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https://www.readbyqxmd.com/read/29779223/gene-editing-vectors-for-studying-nicotinic-acetylcholine-receptors-in-cholinergic-transmission
#1
Can Peng, Yijin Yan, Veronica J Kim, Staci E Engle, Jennifer N Berry, J Michael McIntosh, Rachael L Neve, Ryan M Drenan
Nicotinic acetylcholine receptors (nAChRs), prototype members of the cys-loop ligand gated ion channel family, are key mediators of cholinergic transmission in the central nervous system. Despite their importance, technical gaps exist in our ability to dissect the function of individual subunits in the brain. To overcome these barriers, we designed CRISPR/Cas9 small guide RNA sequences (sgRNAs) for production of loss-of-function alleles in mouse nAChR genes. These sgRNAs were validated in vitro via deep sequencing...
May 19, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29779058/genetics-of-resistant-hypertension-the-missing-heritability-and-opportunities
#2
REVIEW
Samantha K Teixeira, Alexandre C Pereira, Jose E Krieger
PURPOSE OF THE REVIEW: Blood pressure regulation in humans has long been known to be a genetically determined trait. The identification of causal genetic modulators for this trait has been unfulfilling at the least. Despite the recent advances of genome-wide genetic studies, loci associated with hypertension or blood pressure still explain a very low percentage of the overall variation of blood pressure in the general population. This has precluded the translation of discoveries in the genetics of human hypertension to clinical use...
May 19, 2018: Current Hypertension Reports
https://www.readbyqxmd.com/read/29778509/longitudinal-observations-using-simultaneous-fmri-multiple-channel-electrophysiology-recording-and-chemical-microiontophoresis-in-the-rat-brain
#3
Saul Jaime, Jose E Cavazos, Yihong Yang, Hanbing Lu
BACKGROUND: fMRI blood oxygenation level-dependent (BOLD) signal has been widely used as a surrogate for neural activity. However, interpreting differences in BOLD fMRI based on underlying neuronal activity remains a challenge. Concurrent rsMRI data collection and electrophysiological recording in combination with microiontophoretically injected modulatory chemicals allows for improved understanding of the relationship between resting state BOLD and neuronal activity. NEW METHODS: Simultaneous fMRI, multi-channel intracortical electrophysiology and focal pharmacological manipulation data to be acquired longitudinally in rats for up to 2 months...
May 17, 2018: Journal of Neuroscience Methods
https://www.readbyqxmd.com/read/29778216/nitric-oxide-signalling-in-yeast
#4
Rika I Astuti, Ryo Nasuno, Hiroshi Takagi
Nitric oxide (NO) is a cellular signalling molecule widely conserved among organisms, including microorganisms such as bacteria, yeasts, and fungi, and higher eukaryotes such as plants and mammals. NO is mainly produced by the activities of NO synthase (NOS) or nitrite reductase (NIR). There are several NO detoxification systems, including NO dioxygenase (NOD) and S-nitrosoglutathione reductase (GSNOR). NO homeostasis, based on the balance between NO synthesis and degradation, is important for regulating its physiological functions, since an excess of NO causes nitrosative stress due to the high reactivity of NO and NO-derived compounds...
2018: Advances in Microbial Physiology
https://www.readbyqxmd.com/read/29777164/mrna-treatment-produces-sustained-expression-of-enzymatically-active-human-adamts13-in-mice
#5
Susan Liu-Chen, Brendan Connolly, Lei Cheng, Romesh R Subramanian, Zhaozhong Han
Thrombotic thrombocytopenic purpura (TTP) is primarily caused by deficiency of ADAMTS13 within the blood stream due to either genetic defects or presence of inhibitory autoantibodies. Preclinical and clinical studies suggest that enzyme replacement therapy with recombinant human ADAMTS13 protein (rhADAMTS13) is effective and safe in treatment of TTP. However, frequent dosing would be required due to the relatively short half-life of rhADAMTS13 in circulation as well as the presence of inhibitory autoantibodies that collectively result in the poor pharmacological profile of rhADAMTS13...
May 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29775777/antidepressant-potential-of-novel-flavonoids-derivatives-from-sweet-violet-viola-odorata-l-pharmacological-biochemical-and-computational-evidences-for-possible-involvement-of-serotonergic-mechanism
#6
Nasiara Karim, Imran Khan, Abeer Abdelhalim, Ajmal Khan, Sobia Ahsan Halim
Plant-derived natural constituents are of great interest in modern drug discovery due to their natural diversity. Viola odorata L has been traditionally used for the treatment of neuropsychiatric disorders. The present study was undertaken to isolate phytoconstituents including three flavonoids 5,7-Dihydroxy-3,6-dimethoxyflavone[1] 5,7,4'-trihydroxy-3',5'dimethoxyflavone [2] and 5,7,4'-trihydroxy-3'-methoxyflavone [3] from the whole plant of Viola odorata L and to investigate the antidepressant-like effects of these compounds and their possible mechanism of action using antagonists of the serotonergic, dopaminergic and adrenergic system...
