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https://www.readbyqxmd.com/read/28214087/targeting-the-pd-1-pd-l1-axis-in-non-small-cell-lung-cancer
#1
REVIEW
Rajiv Kumar, Dearbhaile Collins, Saoirse Dolly, Fiona McDonald, Mary E R O'Brien, Timothy A Yap
The last decade has witnessed rapid advances in the discovery and development of immune checkpoint inhibitors in cancer medicine, particularly drugs targeting programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC). The proven antitumor efficacy coupled with low rates of drug-related toxicities observed, albeit idiosyncratic, with these novel immunotherapeutics have led to the registration of multiple PD-1 and PD-L1 inhibitors, such as nivolumab, pembrolizumab, and atezolizumab, in second-line advanced NSCLC, whereas durvalumab and avelumab are in late-phase clinical testing...
December 23, 2016: Current Problems in Cancer
https://www.readbyqxmd.com/read/28213944/separation-of-hydroxynorketamine-stereoisomers-using-capillary-electrophoresis-with-sulfated-%C3%AE-cyclodextrin-and-highly-sulfated-%C3%AE-cyclodextrin
#2
Friederike A Sandbaumhüter, Regula Theurillat, Wolfgang Thormann
The racemic N-methyl-d-aspartate receptor antagonist ketamine is used in anesthesia, analgesia and the treatment of depressive disorders. It is known that interactions of hydroxylated norketamine metabolites and 5,6-dehydronorketamine (DHNK) with the α7 -nicotinic acetylcholine receptor and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor are responsible for the antidepressive effects. Ketamine and its first metabolite norketamine are not active on these receptors. As stereoselectivity plays a role in ketamine metabolism, a cationic capillary electrophoresis based method capable of resolving and analyzing the stereoisomers of four hydroxylated norketamine metabolites, norketamine and DHNK was developed...
February 18, 2017: Electrophoresis
https://www.readbyqxmd.com/read/28213881/poor-adherence-to-p2y12-antagonists-increased-cardiovascular-risks-in-chinese-pci-treated-patients
#3
Yang Sun, Chenze Li, Lina Zhang, Dong Hu, Xudong Zhang, Ting Yu, Min Tao, Dao Wen Wang, Xiaoqing Shen
Low adherence to secondary prevention medications (ATM) of patients after acute coronary syndrome (ACS) is associated with poor clinical outcomes. However, literature provides limited data on assessment of ATM and risks associated with poor in Chinese patients with ACS. In the current work, ATM was assessed in consecutively recruited patients with ACS in Tongji Hospital from November 5, 2013 to December 31, 2014. A total of 2126 patients were classified under low adherence (proportion of days covered (PDC) C< 50%) and high adherence (PDC>50%) groups based on their performance after discharge...
February 17, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28213801/efficacy-of-a-neoadjuvant-gonadotropin-releasing-hormone-antagonist-plus-low-dose-estramustine-phosphate-in-high-risk-prostate-cancer-a-single-center-study
#4
Kazuhisa Hagiwara, Takuya Koie, Chikara Ohyama, Hayato Yamamoto, Atsushi Imai, Shingo Hatakeyama, Takahiro Yoneyama, Yasuhiro Hashimoto, Yuki Tobisawa, Tohru Yoneyama
PURPOSE: The optimal treatment for high-risk prostate cancer (Pca) remains to be established. We previously reported favorable biochemical recurrence-free survival (BRFS) for high-risk Pca patients treated with neoadjuvant therapy comprising a luteinizing hormone-releasing hormone agonist plus low-dose estramustine (LHRH + EMP) prior to radical prostatectomy (RP). In the present study, we evaluated the efficacy of neoadjuvant therapy comprising a gonadotropin-releasing hormone antagonist plus low-dose estramustine phosphate (GnRH + EMP) in patients with high-risk Pca...
February 17, 2017: International Urology and Nephrology
https://www.readbyqxmd.com/read/28213660/evidence-of-an-unidentified-extracellular-heat-stable-factor-produced-by-lysobacter-enzymogenes-oh11-that-degrade-fusarium-graminearum-ph1-hyphae
#5
Benard Omondi Odhiambo, Gaoge Xu, Guoliang Qian, Fengquan Liu
Lysobacter enzymogenes OH11 produces heat-stable antifungal factor (HSAF) and lytic enzymes possessing antifungal activity. This study bio-prospected for other potential antifungal factors besides those above. The cells and extracellular metabolites of L. enzymogenes OH11 and the mutants ΔchiA, ΔchiB, ΔchiC, Δclp, Δpks, and ΔpilA were examined for antifungal activity against Fusarium graminearum PH1, the causal agent of Fusarium head blight (FHB). Results evidenced that OH11 produces an unidentified extracellular heat-stable degrading metabolite (HSDM) that exhibit degrading activity on F...
