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https://www.readbyqxmd.com/read/28822839/decreased-surface-expression-of-the-%C3%AE-subunit-of-the-gabaa-receptor-contributes-to-reduced-tonic-inhibition-in-dentate-granule-cells-in-a-mouse-model-of-fragile-x-syndrome
#1
Nianhui Zhang, Zechun Peng, Xiaoping Tong, A Kerstin Lindemeyer, Yliana Cetina, Christine S Huang, Richard W Olsen, Thomas S Otis, Carolyn R Houser
While numerous changes in the GABA system have been identified in models of Fragile X Syndrome (FXS), alterations in subunits of the GABAA receptors (GABAARs) that mediate tonic inhibition are particularly intriguing. Considering the key role of tonic inhibition in controlling neuronal excitability, reduced tonic inhibition could contribute to FXS-associated disorders such as hyperactivity, hypersensitivity, and increased seizure susceptibility. The current study has focused on the expression and function of the δ subunit of the GABAAR, a major subunit involved in tonic inhibition, in granule cells of the dentate gyrus in the Fmr1 knockout (KO) mouse model of FXS...
August 16, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28822650/progressive-and-reversible-conduction-disease-with-checkpoint-inhibitors
#2
Neeti Reddy, Rohit Moudgil, Juan C Lopez-Mattei, Kaveh Karimzad, Elie N Mouhayar, Neeta Somaiah, Anthony P Conley, Shreyaskumar Patel, Dana E Giza, Cezar Iliescu
Novel antineoplastic therapies are focused on harnessing our own immune system to fight cancer. To that end, cytotoxic T-lymphocyte-associated antigen 4 and programmed death ligand 1 are 2 coinhibitory signals that play central roles in decreasing T-cell response and represent a class of medications termed "checkpoint inhibitors." We present an unusual case of progressive conduction abnormalities induced by checkpoint inhibitors. Prompt medical intervention resulted in full recovery. Despite the anticancer efficacy, the newer antineoplastic agents pose a significant and often life-threatening risk of cardiotoxicity...
June 8, 2017: Canadian Journal of Cardiology
https://www.readbyqxmd.com/read/28822287/blue-light-induced-free-radicals-from-riboflavin-in-degradation-of-crystal-violet-by-microbial-viability-evaluation
#3
Ji-Yuan Liang, Jeu-Ming P Yuann, Zong-Jhe Hsie, Shiuh-Tsuen Huang, Chiing-Chang Chen
Crystal violet (CV) is applied in daily use mainly as a commercial dye and antimicrobial agent. Waste water containing CV may affect aquatic ecosystems. Riboflavin, also known as vitamin B2, is non-toxic and an essential vitamin required for the functions of the human body. Riboflavin is photosensitive to UV and visible light in terms of generating reactive oxygen species. This study investigated the potential application of blue light on riboflavin, so as to come up with an effective way of degrading CV during its treatment...
August 12, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28822104/comparison-of-the-toxic-effects-of-quinolinic-acid-and-3-nitropropionic-acid-in-c-elegans-involvement-of-the-skn-1-pathway
#4
Ilan Kotlar, Aline Colonnello, María Fernanda Aguilera-González, Daiana Silva Avila, María Eduarda de Lima, Rodolfo García-Contreras, Alma Ortíz-Plata, Félix Alexandre Antunes Soares, Michael Aschner, Abel Santamaría
The tryptophan metabolite, quinolinic acid (QUIN), and the mitochondrial toxin 3-nitropropionic acid (3-NP) are two important tools for toxicological research commonly used in neurotoxic models of excitotoxicity, oxidative stress, energy depletion, and neuronal cell death in mammals. However, their toxic properties have yet to be explored in the nematode Caenorhabditis elegans (C. elegans) for the establishment of novel, simpler, complementary, alternative, and predictive neurotoxic model of mammalian neurotoxicity...
August 18, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28822012/mtor-co-targeting-strategies-for-head-and-neck-cancer-therapy
#5
Zhiyong Wang, Juan Callejas Valera, Xuefeng Zhao, Qianming Chen, J Silvio Gutkind
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. There is an urgent need to develop effective therapeutic approaches to prevent and treat HNSCC. Recent deep sequencing of the HNSCC genomic landscape revealed a multiplicity and diversity of genetic alterations in this malignancy. Although a large variety of specific molecules were found altered in each individual tumor, they all participate in only a handful of driver signaling pathways. Among them, the PI3K/mTOR pathway is the most frequently activated, which plays a central role in cancer initiation and progression...
