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https://www.readbyqxmd.com/read/29783201/n-4-18-f-fluorobenzyl-cholylglycine-a-novel-tracer-for-pet-of-enterohepatic-circulation-of-bile-acids-radiosynthesis-and-proof-of-concept-studies-in-rats
#1
Kim Frisch, Damion H R Stimson, Taracad Venkatachalam, Gregory K Pierens, Susanne Keiding, David Reutens, Rajiv Bhalla
INTRODUCTION: Enterohepatic circulation (EHC) of conjugated bile acids is an important physiological process crucial for regulation of intracellular concentrations of bile acids and their function as detergents and signal carriers. Only few bile acid-derived imaging agents have been synthesized and hitherto none have been evaluated for studies of EHC. We hypothesized that N-(4-[18 F]fluorobenzyl)cholylglycine ([18 F]FBCGly), a novel fluorine-18 labeled derivative of endogenous cholylglycine, would be a suitable tracer for PET of the EHC of conjugated bile acids, and we report here a radiosynthesis of [18 F]FBCGly and a proof-of-concept study by PET/MR in rats...
May 4, 2018: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/29783148/comparative-study-of-six-sequential-spectrophotometric-methods-for-quantification-and-separation-of-ribavirin-sofosbuvir-and-daclatasvir-an-application-on-laboratory-prepared-mixture-pharmaceutical-preparations-spiked-human-urine-spiked-human-plasma-and-dissolution
#2
Wafaa S Hassan, Manal S Elmasry, Heba M Elsayed, Dalia W Zidan
In accordance with International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines, six novel, simple and precise sequential spectrophotometric methods were developed and validated for the simultaneous analysis of Ribavirin (RIB), Sofosbuvir (SOF), and Daclatasvir (DAC) in their mixture without prior separation steps. These drugs are described as co-administered for treatment of Hepatitis C virus (HCV). HCV is the cause of hepatitis C and some cancers such as liver cancer (hepatocellular carcinoma) and lymphomas in humans...
May 18, 2018: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/29782984/design-and-development-of-novel-hyaluronate-modified-nanoparticles-for-combo-delivery-of-curcumin-and-alendronate-fabrication-characterization-and-cellular-and-molecular-evidence-of-enhanced-bone-regeneration
#3
Jinlei Dong, Hnin Ei Thu, Mohammed A S Abourehab, Zahid Hussain
Osteoporosis is a medical condition of fragile bones with an increased susceptibility to bone fracture. Despite having availability of a wide range of pharmacological agents, prevalence of this metabolic disorder is continuously escalating. Owing to excellent biomedical achievements of nanomedicines in the last few decades, we aimed combo delivery of bone anti-resorptive agent, alendronate (ALN), and bone density enhancing drug, curcumin (CUR), in the form of polymeric nanoparticles. To further optimize the therapeutic efficacy, the prepared ALN/CUR nanoparticles were decorated with hyaluronic acid which is a well-documented biomacromolecule having exceptional bone regenerating potential...
May 18, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29782976/ldiscu-is-a-2fe-2s-scaffold-protein-which-interacts-with-ldiscs-and-its-expression-is-modulated-by-fe-s-proteins-in-leishmania-donovani
#4
Krishn Pratap Singh, Shadab Anwar, Amir Zaidi, Kuljit Singh, Pradeep Das, Samudrala Gourinath, Vahab Ali
The pathogenicity of protozoan parasites is frequently attributed to their ability to circumvent the deleterious effects of ROS and Fe-S clusters are among their susceptible targets with paramount importance for parasite survival. The biogenesis of Fe-S clusters is orchestrated by ISC system; the sulfur donor IscS and scaffold protein IscU being its core components. However, among protozoan parasites including Leishmania, no information is available regarding biochemical aspect of IscU, its interaction partners and regulation...
May 18, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29782972/stat3-and-apoptosis-challenges-in-cancer
#5
REVIEW
Nazanin Fathi, Golnaz Rashdi, Simin Sharifi
Several studies have processed conceivable evidence for the vital role of Signal Transducer and Activator of Transcription 3 (STAT3) in cancer transformation and carcinogenesis. Therefore, one of the important factors in formation of cancer is STAT3 and for design of novel anticancer drugs is a suitable target. On the other hand, apoptosis pathway has a critical role in the cancers pathogenesis. Generally, increasing developments have been existed to expression, production, phosphorylation or activation of STAT3 in the effective or responsible cells of most of the cancers...
