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https://www.readbyqxmd.com/read/29303375/structure-optimization-to-improve-the-delivery-efficiency-and-cell-selectivity-of-a-tumor-targeting-cell-penetrating-peptide
#1
Xue-Wei Cao, Xu-Zhong Yang, Xuan Du, Long-Yun Fu, Tao-Zhu Zhang, Han-Wen Shan, Jian Zhao, Fu-Jun Wang
Cell-penetrating peptide (CPP) is used for the delivery of biomacromolecules across the cell membrane and is limited in cancer therapy due to the lack of cell selectivity. Epidermal growth factor receptor (EGFR) has been widely used in clinical targeted therapy for tumors. Here we reported a novel tumor targeting cell-penetrating peptide (TCPP), EHB (ELBD-C6H) with 20-fold and 3000-fold greater transmembrane ability and tumor cell selectivity than our previously reported S3-HBD and classic CPP TAT, respectively...
January 5, 2018: Journal of Drug Targeting
https://www.readbyqxmd.com/read/29274366/vesicular-glutamate-transporter-1-vglut1-mediated-glutamate-release-and-membrane-glua1-activation-is-involved-in-the-rapid-antidepressant-like-effects-of-scopolamine-in-mice
#2
Hanjie Yu, Mengmeng Li, Dongsheng Zhou, Dan Lv, Qi Liao, Zhongze Lou, Mengxin Shen, Zhen Wang, Ming Li, Xiao Xiao, Yanhua Zhang, Chuang Wang
Emerging data have identified certain drugs such as scopolamine as rapidly acting antidepressants for major depressive disorder (MDD) that increase glutamate release and induce neurotrophic factors through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) activation in rodent models. However, little research has addressed the direct mechanisms of scopolamine on AMPAR activation or vesicular glutamate transporter 1 (VGLUT1)-mediated glutamate release in the prefrontal cortex (PFC) of mice...
December 20, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29209432/epigenetic-modifications-of-the-vgf-gene-in-human-non-small-cell-lung-cancer-tissues-pave-the-way-towards-enhanced-expression
#3
Sebastian Marwitz, Lena Heinbockel, Swetlana Scheufele, Dörte Nitschkowski, Christian Kugler, Sven Perner, Martin Reck, Ole Ammerpohl, Torsten Goldmann
Hwang et al. recently showed that VGF substantially contributes to the resistance of human lung cancer cells towards epidermal growth factor receptor kinase inhibitors. This was further linked to enhanced epithelial-mesenchymal transition. Here, we demonstrate that VGF is epigenetically modified in non-small cell lung cancer tissues compared to corresponding tumor-free lung tissues from the same donors by using methylome bead chip analyses. These epigenetic modifications trigger an increased transcription of the VGF gene within the tumors, which then leads to an increased expression of the protein, facilitating epithelial-mesenchymal transition, and the resistance to kinase inhibitors...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/29187753/subchronic-olanzapine-exposure-leads-to-increased-expression-of-myelination-related-genes-in-rat-fronto-medial-cortex
#4
Kari M Ersland, Silje Skrede, Christine Stansberg, Vidar M Steen
Schizophrenia is a psychotic disorder with severe and disabling symptoms, such as hallucinations, delusions, blunted affect and social withdrawal. The neuropathology remains elusive, but disturbances in immunity-related processes, neuronal connectivity and myelination have consistently been linked to schizophrenia. Antipsychotic drugs can be efficient in reducing symptoms, acting primarily on the dopamine system, but additional biological targets are likely to exist. Here we have screened for novel mechanisms of action in an animal model, using adult rats exposed to long-acting olanzapine, achieving stable and clinically relevant antipsychotic drug concentrations...
November 30, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/29158577/vgf-function-in-depression-and-antidepressant-efficacy
#5
C Jiang, W-J Lin, M Sadahiro, B Labonté, C Menard, M L Pfau, C A Tamminga, G Turecki, E J Nestler, S J Russo, S R Salton
Brain-derived neurotrophic factor (BDNF) is a critical effector of depression-like behaviors and antidepressant responses. Here, we show that VGF (non-acronymic), which is robustly regulated by BDNF/TrkB signaling, is downregulated in hippocampus (male/female) and upregulated in nucleus accumbens (NAc) (male) in depressed human subjects and in mice subjected to chronic social defeat stress (CSDS). Adeno-associated virus (AAV)-Cre-mediated Vgf ablation in floxed VGF mice, in dorsal hippocampus (dHc) or NAc, led to pro-depressant or antidepressant behaviors, respectively, while dHc- or NAc-AAV-VGF overexpression induced opposite outcomes...