August 18, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28821875/convenient-and-effective-icgylation-of-magnetic-nanoparticles-for-biomedical-applications
#6
Hye Sun Park, Jongwoo Kim, Mi Young Cho, Hyunseung Lee, Sang Hwan Nam, Yung Doug Suh, Kwan Soo Hong
Nanoprobes used for biomedical applications usually require surface modifications with amphiphilic surfactants or inorganic coating materials to enhance their biocompatibility. We proposed a facile synthetic approach for the phase transfer of hydrophobic magnetic nanoparticles by the direct adherence of fluorescent probes, without any chemical modifications, for use as a magnetic resonance (MR)/near-infrared (NIR) fluorescence bimodal imaging contrast agent. Indocyanine green (ICG) was used not only as an optical component for NIR imaging, but also as a surfactant for phase transfer with no superfluous moiety: we therefore called the process "ICGylation"...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821646/location-of-the-mesopontine-neurons-responsible-for-maintanance-of-anesthetic-loss-of-consciousness
#7
Anne Minert, Shai-Lee Yatziv, Marshall Devor
The transition from wakefulness to general anesthesia is widely attributed to suppressive actions of anesthetic molecules distributed by the systemic circulation to the cerebral cortex (for amnesia and loss-of-consciousness) and to the spinal cord (for atonia and antinociception). An alternative hypothesis proposes that anesthetics act on one or more brainstem or diencephalic nuclei, with suppression of cortex and spinal cord mediated by dedicated axonal pathways. We previously documented induction of an anesthesia-like state in rats by microinjection of small amounts of GABAA-R agonists into an upper brainstem region named the mesopontine tegmental anesthesia area(MPTA)...
August 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28821610/a-screen-for-kinase-inhibitors-identifies-antimicrobial-imidazopyridine-aminofurazans-as-specific-inhibitors-of-the-listeria-monocytogenes-pasta-kinase-prka
#8
Adam J Schaenzer, Nathan Wlodarchak, David H Drewry, William J Zuercher, Warren E Rose, Rob Striker, John-Demian Sauer
Bacterial signaling systems such as protein kinases and quorum sensing have become increasingly attractive targets for the development of novel antimicrobial agents in a time of rising antibiotic resistance. The family of bacterial Penicillin-binding-protein And Serine/Threonine kinase-Associated (PASTA) kinases is of particular interest due to the role of these kinases in regulating resistance to β-lactam antibiotics. As such, small-molecule kinase inhibitors that target PASTA kinases may prove beneficial as treatments adjunctive to β-lactam therapy...
August 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821555/p53-non-genotoxic-activation-and-mtorc1-inhibition-lead-to-effective-combination-for-neuroblastoma-therapy
#9
Myrthala Moreno-Smith, Anna Lakoma, Zaowen Chen, Ling Tao, Kathleen A Scorsone, Linda Schild, Kevin Aviles-Padilla, Rana Nikzad, Yankai Zhang, Rikhia Chakraborty, Jan J Molenaar, Sanjeev Vasudevan, Vivien Sheehan, Eugene S Kim, Silke Paust, Jason M Shohet, Eveline Barbieri
mTORC1 inhibitors are promising agents for neuroblastoma therapy, however they have shown limited clinical activity as monotherapy, thus rational drug combinations need to be explored to improve efficacy. Importantly, neuroblastoma maintains both an active p53 and an aberrant mTOR signaling. <br /><br />Experimental Design: Using an orthotopic xenograft model and modulating p53 levels, we investigated the anti-tumor effects of the mTORC1 inhibitor temsirolimus in neuroblastoma expressing normal, decreased, or mutant p53, both as single agent and in combination with first and second generation MDM2 inhibitors to reactivate p53...
August 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28821255/the-whole-genomic-analysis-of-orf-virus-strain-hn3-12-isolated-from-henan-province-central-china
#10
Huiqin Chen, Wei Li, Zhenzhan Kuang, Daxiang Chen, Xiaoqing Liao, Ming Li, Shuhong Luo, Wenbo Hao
BACKGROUND: The Orf virus (ORFV) is the causative agent of orf, a globally-occurring, acute, pustular, contagious disease affecting sheep, goats and humans with a worldwide distribution. Currently, the genomic analysis of four ORFV strains from the Fujian province in southern China and a NA1/11 strain isolated from the Jilin province in northeast China have been reported. However, little is known about the genomic information of ORFV strains from central China. RESULTS: From a recent outbreak in a sheep herd in the Henan province of central China, a novel ORFV strain (HN3/12) was isolated and cultured in ovine fetal turbinate (OFTu) cells...