May 18, 2018: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/29782944/a-comprehensive-review-on-contact-lens-for-ophthalmic-drug-delivery
#6
REVIEW
Jiawen Xu, Yingyan Xue, Gaoyong Hu, Tianyu Lin, Jingxin Gou, Tian Yin, Haibing He, Yu Zhang, Xing Tang
With the prevalence of electronic devices and an aging population, the number of people affected with eye disease is increasing year by year. In spite of a large number of eye drops on the market, most of them do not perform sufficiently, due to rapid clearance mechanisms and ocular barriers. To enhance drug delivery to the eye, a number of novel formulations for ocular diseases have been investigated over recent decades, aiming to increase drug retention and permeation while also allowing for sustained drug release over prolonged periods...
May 18, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29782889/development-of-robust-genotype-1a-hepatitis-c-replicons-harboring-adaptive-mutations-for-facilitating-the-antiviral-drug-discovery-and-study-of-virus-replication
#7
Hui-Mei Lin, Pei-Shan Wu, Han-Shu Hu, Wan-Chun Chang, Ren-Huang Wu, Jia-Ni Tian, Jyh-Haur Chern, Andrew Yueh
The hepatitis C virus (HCV) subgenomic replicon is a valuable tool for studying virus replication and HCV drug development. Despite the fact that HCV genotype 1a (HCV1a) is the most prevalent genotype in the United States, few HCV1a reporter replicon constructs have been reported, and their replication capacities are not as efficient as those of HCV1b or 2a, especially in transient expression. In this study, we selected efficient HCV1a replicons and characterized the novel adaptive mutations derived from stable HCV1a (strain H77) replicon cells after G418 selection...
May 18, 2018: Journal of Virological Methods
https://www.readbyqxmd.com/read/29782872/oxyfadichalcone-c-inhibits-melanoma-a375-cell-proliferation-and-metastasis-via-suppressing-pi3k-akt-and-mapk-erk-pathways
#8
Xiaolin Peng, Zhengming Wang, Yang Liu, Xin Peng, Yao Liu, Shan Zhu, Zhe Zhang, Yuling Qiu, Meihua Jin, Ran Wang, Qingying Zhang, Dexin Kong
AIMS: Melanoma remains to be one of the most incurable cancers. Discovery of novel antitumor agent for melanoma therapy is expected. We recently isolated Oxyfadichalcone C from Oxytropis falcate and investigated the anti-proliferative and anti-metastatic activity on human melanoma A375 cells in vitro. MAIN METHODS: Cell viability was determined using MTT assay and soft agar cloning formation assay. The effect of Oxyfadichalcone C on cell cycle distribution and apoptosis were analyzed by flow cytometry...
May 18, 2018: Life Sciences
https://www.readbyqxmd.com/read/29782803/amphiphilic-hybrid-dendritic-linear-molecules-as-nanocarriers-for-shape-dependent-antitumor-drug-delivery
#9
Yifei Guo, Ting Wang, Shuang Zhao, Meihua Han, Zhengqi Dong, Xiangtao Wang, Yanhong Wang
Nanoparticles based on hybrid block copolymers had been expected as effective nanocarriers for hydrophobic drug delivery. Herein, the novel dendritic-linear molecules from OEG dendron conjugated with octadecylamine (G2-C18) was designed, synthesized and further applied as nanocarrier to prepare 10-hydroxycamptothecin (HCPT) nanoparticles via antisolvent precipitation method. It seemed that the feed weight ratio of HCPT vs. G2-C18 not only affected the drug-loading content of nanoparticles, but also influenced the morphology of HCPT nanoparticles, the morphology of HCPT nanoparticles was changed from nanosphere (NSs) to nanorod (NRs) with increasing the feed weight ratio...