November 21, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29028155/a-parallel-reaction-monitoring-mass-spectrometric-method-for-analysis-of-potential-csf-biomarkers-for-alzheimer-s-disease
#6
Gunnar Brinkmalm, Simon Sjödin, Anja Hviid Simonsen, Steen Gregers Hasselbalch, Henrik Zetterberg, Ann Brinkmalm, Kaj Blennow
PURPOSE: The aim of this study was to develop and evaluate a parallel reaction monitoring mass spectrometry (PRM-MS) assay consisting of a panel of potential protein biomarkers in cerebrospinal fluid (CSF). EXPERIMENTAL DESIGN: Thirteen proteins were selected based on their association with neurodegenerative diseases and involvement in synaptic function, secretory vesicle function, or innate immune system. CSF samples were digested and 2-3 peptides per protein were quantified using stable isotope-labeled peptide standards...
October 13, 2017: Proteomics. Clinical Applications
https://www.readbyqxmd.com/read/29020410/the-requirement-of-l-type-voltage-dependent-calcium-channel-l-vdcc-in-the-rapid-acting-antidepressant-like-effects-of-scopolamine-in-mice
#7
Hanjie Yu, Mengmeng Li, Xinbei Shen, Dan Lv, Xin Sun, Jinting Wang, Xinmei Gu, Jingning Hu, Chuang Wang
Background: Previous studies have shown that a low dose of scopolamine produces rapid-acting antidepressant-like actions in rodents. Understanding the mechanisms underlying this effect and the dose-dependent variations of drug responses remains an important task. L-type voltage-dependent calcium channels (L-VDCC) were found to mediate rapid-acting antidepressant effects of certain medications (e.g., ketamine). Therefore, it is of great interest to determine the involvement of L-VDCC in the action of scopolamine...
August 25, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28944862/ing2-a-tumor-associated-gene-enhances-pai%C3%A2-1-and-hspa1a-expression-with-hdac1-and-msin3a-through-the-phd-domain-and-c%C3%A2-terminal
#8
Chiyo Ohkouchi, Kensuke Kumamoto, Motonobu Saito, Teruhide Ishigame, Shin-Ichi Suzuki, Seiichi Takenoshita, Cutis C Harris
Inhibitor of growth 2 (ING2) is involved in chromatin remodeling and it has previously been suggested that ING2 may regulate gene expression. The authors previously identified matrix metalloproteinase 13 (MMP13) as a target gene of ING2 in colorectal cancer. The aim of the present study was to identify novel genes regulated by ING2 and histone deacetylase 1 (HDAC1) and to clarify the biological significance of the ING2 structure. The present study generated the point mutant constructs of ING2 and deletion constructs consisting of partial ING2 to investigate the effect on gene expression and verify the interaction with HDAC1, mSin3A and sap30...
November 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28934328/the-human-vgf-derived-bioactive-peptide-tlqp-21-binds-heat-shock-71-kda-protein-8-hspa8-on-the-surface-of-sh-sy5y-cells
#9
Shamim Akhter, Sandipan Chakraborty, Daniela Moutinho, Elia Álvarez-Coiradas, Isaac Rosa, Juan Viñuela, Eduardo Domínguez, Angel García, Jesús R Requena
VGF (non-acronymic)is a secreted chromogranin/secretogranin that gives rise to a number of bioactive peptides by a complex proteolysis mechanism. VGF-derived peptides exert an extensive array of biological effects in energy metabolism, mood regulation, pain, gastric secretion function, reproduction and, perhaps, cancer. It is therefore surprising that very little is known about receptors and binding partners of VGF-derived peptides and their downstream molecular mechanisms of action. Here, using affinity chromatography and mass spectrometry-based protein identification, we have identified the heat shock cognate 71 kDa protein A8 (HSPA8)as a binding partner of human TLQP-21 on the surface of human neuroblastomaSH-SY5Y cells...
2017: PloS One
https://www.readbyqxmd.com/read/28931410/lentivirus-mediated-interleukin-1%C3%AE-il-1%C3%AE-knock-down-in-the-hippocampus-alleviates-lipopolysaccharide-lps-induced-memory-deficits-and-anxiety-and-depression-like-behaviors-in-mice
#10
Mengmeng Li, Chenli Li, Hanjie Yu, Xiongxiong Cai, Xinbei Shen, Xin Sun, Jinting Wang, Yanhua Zhang, Chuang Wang
BACKGROUND: Recent evidence has suggested that peripheral inflammatory responses induced by lipopolysaccharides (LPS) play an important role in neuropsychiatric dysfunction in rodents. Interleukin-1β (IL-1β), a pro-inflammatory cytokine, has been proposed to be a key mediator in a variety of behavioral dysfunction induced by LPS in mice. Thus, inhibition of IL-1β may have a therapeutic benefit in the treatment of neuropsychiatric disorders. However, the precise underlying mechanism of knock-down of IL-1β in repairing behavioral changes by LPS remains unclear...
