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mRNA display

Jie Li, Yanli Zhang, Xianhui Cai, Qingqing Xia, Jingmeng Chen, Yi Liao, Zuguo Liu, Yalin Wu
Effective clearance of all-trans-retinal (atRAL) from retinal pigment epithelial (RPE) cells is important for avoiding its cytotoxicity. However, the metabolism of atRAL in RPE cells is poorly clarified. The present study was designed to analyze metabolic products of atRAL and to compare the cytotoxicity of atRAL versus its derivative all-trans-retinal dimer (atRAL-dimer) in human RPE cells. We found that all-trans-retinol (atROL) and a mixture of atRAL condensation metabolites including atRAL-dimer and A2E were generated after incubating RPE cells with atRAL for 6h, and the amount of atRAL-dimer was significantly higher than that of A2E...
October 14, 2016: Toxicology
Erik Nylander, Alfhild Grönbladh, Sofia Zelleroth, Shanti Diwakarla, Fred Nyberg, Mathias Hallberg
Human growth hormone (GH) displays promising protective effects in the central nervous system after damage caused by various insults. Current evidence suggests that these effects may involve N-methyl-D-aspartate (NMDA) receptor function, a receptor that also is believed to play a role in opioid-induced neurotoxicity. The aims of the present study were to examine the acute toxic effects of methadone, an opioid receptor agonist and NMDA receptor antagonist, as well as to evaluate the protective properties of recombinant human GH (rhGH) on methadone-induced toxicity...
October 13, 2016: Neuroscience
Natasha M Rogers, Maryam Sharifi-Sanjani, Mingyi Yao, Kedar Ghimire, Raquel Bienes-Martinez, Stephanie M Mutchler, Heather E Knupp, Jeffrey Baust, Enrico M Novelli, Mark Ross, Claudette St Croix, Johannes C Kutten, Caitlin A Czajka, John C Sembrat, Mauricio Rojas, David Labrousse-Arias, Timothy N Bachman, Rebecca R Vanderpool, Brian S Zuckerbraun, Hunter C Champion, Ana L Mora, Adam C Straub, Richard A Bilonick, Maria J Calzada, Jeffrey S Isenberg
AIMS: Thrombospondin-1 (TSP1) is a ligand for CD47 and TSP1(-/-) mice are protected from pulmonary hypertension (PH). We hypothesized the TSP1-CD47 axis is upregulated in human PH and promotes pulmonary arterial vasculopathy. METHODS AND RESULTS: We analyzed the molecular signature and functional response of lung tissue and distal pulmonary arteries (PAs) from individuals with (n=23) and without (n=16) PH. Compared to controls, lungs and distal PAs from PH patients showed induction of TSP1-CD47 and endothelin-1/endothelin A receptor (ET-1/ETA) protein and mRNA...
October 13, 2016: Cardiovascular Research
A E Hoban, R D Moloney, A V Golubeva, K A McVey Neufeld, O O'Sullivan, E Patterson, C Stanton, T G Dinan, G Clarke, J F Cryan
Gut microbiota colonization is a key event for host physiology that occurs early in life. Disruption of this process leads to altered brain development which ultimately manifests as changes in brain function and behaviour in adulthood. Studies using germ-free mice highlight the extreme impact on brain health that results from life without commensal microbes, however the impact of microbiota disturbances occurring in adulthood is less studied. To this end, we depleted the gut microbiota of 10-week-old male Sprague Dawley rats via chronic antibiotic treatment...
October 11, 2016: Neuroscience
Nermeen El-Moataz Bellah Ahmed, Masashi Murakami, Satoru Kaneko, Misako Nakashima
Recent studies have demonstrated that culture under hypoxia has beneficial effects on mesenchymal stem cells (MSCs). However, there are limitations to achieving a stable condition in conventional hypoxic CO2 incubators. DPSCs are a unique type of MSCs which are promising in many regenerative therapies. In this study, we investigated the ideal hypoxic culture environment for DPSCs using a new system that can provide controlled O2 environment. The effects of hypoxia (3%, 5%) on the stemness properties of DPSCs...