May 21, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29782545/rosmarinic-acid-is-a-novel-inhibitor-for-hepatitis-b-virus-replication-targeting-viral-epsilon-rna-polymerase-interaction
#10
Yuta Tsukamoto, Sotaro Ikeda, Koji Uwai, Riho Taguchi, Kazuaki Chayama, Takemasa Sakaguchi, Ryo Narita, Wan-Ling Yao, Fumihiko Takeuchi, Yukie Otakaki, Koichi Watashi, Takaji Wakita, Hiroki Kato, Takashi Fujita
Current therapeutics for hepatitis B virus (HBV) patients such as nucleoside analogs (NAs) are effective; however, new antiviral drugs against HBV are still desired. Since the interaction between the epsilon (ε) sequence of HBV pregenomic RNA and viral polymerase (Pol) is a key step in the HBV replication cycle, we aimed to identify small compounds for its inhibition, and established a pull-down assay system for the detection of ε-RNA-binding-Pol. Screening showed that 5 out of 3,965 compounds inhibited ε-Pol binding, and we identified rosmarinic acid, which exhibited specificity, as a potential antiviral agent...
2018: PloS One
https://www.readbyqxmd.com/read/29782496/development-of-a-toolkit-for-piggybac-mediated-integrative-transfection-of-the-human-filarial-parasite-brugia-malayi
#11
Canhui Liu, Amruta S Mhashilkar, Johan Chabanon, Shulin Xu, Sara Lustigman, John H Adams, Thomas R Unnasch
BACKGROUND: The human filarial parasites cause diseases that are among the most important causes of morbidity in the developing world. The elimination programs targeting these infections rely on a limited number of drugs, making the identification of new chemotherapeutic agents a high priority. The study of these parasites has lagged due to the lack of reverse genetic methods. METHODOLOGY/PRINCIPAL FINDINGS: We report a novel co-culture method that results in developmentally competent infective larvae of one of the human filarial parasites (Brugia malayi) and describe a method to efficiently transfect the larval stages of this parasite...
May 21, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29782355/inhibition-of-vascular-endothelial-cell-leak-following-escherichia-coli-attachment-in-an-experimental-model-of-sepsis
#12
Tony M McHale, Carolina D Garciarena, Robert P Fagan, Stephen G J Smith, Ignacio Martin-Loches, Gerard F Curley, Fidelma Fitzpatrick, Steve W Kerrigan
OBJECTIVES: The vascular endothelium is a major target of sepsis-induced events, and endothelial activation accounts for much of the pathology of sepsis. Urinary tract infections and pneumonia caused by Escherichia coli are among of the most common infections causing sepsis in both community and hospital settings. Currently, there are no approved drugs on the market to treat the underlying pathophysiology of sepsis. The aim of this study is to elucidate the molecular mechanism by which E...
May 18, 2018: Critical Care Medicine
https://www.readbyqxmd.com/read/29782261/-chronic-kidney-disease-as-basis-of-high-thrombotic-and-bleeding-risk-in-patients-with-atrial-fibrillation-place-of-oral-anticoagulants
#13
A G Obrezan, A Y Zemchenkov
Chronic kidney disease (CKD) aggravates course of practically all diseases by worsening outcomes and hindering adequate treatment. Specificities of renal excretion of various drugs, changes of parameters of their pharmacokinetics and pharmacodynamics, nephrotoxic effects of drugs, tactics of drug therapy in conditions of CKD, terminal stage of kidney failure and dialysis are in the focus of attention of internists. To a greatest degree difficulties of drug therapy in CKD and associated clinical states refer to the group of anticoagulants...
April 2018: Kardiologiia
https://www.readbyqxmd.com/read/29782051/the-novel-sodium-channel-modulator-gs-458967-gs967-is-an-effective-treatment-in-a-mouse-model-of-scn8a-encephalopathy
#14
Erin M Baker, Christopher H Thompson, Nicole A Hawkins, Jacy L Wagnon, Eric R Wengert, Manoj K Patel, Alfred L George, Miriam H Meisler, Jennifer A Kearney
OBJECTIVE: De novo mutations of SCN8A, encoding the voltage-gated sodium channel NaV 1.6, have been associated with a severe infant onset epileptic encephalopathy. Individuals with SCN8A encephalopathy have a mean age of seizure onset of 4-5 months, with multiple seizure types that are often refractory to treatment with available drugs. Anecdotal reports suggest that high-dose phenytoin is effective for some patients, but there are associated adverse effects and potential for toxicity...