September 20, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28881587/mgmt-and-calca-promoter-methylation-are-associated-with-poor-prognosis-in-testicular-germ-cell-tumor-patients
#11
Camila Maria da Silva Martinelli, André van Helvoort Lengert, Flavio Mavignier Cárcano, Eduardo Caetano Albino Silva, Mariana Brait, Luiz Fernando Lopes, Daniel Onofre Vidal
Testicular germ cell tumors (TGCT) represent the second main cause of cancer-related death in young men. Despite high cure rates, refractory disease results in poor prognosis. Epigenetic reprogramming occurs during the development of seminomas and non-seminomas. Understanding the molecular and genetic basis of these tumors would represent an important advance in the search for new TGCT molecular markers. Hence the frequency of methylation of a gene panel (VGF, MGMT, ADAMTS1, CALCA, HOXA9, CDKN2B, CDO1 and NANOG) was evaluated in 72 primary TGCT by quantitative methylation specific PCR...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28877479/the-prohormone-vgf-regulates-%C3%AE-cell-function-via-insulin-secretory-granule-biogenesis
#12
Samuel B Stephens, Robert J Edwards, Masato Sadahiro, Wei-Jye Lin, Cheng Jiang, Stephen R Salton, Christopher B Newgard
The prohormone VGF is expressed in neuroendocrine and endocrine tissues and regulates nutrient and energy status both centrally and peripherally. We and others have shown that VGF-derived peptides have direct action on the islet β cell as secretagogues and cytoprotective agents; however, the endogenous function of VGF in the β cell has not been described. Here, we demonstrate that VGF regulates secretory granule formation. VGF loss-of-function studies in both isolated islets and conditional knockout mice reveal a profound decrease in stimulus-coupled insulin secretion...
September 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/28753681/correction-hypothalamic-over-expression-of-vgf-in-the-siberian-hamster-increases-energy-expenditure-and-reduces-body-weight-gain
#13
Jo E Lewis, John M Brameld, Phil Hill, Cristina Cocco, Barbara Noli, Gian-Luca Ferri, Perry Barrett, Francis J P Ebling, Preeti H Jethwa
[This corrects the article DOI: 10.1371/journal.pone.0172724.].
2017: PloS One
https://www.readbyqxmd.com/read/28680036/behavioral-abnormalities-with-disruption-of-brain-structure-in-mice-overexpressing-vgf
#14
Takahiro Mizoguchi, Hiroko Minakuchi, Mitsue Ishisaka, Kazuhiro Tsuruma, Masamitsu Shimazawa, Hideaki Hara
VGF nerve growth factor inducible (VGF) is a neuropeptide induced by nerve growth factor and brain-derived neurotrophic factor. This peptide is involved in synaptic plasticity, neurogenesis, and neurite growth in the brain. Patients with depression and bipolar disorder have lower-than-normal levels of VGF, whereas patients with schizophrenia and other cohorts of patients with depression have higher-than-normal levels. VGF knockout mice display behavioral abnormalities such as higher depressive behavior and memory dysfunction...
July 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28639574/mir-551b-5p-contributes-to-pathogenesis-of-vein-graft-failure-via-upregulating-early-growth-response-1-expression
#15
Ran Dong, Kui Zhang, Yue-Li Wang, Feng Zhang, Jian Cao, Ju-Bing Zheng, Hong-Jia Zhang
BACKGROUND: Vein graft failure (VGF) is a serious complication of coronary artery bypass graft, although the mechanism remains unclear. The study aimed to investigate the effects of microRNAs (miRNAs) on the endothelial dysfunction involved in VGF. METHODS: Human umbilical vein endothelial cells (HUVECs) were subjected to mechanical stretch stimulation to induce endothelial dysfunction. Genome-wide transcriptome profiling was performed using the Human miRNA OneArray® V4 (PhalanxBio Inc...
