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https://www.readbyqxmd.com/read/28719882/antileishmanial-activity-and-tubulin-polymerization-inhibition-of-podophyllotoxin-derivatives-on-leishmania-infantum
#1
José Miguel Escudero-Martínez, Yolanda Pérez-Pertejo, Rosa M Reguera, María Ángeles Castro, María Victoria Rojo, Carolina Santiago, Andrés Abad, Pablo Anselmo García, José Luis López-Pérez, Arturo San Feliciano, Rafael Balaña-Fouce
Leishmania microtubules play an important role not only in cell division, but also in keeping the shape of the parasite and motility of its free-living stages. Microtubules result from the self-assembly of alpha and beta tubulins, two phylogenetically conserved and very abundant eukaryotic proteins in kinetoplastids. The colchicine binding domain has inspired the discovery and development of several drugs currently in clinical use against parasites. However, this domain is less conserved in kinetoplastids and may be selectively targeted by new compounds...
June 28, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28719801/biology-oriented-drug-synthesis-biods-of-2-2-methyl-5-nitro-1h-imidazol-1-yl-ethyl-aryl-ether-derivatives-in-vitro-%C3%AE-amylase-inhibitory-activity-and-in-silico-studies
#2
Muhammad Taha, Syahrul Imran, Nor Hadiani Ismail, Manikandan Selvaraj, Fazal Rahim, Sridevi Chigurupati, Hayat Ullah, Fahad Khan, Uzma Salar, Muhammad Tariq Javid, Shantini Vijayabalan, Khalid Zaman, Khalid Mohammed Khan
A new library of 2-(2-methyl-5-nitro-1H-imidazol-1-yl)ethyl aryl ether derivatives (1-23) were synthesized and characterized by EI-MS and (1)H NMR, and screened for their α-amylase inhibitory activity. Out of twenty-three derivatives, two molecules 19 (IC50=0.38±0.82µM) and 23 (IC50=1.66±0.14µM), showed excellent activity whereas the remaining compounds, except 10 and 17, showed good to moderate inhibition in the range of IC50=1.77-2.98µM when compared with the standard acarbose (IC50=1.66±0.1µM). A plausible structure-activity relationship has also been presented...
July 11, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28719744/high-resolution-insights-into-the-stepwise-self-assembly-of-nanofiber-from-bioactive-peptides
#3
Fude Sun, Long Chen, Xiufang Ding, Lida Xu, Xirui Zhou, Peng Wei, Jun-Feng Liang, Shi-Zhong Luo
Peptide self-assembly has a profound biological significance since self-assembled bioactive peptides are gifted with improved bioactivity as well as life-span. In this study, peptide self-assembly was investigated using a therapeutic peptide, PTP-7S (EENFLGALFKALSKLL). Combining experiments of atomic force microscopy (AFM), circular dichroism (CD) and 8-anilino-1-naphthalenesulfonic acid (ANS) fluorescence spectra, PTP-7S showing α-helix was found self-assembling into nanofibers in solution. Relying on the coarse-grained (CG) dynamic simulations, the self-assembling of PTP-7S was revealed as a stepwise process that peptide monomers first clustered into peptide-assembling units (PUs) with charged surface, and then the PUs integrated together to construct nano-fibril aggregates...
July 18, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28719234/the-in-vivo-effects-of-the-cb1-positive-allosteric-modulator-gat229-on-intraocular-pressure-in-ocular-normotensive-and-hypertensive-mice
#4
Elizabeth A Cairns, Anna-Maria Szczesniak, Alex J Straiker, Pushkar M Kulkarni, Roger G Pertwee, Ganesh A Thakur, William H Baldridge, Melanie E M Kelly
PURPOSE: Orthosteric cannabinoid receptor 1 (CB1) activation leads to decreases in intraocular pressure (IOP). However, use of orthosteric CB1 agonists chronically has several disadvantages, limiting their usefulness as clinically relevant drugs. Allosteric modulators interact with topographically distinct sites to orthosteric ligands and may be useful to circumvent some of these disadvantages. The purpose of this study was to investigate the effects of the novel CB1-positive allosteric modulator (PAM) GAT229 on IOP...
