive cancer cell line H2228...
February 16, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29458017/synergistic-and-additive-effects-of-atra-in-combination-with-different-anti-tumor-compounds
#9
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/29458016/renal-toxicological-evaluations-of-sulphonated-nanocellulose-from-khaya-sengalensis-seed-in-wistar-rats
#10
Adewale Adewuyi, Chiagoziem A Otuechere, Olusegun L Adebayo, Chibuzo Anazodo, Fabiano V Pereira
Nanocellulose is currently gaining attention due to its unique properties. This attention includes its application as building blocks for developing novel functional materials, plant drug and also in drug delivery systems. However, its safety remains largely untested or less understood. Thus, sulphonated nanocellulose (KSS) was prepared from cellulose (KSC) isolated from Khaya senegalensis seed (KS). KS, KSC and KSS were characterized using Fourier transformed infrared (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TG), particle size distribution (PSD), zeta potential and scanning electron microscopy (SEM)...
February 16, 2018: Chemico-biological Interactions
https://www.readbyqxmd.com/read/29457989/propylthiouracil-induced-anti-neutrophil-cytoplasmic-antibody-associated-vasculitis-mimicking-kawasaki-disease
#11
Yoshihiro Aoki, Katsuhiko Kitazawa, Hironobu Kobayashi
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is rare in children and is characterised as necrotising vasculitis predominantly affecting small and medium-sized vessels. Propylthiouracil (PTU), an antithyroid drug, has been implicated in drug-induced AAV. In contrast, Kawasaki disease (KD) is a common systemic vasculitis, typically observed in children, which affects the medium-sized vessels, including the coronary arteries. An 11-year-old girl who developed AAV while receiving PTU therapy for Graves' disease is described...
February 19, 2018: Paediatrics and International Child Health
https://www.readbyqxmd.com/read/29457931/synthesis-and-characterization-of-nanodiamond-growth-factor-complexes-towards-applications-in-oral-implantation-and-regenerative-medicine
#12
Julie Bang, Caleb Ting, Peter Wang, Ted Kim, Kenneth Wang, Theodore Kee, Darron Miya, Dean Ho, Dong-Keun Lee
Current challenges in the field of regenerative medicine include the need to deliver sustained concentrations of growth factors and genes that are required to induce the repair of deficient tissues. Enhancement of drug delivery and uptake may result in improved growth factor efficacy. Nanodiamonds (NDs) were explored as potential growth factor delivery agents due to the many favorable properties that they possess. For example, ND's biocompatibility has been extensively validated pre-clinically. In addition, they can be scalably produced through impact events such as detonation...
February 19, 2018: Journal of Oral Implantology
https://www.readbyqxmd.com/read/29457828/dihydrodiosgenin-protects-against-experimental-acute-pancreatitis-and-associated-lung-injury-through-mitochondrial-protection-and-pi3k%C3%AE-akt-inhibition
#13
Yan Shen, Li Wen, Rui Zhang, Zeliang Wei, Na Shi, Qiuyang Xiong, Qing Xia, Zhihua Xing, Zhi Zeng, Hai Niu, Wen Huang
BACKGROUND AND PURPOSE: Acute pancreatitis (AP) is a painful and burdensome exocrine pancreatic disorder with no specific drug treatment. Diosgenyl saponin extracts from Dioscorea zingiberensis C. H. Wright were reported to protect against experimental models of AP and diosgenin or its derivatives have anti-inflammatory effects in various diseases. However, the effects of diosgenin and its spiroacetal ring opened analog dihydrodiosgenin (Dydio) have not yet been determined in AP. EXPERIMENTAL APPROACH: Various concentrations of diosgenin and Dydio were tested for sodium taurocholate hydrate (Tauro)-induced necrosis in freshly isolated murine pancreatic acinar cells...
February 19, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29457796/h3b-8800-an-orally-available-small-molecule-splicing-modulator-induces-lethality-in-spliceosome-mutant-cancers
#14
Michael Seiler, Akihide Yoshimi, Rachel Darman, Betty Chan, Gregg Keaney, Michael Thomas, Anant A Agrawal, Benjamin Caleb, Alfredo Csibi, Eckley Sean, Peter Fekkes, Craig Karr, Virginia Klimek, George Lai, Linda Lee, Pavan Kumar, Stanley Chun-Wei Lee, Xiang Liu, Crystal Mackenzie, Carol Meeske, Yoshiharu Mizui, Eric Padron, Eunice Park, Ermira Pazolli, Shouyong Peng, Sudeep Prajapati, Justin Taylor, Teng Teng, John Wang, Markus Warmuth, Huilan Yao, Lihua Yu, Ping Zhu, Omar Abdel-Wahab, Peter G Smith, Silvia Buonamici
Genomic analyses of cancer have identified recurrent point mutations in the RNA splicing factor-encoding genes SF3B1, U2AF1, and SRSF2 that confer an alteration of function. Cancer cells bearing these mutations are preferentially dependent on wild-type (WT) spliceosome function, but clinically relevant means to therapeutically target the spliceosome do not currently exist. Here we describe an orally available modulator of the SF3b complex, H3B-8800, which potently and preferentially kills spliceosome-mutant epithelial and hematologic tumor cells...