July 5, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28635540/reduced-serum-vgf-levels-were-reversed-by-antidepressant-treatment-in-depressed-patients
#16
Haitang Jiang, Suzhen Chen, Na Lu, Yingying Yue, Yingying Yin, Yuqun Zhang, Wenhao Jiang, Jinfeng Liang, Yonggui Yuan
OBJECTIVES: VGF, a non-acronymic neuropeptide, is important in the pathogenesis of major depressive disorder (MDD) and in the functioning and efficacy of some antidepressant drugs. In this study we assessed whether serum VGF levels change in MDD patients and if antidepressant treatments can restore these changes. METHODS: We measured serum VGF concentrations using sandwich ELISA in drug-free MDD patients before treatment began (n = 26) and at 8 weeks after antidepressant treatment (n = 26) with escitalopram and duloxetine, two common antidepressants...
September 22, 2016: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/28626390/profiles-of-vgf-peptides-in-the-rat-brain-and-their-modulations-after-phencyclidine-treatment
#17
Barbara Noli, Fabrizio Sanna, Carla Brancia, Filomena D'Amato, Barbara Manconi, Federica Vincenzoni, Irene Messana, Maria R Melis, Antonio Argiolas, Gian-Luca Ferri, Cristina Cocco
From the VGF precursor protein originate several low molecular weight peptides, whose distribution in the brain and blood circulation is not entirely known. Among the VGF peptides, those containing the N-terminus portion were altered in the cerebro-spinal fluid (CSF) and hypothalamus of schizophrenia patients. "Hence, we aimed to better investigate the involvement of the VGF peptides in schizophrenia by studying their localization in the brain regions relevant for the disease, and revealing their possible modulations in response to certain neuronal alterations occurring in schizophrenia"...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28594546/neuropeptide-vgf-c-terminal-peptide-tlqp-62-alleviates-lipopolysaccharide-induced-memory-deficits-and-anxiety-like-and-depression-like-behaviors-in-mice-the-role-of-bdnf-trkb-signaling
#18
Chenli Li, Mengmeng Li, Hanjie Yu, Xinbei Shen, Jinting Wang, Xin Sun, Qinwen Wang, Chuang Wang
Peripheral inflammatory responses affect central nervous system (CNS) function, manifesting in symptoms of memory deficits, depression, and anxiety. Previous studies have revealed that neuropeptide VGF (nonacronymic) C-terminal peptide TLQP-62 rapidly reinforces brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling, regulating memory consolidation and antidepressant-like action. However, whether it is beneficial for lipopolysaccharide (LPS)-induced neuropsychiatric dysfunction in mice is unknown...
June 21, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28439815/the-effects-of-voluntary-physical-exercise-activated-neurotrophic-signaling-in-rat-hippocampus-on-mrna-levels-of-downstream-signaling-molecules
#19
Christina A E Solvsten, Tina F Daugaard, Yonglun Luo, Frank de Paoli, Jane H Christensen, Anders L Nielsen
Physical exercise results in the increased expression of neurotrophic factors and the subsequent induction of signal transduction cascades with a positive impact on neuronal functions. In this study, we used a voluntary physical exercise rat model to determine correlations in hippocampus mRNA expression of the neurotropic factors Bdnf, VegfA, and Igf1; their receptors TrkB, Igf1R, VegfR1, and VegfrR2; and downstream signal transducers Creb, Syn1, and Vgf. In hippocampi of physically exercised rats, the mRNA expression levels of Bdnf transcript 4 (Bdnf-t4), VegfA, and Igf1, as well as VegfR1, TrkB, Creb, Vgf, and Syn1, were increased...
June 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28424618/pharmacological-and-biochemical-characterization-of-tlqp-21-activation-of-a-binding-site-on-cho-cells
#20
Laura Molteni, Laura Rizzi, Elena Bresciani, Roberta Possenti, Pamela Petrocchi Passeri, Corrado Ghè, Giampiero Muccioli, Jean-Alain Fehrentz, Pascal Verdié, Jean Martinez, Robert J Omeljaniuk, Giuseppe Biagini, Anna Binda, Ilaria Rivolta, Vittorio Locatelli, Antonio Torsello
VGF is a propeptide of 617 amino acids expressed throughout the central and the peripheral nervous system. VGF and peptides derived from its processing have been found in dense core vesicles and are released from neuronal and neuroendocrine cells via the regulated secretory pathway. Among VGF-derived neuropeptides, TLQP-21 (VGF(556-576)) has raised a huge interest and is one of most studied. TLQP-21 is a multifunctional neuropeptide involved in the control of several physiological functions, potentially including energy homeostasis, pain modulation, stress responsiveness and reproduction...
2017: Frontiers in Pharmacology
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