July 18, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28719196/thermoresponsive-elastin-b-collagen-like-peptide-bioconjugate-nanovesicles-for-targeted-drug-delivery-to-collagen-containing-matrices
#5
Tianzhi Luo, Michael A David, Lucas C Dunshee, Rebecca A Scott, Morgan A Urello, Christopher Price, Kristi L Kiick
Over the past few decades, (poly)peptide block copolymers have been widely employed in generating well-defined nanostructures as vehicles for targeted drug delivery applications. We previously reported the assembly of thermoresponsive nanovesicles from an elastin-b-collagen like peptide (ELP-CLP). The nanoparticles were observed to dissociate at elevated temperatures, despite the LCST-like behavior of the tethered ELP domain, which is suggested to be triggered by the unfolding of the CLP domain. Here, the potential of using the nanoparticles as drug delivery vehicles for targeting collagen-containing matrices is evaluated...
July 18, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28718810/dna2-an-important-player-in-dna-damage-response-or-just-another-dna-maintenance-protein
#6
REVIEW
Elzbieta Pawłowska, Joanna Szczepanska, Janusz Blasiak
The human DNA2 (DNA replication helicase/nuclease 2) protein is expressed in both the nucleus and mitochondria, where it displays ATPase-dependent nuclease and helicase activities. DNA2 plays an important role in the removing of long flaps in DNA replication and long-patch base excision repair (LP-BER), interacting with the replication protein A (RPA) and the flap endonuclease 1 (FEN1). DNA2 can promote the restart of arrested replication fork along with Werner syndrome ATP-dependent helicase (WRN) and Bloom syndrome protein (BLM)...
July 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28718777/an-assembly-and-interaction-of-upconversion-and-plasmonic-nanoparticles-on-organometallic-nanofibers-enhanced-multicolor-upconversion-downshifting-emission-and-plasmonic-effect
#7
Priyam Singh, Praveen Kumar Shahi, Rajiv Prakash, S B Rai
We herein present a novel inorganic-organic hybrid nanoparticle (HNPs) constituted of inorganic NPs, NaY0.78Er0.02Yb0.2F4, and organometallic nanofiber, Tb(ASA)3Phen (TAP). The X-ray diffraction, Fourier transform infrared absorption and TEM analyse reveal that, the prepared ultrafine upconversion nanoparticles {UCNPs (6-9 nm)} are dispersed on the surface of TAP nanofibers. We observe that addition of TAP in UCNPs, effectively prevents the surface quenching to boost the UC intensity and enables tuning of UC emission from green to red region by controlling the phonon frequency around Er3+ ion...
July 18, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28718636/long-chain-alkyl-esters-of-hydroxycinnamic-acids-as-promising-anticancer-agents-selective-induction-of-apoptosis-in-cancer-cells
#8
José C J M D S Menezes, Najmeh Edraki, Shrivallabh Kamat, Mahsima Khoshneviszadeh, Zahra Kayani, Hossein Hadavand Mirzaei, Ramin Miri, Nasrollah Erfani, Maryam Nejati, José A S Cavaleiro, Tiago B Silva, Luciano Saso, Fernanda M Borges, Omidreza Firuzi
Cancer is the major cause of morbidity and mortality worldwide. Hydroxycinnamic acids (HCAs) are naturally-occurring compounds and their alkyl esters may possess enhanced biological activities. We evaluated C4, C14, C16 and C18 alkyl esters of p-coumaric, ferulic, sinapic and caffeic acids (19 compounds) for their cytotoxic activity against four human cancer cells and also examined their effect on cell cycle alteration and apoptosis induction. The tetradecyl (1c) and hexadecyl (1d) esters of p-coumaric acid and tetradecyl ester of caffeic acid (4c), but not the parental HCAs, were selectively effective against MOLT-4 (human lymphoblastic leukemia) cells with IC50 values of 0...
July 18, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28718456/graphene-oxide-and-dna-aptamer-based-sub-nanomolar-potassium-detecting-optical-nanosensor
#9
Debopam Datta, Ketaki Sarkar, Souvik Mukherjee, Xenia Meshik, Michael A Stroscio, Mitra Dutta
Quantum-dot (QD) based nanosensors are frequently used by researchers to detect small molecules, ions and different biomolecules. In this article, we present a sensor complex/system comprised of deoxyribonucleic acid (DNA) aptamer, gold nanoparticle and semiconductor QD, attached to a graphene oxide (GO) flake for detection of potassium. As reported herein, it is demonstrated that QD-aptamer-quencher nanosensor functions even when tethered to GO, opening the way to future applications where sensing can be accomplished simultaneously with other previously demonstrated applications of GO such as serving as a nanocarrier for drug delivery...