May 15, 2018: Fitoterapia
https://www.readbyqxmd.com/read/29775223/curcumin-down-regulates-il-17a-mediated-p53-fibrinolytic-system-in-bleomycin-induced-acute-lung-injury-in-vivo
#7
Mahesh M Gouda, Yashodhar P Bhandary
Bleomycin (BLM) induced cellular damage causes inflammation in the alveolar compartment and impairment of fibrinolytic system leads to alveolar epithelial cell apoptosis. Here, we describe novel inflammatory pathway associated with p53-fibrinolytic system and apoptosis of alveolar epithelial cells and pharmacological efficiency of curcumin against this action. In the present study we used C57BL/6 mice. The specific dose and time interval of curcumin were analyzed to assess the intervention. Experiments were designed to investigate the IL-17A mediated modulation in the alveolar epithelial cell apoptosis and injury...
May 18, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29774530/cardiomyocyte-programmed-necrosis-mitochondria-death-receptor-and-beyond
#8
REVIEW
Junxia Zhang, Dairu Liu, Mao Zhang, Yan Zhang
Excessive death of cardiac myocytes leads to multiple cardiac diseases, including myocardial infarction, arrhythmia, heart failure and sudden cardiac death. For the last several decades, most work on cell death has focused on apoptosis, which is generally considered as the only form of regulated cell death, whereas necrosis has been regarded to be an unregulated process. Recent findings reveal that necrosis also occurs in a regulated manner and that it is closely related to the physiology and pathophysiology of multiple organs, including the heart...
May 18, 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29774524/%C3%AE-e-catenin-is-a-candidate-tumor-suppressor-for-the-development-of-e-cadherin-expressing-lobular-type-breast-cancer
#9
Jolien S de Groot, Max A K Rätze, Miranda van Amersfoort, Tanja Eisemann, Eva J Vlug, Mijanou T Niklaas, Suet-Feung Chin, Carlos Caldas, Paul J van Diest, Jos Jonkers, Johan de Rooij, Patrick W B Derksen
Mutational inactivation of E-cadherin (CDH1) is the main driver of invasive lobular breast cancer (ILC), although approximately 10-15% of all ILCs retain membrane-localized E-cadherin, despite the presence of an apparent non-cohesive and invasive lobular growth pattern. Given that ILC is dependent on constitutive actomyosin contraction for tumor development and progression, we used a combination of cell systems and in vivo experiments to investigate the consequences of α-catenin (CTNNA1) loss in the regulation of anchorage independence of non-invasive breast carcinoma...
May 17, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29774428/inter-individual-differences-in-serotonin-and-glutamate-co-transmission-reflect-differentiation-in-context-induced-conditioned-50-khz-usvs-response-after-morphine-withdrawal
#10
Adam Hamed, Miron Bartosz Kursa
A growing body of research provides compelling evidence that in rats 50-kHz USVs are a form of expression of positive emotions. Context-induced 50-kHz USVs emission is variable among rats, indicating individual differences in contextual response bound up with pharmacological reward. The aims of this study were to: extract the most important neurotransmitters related to context-induced conditioned 50-kHz USVs response; find biological basis of existing inter-individual differences in context-induced conditioned 50-kHz USVs response; create a model of all-to-all neurotransmitters correlations...
May 17, 2018: Brain Structure & Function
https://www.readbyqxmd.com/read/29774203/small-rho-gtpases-and-the-effector-vipa-mediate-the-invasion-of-epithelial-cells-by-filamentous-legionella-pneumophila
#11
Akriti Prashar, María Eugenia Ortiz, Stefanie Lucarelli, Elizabeth Barker, Zohreh Tabatabeiyazdi, Feras Shamoun, Deepa Raju, Costin Antonescu, Cyril Guyard, Mauricio R Terebiznik
Legionella pneumophila (Lp) exhibits different morphologies with varying degrees of virulence. Despite their detection in environmental sources of outbreaks and in respiratory tract secretions and lung autopsies from patients, the filamentous morphotype of Lp remains poorly studied. We previously demonstrated that filamentous Lp invades lung epithelial cells (LECs) and replicates intracellularly in a Legionella containing vacuole. Filamentous Lp activates β1integrin and E-cadherin receptors at the surface of LECs leading to the formation of actin-rich cell membrane structures we termed hooks and membrane wraps...