February 17, 2017: Current Microbiology
https://www.readbyqxmd.com/read/28213512/27-hydroxycholesterol-impairs-neuronal-glucose-uptake-through-an-irap-glut4-system-dysregulation
#6
Muhammad-Al-Mustafa Ismail, Laura Mateos, Silvia Maioli, Paula Merino-Serrais, Zeina Ali, Maria Lodeiro, Eric Westman, Eran Leitersdorf, Balázs Gulyás, Lars Olof-Wahlund, Bengt Winblad, Irina Savitcheva, Ingemar Björkhem, Angel Cedazo-Mínguez
Hypercholesterolemia is associated with cognitively deteriorated states. Here, we show that excess 27-hydroxycholesterol (27-OH), a cholesterol metabolite passing from the circulation into the brain, reduced in vivo brain glucose uptake, GLUT4 expression, and spatial memory. Furthermore, patients exhibiting higher 27-OH levels had reduced (18)F-fluorodeoxyglucose uptake. This interplay between 27-OH and glucose uptake revealed the engagement of the insulin-regulated aminopeptidase (IRAP). 27-OH increased the levels and activity of IRAP, countered the IRAP antagonist angiotensin IV (AngIV)-mediated glucose uptake, and enhanced the levels of the AngIV-degrading enzyme aminopeptidase N (AP-N)...
February 17, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28213497/mitochondrial-damage-elicits-a-tcdd-inducible-poly-adp-ribose-polymerase-mediated-antiviral-response
#7
Tatsuya Kozaki, Jun Komano, Daiki Kanbayashi, Michihiro Takahama, Takuma Misawa, Takashi Satoh, Osamu Takeuchi, Taro Kawai, Shigeomi Shimizu, Yoshiharu Matsuura, Shizuo Akira, Tatsuya Saitoh
The innate immune system senses RNA viruses by pattern recognition receptors (PRRs) and protects the host from virus infection. PRRs mediate the production of immune modulatory factors and direct the elimination of RNA viruses. Here, we show a unique PRR that mediates antiviral response. Tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly(ADP ribose) polymerase (TIPARP), a Cysteine3 Histidine (CCCH)-type zinc finger-containing protein, binds to Sindbis virus (SINV) RNA via its zinc finger domain and recruits an exosome to induce viral RNA degradation...
February 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28213318/efficacy-of-fungal-and-bacterial-antagonists-for-controlling-growth-fum1-gene-expression-and-fumonisin-b1-production-by-fusarium-verticillioides-on-maize-cobs-of-different-ripening-stages
#8
Nik Iskandar Putra Samsudin, Alicia Rodriguez, Angel Medina, Naresh Magan
This study was carried out to examine the efficacy of two biocontrol agents (Clonostachys rosea 016, BCA1; Gram-negative bacterium, BCA5) for control of FUM1 gene expression and fumonisin B1 (FB1) production by F. verticillioides FV1 on maize cobs of different ripening stages: R3, Milk (0.985 aw); R4, Dough (0.976 aw); R5, Dent (0.958 aw). Initially, temporal studies on FUM1 gene expression and FB1 production were performed on maize kernels for up to 14days. This revealed that day 10 was optimum for both parameters, and was used in the biocontrol studies...
February 9, 2017: International Journal of Food Microbiology
https://www.readbyqxmd.com/read/28213131/nerp-2-regulates-gastric-acid-secretion-and-gastric-emptying-via-the-orexin-pathway
#9
Cherl Namkoong, Koji Toshinai, T M Zaved Waise, Hideyuki Sakoda, Kazuki Sasaki, Yoichi Ueta, Min-Seon Kim, Naoto Minamino, Masamitsu Nakazato
Neuroendocrine regulatory peptide (NERP)-2 is derived from a distinct region of VGF, a neurosecretory protein originally identified as a product of a nerve growth factor-responsive gene in rat PC12 cells. Colocalization of NERP-2 with orexin-A in the lateral hypothalamus increases orexin-A-induced feeding and energy expenditure in both rats and mice. Orexigenic and anorectic peptides in the hypothalamus modulate gastric function. In this study, we investigated the effect of NERP-2 on gastric function in rats...