August 18, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28821159/inhibition-of-dna-pk-enhances-chemosensitivity-of-b-cell-precursor-acute-lymphoblastic-leukemia-cells-to-doxorubicin
#11
Fatemeh Alikarami, Majid Safa, Mohammad Faranoush, Parisa Hayat, Ahmad Kazemi
DNA damage repair pathways greatly affect the response to genotoxic drugs in cancer cells, so inhibition of such pathways could be a potentially useful strategy to enhance chemosensitivity. DNA-dependent protein kinase (DNA-PK) plays a crucial role in the repair of DNA double-strand breaks (DSBs) that are probably one of the most detrimental types of DNA damage. It has been shown that DNA-PK is highly expressed in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cells. Less well appreciated was the effect of DNA-PK inhibition on sensitivity of BCP-ALL cells to DNA-damaging agents...
August 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28820497/anesthetic-agents-of-plant-origin-a-review-of-phytochemicals-with-anesthetic-activity
#12
REVIEW
Hironori Tsuchiya
The majority of currently used anesthetic agents are derived from or associated with natural products, especially plants, as evidenced by cocaine that was isolated from coca (Erythroxylum coca, Erythroxylaceae) and became a prototype of modern local anesthetics and by thymol and eugenol contained in thyme (Thymus vulgaris, Lamiaceae) and clove (Syzygium aromaticum, Myrtaceae), respectively, both of which are structurally and mechanistically similar to intravenous phenolic anesthetics. This paper reviews different classes of phytochemicals with the anesthetic activity and their characteristic molecular structures that could be lead compounds for anesthetics and anesthesia-related drugs...
August 18, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28820469/a-third-generation-glucose-biosensor-based-on-cellobiose-dehydrogenase-immobilized-on-a-glassy-carbon-electrode-decorated-with-electrodeposited-gold-nanoparticles-characterization-and-application-in-human-saliva
#13
Paolo Bollella, Lo Gorton, Roland Ludwig, Riccarda Antiochia
Efficient direct electron transfer (DET) between a cellobiose dehydrogenase mutant from Corynascus thermophilus (CtCDH C291Y) and a novel glassy carbon (GC)-modified electrode, obtained by direct electrodeposition of gold nanoparticles (AuNPs) was realized. The electrode was further modified with a mixed self-assembled monolayer of 4-aminothiophenol (4-APh) and 4-mercaptobenzoic acid (4-MBA), by using glutaraldehyde (GA) as cross-linking agent. The CtCDH C291Y/GA/4-APh,4-MBA/AuNPs/GC platform showed an apparent heterogeneous electron transfer rate constant (ks) of 19...
August 18, 2017: Sensors
https://www.readbyqxmd.com/read/28820428/pharmacokinetic-analysis-of-an-oral-multicomponent-joint-dietary-supplement-phycox-%C3%A2-in-dogs
#14
Stephanie E Martinez, Ryan Lillico, Ted M Lakowski, Steven A Martinez, Neal M Davies
Despite the lack of safety, efficacy and pharmacokinetic (PK) studies, multicomponent dietary supplements (nutraceuticals) have become increasingly popular as primary or adjunct therapies for clinical osteoarthritis in veterinary medicine. Phycox(®) is a line of multicomponent joint support supplements marketed for joint health in dogs and horses. Many of the active constituents are recognized anti-inflammatory and antioxidant agents. Due to a lack of PK studies in the literature for the product, a pilot PK study of select constituents in Phycox(®) was performed in healthy dogs...
August 18, 2017: Pharmaceutics
https://www.readbyqxmd.com/read/28820387/infectious-polymorphic-toxins-delivered-by-outer-membrane-exchange-discriminate-kin-in-myxobacteria
#15
Christopher N Vassallo, Pengbo Cao, Austin Conklin, Hayley Finkelstein, Christopher S Hayes, Daniel Wall
Myxobacteria are known for complex social behaviors including outer membrane exchange (OME), in which cells exchange large amounts of outer membrane lipids and proteins upon contact. The TraA cell surface receptor selects OME partners based on a variable domain. However, traA polymorphism alone is not sufficient to precisely discriminate kin. Here, we report a novel family of OME-delivered toxins that promote kin discrimination of OME partners. These SitA lipoprotein toxins are polymorphic and widespread in myxobacteria...
