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https://www.readbyqxmd.com/read/28550816/designing-an-hcv-vaccine-a-unique-convergence-of-prevention-and-therapy
#1
REVIEW
Christopher M Walker
Direct acting antivirals can cure chronic hepatitis C virus (HCV) infection but whether they will reduce global liver disease burden is uncertain. Most chronic infections are undiagnosed and transmission has increased in recent years. The first trial of a preventive vaccine is now underway in humans at risk for HCV infection. It will test the novel hypothesis that T cell-mediated immunity alone can prevent persistent HCV infection. Another vaccine that elicits neutralizing antibodies is at an advanced stage of development...
May 24, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28550736/piperine-attenuates-uv-r-induced-cell-damage-in-human-keratinocytes-via-nf-kb-bax-bcl-2-pathway-an-application-for-photoprotection
#2
Ankit Verma, Hari N Kushwaha, Ajeet K Srivastava, Saumya Srivastava, Naseem Jamal, Kriti Srivastava, Ratan Singh Ray
Chronic ultraviolet radiation (UV-R) exposure causes skin disorders like erythema, edema, hyperpigmentation, photoaging and photocarcinogenesis. Recent research trends of researchers have focused more attention on the identification and use of photo stable natural agents with photoprotective properties. Piperine (PIP), as a plant alkaloid, is an important constituent present in black pepper (Piper nigrum), used widely in ayurvedic and other traditional medicines and has broad pharmacological properties. The study was planned to photoprotective efficacy of PIP in human keratinocyte (HaCaT) cell line...
May 19, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28550735/clarithromycin-inhibits-tnf-%C3%AE-induced-muc5ac-mucin-gene-expression-via-the-mkp-1-p38mapk-dependent-pathway
#3
Said Ahmad Shah, Hajime Ishinaga, Kazuhiko Takeuchi
Clarithromycin is a 14-membered macrolide antibiotic. Low-dose, long-term macrolide therapy is effective in patients with chronic airway diseases, such as diffuse panbronchitis, chronic bronchitis, and chronic sinusitis. However, the mechanism underlying this clinical efficacy remains unclear. The dual specificity phosphatase MKP-1 (MAPK phosphatase-1), also called DUSP (dual specificity phosphatase-1), was initially identified as an in vitro ERK-specific phosphatase, but depending on the cell type, it can also dephosphorylate other members of the MAPK family, such as p38 and JNK, and thus suppress downstream signaling of these kinases...
May 24, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28550731/xanthotoxin-suppresses-lps-induced-expression-of-inos-cox-2-tnf-%C3%AE-and-il-6-via-ap-1-nf-%C3%AE%C2%BAb-and-jak-stat-inactivation-in-raw-264-7-macrophages
#4
Seung-Bin Lee, Woo Seok Lee, Ji-Sun Shin, Dae Sik Jang, Kyung Tae Lee
Although xanthotoxin has been reported to possess skin-protective and anti-oxidative properties, its anti-inflammatory capacity has not been studied to date. Therefore, we investigated this role as well as the molecular mechanisms of xanthotoxin in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. Xanthotoxin inhibited production of nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor (TNF-α), and interleukin-6 (IL-6) by the LPS-induced macrophages in a concentration-dependent manner. It also suppressed the LPS-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression at the protein levels and iNOS, COX-2, TNF-α, and IL-6 at the mRNA levels...
May 24, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28550687/tanshinone-suppresses-arecoline-induced-epithelial-mesenchymal-transition-in-oral-submucous-fibrosis-by-epigenetically-reactivating-the-p53-pathway
#5
Lian Zheng, Zhen-Jie Guan, Wen-Ting Pan, Tian-Fang Du, Yu-Jia Zhai, Jia Guo
Oral submucous fibrosis (OSF) induced by the chewing of areca nut has been considered as a precancerous lesion with a higher probability of developing oral squamous cell carcinoma. Tanshinone (TSN) is the main component extracted from Salvia miltiorrhiza, a traditional Chinese medicine, which was found to have diverse pharmacological effects such as anti-inflammatory and anti-tumor effects. In current study, we aim to identify inhibitory effects and the underlying mechanism of Tanshinone on OSF progress. We found that treatment of TSN inhibited arecoline-mediated proliferation of primary human oral mucosal fibroblasts, and reversed the promotive effects of arecoline on EMT process...