February 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28213105/anxiolytic-and-antidepressant-like-effects-of-an-aqueous-extract-of-tanacetum-parthenium-l-schultz-bip-asteraceae-in-mice
#10
Jorge Cárdenas, Valeria Reyes-Pérez, María Dolores Hernández-Navarro, Ana María Dorantes-Barrón, Salvador Almazán, Rosa Estrada-Reyes
AIM: Tanacetum parthenium L. Schultz-Bip (Asteraceae) is widely used worldwide in traditional medicine for the treatment of convulsions and culture-bound syndromes such as susto (fear). The aim of this work was to evaluate the anxiolytic- and antidepressant-like effects of an aqueous extract of T. parthenium in behavioral paradigms in mice. The effects of T. parthenium were compared with those produced by anxiolytic and antidepressant drugs. We carried out the chemical characterization of the main constituents of T...
February 14, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28213070/selective-a2a-receptors-blockade-reduces-degeneration-of-substantia-nigra-dopamine-neurons-in-a-rotenone-induced-rat-model-of-parkinson-s-disease-a-histological-study
#11
Ahmed M Fathalla, Amira M Soliman, Ahmed A Moustafa
Parkinson's disease (PD) is characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Adenosine is a neuromodulator that inhibit the release of dopamine via a disinhibitory mechanism. In this study, we investigated the neuroprotective effect of 8-cyclopentyl-1,3-dipropylxanthine and ZM241385 (respectively, A1 and A2A receptors antagonists), on nigrostriatal dopamine neurons degradation reduction in a rotenone-induced PD model using histopathological and immunohistochemical methods...
February 14, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28213064/juvenile-treatment-with-a-novel-mglur2-agonist-mglur3-antagonist-compound-ly395756-reverses-learning-deficits-and-cognitive-flexibility-impairments-in-adults-in-a-neurodevelopmental-model-of-schizophrenia
#12
Meng-Lin Li, Yelena Gulchina, Sarah A Monaco, Bo Xing, Brielle R Ferguson, Yan-Chun Li, Feng Li, Xi-Quan Hu, Wen-Jun Gao
Schizophrenia (SCZ) is a neurodevelopmental psychiatric disorder, in which cognitive function becomes disrupted at early stages of the disease. Although the mechanisms underlying cognitive impairments remain unclear, N-methyl-D-aspartate receptors (NMDAR) hypofunctioning in the prefrontal cortex (PFC) has been implicated. Moreover, cognitive symptoms in SCZ are usually unresponsive to treatment with current antipsychotics and by onset, disruption of the dopamine system, not NMDAR hypofunctioning, dominates the symptoms...
February 14, 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/28212943/effects-of-acute-dopaminergic-and-serotonergic-manipulations-in-the-aci-paradigm-depend-on-the-basal-valence-of-cognitive-judgement-bias-in-rats
#13
Joanna Golebiowska, Rafal Rygula
Recent findings have revealed that pharmacological enhancement of dopaminergic (DA) function by the administration of a DA precursor (dihydroxy-L-phenylalanine; L-DOPA), but not the selective serotonin reuptake inhibitor (SSRI) citalopram, increases an optimism bias in humans. To test whether dopamine might play a similar role in non-human animals, in the present study, we evaluated the effects of acute injections of L-DOPA, the D2 receptor antagonist haloperidol, and the SSRI escitalopram on cognitive judgement bias of rats in the ambiguous-cue interpretation (ACI) paradigm...
February 14, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28212942/activation-of-type-4-dopaminergic-receptors-in-the-prelimbic-area-of-medial-prefrontal-cortex-is-necessary-for-the-expression-of-innate-fear-behavior
#14
Macarena D Vergara, Victor N Keller, José A Fuentealba, Katia Gysling
The prelimbic area (PL) of the medial Prefrontal cortex (mPFC) is involved in the acquisition and expression of conditioned and innate fear. Both types of fear share several neuronal pathways. It has been documented that dopamine (DA) plays an important role in the regulation of aversive memories in the mPFC. The exposure to an aversive stimulus, such as the smell of a predator odor or the exposure to footshock stress is accompanied by an increase in mPFC DA release. Evidence suggests that the type 4 dopaminergic receptor (D4R) is the molecular target through which DA modulates fear expression...
