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https://www.readbyqxmd.com/read/28437839/semicarbazide-sensitive-amine-oxidase-vascular-adhesion-protein-1-inhibition-reduces-lipopolysaccharide-induced-neuroinflammation
#1
Serena Becchi, Alberto Buson, Jonathan Foot, Wolfgang Jarolimek, Bernard W Balleine
BACKGROUND AND PURPOSE: Neuroinflammation is initiated by a variety of stimuli including infections, sepsis, neurodegenerative diseases or traumatic brain injury and if not adequately controlled can lead to various degrees of neuronal damage and behavioural impairment. A critical event in the initial steps of inflammation is neutrophil extravasation. Semicarbazide sensitive amine oxidase (SSAO, also known as vascular adhesion protein 1 or VAP-1) regulates neutrophil adhesion and extravasation...
April 24, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28437766/cyanobacterial-lectins-characteristics-and-their-role-as-antiviral-agents
#2
REVIEW
Ram Sarup Singh, Amandeep Kaur Walia, Jasvirinder Singh Khattar, Davinder Pal Singh, John F Kennedy
Lectins are ubiquitous proteins/glycoproteins of non-immune origin that bind reversibly to carbohydrates in non-covalent and highly specific manner. These lectin-glycan interactions could be exploited for establishment of novel therapeutics, targeting the adherence stage of viruses and thus helpful in eliminating wide spread viral infections. Here the review focuses on the haemagglutination activity, carbohydrate specificity and characteristics of cyanobacterial lectins. Cyanobacterial lectins exhibiting high specificity towards mannose or complex glycans have potential role as anti-viral agents...
April 21, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28436480/dihydromyricetin-induces-apoptosis-and-reverses-drug-resistance-in-ovarian-cancer-cells-by-p53-mediated-downregulation-of-survivin
#3
Yingqi Xu, Shengpeng Wang, Hon Fai Chan, Huaiwu Lu, Zhongqiu Lin, Chengwei He, Meiwan Chen
Ovarian cancer is one of the leading causes of death in gynecological malignancies, and the resistance to chemotherapeutic agents remains a major challenge to successful ovarian cancer chemotherapy. Dihydromyricetin (DHM), a natural flavonoid derived from Ampeopsis Grossdentata, has been widely applied in food industry and medicine for a long time. However, little is known about the effects of DHM on ovarian cancer and the underlying mechanisms. In this study, we demonstrated that DHM could effectively inhibit the proliferation of ovarian cancer cells and induce cell apoptosis...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28436198/effects-of-selenium-on-apoptosis-and-abnormal-amino-acid-metabolism-induced-by-excess-fatty-acid-in-isolated-rat-hepatocytes
#4
Zhigang Zhang, Siyu Li, Huijie Jiang, Biying Liu, Zhanjun Lv, Changming Guo, Haili Zhang
SCOPE: Increased serum free fatty acid (FFA) occurs in subjects with non-alcoholic fatty liver disease (NAFLD) and also triggers oxidative stress, apoptosis, and insulin resistance. Selenium (Se) is an antioxidant agent. However, the effect of Se on NAFLD or diabetes is still unclear. We investigated the effect of Se on apoptosis and abnormal amino acid metabolism initiated by excess FFA in isolated rat hepatocytes. METHODS AND RESULTS: Primary hepatocytes from rats were isolated and exposed to excessive FFA (0...
April 24, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28435891/detection-of-anaplasma-phagocytophilum-babesia-microti-borrelia-burgdorferi-borrelia-miyamotoi-and-powassan-virus-in-ticks-by-a-multiplex-real-time-reverse-transcription-pcr-assay
#5
Rafal Tokarz, Teresa Tagliafierro, D Moses Cucura, Ilia Rochlin, Stephen Sameroff, W Ian Lipkin
Ixodes scapularis ticks are implicated in transmission of Anaplasma phagocytophilum, Borrelia burgdorferi, Borrelia miyamotoi, Babesia microti, and Powassan virus. We describe the establishment and implementation of the first multiplex real-time PCR assay with the capability to simultaneously detect and differentiate all five pathogens in a single reaction. The application of this assay for analysis of ticks at sites in New York and Connecticut revealed a high prevalence of B. microti in ticks from Suffolk County, NY...