February 19, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29457729/assessing-interactions-between-a-polytopic-membrane-protein-and-lipid-bilayers-using-differential-scanning-calorimetry-and-solid-state-nmr
#15
James R Banigan, Maureen Leninger, Ampon Sae Her, Nathaniel J Traaseth
It is known that the lipid composition within a cellular membrane can influence membrane protein structure and function. In this Article, we investigated how structural changes to a membrane protein upon substrate binding can impact the lipid bilayer. To carry out this study, we reconstituted the secondary active drug transporter EmrE into a variety of phospholipid bilayers varying in headgroup and chain length and carried out differential scanning calorimetry (DSC) and solid-state NMR experiments. The DSC results revealed a difference in cooperativity of the lipid phase transition for drug-free EmrE protonated at glutamic acid 14 (i...
February 19, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29457656/fatty-acid-binding-protein-deletion-prevents-stress-induced-preference-for-cocaine-and-dampens-stress-induced-corticosterone-levels
#16
John Hamilton, Matthew Marion, Antonio Figueiredo, Brendan H Clavin, Dale Deutsch, Martin Kaczocha, Samir Haj-Dahmane, Panayotis K Thanos
Genetic and pharmacological manipulation of endocannabinoid (eCB) signaling has previously been shown to have an important role on the rewarding properties of drugs of abuse, including cocaine. Recently, fatty acid binding proteins (FABPs) have been proposed as intracellular transporters of the endocannabinoid anandamide (AEA) as well as other bioactive lipids to their catabolic enzyme, fatty acid amide hydrolase (FAAH). The role of these transporters in modulating the brains reward system has yet to be investigated...
February 19, 2018: Synapse
https://www.readbyqxmd.com/read/29457517/the-protection-of-resveratrol-and-its-combination-with-glibenclamide-but-not-berberine-on-the-diabetic-hearts-against-reperfusion-induced-arrhythmias-the-role-of-myocardial-k-atp-channel
#17
Salih T Kaya, Omer Bozdogan, Talat O Ozarslan, Eylem Taskin, Didem Eksioglu, Firdevs Erim, Tulin Firat, Selcuk Yasar
CONTEXT: Cardiovascular dysfunctions such as life-threatening arrhythmias are one of the main reasons of mortality and morbidity in diabetic patients Objective: We aimed to investigate the long-term effects of resveratrol, berberine and glibenclamide combinations on the ischemia/reperfusion (I/R) induced arrhythmias in streptozotocin (STZ)-induced diabetic rats and to investigate the role of myocardial KATP channel in the possible anti-arrhythmic actions of the treatments. METHODS: Two days after induction of diabetes, diabetic rats were treated with resveratrol [5 mg/kg, intraperitoneally (i...
February 18, 2018: Archives of Physiology and Biochemistry
https://www.readbyqxmd.com/read/29457449/catalytically-active-single-chain-polymeric-nanoparticles-exploring-their-functions-in-complex-biological-media
#18
Yiliu Liu, Silvia Pujals, Patrick J M Stals, Thomas Pauloehrl, Stanislav I Presolski, E W Meijer, Lorenzo Albertazzi, Anja R A Palmans
Dynamic single-chain polymeric nanoparticles (SCPNs) are intriguing, bioinspired architectures that result from the collapse or folding of an individual polymer chain into a nanometer-sized particle. Here we present a detailed biophysical study on the behavior of dynamic SCPNs in living cells and an evaluation of their catalytic functionality in such a complex medium. We first developed a number of delivery strategies that allowed the selective localization of SCPNs in different cellular compartments. Live/dead tests showed that the SCPNs were not toxic to cells while spectral imaging revealed that SCPNs provide a structural shielding and reduced the influence from the outer biological media...
February 19, 2018: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29457309/severe-intestinal-malabsorption-associated-with-ace-inhibitor-or-angiotensin-receptor-blocker-treatment-an-observational-cohort-study-in-germany-and-italy
#19
Peter Malfertheiner, Claudio Ripellino, Nazarena Cataldo
PURPOSE: The angiotensin II receptor blocker (ARB) olmesartan has been recently associated with sprue-like enteropathy (SLE), a gastrointestinal condition characterized by intestinal malabsorption (IM) and severe diarrhea. Whether the increased risk of SLE is substance-specific or a class effect involving all ARBs is uncertain. The aim of this study is to assess the risk of enteropathy associated with ARBs and angiotensin converting enzyme inhibitors (ACE-i) by using data from large administrative and claim databases...
February 19, 2018: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/29457278/zwitterionic-nanocages-overcome-the-efficacy-loss-of-biologic-drugs
#20
Bowen Li, Zhefan Yuan, Peng Zhang, Andrew Sinclair, Priyesh Jain, Kan Wu, Caroline Tsao, Jingyi Xie, Hsiang-Chieh Hung, Xiaojie Lin, Tao Bai, Shaoyi Jiang
For biotherapeutics that require multiple administrations to fully cure diseases, the induction of undesirable immune response is one common cause for the failure of their treatment. Covalent binding of hydrophilic polymers to proteins is commonly employed to mitigate potential immune responses. However, while this technique is proved to partially reduce the antibodies (Abs) reactive to proteins, it may induce Abs toward their associated polymers and thus result in the loss of efficacy. Zwitterionic poly(carboxybetaine) (PCB) is recently shown to improve the immunologic properties of proteins without inducing any antipolymer Abs against itself...
February 19, 2018: Advanced Materials
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