May 21, 2018: Epilepsia
https://www.readbyqxmd.com/read/29781803/tendency-of-k562-chronic-myeloid-leukemia-cells-towards-cell-reprogramming
#15
Açelya Yılmazer Aktuna
Cancer cell reprogramming is a potential tool to study cancer progression, disease pathology and drug sensitivity. Prior to performing cancer reprogramming studies, it is important to evaluate the stemness predisposition of cells that will be reprogrammed. Here, we performed a proof-of-concept study with chronic myeloid leukemia K562 cells in order to evaluate their tendency for cancer cell reprogramming. Expression of reprogramming factors, pluripotency markers and tumor-suppressor genes were analyzed at gene and protein level via real-time RT-PCR and flow cytometry...
May 21, 2018: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/29781380/finally-a-regimen-to-extend-human-life-expectancy
#16
James Larrick, Andrew R Mendelsohn
The US has the most expensive healthcare system worldwide. Yet measures of healthspan and life expectancy are well below the major industrialized nations. With the US population aged 65 and older projected to double by mid-century a healthcare crisis is looming. Within this context huge interest and investment has emerged in technologies and drugs to address aging with an expected benefit to healthspan. The thesis being that such basic interventions will reduce morbidity caused by many chronic diseases where biological age itself is the major risk factor...
May 21, 2018: Rejuvenation Research
https://www.readbyqxmd.com/read/29781349/recent-advances-in-targeting-protein-arginine-methyltransferase-enzymes-in-cancer-therapy
#17
Emily Smith, Wei Zhou, Polina Shindiapina, Said Sif, Chenglong Li, Robert A Baiocchi
Exploration in the field of epigenetics has revealed the diverse roles of the protein arginine methyltransferase (PRMT) family of proteins in multiple disease states. These findings have led to the development of specific inhibitors and discovery of several new classes of drugs with potential to treat both benign and malignant conditions. Areas covered: We provide an overview on the role of PRMT enzymes in healthy and malignant cells, highlighting the role of arginine methylation in specific pathways relevant to cancer pathogenesis...
May 21, 2018: Expert Opinion on Therapeutic Targets
https://www.readbyqxmd.com/read/29781332/a-novel-phenolic-propanediamine-moiety-based-lung-targeting-therapy-for-asthma
#18
Jianbo Li, Yang Yang, Didi Wan, Youmei Peng, Jinjie Zhang
Asthma is one of the most prevalent chronic inflammatory diseases of lung. Current asthma therapy using inhaled corticosteroid often results in undesired treatment outcome due to poor compliance and drugs' lack of tissue specificity. N,N,N'-trimethyl-N'-(2-hydroxyl-3-methyl-5-123 Iiodobenzyl)-1,3-propanediamine (HIPD), a phenolic propanediamine derivative, has been used as an imaging agent for localized pulmonary diseases. Inspired by this, N,N,N'-trimethyl-N'-(4-hydroxyl-benzyl)-1,3-propanediamine (TPD), a new HIPD analog, was proposed as a lung-targeting ligand and covalently conjugated to an anti-inflammatory compound Rhein for asthma therapy...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29781323/targeting-the-b-cell-receptor-pathway-a-review-of-current-and-future-therapies-for-non-hodgkin-s-lymphoma
#19
Thomas D Rodgers, Patrick M Reagan
The B-cell receptor (BCR) pathway is a crucial aspect of mature lymphocytes and is maintained in B-cell neoplasms. Many small module inhibitors targeting kinases within the BCR pathway are approved, with others in development, offering alternative treatment options to standard chemoimmunotherapy. Areas Covered: This review covers both approved inhibitors and investigational inhibitors of spleen tyrosine kinase (SYK), Bruton's tyrosine kinase (BTK), and phosphoinositide-3-kinase (PI3K) in the treatment of B-cell lymphomas...
May 20, 2018: Expert Opinion on Emerging Drugs
https://www.readbyqxmd.com/read/29781322/the-impact-of-chronic-kidney-disease-on-medication-choice-and-pharmacologic-management-in-patients-with-heart-failure
#20
Syed Raza Shah, David E Winchester
In the past few years, medical community, including doctors, have become increasingly aware of the fact that chronic kidney disease (CK) and heart failure (HF) have common risk factors which impacts one another in terms of choice of therapy. Areas covered: Management of these two diseases has been a challenge for physicians. The treatment goals for HF patients in CK are very important. They serve as the end-point in using a specific treatment for management and treatment of CK patients hence, decreasing mortality rates...
May 21, 2018: Expert Review of Clinical Pharmacology
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