October 14, 2016: Scientific Reports
Ziye Pan, Jinjiao He, Lubna M Rasoul, Yunye Liu, Ruixiang Che, Yun Ding, Xiaocheng Guo, Jiarui Yang, Dehua Zou, Hua Zhang, Deshan Li, Hongwei Cao
Recombinant Newcastle disease virus (rNDV) is tumor selective and intrinsically oncolytic, which has been developed as a vector to express exogenous genes to enhance its oncolytic efficacy. Our previous studies found that insertion sites of foreign gene in rNDV vector affected its expression and anti-tumor activities. However, the optimal insertion site for foreign genes remains unknown. In this study, we inserted the enhanced green fluorescence protein (EGFP) and IL2 genes into four different intergenic regions of the rNDV using reverse genetics technology...
2016: PloS One
Zhi Su, Deborah Widomski, Ji Ma, Marian Namovic, Arthur Nikkel, Laura Leys, Lauren Olson, Katherine Salte, Diana Donnelly-Roberts, Timothy Esbenshade, Steve McGaraughty
BACKGROUND: Obese ZSF-1 rats display many features of human type II diabetes including nephropathy (DN). The study aimed to further understand the relevance of this model to DN, for which glomerular filtration rate (GFR), renal fibrosis and several urinary/tissue biomarkers was followed over 24 weeks in ZSF-1 rats. METHODS: Intact/sham or uninephrectomized male and female ZSF-1 rats were studied. GFR was measured by transdermal clearance of fluorescein isothiocyanate-sinistrin...
October 14, 2016: American Journal of Nephrology
Yue Xu, Boyu Yang, Yaguang Hu, Lin Lu, Xi Lu, Jiawei Wang, Qinmeng Shu, Qiaochu Cheng, Shanshan Yu, Fan Xu, Jingjing Huang, Xiaoling Liang
Down syndrome candidate region 1 (DSCR1) has two differentially regulated isoforms (DSCR1-1 and DSCR1-4) and is reported to play a role in a number of physiological processes, such as the inhibition of cardiac hypertrophy, attenuation of angiogenesis and carcinogenesis, and protection against neuronal death. However, the function of DSCR1 in the retina is still not clear. Therefore, we analyzed the expression and location of DSCR1 in the retina of neonatal mice with oxygen-induced retinopathy (OIR), and studied its effects on angiogenesis...
October 12, 2016: Molecular Neurobiology
Ai-Ling Chen, Xi Sun, Wei Wang, Jin-Feng Liu, Xin Zeng, Jing-Fan Qiu, Xin-Jian Liu, Yong Wang
BACKGROUND: Immunosuppression has been described as a consequence of brain injury and infection by different mechanisms. Angiostrongylus cantonensis can cause injury to the central nervous system and eosinophilic meningitis to human. Both T cell and B cell immunity play an essential role in the resistance of the infection. However, whether brain injury caused by A. cantonensis infection can lead to immunosuppression is not clear. Therefore, the present study sought to observe the alteration of immune responses in mice infected with A...
October 12, 2016: Journal of Neuroinflammation
Martina Štěpánková, Kristýna Krasulová, Aneta Dořičáková, Ondřej Kurka, Pavel Anzenbacher, Zdeněk Dvořák
Dihydropyridine calcium channel blockers (CCBs) are used as anti-hypertensives and in the treatment of angina pectoris. Structurally, CCBs have at least one chiral center in the molecule, thereby existing in two or more different enantiomers. In the current paper we examined effects of benidipine, felodipine and isradipine enantiomers on the expression and enzyme activities of human xenobiotics-metabolizing cytochromes P450. All CCBs dose-dependently activated aryl hydrocarbon receptor (AhR) and pregnane X receptor (PXR), as revealed by gene reporter assays...