March 2017: MSphere
https://www.readbyqxmd.com/read/28435221/phenotypic-evaluation-and-in-silico-admet-properties-of-novel-arylimidamides-in-acute-mouse-models-of-trypanosoma-cruzi-infection
#6
Cristiane França da Silva, Denise da Gama Jaén Batista, Julianna Siciliano de Araújo, Edézio Ferreira Cunha-Junior, Chad E Stephens, Moloy Banerjee, Abdelbasset A Farahat, Senol Akay, Mary K Fisher, David W Boykin, Maria de Nazaré Correia Soeiro
Arylimidamides (AIAs), previously termed as reversed amidines, present a broad spectrum of activity against intracellular microorganisms. In the present study, three novel AIAs were evaluated in a mouse model of Trypanosoma cruzi infection, which is the causative agent of Chagas disease. The bis-AIAs DB1957, DB1959 and DB1890 were chosen based on a previous screening of their scaffolds that revealed a very promising trypanocidal effect at nanomolar range against both the bloodstream trypomastigotes (BTs) and the intracellular forms of the parasite...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28433626/thrombin-impairs-human-endometrial-endothelial-angiogenesis-implications-for-progestin-only-contraceptive-induced-abnormal-uterine-bleeding
#7
John P Shapiro, Ozlem Guzeloglu-Kayisli, Umit A Kayisli, Nihan Semerci, S Joseph Huang, Sefa Arlier, Kellie Larsen, Paolo Fadda, Frederick Schatz, Charles J Lockwood
OBJECTIVE: Progestin-only contraceptives induce abnormal uterine bleeding, accompanied by pro-thrombin leakage from dilated endometrial microvessels and increased thrombin generation by human endometrial stromal cell (HESC)-expressed tissue factor. Initial studies of the thrombin-treated HESC secretome identified elevated levels of cleaved chondroitin sulfate proteoglycan 4 (CSPG4), impairing pericyte-endothelial interactions. Thus, we investigated direct and CSPG4-mediated effects of thrombin in eliciting abnormal uterine bleeding by disrupting endometrial angiogenesis...
April 19, 2017: Contraception
https://www.readbyqxmd.com/read/28432778/cross-species-studies-of-cognition-relevant-to-drug-discovery-a-translational-approach
#8
REVIEW
T W Robbins
This Review advances the case that bidirectional, cross-species translation of findings from experimental animals to and from humans is an important strategy for drug discovery. Animal models of mental disorders require appropriate behavioural or cognitive outcome variables that can be generalized cross-species. One example is the treatment of impulsive behaviour in attention deficit hyperactivity disorder (ADHD) with stimulant drugs. Performance on the stop signal reaction task as an index of impulsivity is improved both in healthy human volunteers and in patients with adult ADHD by stimulant drugs and also by the selective noradrenergic reuptake blocker atomoxetine...
April 22, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28431781/clenbuterol-hydrochloride
#9
Abdulrahman A Al-Majed, Nasr Y Khalil, Ibraheem Khbrani, Hatem A Abdel-Aziz
Clenbuterol (Broncodil and trade) is a direct-acting sympathomimetic agent with mainly beta-adrenergic activity and a selective action on β2 receptors (a β2 agonist). It has properties similar to those of salbutamol. It is used as a bronchodilator in the management of reversible airways obstruction, as in asthma and in certain patients with chronic obstructive pulmonary disease. The uses, applications, and the synthetic pathways of this drug are outlined. Physical characteristics including: ionization constant, solubility, X-ray powder diffraction pattern, thermal methods of analysis, UV spectrum, IR spectrum, mass spectrum are all produced...
2017: Profiles of Drug Substances, Excipients, and related Methodology
https://www.readbyqxmd.com/read/28431490/new-challenges-in-therapeutic-vaccines-against-hiv-infection
#10
Lorna Leal, Constanza Lucero, Josep M Gatell, Teresa Gallart, Montserrat Plana, Felipe García
There is a growing interest in developing curative strategies for HIV infection. Therapeutic vaccines are one of the most promising approaches. We will review the current knowledge and the new challenges in this research field. Areas covered: PubMed and ClinicalTrial.gov databases were searched to review the progress and prospects for clinical development of immunotherapies aimed to cure HIV infection. Dendritic cells (DC)-based vaccines have yielded the best results in the field. However, major immune-virologic barriers may hamper current vaccine strategies...
April 21, 2017: Expert Review of Vaccines
https://www.readbyqxmd.com/read/28431353/discovery-of-potential-anticancer-multi-targeted-ligustrazine-based-cyclohexanone-and-oxime-analogs-overcoming-the-cancer-multidrug-resistance
#11
Gao-Feng Zha, Hua-Li Qin, Bahaa G M Youssif, Muhammad Wahab Amjad, Maria Abdul Ghafoor Raja, Ahmed H Abdelazeem, Syed Nasir Abbas Bukhari
The drug research and development nowadays is focusing on multi-target drugs. In the treatment of cancer, therapies using drugs inhibiting one numerous targets signify a novel viewpoint. In comparison with traditional therapy, multi-targeted drugs directly aim cell subpopulations which are involved in progression of tumor. The current study comprises the synthesis of 34 novel ligustrazine-containing α, β-unsaturated carbonyl-based compounds and oximes. The growth of 5 various cancer cell types was strongly inhibited by ligustrazine-containing oximes as revealed by biological evaluation...