July 18, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28718434/undercover-agents-targeting-tumours-with-modified-platelets
#10
REVIEW
Stephanie R Hyslop, Emma C Josefsson
Platelets have long been recognised to colocalise with tumour cells throughout haematogenous metastasis. Interactions between these cells contribute to tumour cell survival and motility through the vasculature into other tissues. Now, the research focus is shifting towards developing means to exploit this relationship to provide accurate diagnostics and therapies. Alterations to platelet count, RNA profile, and platelet ultrastructure are associated with the presence of certain malignancies, and may be used for cancer detection...
March 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28717993/probing-the-binding-affinities-of-imipenem-and-ertapenem-for-outer-membrane-carboxylate-channel-d1-occd1-from-p-aeruginosa-simulation-studies
#11
Kamolrat Somboon, Jitti Niramitranon, Prapasiri Pongprayoon
Pseudomonas aeruginosa is an important nosocomial human pathogen. The major difficulty in the fight against this pathogen is the relative impermeability of its outer membrane (OM). Only specific substrates can penetrate through the OM of P. aeruginosa via substrate-specific porins, so this has become one of the most problematic drug-resistant pathogens. Carbapenems are the most effective drugs for treating P. aeruginosa infections. One such carbapenem that is applied in cases of P. aeruginosa infection is imipenem (IMI), which uses outer membrane carboxylate channel D1 (OccD1) as a point of entry into the pathogen...
August 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/28717974/improvement-of-oral-bioavailability-of-lopinavir-without-co-administration-of-ritonavir-using-microspheres-of-thiolated-xyloglucan
#12
Ashwini R Madgulkar, Mangesh R Bhalekar, Ashwini A Kadam
Lopinavir is a BCS Class IV drug exhibiting poor bioavailability due to P-gp efflux and limited permeation. The aim of this research was to formulate and characterize microspheres of lopinavir using thiolated xyloglucan (TH-MPs) as carrier to improve its oral bioavailability without co-administration of ritonavir. Thiomeric microspheres were prepared by ionotropic gelation between alginic acid and calcium ions. Interaction studies were performed using Fourier transform infrared spectroscopy (FT-IR). The thiomeric microspheres were characterized for its entrapment efficiency, T80, surface morphology, and mucoadhesion employing in vitro wash off test...
July 17, 2017: AAPS PharmSciTech
https://www.readbyqxmd.com/read/28717926/clinical-evaluation-of-modified-release-and-immediate-release-tacrolimus-formulations
#13
Simon Tremblay, Rita R Alloway
The science of drug delivery has evolved considerably and has led to the development of multiple sustained release formulations. Each of these formulations can present particular challenges in terms of clinical evaluation and necessitate careful study to identify their optimal use in practice. Tacrolimus is an immunosuppressive agent that is widely used in organ transplant recipients. However, it is poorly soluble, has an unpredictable pharmacokinetic profile subject to important genetic polymorphisms and drug-drug interactions, and has a narrow therapeutic index...
July 17, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28717873/orchestration-of-h3k27-methylation-mechanisms-and-therapeutic-implication
#14
REVIEW
Mei-Ren Pan, Ming-Chuan Hsu, Li-Tzong Chen, Wen-Chun Hung
Histone proteins constitute the core component of the nucleosome, the basic unit of chromatin. Chemical modifications of histone proteins affect their interaction with genomic DNA, the accessibility of recognized proteins, and the recruitment of enzymatic complexes to activate or diminish specific transcriptional programs to modulate cellular response to extracellular stimuli or insults. Methylation of histone proteins was demonstrated 50 years ago; however, the biological significance of each methylated residue and the integration between these histone markers are still under intensive investigation...
July 17, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28717830/a-review-of-drug-induced-liver-injury-databases
#15
REVIEW
Guangwen Luo, Yiting Shen, Lizhu Yang, Aiping Lu, Zheng Xiang
Drug-induced liver injuries have been a major focus of current research in drug development, and are also one of the major reasons for the failure and withdrawal of drugs in development. Drug-induced liver injuries have been systematically recorded in many public databases, which have become valuable resources in this field. In this study, we provide an overview of these databases, including the liver injury-specific databases LiverTox, LTKB, Open TG-GATEs, LTMap and Hepatox, and the general databases, T3DB, DrugBank, DITOP, DART, CTD and HSDB...