February 14, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28212941/injections-of-the-of-the-%C3%AE-1-adrenoceptor-antagonist-prazosin-into-the-median-raphe-nucleus-increase-food-intake-and-fos-expression-in-orexin-neurons-of-free-feeding-rats
#15
Eduardo Simão da Silva, Rafael Appel Flores, Anderson Savaris Ribas, Ana Paula Taschetto, Moacir Serralvo Faria, Leandro Bueno Lima, Martin Metzger, José Donato, Marta Aparecida Paschoalini
Previously, we showed that the blockade of α1-adrenoreceptors in the median raphe nucleus (MnR) increased food intake in free-feeding rats, indicating that adrenergic mechanisms in the MnR participate in the regulation of food intake. However, the impact of such a pharmacological manipulation on other neural circuits related to food intake remains unknown. In the current study, we sought to identify forebrain regions which are responsive to α1-adrenergic receptor blockade and presumably involved in the modulation of the feeding response...
February 14, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28212543/metabotropic-glutamate-receptors-as-a-new-therapeutic-target-for-malignant-gliomas
#16
REVIEW
Mery Stefani Leivas Pereira, Fábio Klamt, Chairini Cássia Thomé, Paulo Valdeci Worm, Diogo Losch de Oliveira
Metabotropic glutamate receptors (mGluR) are predominantly involved in maintenance of cellular homeostasis of central nervous system. However, evidences have suggested other roles of mGluR in human tumors. Aberrant mGluR signaling has been shown to participate in transformation and maintenance of various cancer types, including malignant brain tumors. This review intends to summarize recent findings regarding the involvement of mGluR-mediated intracellular signaling pathways in progression, aggressiveness, and recurrence of malignant gliomas, mainly glioblastomas (GBM), highlighting the potential therapeutic applications of mGluR ligands...
February 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212466/withdrawn-propranolol-for-migraine-prophylaxis
#17
REVIEW
Klaus Linde, Karin Rossnagel
BACKGROUND: Propranolol is one of the most commonly prescribed drugs for migraine prophylaxis. OBJECTIVES: We aimed to determine whether there is evidence that propranolol is more effective than placebo and as effective as other drugs for the interval (prophylactic) treatment of patients with migraine. SEARCH METHODS: Potentially eligible studies were identified by searching MEDLINE/PubMed (1966 to May 2003) and the Cochrane Central Register of Controlled Trials (Issue 2, 2003), and by screening bibliographies of reviews and identified articles...
February 17, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28212464/oxytocin-reduces-ethanol-self-administration-in-mice
#18
Courtney E King, William C Griffin, Lauryn N Luderman, Malcolm M Kates, Jacqueline F McGinty, Howard C Becker
BACKGROUND: Excessive ethanol consumption remains an important health concern and effective treatments are lacking. The central oxytocin system has emerged as a potentially important therapeutic target for alcohol and drug addiction. These studies tested the hypothesis that oxytocin reduces ethanol consumption. METHODS: Male C57BL/6J mice were given access to ethanol (20% v/v) using a model of binge-like drinking ("drinking-in-the-dark") that also included the use of lickometer circuits to evaluate the temporal pattern of intake as well as 2-bottle choice drinking in the home cage...
February 17, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28212264/correlated-emg-oscillations-between-antagonists-during-cocontraction-in-men
#19
Yasuhide Yoshitake, Hiroaki Kanehisa, Minoru Shinohara
PURPOSE: The purpose of this study was to determine the modulation of common low-frequency oscillations in pools of motor units across antagonistic muscles because of the difference in the activation level of pools of spinal motor neurons and the presence of neuromuscular fatigue during intended cocontraction. METHODS: Ten healthy young men (21.8 ± 1.5 yr) performed intended steady cocontractions of elbow flexors and extensors at maximal and a submaximal (10% of maximal EMG) effort...
March 2017: Medicine and Science in Sports and Exercise
https://www.readbyqxmd.com/read/28212183/cxcl12-cxcr4-signaling-contributes-to-the-pathogenesis-of-opioid-tolerance-a-translational-study
#20
Chih-Peng Lin, Kai-Hsiang Kang, Huang-Ju Tu, Ming-Yueh Wu, Tzu-Hung Lin, Houng-Chi Liou, Wei-Zen Sun, Wen-Mei Fu
BACKGROUND: Long-term opioid therapy for chronic pain may lead to analgesic tolerance, especially when administered intrathecally, thus preventing adequate pain relief. Discovering drug targets to treat opioid tolerance using a mechanism-based approach targeting opioid-induced neuroinflammation provides new therapeutic opportunities. In this study, we provide translational evidence that CXCL12/CXCR4 signaling contributes to the pathogenesis of opioid tolerance. METHODS: The CXCL12 levels in the cerebrospinal fluid of opioid-tolerant patients were compared with those of opioid-naive subjects...
March 2017: Anesthesia and Analgesia
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