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https://www.readbyqxmd.com/read/28734226/inhibition-of-prb-pathway-differentially-modulates-apoptosis-in-esophageal-cancer-cells
#1
Rossana C Soletti, Deborah Biasoli, Nathassya A L V Rodrigues, João M A Delou, Renata Maciel, Vera L A Chagas, Rodrigo A P Martins, Stevens K Rehen, Helena L Borges
Esophageal cancer is the sixth most common cause of cancer-related death worldwide. Current chemotherapy regimens include a combination of 5-fluorouracil (5-FU) and cisplatin, but more efficient therapy strategies are needed to increase 5-year survival. Alterations in the signaling pathway of the tumor suppressor gene Rb-1, which encodes a phosphoprotein (pRB) that negatively regulates the G1/S transition of the cell cycle, are present in 70% of all tumors, but its role in esophageal cancer is still unclear...
July 19, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28734205/identification-of-mycobacterium-tuberculosis-enoyl-acyl-carrier-protein-reductase-inhibitors-a-combined-in-silico-and-in-vitro-analysis
#2
Mohsin Y Lone, Mohd Athar, Vivek K Gupta, Prakash C Jha
Mycobacterium tuberculosis (Mtb), had developed evolutionary changes in its genome to adapt for survival and thereby generated multi-drug resistant strains. However, novel drug targets that remained unchanged for their biochemical role has impressed the research community to target such proteins. The comprehensive analysis of multiple protein targets has influenced us to make a consensus structural rule exploited by pharmacophore and other allied techniques from a large repository of protein structures. In this pursuit, we made a retrospective analysis of pharmacophores mapped from the tuberculosis structural proteome and identified unique patterns that can be employed for the novel molecules design...
July 14, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28732367/significantly-more-intense-pain-in-methadone-maintained-patients-who-are-addicted-to-nicotine
#3
Lian-Zhong Liu, Lin-Xiang Tan, Yan-Min Xu, Xue-Bing Liu, Wen-Cai Chen, Jun-Hong Zhu, Jin Lu, Bao-Liang Zhong
Pain and cigarette smoking are very common in heroin-dependent patients (HDPs) receiving methadone maintenance treatment (MMT) and both have substantial negative effects on HDPs' physical and mental health. Nevertheless, very few studies have assessed the relationship between the two in HDPs. This study examined the association between pain intensity and smoking in Chinese methadone-maintained HDPs. A total of 603 HDPs were consecutively recruited from three MMT clinics in Wuhan, China, and administered with a socio-demographic and drug use questionnaire, a smoking questionnaire concerning average number of cigarettes smoked daily and Heaviness of Smoking Index, and Zung's Self-rating Depression Scale...
July 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732359/resveratrol-inhibits-age-dependent-spontaneous-tumorigenesis-by-sirt1-mediated-post-translational-modulations-in-the-annual-fish-nothobranchius-guentheri
#4
Tingting Liu, Long Ma, Zhaodi Zheng, Fenglin Li, Shan Liu, Yingbo Xie, Guorong Li
Resveratrol, SIRT1 activator, inhibits carcinogenesis predominantly performed in transgenic animal models, orthotopic cancers of nude mice or different cancer cell lines, but its effects during process of spontaneous tumors using vertebrate models remain untested. Spontaneous liver neoplasm is an age-related disease and is inhibited by resveratrol in the annual fish Nothobranchius guentheri, which indicates that the fish can act as an excellent model to study spontaneous tumorigenesis. Totally, 175 fish were fed with resveratrol and another 175 fish for controls...
July 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732319/did-the-dependent-coverage-expansion-increase-risky-substance-use-among-young-adults
#5
Joshua Breslau, Hao Yu, Bing Han, Rosalie L Pacula, Rachel M Burns, Bradley D Stein
BACKGROUND: The dependent coverage expansion (DCE) enacted through the Affordable Care Act increased health insurance coverage among young adults. Increasing insurance coverage in this age group has the potential for unintended consequences on risky substance use. METHODS: Repeated cross-sectional surveys were used to compare change in substance use during the period the DCE was implemented in the 19-25year old target age group (Pre-DCE n=15,772, Post-DCE n=22,719) with contemporaneous change in a slightly older age group that was not targeted by the policy (Pre-DCE=19,851, Post-DCE n=28,157)...