May 21, 2017: Oncology Research
https://www.readbyqxmd.com/read/28550681/antibiotic-associated-manipulation-of-the-gut-microbiota-and-phenotypic-restoration-in-nod-mice
#6
James R Fahey, Bonnie L Lyons, Haiyan L Olekszak, Anthony J Mourino, Jeremy J Ratiu, Jeremy J Racine, Harold D Chapman, David V Serreze, Dina L Baker, N Ken Hendrix
Segmented filamentous bacterium (SFB) a gram-positive, anaerobic, and intestinal commensal organism directly influencesthe development of Th17 helper cells in the small intestine of mice. In NOD mice, SFB colonization interferes with the developmentof type 1 diabetes (T1D), a T-cell-mediated autoimmune disease, suggesting that SFB may influence Th17 cells to inhibit Th1populations associated with the anti-β-cell immune response. This effect is a serious concern for investigators who use NOD micefor diabetes research because the expected incidence of disease decreases markedly when they are colonized by SFB...
May 26, 2017: Comparative Medicine
https://www.readbyqxmd.com/read/28550663/-sensitivity-of-doxorubicin-resistant-osteosarcoma-cells-to-doxorubicin-regulated-by-long-non-coding-rna-nr_036444
#7
K P Zhu, C L Zhang
Objective: To investigate the mechanism of long non-coding RNA (LncRNA) NR_036444 mediated sensitivity of multidrug-resistant osteosarcoma to doxorubicin. Methods: LncRNA-mRNA combined microarray was used to screen the differential expressions of lncRNA and mRNA in doxorubicin-resistant MG63/DXR osteosarcoma cells and their paired doxorubicin-sensitive MG63 cells; qRT-PCR was used to check the consistency of microarray. LncRNA NR_036444 was over-expressed in MG63/DXR cells by lentrvirus. CCK-8 array was used to evaluate cell proliferation and the sensitivity of cells to doxorubicin; Flow cytometry was used to evaluate cell cycle and apoptosis...
April 23, 2017: Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology]
https://www.readbyqxmd.com/read/28550642/post-heroin-dose-tissue-distribution-of-6-monoacetylmorphine-6-mam-with-maldi-imaging
#8
Belin G Teklezgi, Annapurna Pamreddy, Sooraj Baijnath, Nirmala D Gopal, Tricia Naicker, Hendrik G Kruger, Thavendran Govender
Heroin is an illicit opioid drug which is commonly abused and leads to dependence and addiction. Heroin is considered a pro-drug and is rapidly converted to its major active metabolite 6-monoacetylmorphine (6-MAM) which mediates euphoria and reward through the stimulation of opioid receptors in the brain. The aim of this study was to investigate the distribution and localization of 6-MAM in the healthy Sprague Dawley rat brain following intraperitoneal (i.p) administration of heroin (10 mg/kg), using matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI), in combination with quantification via liquid chromatography mass spectrometry (LC-MS/MS)...
May 26, 2017: Journal of Molecular Histology
https://www.readbyqxmd.com/read/28550640/endogenous-tissue-factor-pathway-inhibitor-in-vascular-smooth-muscle-cells-inhibits-arterial-thrombosis
#9
Jichun Yang, Kaiyue Jin, Jiajun Xiao, Jing Ma, Duan Ma
Tissue factor pathway inhibitor (TFPI) is the main inhibitor of tissue factor-mediated coagulation. TFPI is expressed by endothelial and smooth muscle cells in the vasculature. Endothelium-derived TFPI has been reported to play a regulatory role in arterial thrombosis. However, the role of endogenous TFPI in vascular smooth muscle cells (VSMCs) in thrombosis and vascular disease development has yet to be elucidated. In this TFPI(Flox) mice crossbred with Sma-Cre mice were utilized to establish TFPI conditional knockout mice and to examine the effects of VSMC-directed TFPI deletion on development, hemostasis, and thrombosis...
May 27, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28550595/clinical-pharmacokinetics-and-pharmacodynamics-of-colistin
#10
REVIEW
Nicolas Grégoire, Vincent Aranzana-Climent, Sophie Magréault, Sandrine Marchand, William Couet
In this review, we provide an updated summary on colistin pharmacokinetics and pharmacodynamics. Colistin is an old molecule that is frequently used as last-line treatment for infections caused by multidrug-resistant Gram-negative bacteria. Colistin is a decapeptide administered either as a prodrug, colistin methanesulfonate (CMS), when used intravenously, or as colistin sulfate when used orally. Because colistin binds to laboratory materials, many experimental issues are raised and studies on colistin can be tricky...