April 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28431163/an-evaluation-of-the-human-relevance-of-the-lung-tumors-observed-in-female-mice-treated-with-permethrin-based-on-mode-of-action
#12
Tomoya Yamada, Miwa Kondo, Kaori Miyata, Keiko Ogata, Masahiko Kushida, Kayo Sumida, Satoshi Kawamura, Thomas G Osimitz, Brian G Lake, Samuel M Cohen
Permethrin increased the incidence of bronchiolo-alveolar adenomas in female mice but not male mice or female or male rats. Studies were conducted to determine whether permethrin has mitogenic activity in Club cells in mouse lung as the basis for the mode of action (MOA) for the lung adenoma induction. Several short term experiments focusing on time-course, dose-response, reversibility, sex difference, strain difference, and species difference were evaluated for Club cell proliferation and morphology. The findings demonstrated that permethrin slightly and continuously enhanced Club cell proliferation at tumor-associated dose levels in female mice, but did not increase proliferation in male mice or in female rats...
April 18, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28431161/engineering-a-high-affinity-peptide-binding-site-into-the-anti-cea-mab-m5a
#13
Cindy Zer, Kendra N Avery, Kassondra Meyer, Leah Goodstein, Krzysztof P Bzymek, Gagandeep Singh, John C Williams
We have previously identified a cyclic peptide called meditope which binds to the central cavity of the Fab portion of cetuximab and shown that this peptide binding site can be grafted, or 'meditope-enabled', onto trastuzumab. This peptide has been shown to act as a hitch for the non-covalent attachment of imaging agents to meditope-enabled antibodies. Herein, we explore the process of grafting this peptide binding site onto M5A, an anti-CEA antibody in clinical trials for cancer diagnostics. In order to explore the contributions of the amino acids, we sequentially introduced pairs of amino acid substitutions into the Fab and then we reverse-substituted key residues in the presence of the other substitutions...
April 19, 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/28429852/anti-inflammatory-and-retinal-protective-effects-of-capsaicin-on-ischemia-induced-injuries-through-the-release-of-endogenous-somatostatin
#14
Jun Wang, Wenke Tian, Shuaiwei Wang, Wenqiang Wei, Dongdong Wu, Honggang Wang, Li Wang, Ruisheng Yang, Ailing Ji, Yanzhang Li
The mechanisms regarding the retinal protective and anti-inflammatory effects of capsaicin (CAP) remain unclear. Somatostatin is contained in CAP-sensitive sensory neurons, including nerve terminals, from which it can be released by capsaicin. The present study provides a novel neurohumoral regulatory mechanism for CAP-induced-endogenous somatostatin in a retinal ischemic-reperfusion (I/R) mouse model. CAP (0.5 mg kg(-1) ) was injected subcutaneously 5 min after I/R. A selective somatostatin-depleting agent, cysteamine, was applied subcutaneously 4 hours before the experiment to examine the effects of endogenous somatostatin...
April 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28429809/successful-pegylation-of-hollow-encapsulin-nanoparticles-from-rhodococcus-erythropolis-n771-without-affecting-their-disassembly-and-reassembly-properties
#15
Seiichi Sonotaki, Taku Takami, Keiichi Noguchi, Masafumi Odaka, Masafumi Yohda, Yoshihiko Murakami
We developed a hollow PEGylated encapsulin nanoparticle from Rhodococcus erythropolis N771. The hollow engineered encapsulin nanoparticles with His-Tag and Lys residues on the surface were constructed by means of genetic recombination. The Lys residues on the particle surface were successfully PEGylated with a PEG derivative, methoxy-PEG-SCM. Consequently, we demonstrated that the hollow PEGylated engineered encapsulin nanoparticle could successfully disassemble or reassemble even after PEGylation in the presence or absence of a protein denaturing agent...