July 14, 2017: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/28732254/going-down-the-tubes-impact-on-seizure-control-of-antiepileptic-medication-given-via-percutaneous-feeding-tubes
#6
REVIEW
Caryn Jory, Rohit Shankar, Katy Oak, Janina Oates, Mike Wilcock
BACKGROUND: Long-term feeding by percutaneous endoscopic gastrostomy tube (PEG) is uncommon but can present significant issues when both nutrition and medication have to be fed down the same tube. This is especially important in people with epilepsy where the dose and bioavailability of antiepileptic drugs are critical to maintain adequate seizure control. This group with long-term PEG tubes is particularly vulnerable and dependent on their carers to provide high standard of care. Indeed, approximately half of the people with long-term feeding tubes suffer from severe intellectual disability which requires careful coordination of all members of the multidisciplinary team...
July 18, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28731962/polymorphisms-in-cytochrome-p450-oxidoreductase-and-its-effect-on-drug-metabolism-and-efficacy
#7
Liang Gong, Cong-Min Zhang, Jin-Feng Lv, Hong-Hao Zhou, Lan Fan
Cytochrome P450 oxidoreductase (POR) has played a potential role in the metabolism of drugs and steroids by supplying electrons to microsomal cytochrome P450 (CYP) enzymes. More than 200 different POR mutations and polymorphisms causing more than 130 amino acid changes in the POR protein have been reported since 2004. A503V is a common amino acid sequence variant encoded by POR*28, whereas A287P and R457H are the most common disease-causing mutations in Europeans and Asians, respectively. Polymorphisms in the POR gene can affect POR activity, CYP-mediated drug metabolism activities, and the efficacy of several clinically used drugs...
July 20, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28731321/conjugation-dependent-interaction-of-folic-acid-with-folate-binding-protein
#8
Rachel Leah Merzel, Carolina Frey, Junjie Chen, Rachel Garn, Mallory A van Dongen, Casey A Dougherty, Ananda Kandaluru, Philip S Low, E Neil G Marsh, Mark M Banaszak Holl
Serum proteins play a critical role in the transport, uptake, and efficacy of targeted drug therapies, and here we investigate the interactions between folic acid-polymer conjugates and serum folate binding protein (FBP), the soluble form of the cellular membrane-bound folate receptor. We demonstrate that both choice of polymer and method of ligand conjugation affect the interactions between folic acid-polymer conjugates and serum FBP, resulting in changes in the folic acid-induced protein aggregation process...
July 21, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28731281/glycaemic-control-and-the-risk-of-hospitalisation-for-infection-in-patients-with-type-2-diabetes-hong-kong-diabetes-registry
#9
Andrea O Y Luk, Eric S H Lau, Kitty K T Cheung, Alice P Kong, Ronald C W Ma, Risa Ozaki, Francis C C Chow, Wing-Yee So, Juliana C N Chan
BACKGROUND: Infection occurs more commonly in diabetic compared to general population and is an under-recognised but important morbidity in patients with diabetes. We examined the impact of glycaemic control on hospitalisation for infection in a large prospective cohort of Chinese adults with type 2 diabetes. METHODS: Between July 1994 and June 2014, 22,846 patients with type 2 diabetes underwent detailed assessment of metabolic control and diabetes complications...