May 26, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28550532/drug-induced-hsp90-inhibition-alleviates-pain-in-monoarthritic-rats-and-alters-the-expression-of-new-putative-pain-players-at-the-drg
#11
Diana Sofia Marques Nascimento, Catarina Soares Potes, Miguel Luz Soares, António Carlos Ferreira, Marzia Malcangio, José Manuel Castro-Lopes, Fani Lourença Moreira Neto
Purinergic receptors (P2XRs) have been widely associated with pain states mostly due to their involvement in neuron-glia communication. Interestingly, we have previously shown that satellite glial cells (SGC), surrounding dorsal root ganglia (DRG) neurons, become activated and proliferate during monoarthritis (MA) in the rat. Here, we demonstrate that P2X7R expression increases in ipsilateral DRG after 1 week of disease, while P2X3R immunoreactivity decreases. We have also reported a significant induction of the activating transcriptional factor 3 (ATF3) in MA...
May 26, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28550524/cop9-signalosome-subunit-pfcsne-regulates-secondary-metabolism-and-conidial-formation-in-pestalotiopsis-fici
#12
Yanjing Zheng, Xiuna Wang, Xiaoling Zhang, Wei Li, Gang Liu, Shihua Wang, Xiufeng Yan, Huixi Zou, Wen-Bing Yin
The COP9 signalosome (CSN) is a highly conserved multiprotein complex in all eukaryotes and involved in regulation of organism development. In filamentous fungi, several lines of evidence indicate that fungal development and secondary metabolism (SM) are mediated by the fifth subunit of CSN, called CsnE. Here we uncover a connection with CsnE and conidial formation as well as SM regulation in the plant endophytic fungus Pestalotiopsis fici. A homology search of the P. fici genome with CsnE, involved in sexual development and SM in Aspergillus nidulans, identified PfCsnE...
May 25, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28550523/morphological-evaluation-of-retinal-ganglion-cells-expressing-the-l132c-t159c-chr2-mutant-transgene-in-young-adult-cynomolgus-monkeys
#13
Wenyao Wang, Yan Nan, Zhuo-Hua Pan, Mingliang Pu
To characterize recombinant AAV2 (rAAV2)-mediated expression of L132C/T159C ChR2 mutant in retinal ganglion cells (RGCs) of young adult cynomolgus monkeys. rAAV2 vectors carrying a fusion construct of the ChR2 mutant and GFP (ChR2-GFP) were delivered to the vitreous chamber by intravitreal injection. Expression patterns of the ChR2 mutant in RGCs were examined by immunohistochemical methods three months after injection. The RNA-binding protein with multiple splicing (RBPMS) was used as an RGC specific marker to differentiate RGCs from other retinal neurons and non-neuronal cells...
May 25, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28550492/microrna-889-is-downregulated-by-histone-deacetylase-inhibitors-and-confers-resistance-to-natural-killer-cytotoxicity-in-hepatocellular-carcinoma-cells
#14
Haitao Xie, Qiugui Zhang, Hui Zhou, Jun Zhou, Ji Zhang, Yan Jiang, Jinghong Wang, Xianglin Meng, Leping Zeng, Xiaoxin Jiang
Major histocompatibility complex class I chain-related gene B (MICB) is expressed on tumor cells and participates in natural killer (NK) cell-mediated antitumor immune response through engagement with the NKG2D receptor. This study was undertaken to identify novel microRNA (miRNA) regulators of MICB and clarify their functions in NK cell-mediated cytotoxicity to hepatocellular carcinoma (HCC) cells. Bioinformatic analysis and luciferase reporter assay were conducted to search for MICB-targeting miRNAs. Overexpression and knockdown experiments were performed to determine the roles of candidate miRNAs in the susceptibility of HCC cells to NK lysis...
May 26, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28550472/salt-induced-na-k-atpase-%C3%AE-%C3%AE-expression-involves-soluble-adenylyl-cyclase-in-endothelial-cells
#15
Mirja Mewes, Johanna Nedele, Katrin Schelleckes, Olga Bondareva, Malte Lenders, Kristina Kusche-Vihrog, Hans-Joachim Schnittler, Stefan-Martin Brand, Boris Schmitz, Eva Brand
High dietary salt intake may lead to vascular stiffness, which predicts cardiovascular diseases such as heart failure, and myocardial and cerebral infarctions as well as renal impairment. The vascular endothelium is a primary target for deleterious salt effects leading to dysfunction and endothelial stiffness. We hypothesize that the Ca(2+)- and bicarbonate-activated soluble adenylyl cyclase (sAC) contributes to Na(+)/K(+)-ATPase expression regulation in vascular endothelial cells and is an important regulator of endothelial stiffness...