August 18, 2017: ELife
https://www.readbyqxmd.com/read/28820000/novel-combination-strategies-for-enhancing-efficacy-of-immune-checkpoint-inhibitors-in-the-treatment-of-metastatic-solid-malignancies
#16
Michael J Flynn, James M G Larkin
Immune-checkpoint inhibitor (ICPI) drugs, which include antibodies against CTLA-4, PD-1 and PD-L1, have been shown to induce durable complete responses in a proportion of patients with particular efficacy demonstrated in both the first line and refractory setting in advanced NSCLC and melanoma. However, these drugs remain effective only in a minority of unselected patients. Areas covered: This review will focus on mechanisms of resistance to ICPI and underline the importance of identification of novel predictive markers of responsiveness...
August 18, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28819994/the-mechanistic-antitumor-study-of-myricanol-5-fluorobenzyloxy-ether-in-human-leukemic-cell-hl-60
#17
Guan-Hai Dai, Chen-Jie Fan, Ze-Ming Ren, Xuan Chen, Ye-Ling Tong, Zhen-Hua Li, Xiao-Jing Nie, Ke-Qun Chai
AIM: The aim of the study was to explore the growth inhibitory effect of myricanol 5-fluorobenzyloxy ether (5FEM) and the underlying mechanism in human leukemic cells HL-60. MATERIALS & METHODS: 5FEM was obtained by chemical modification of myricanol with fluorobenzyloxy ether at the OH(5) position. The cytotoxicity, cell apoptosis, cell cycle and the expression of key apoptosis-related genes in HL-60 were evaluated. RESULTS & CONCLUSION: 5FEM can significantly inhibited growth of HL-60 cells, increased the G2/M population and upregulated the expression of Bax, Fas, FasL, caspase-9 and p21 and downregulated that of Bcl-2 and survivin...
August 18, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28819719/activity-of-cabazitaxel-in-patients-with-metastatic-castration-resistant-prostate-cancer-after-treatment-with-single-or-dual-regimens-of-novel-androgen-receptor-targeting-agents
#18
Yukari Bando, Nobuyuki Hinata, Tomoaki Terakawa, Junya Furukawa, Ken-Ichi Harada, Yuzo Nakano, Masato Fujisawa
The purpose of this study was to evaluate the efficacy of cabazitaxel for patients with metastatic castration-resistant prostate cancer (mCRPC) after sequential therapy with docetaxel (DTX) and single or dual regimens of novel androgen receptor-axis-targeted (ARAT) agents. We retrospectively reviewed 84 consecutive patients treated with cabazitaxel at Kobe University Hospital and related hospitals from September 2014 to September 2016. The association of each prognostic parameter with progression-free survival (PFS) was evaluated, including the sequence of therapy...
August 17, 2017: Medical Oncology
https://www.readbyqxmd.com/read/28819707/metastatic-melanoma-prognostic-factors-and-survival-in-patients-with-brain-metastases
#19
E Frinton, D Tong, J Tan, G Read, V Kumar, S Kennedy, C Lim, R E Board
Brain metastases from malignant melanoma carry a poor prognosis. Novel systemic agents have improved overall survival (OS), but the value of whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) remains uncertain. The melanoma-specific graded prognostic assessment (msGPA) provides useful prognostic information, but the relevance to the modern-day population has not been validated. Since 2011, 53 patients received treatment for brain metastases from malignant melanoma at the Rosemere Cancer Centre medical oncology clinic...
August 17, 2017: Journal of Neuro-oncology
https://www.readbyqxmd.com/read/28819666/ph-responsive-prodrug-nanoparticles-based-on-a-sodium-alginate-derivative-for-selective-co-release-of-doxorubicin-and-curcumin-into-tumor-cells
#20
Cheng Gao, Fan Tang, Guiyi Gong, Jianxiang Zhang, Maggie P M Hoi, Simon M Y Lee, Ruibing Wang
In order to realize a combination of chemotherapy and selective drug release into tumor cells, novel pH-sensitive prodrugnanoparticles were designed and prepared via the self-assembly of a synthetic amphiphilic macromolecular prodrug for the selective co-delivery of doxorubicin (Dox) and curcumin (Cur). Dox was covalently conjugated to the oxidized sodium alginate through a Schiff base reaction to produce an amphiphilic macromolecular prodrug, and the prodrug was subsequently self-assembled into nanoparticles (Dox-NPs) in an aqueous solution, which were responsive to the acidic environment in tumor cells...
August 18, 2017: Nanoscale
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