July 21, 2017: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/28731124/bmp7-mediates-the-anticancer-effect-of-honokiol-by-upregulating-p53-in-hct116-cells
#10
Rong-Xing Liu, Wen-Yan Ren, Yan Ma, Yun-Peng Liao, Han Wang, Jia-Hui Zhu, Hai-Tao Jiang, Ke Wu, Bai-Cheng He, Wen-Juan Sun
Colorectal cancer (CRC) is the second leading cause of cancer death. Hence, there is a great need to explore new efficacious drugs for the treatment of CRC. Honokiol (HNK), a natural product extracted from magnolia bark, processes various biological activities, including anticancer. In this study, we introduced cell viability assay, western blotting, real-time PCR and immunofluorescent staining to determine the anticancer effect of HNK, and the possible mechanism underlying this biological process. We found that HNK can inhibit the proliferation and induce apoptosis in HCT116 cells in a concentration- and time-dependent manner...
July 21, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28730969/the-battle-for-iron-between-humans-and-microbes
#11
Peggy L Carver
Iron is an essential micronutrient for bacteria, fungi, and humans; as such, each has evolved specialized iron uptake systems to acquire iron from the extracellular environment and a complex 'tug of war' has evolved between human hosts and pathogenic microorganisms in the battle for this vital nutrient. In humans, sequestration (hiding) of iron from invading pathogens is often successful; however, many pathogens have evolved mechanisms to circumvent this approach. Clinically, controversy continues whether iron overload or administration of iron results in an increased risk of infection...
July 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28730828/the-effect-of-hypertension-on-adult-hippocampal-neurogenesis-in-young-adult-spontaneously-hypertensive-rats-and-dahl-rats
#12
A Pistikova, H Brozka, M Bencze, D Radostova, K Vales, A Stuchlik
The dentate gyrus of the hippocampus is one of the few places in the brain where neurogenesis occurs in adulthood. Nowadays, an increasing number of children and young adults are affected by hypertension, one of the factors in the development of cerebrovascular diseases and age-related cognitive deficits. Since these cognitive deficits are often hippocampus-dependent, it is possible that hypertension exerts this effect via decreasing adult neurogenesis which has been shown to be essential for a range of cognitive tasks...
July 18, 2017: Physiological Research
https://www.readbyqxmd.com/read/28730718/impact-of-binding-mechanism-on-selective-inhibition-of-histone-deacetylase-isoforms
#13
Christian Meyners, Franz-Josef Meyer-Almes
Industrialized drug screening campaigns usually deliver hundreds of compounds that are active on a particular pharmaceutical target. In light of high failure rates of drug candidates due to unforeseeable off-target toxicity, the early identification of the most promising compounds with high potential for target selectivity is an urgent need to improve the quality of lead compounds and lower attrition rates in the drug development process. The reliable prediction of the selectivity of active substances for a target protein is a challenging task...
June 14, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28730694/pharmacodynamics-pharmacokinetics-and-safety-of-multiple-ascending-doses-of-the-novel-dual-glucose-dependent-insulinotropic-polypeptide-glucagon-like-peptide-1-agonist-rg7697-in-people-with-type-2-diabetes-mellitus
#14
Christophe Schmitt, Agnès Portron, Shirin Jadidi, Neena Sarkar, Richard DiMarchi
AIMS: To investigate the pharmacodynamics, pharmacokinetics and safety of multiple ascending doses of RG7697, a dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 agonist, in patients with type 2 diabetes mellitus (T2D). METHODS: A total of 56 patients with T2D received once-daily subcutaneous (s.c.) injection of RG7697 (0.25-2.5 mg) or placebo for 14 days in a randomized, double-blind, dose-escalation study. Adverse events (AEs), vital signs, ECGs and routine laboratory variables were intensively monitored...