October 9, 2016: Toxicology Letters
Marcio A Torsoni, Beatriz C Borges, Jessica L Cote, Susan J Allen, Erica Mahany, David Garcia-Galiano, Carol F Elias
A temporary and reversible inhibition of the hypothalamo-pituitary-gonadal (HPG) axis is adaptive when energy reserves are diminished, allowing individual survival and energy accumulation for eventual reproduction. The AMP-activated protein kinase (AMPK) works as a cellular sensor of the AMP/ATP ratio and ultimately of energy availability. Activation of AMPK suppresses ATP-consuming processes and stimulates ATP-producing pathways. The AMPK α2 catalytic subunit is expressed in multiple hypothalamic nuclei including those associated with reproductive control, i...
October 12, 2016: Endocrinology
Emily K Law, Anieta M Sieuwerts, Kelly LaPara, Brandon Leonard, Gabriel J Starrett, Amy M Molan, Nuri A Temiz, Rachel Isaksson Vogel, Marion E Meijer-van Gelder, Fred C G J Sweep, Paul N Span, John A Foekens, John W M Martens, Douglas Yee, Reuben S Harris
Breast tumors often display extreme genetic heterogeneity characterized by hundreds of gross chromosomal aberrations and tens of thousands of somatic mutations. Tumor evolution is thought to be ongoing and driven by multiple mutagenic processes. A major outstanding question is whether primary tumors have preexisting mutations for therapy resistance or whether additional DNA damage and mutagenesis are necessary. Drug resistance is a key measure of tumor evolvability. If a resistance mutation preexists at the time of primary tumor presentation, then the intended therapy is likely to fail...
October 2016: Science Advances
Daniel García-Pérez, Szilamer Ferenczi, Krisztina J Kovács, M Luisa Laorden, M Victoria Milanés, Cristina Núñez
Drug-withdrawal aversive memories generate a motivational state leading to compulsive drug taking, with plasticity changes in the basolateral amygdala (BLA) being essential in aversive motivational learning. The conditioned-place aversion (CPA) paradigm allows for measuring the negative affective component of drug withdrawal. First, CPA triggers association between negative affective consequences of withdrawal with context (memory consolidation). Afterwards, when the animals are re-exposed to the paired environment, they avoid it due to the association between the context and aversive memories (memory retrieval)...
September 28, 2016: Psychoneuroendocrinology
Ali Akbar Alizadeh, Maryam Hamzeh-Mivehroud, Malak Farajzadeh, Siavoush Dastmalchi
The aim of this study was to identify novel TNF-α blocking peptide(s) using phage display technology. Two novel 7-mer TNF-α binding peptides P51 and P52 with Kd values of 1.47 and 0.51nM were identified. Phage particles displaying P51 and P52 peptides at 0.318nM concentration prevent cytotoxic effect of TNF-α on L929 cells by 8.2% and 16.15%, respectively. Synthesized P51 and P52 peptides also inhibited TNF-α induced cytotoxicity with IC50 values of 25.15±2.18 and 7.08±2.24μM, respectively. The result of RT-PCR also supports the inhibitory activity of the identified peptides, where P51 and P52 significantly inhibit the inductive effect of TNF-α on IκB-α mRNA levels...
October 5, 2016: European Journal of Pharmaceutical Sciences
Kotaro Sakamoto, Yayoi Kawata, Yasushi Masuda, Tadashi Umemoto, Takashi Ito, Taiji Asami, Shiro Takekawa, Tetsuya Ohtaki, Hiroshi Inooka
Fibroblast growth factor receptor-1c (FGFR1c)/βKlotho (KLB) complex is a receptor of fibroblast growth factor 21 (FGF21). Pharmacologically, FGF21 shows anti-obesity and anti-diabetic effects upon peripheral administration. Here, we report the development of an artificial peptide agonist to the FGFR1c/KLB heterodimer complex. The peptide, F91-8A07 (LPGRTCREYPDLWWVRCY), was discovered from random peptide T7 phage display and selectively bound to the FGFR1c/KLB complex, but not to FGFR1c and KLB individually...