May 26, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28550467/resource-partitioning-between-pacific-walruses-and-bearded-seals-in-the-alaska-arctic-and-sub-arctic
#16
L E Oxtoby, L Horstmann, S M Budge, D M O'Brien, S W Wang, T Schollmeier, M J Wooller
Climate-mediated changes in the phenology of Arctic sea ice and primary production may alter benthic food webs that sustain populations of Pacific walruses (Odobenus rosmarus divergens) and bearded seals (Erignathus barbatus). Interspecific resource competition could place an additional strain on ice-associated marine mammals already facing loss of sea ice habitat. Using fatty acid (FA) profiles, FA trophic markers, and FA stable carbon isotope analyses, we found that walruses and bearded seals partitioned food resources in 2009-2011...
May 26, 2017: Oecologia
https://www.readbyqxmd.com/read/28550455/-effects-of-the-novel-relatively-short-acting-kappa-opioid-receptor-antagonist-ly2444296-in-behaviors-observed-after-chronic-extended-access-cocaine-self-administration-in-rats
#17
Marta Valenza, Eduardo R Butelman, Mary Jeanne Kreek
RATIONALE: The recruitment of the stress circuitry contributes to a shift from positive to negative reinforcement mechanisms sustaining long-term cocaine addiction. The kappa opioid receptor (KOPr) signaling is upregulated by stress and chronic cocaine exposure. While KOPr agonists induce anhedonia and dysphoria, KOPr antagonists display antidepressant and anxiolytic properties. Most of the knowledge on KOPr antagonism is based on drugs with unusual pharmacokinetic and pharmacodynamic properties, complicating interpretation of results...
May 27, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28550454/oncogenic-roles-of-the-pi3k-akt-mtor-axis
#18
Masahiro Aoki, Teruaki Fujishita
The PI3K/AKT/mTOR pathway is frequently activated in various human cancers and has been considered a promising therapeutic target. Many of the positive regulators of the PI3K/AKT/mTOR axis, including the catalytic (p110α) and regulatory (p85α), of class IA PI3K, AKT, RHEB, mTOR, and eIF4E, possess oncogenic potentials, as demonstrated by transformation assays in vitro and by genetically engineered mouse models in vivo. Genetic evidences also indicate their roles in malignancies induced by activation of the upstream oncoproteins including receptor tyrosine kinases and RAS and those induced by the loss of the negative regulators of the PI3K/AKT/mTOR pathway such as PTEN, TSC1/2, LKB1, and PIPP...
May 28, 2017: Current Topics in Microbiology and Immunology
https://www.readbyqxmd.com/read/28550441/dyadic-interdependence-of-psychosocial-outcomes-among-haematological-cancer-survivors-and-their-support-persons
#19
Christine Paul, Alix Hall, Christopher Oldmeadow, Marita Lynagh, Sharon Campbell, Ken Bradstock, Anna Williamson, Mariko Carey, Rob Sanson-Fisher
PURPOSE: This study aimed to explore the dyadic relationships between unmet need, depression, and anxiety in people diagnosed with haematological cancer and their support persons. METHODS: Adult survivors (18 years+) who had been diagnosed with a haematological cancer were recruited to a cross-sectional mailed survey via five state cancer registries in Australia. Participating survivors invited a support person to also complete a survey. Structural equation modelling was used to explore the relationships among survivor and support person self-reported depression, anxiety, and unmet needs...
May 26, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28550425/cpg-oligonucleotide-mediated-co-stimulation-of-mouse-invariant-natural-killer-t-cells-negatively-regulates-their-activation-status
#20
Raveendra R Kulkarni, Alexander Ian Villanueva, Leah R Read, Jennifer T Brisbin, Siddhartha Kumar Bhaumik, Jonathan LaMarre, Kaja Murali-Krishna, Shayan Sharif
Invariant natural killer T (iNKT) cells play important roles in antimicrobial defense and immune-regulation. We have previously shown that iNKT cells express certain toll-like receptors (TLR), and that TLR co-stimulation of iNKT cells in the presence of suboptimal concentrations of T cell receptor (TCR) agonists enhances cellular activation. In the present study, we investigated the regulatory effects of CpG oligonucleotides in mouse primary hepatic and splenic iNKT cells and in DN32.D3 iNKT cells. We show that CpG treatment of iNKT cells in the presence of higher concentrations of TCR agonists (α-GalCer or anti-CD3 mAb) results in the up-regulation of TLR9 in iNKT cells with a concurrent reduction in their cellular activation, as assessed by their production of IL-2, IL-4 and IFN-γ compared with controls...
May 27, 2017: Cell and Tissue Research
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