July 20, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28730479/analysis-of-drug-resistance-using-kinome-wide-functional-screens
#15
Katherine R Singleton, Keith T Earley, Lynn E Heasley
The clinical success of tyrosine kinase inhibitors specific for BCR-ABL-, EGFR-, ALK-, and ROS1-driven cancers continues to spur the quest to match specific oncogene-defined tumor types with an appropriate molecularly targeted therapy. Unfortunately, responses to these agents are not durable with intrinsic or acquired resistance limiting benefit. Additionally, efforts to identify the appropriate targets of new drugs have focused on nonfunctional assays such as large-scale sequencing for somatic mutations or analysis of gene copy number...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28730281/pk-pd-studies-on-non-selective-pde-inhibitors-in-rats-using-camp-as-a-marker-of-pharmacological-response
#16
Artur Świerczek, Elżbieta Wyska, Sebastian Baś, Marta Woyciechowska, Jacek Mlynarski
In recent years, phosphodiesterase (PDE) inhibitors have been frequently tested for the treatment of experimental inflammatory and immune disorders. It is suggested that anti-inflammatory properties of PDE inhibitors are related to their ability to increase cAMP levels. The aim of this study was to verify the hypothesis that cAMP may be a useful marker of pharmacological response following administration of non-selective PDE inhibitors (pentoxifylline and (±)-lisofylline) to endotoxemic rats. Male Wistar rats were administered LPS (1 mg kg(-1), i...
July 20, 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28729934/effect-of-lamotrigine-on-seizure-development-in-a-rat-pentylenetetrazole-kindling-model
#17
Yishu Chen, Xiaokuo He, Qianqian Sun, Ziyan Fang, Liemin Zhou
INTRODUCTION: Epileptogenesis is a process of seizure development. Lamotrigine is a novel antiepileptic drug which is also used for antiepileptogenic research. Kindling models are recommended as potentially useful tools for antiepileptogenic treatment discovery. However, previous studies demonstrated that the antiepileptogenic effect of lamotrigine is controversial in the electrical kindling model. Chemical kindling such as with pentylenetetrazole is another kindling model. The aims of this study were to examine whether lamotrigine could prevent the development of seizure in pentylenetetrazole kindling rats...
July 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28729837/optimization-and-in-vivo-profiling-of-a-refined-rat-model-of-walker-256-breast-cancer-cell-induced-bone-pain-using-behavioral-radiological-histological-immunohistochemical-and-pharmacological-methods
#18
Priyank Shenoy, Andy Kuo, Irina Vetter, Maree T Smith
In the majority of patients with advanced breast cancer, there is metastatic spread to bones resulting in pain. Clinically available drug treatments for alleviation of breast cancer-induced bone pain (BCIBP) often produce inadequate pain relief due to dose-limiting side-effects. A major impediment to the discovery of novel well-tolerated analgesic agents for the relief of pain due to bony metastases is the fact that most cancer-induced bone pain models in rodents relied on the systemic injection of cancer cells, causing widespread formation of cancer metastases and poor general animal health...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28729713/tunable-uptake-release-mechanism-of-protein-microgel-particles-in-biomimicking-environment
#19
A Pepe, P Podesva, G Simone
Microgels are intra-molecular crosslinked macromolecules that can be used as vehicles to deliver and release drugs at the point-of-need in the patient's body. Here, gelatin microgels were formed from microfluidics droplets, stabilised by aldehydes and frozen into a spheroidal shape. Microgel morphology and response to external stimuli were characterised. It was found that the behaviour of the spheroidal microgels was sensitive to both pH and ionic strength and that the distribution of charges into the microgels affected the behaviour of swelling and uptake...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729619/effects-of-4-1h-quinolinone-derivative-a-novel-non-nucleotide-allosteric-purinergic-p2y-2-agonist-on-cardiomyocytes-in-neonatal-rats
#20
Kensuke Sakuma, Hideyuki Nakagawa, Tatsuo Oikawa, Masakuni Noda, Shota Ikeda
Purinergic P2Y 2 receptors, G-protein coupled receptors that primarily couple with Gαq/11-proteins, are activated equipotently by adenosine-5'-triphosphate (ATP) and uridine-5'-triphosphate. Evidence suggests that P2Y 2 agonists make potential drug candidates for the treatment of cardiovascular diseases. However, selective non-nucleotide, small-molecule P2Y 2 agonists have yet to be developed. In this report, we discuss Compound 89, a novel non-nucleotide allosteric P2Y 2 agonist that was active in signal transduction and gene induction, and in our in vitro cardiac hypertrophy model...
July 20, 2017: Scientific Reports
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