July 17, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28717648/response-detection-of-castrate-resistant-prostate-cancer-to-clinically-utilised-and-novel-treatments-by-monitoring-phospholipid-metabolism
#16
Tim A D Smith, Su M Phyu, Kholoud S Alzyoud, Chih-Chung Tseng
Androgen receptor (AR) activation is the primary driving factor in prostate cancer which is initially responsive to castration but then becomes resistant (castration-resistant prostate cancer (CRPC)). CRPC cells still retain the functioning AR which can be targeted by other therapies. A recent promising development is the use of inhibitors (Epi-1) of protein-protein interaction to inhibit AR-activated signalling. Translating novel therapies into the clinic requires sensitive early response indicators. Here potential response markers are explored...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28717424/low-active-loading-of-cargo-into-engineered-extracellular-vesicles-results-in-inefficient-mirna-mimic-delivery
#17
Dhruvitkumar S Sutaria, Jinmai Jiang, Ola A Elgamal, Steven M Pomeroy, Mohamed Badawi, Xiaohua Zhu, Ryan Pavlovicz, Ana Clara P Azevedo-Pouly, Jeffrey Chalmers, Chenglong Li, Mitch A Phelps, Thomas D Schmittgen
Extracellular vesicles (EVs) hold great potential as novel systems for nucleic acid delivery due to their natural composition. Our goal was to load EVs with microRNA that are synthesized by the cells that produce the EVs. HEK293T cells were engineered to produce EVs expressing a lysosomal associated membrane, Lamp2a fusion protein. The gene encoding pre-miR-199a was inserted into an artificial intron of the Lamp2a fusion protein. The TAT peptide/HIV-1 transactivation response (TAR) RNA interacting peptide was exploited to enhance the EV loading of the pre-miR-199a containing a modified TAR RNA loop...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28717337/effect-of-surface-modification-on-the-in-vitro-protein-adsorption-and-cell-cytotoxicity-of-vinorelbine-nanoparticles
#18
Nandhakumar Sathyamoorthy, Dhanaraju Dasaratha Magharla, Sundar Devendaran Vankayalu
CONTEXT: Nanocarriers possessing long-circulating abilities could take advantage of the pathophysiology of tumor vasculature to achieve spatial placement. To attain such qualities, the drug carriers should possess suitable physicochemical properties such as size and surface hydrophilicity. AIM: The aim of this study was to prepare poly(ε-caprolactone) nanoparticles (NPs) loaded with vinorelbine bitartrate (VB) and to modify its steric properties using polyethylene glycol and poloxamer...
April 2017: Journal of Pharmacy & Bioallied Sciences
https://www.readbyqxmd.com/read/28717247/characterization-of-hiv-1-integrase-interaction-with-human-ku70-protein-and-initial-implications-for-drug-targeting
#19
Andrey N Anisenko, Ekaterina S Knyazhanskaya, Artur O Zalevsky, Julia Yu Agapkina, Aleksander I Sizov, Timofey S Zatsepin, Marina B Gottikh
Human Ku70/Ku80 protein is known to influence HIV-1 replication. One of the possible reasons may be the protection of integrase from proteasomal degradation by Ku70 subunit. We demonstrated that recombinant HIV-1 integrase and Ku70 form a stable complex, while no interaction of Ku70 with integrase from prototype foamy virus was observed. By analyzing protein subdomains we determined two binding sites in the structure of both Ku70 and integrase: the 51-160 a.a. region of integrase interacts with residues 251-438 of Ku70, whereas Ku70 N-terminal domain (1-250 a...
July 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716999/improving-recognition-of-anxiety-and-depression-in-rheumatoid-arthritis-a-qualitative-study-in-a-community-clinic
#20
Annabelle Machin, Samantha Hider, Nicky Dale, Carolyn Chew-Graham
BACKGROUND: Comorbid anxiety and depression are common in patients with rheumatoid arthritis (RA) but are often under-recognised and treated, contributing to worse outcomes. National Institute for Health and Care Excellence (NICE) recommends that patients with RA should be offered a holistic annual review, including an assessment of mood. AIM: To explore patients' perspectives of anxiety and depression in RA and preferences for disclosure and management of mood problems...
July 17, 2017: British Journal of General Practice: the Journal of the Royal College of General Practitioners
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