April 21, 2017: Biomaterials Science
https://www.readbyqxmd.com/read/28429198/managing-the-perioperative-patient-on-direct-oral-anticoagulants
#16
Jordan Leitch, Janet van Vlymen
PURPOSE: Patients are increasingly treated with direct oral anticoagulants (DOACs) for the prevention of stroke due to non-valvular atrial fibrillation and for the treatment of venous thromboembolism. When these patients present for urgent or emergent surgical procedures, they present a challenge to the anesthesiologist who must manage perioperative risk due to anticoagulation. The purpose of this module is to review the literature surrounding the perioperative management of DOACs. Timing, laboratory monitoring, and availability of reversal agents are important considerations to optimize patients being treated with DOACs who require emergent surgery...
April 20, 2017: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
https://www.readbyqxmd.com/read/28427845/development-of-a-micro-neutralization-assay-for-ebolaviruses-using-a-replication-competent-vesicular-stomatitis-hybrid-virus-and-a-quantitative-pcr-readout
#17
Stella S Lee, Kathryn Phy, Keith Peden, Li Sheng-Fowler
Development of vaccines against highly pathogenic viruses that could also be used as agents of bioterrorism is both a public health issue and a national security priority. Methods that can quantify neutralizing antibodies will likely be crucial in demonstrating vaccine effectiveness, as most licensed viral vaccines are effective due to their capacity to elicit neutralizing antibodies. Assays to determine whether antibodies are neutralizing traditionally involve infectious virus, and the assay most commonly used is the plaque-reduction neutralization test (PRNT)...
April 17, 2017: Vaccine
https://www.readbyqxmd.com/read/28427004/enzymatic-activity-of-the-cam-pde1-system-upon-addition-of-actinyl-ions
#18
Florian Brulfert, Samir Safi, Aurélie Jeanson, Harald Foerstendorf, Stephan Weiss, Catherine Berthomieu, Sandrine Sauge-Merle, Éric Simoni
The threat of a dirty bomb which could cause internal contamination has been of major concern for the past decades. Because of their high chemical toxicity and their presence in the nuclear fuel cycle, uranium and neptunium are two actinides of high interest. Calmodulin (CaM) which is a ubiquitous protein present in all eukaryotic cells and is involved in calcium-dependent signaling pathways has a known affinity for uranyl and neptunyl ions. The impact of the complexation of these actinides on the physiological response of the protein remains, however, largely unknown...
April 8, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28426260/the-effects-of-intermittent-use-of-the-sglt-2-inhibitor-dapagliflozin-in-overweight-patients-with-type-2-diabetes-in-japan-a-randomized-crossover-controlled-clinical-trial
#19
Kanako Kato, Kunihiro Suzuki, Chie Aoki, Masaaki Sagara, Takafumi Niitani, Sho Wakamatsu, Kazunori Yanagi, Yoshimasa Aso
BACKGROUND: This study examined the effects of short-term administration of the sodium glucose cotransporter 2 (SGLT-2) inhibitor, dapagliflozin, on visceral fat area (VFA) in Japanese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: In this randomized, crossover, controlled clinical trial, overweight patients with type 2 diabetes were randomized to treatment with 5 mg dapagliflozin for the first (n = 27) or second 12-week study period (n = 29). The parameters evaluated at baseline and after 12 and 24 weeks included blood pressure, hemoglobin A1c (HbA1c), body composition, VFA, and subcutaneous fat area (SFA)...
April 21, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28424738/protective-effects-of-li-fei-xiao-yan-prescription-on-lipopolysaccharide-induced-acute-lung-injury-via-inhibition-of-oxidative-stress-and-the-tlr4-nf-%C3%AE%C2%BAb-pathway
#20
Lie-Qiang Xu, Xiu-Ting Yu, Shu-Hua Gui, Jian-Hui Xie, Xiu-Fen Wang, Zu-Qing Su, Yu-Cui Li, Xiao-Ping Lai, Janis Ya-Xian Zhan, You-Liang Xie
Li-Fei-Xiao-Yan prescription (LFXY) has been clinically used in China to treat inflammatory and infectious diseases including inflammatory lung diseases. The present study was aimed at evaluating the potential therapeutic effects and potential mechanisms of LFXY in a murine model of lipopolysaccharide- (LPS-) induced acute lung injury (ALI). In this study, the mice were orally pretreated with LFXY or dexamethasone (positive drug) before the intratracheal instillation of LPS. Our data indicated that pretreatment with LFXY enhanced the survival rate of ALI mice, reversed pulmonary edema and permeability, improved LPS-induced lung histopathology impairment, suppressed the excessive inflammatory responses via decreasing the expression of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and chemokine (MIP-2) and inhibiting inflammatory cells migration, and repressed oxidative stress through the inhibition of MPO and MDA contents and the upregulation of antioxidants (SOD and GSH) activities...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
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