October 4, 2016: Biochemical and Biophysical Research Communications
Hélène Volkoff, Rafael Esatevan Sabioni, Luiz Lehmann Coutinho, José Eurico Possebon Cyrino
The pacu Piaractus mesopotamicus is an omnivorous fish considered a promising species for aquaculture. Little is known about the endocrine regulation of feeding in this species. In this study, transcripts for orexin, cocaine and amphetamine regulated transcript (CART), cholecystokinin (CCK) and leptin were isolated in pacu. Orexin, CCK and leptin have widespread mRNA distributions in brain and periphery, CART is limited to the brain. To examine the role of these peptides in the regulation of feeding and energy status, mRNA expression levels were compared between fed and fasted fish and around feeding time...
October 4, 2016: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
Christian Wake, Adam Labadorf, Alexandra Dumitriu, Andrew G Hoss, Joli Bregu, Kenneth H Albrecht, Anita L DeStefano, Richard H Myers
BACKGROUND: MicroRNAs (miRNAs) are short, non-coding RNAs that regulate gene expression mainly through translational repression of target mRNA molecules. More than 2700 human miRNAs have been identified and some are known to be associated with disease phenotypes and to display tissue-specific patterns of expression. METHODS: We used high-throughput small RNA sequencing to discover novel miRNAs in 93 human post-mortem prefrontal cortex samples from individuals with Huntington's disease (n = 28) or Parkinson's disease (n = 29) and controls without neurological impairment (n = 36)...
October 4, 2016: BMC Genomics
Li Zhang, Shudai Lin, Lilong An, Jinge Ma, Fengfang Qiu, Rumin Jia, Qinghua Nie, Dexiang Zhang, Qingbin Luo, Ting Li, Zhang Wang, Xiquan Zhang
Growth hormone receptor (GHR) played key roles in human and animal growth. Both human laron type dwarfism and sex linked dwarf chicken were caused by the mutation of GHR gene. In this study, we identified an endogenously expressed long non-coding natural antisense transcript, GHR-AS, which overlapped with the GHR mRNA (GHR-S) in a tail to tail manner. Spatial and temporal expression analyses indicated that GHR-AS were highly expressed in chicken liver and displayed ascending with the development of chicken from E10 to 3 w of age...
October 4, 2016: Oncotarget
Jianqi Yang, Lance T Platt, Biswanath Maity, Katelin E Ahlers, Zili Luo, Zhibo Lin, Bandana Chakravarti, Stella-Rita Ibeawuchi, Ryan W Askeland, Jolanta Bondaruk, Bogdan A Czerniak, Rory A Fisher
Urinary bladder cancer (UBC) is largely caused by exposure to toxic chemicals including those in cigarette smoke (i.e. BBN). An activating SNP in RGS6 is associated with a pronounced reduction in UBC risk, especially among smokers. However, the mechanism underlying this reduction remains unknown. Here we demonstrate that RGS6 is robustly expressed in human urothelium, where urothelial cell carcinoma originates, and is downregulated in human UBC. Utilizing RGS6-/- mice we interrogated a possible role for RGS6 as a tumor suppressor using the BBN-induced bladder carcinogenesis model that closely recapitulates human disease...
October 4, 2016: Oncotarget
Yue Wang, Yulong Han, Fangni Chai, Hongmei Xiang, Tao Huang, Shuming Kou, Bing Han, Xiaobao Gong, Xiaoli Ye
The aim of this study was to investigate the antihypercholesterolemic activity and potential molecular mechanism of columbamine (COL) that was prepared by extraction from Rhizoma Coptidis in hamsters and HepG2 cells. The results displayed that the COL from Rhizoma Coptidis was a safe natural compound with a LD50 0f 1524.6mg/kg and no detectable toxic symptoms during the observation of chronic toxicity. COL dose-dependently reversed the abnormal lipid levels induced by HFHC diet. Specifically, COL(M) and COL(H) significantly reduced the blood lipid levels(TC, TG and LDL-c) and enhanced the fecal contents of TBA by 21...
October 3, 2016: Fitoterapia
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