2018: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/29772355/safety-assessment-of-morus-nigra-l-leaves-acute-and-subacute-oral-toxicity-studies-in-wistar-rats
#12
Kassia Caroline Figueredo, Camille Gaube Guex, Fernanda Ziegler Reginato, Andreia Regina Haas da Silva, Gabriela Buzatti Cassanego, Cibele Lima Lhamas, Aline Augusti Boligon, Gilberti Helena Hübscher Lopes, Liliane de Freitas Bauermann
ETHNOPHARMACOLOGICAL RELEVANCE: Morus nigra L. is a plant native to Asia, and well adapted to the Brazilian climate. It is popularly known as "amoreira preta", and is part of the National List of Plants of Interest to the Brazilian Unified Health System. It is used in folk medicine mainly to soften the effects of menopause, as anti-inflammatory, antidiabetic and antihypertensive. However, information on safe doses and use is still precarious. AIM OF THE STUDY: To identify the chemical composition of the ethanolic extract of Morus nigra L...
May 14, 2018: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/29771909/receptors-of-intermediates-of-carbohydrate-metabolism-gpr91-and-gpr99-mediate-axon-growth
#13
Hosni Cherif, François Duhamel, Bruno Cécyre, Alex Bouchard, Ariane Quintal, Sylvain Chemtob, Jean-François Bouchard
During the development of the visual system, high levels of energy are expended propelling axons from the retina to the brain. However, the role of intermediates of carbohydrate metabolism in the development of the visual system has been overlooked. Here, we report that the carbohydrate metabolites succinate and α-ketoglutarate (α-KG) and their respective receptor-GPR91 and GPR99-are involved in modulating retinal ganglion cell (RGC) projections toward the thalamus during visual system development. Using ex vivo and in vivo approaches, combined with pharmacological and genetic analyses, we revealed that GPR91 and GPR99 are expressed on axons of developing RGCs and have complementary roles during RGC axon growth in an extracellular signal-regulated kinases 1 and 2 (ERK1/2)-dependent manner...
May 17, 2018: PLoS Biology
https://www.readbyqxmd.com/read/29771182/ciliogenesis-is-reciprocally-regulated-by-ppara-and-nr1h4-fxr-through-controlling-autophagy-in-vitro-and-in-vivo
#14
Zhi-Qiang Liu, Joon No Lee, Myeongjoo Son, Jae-Young Lim, Raghbendra Kumar Dutta, Yunash Maharjan, SeongAe Kwak, Goo Taeg Oh, Kyunghee Byun, Seong-Kyu Choe, Raekil Park
The primary cilia are evolutionarily conserved microtubule-based cellular organelles that perceive metabolic status and thus link the sensory system to cellular signaling pathways. Therefore, ciliogenesis is thought to be tightly linked to autophagy, which is also regulated by nutrient-sensing transcription factors, such as PPARA (peroxisome proliferator activated receptor alpha) and NR1H4/FXR (nuclear receptor subfamily 1, group H, member 4). However, the relationship between these factors and ciliogenesis has not been clearly demonstrated...
May 17, 2018: Autophagy
https://www.readbyqxmd.com/read/29770796/suppression-of-mif-induced-neuronal-apoptosis-may-underlie-the-therapeutic-effects-of-effective-components-of-fufang-danshen-in-the-treatment-of-alzheimer-s-disease
#15
Cheng-Jie Liang, Jia-Huang Li, Zhen Zhang, Ju-Yan Zhang, Shu-Qun Liu, Jie Yang
Fufang Danshen (FFDS or Compound Danshen) consists of three Chinese herbs Danshen (Salviae miltiorrhizae radix et rhizome), Sanqi (Notoginseng radix et rhizome) and Tianranbingpian (Borneolum, or D-borneol), which has been show to significantly improve the function of the nervous system and brain metabolism. In this study we explored the possible mechanisms underlying the therapeutic effects of the combination of the effective components of FFDS (Tan IIA, NG-R1 and Borneol) in the treatment of Alzheimer's disease (AD) based on network pharmacology...
May 17, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29770207/recent-advances-in-bioreactors-for-cell-based-therapies
#16
REVIEW
Makeda Stephenson, Warren Grayson
Bioreactors have become indispensable tools in the cell-based therapy industry. Various forms of bioreactors are used to maintain well-controlled microenvironments to regulate cell growth, differentiation, and tissue development. They are essential for providing standardized, reproducible cell-based products for regenerative medicine applications or to establish physiologically relevant in vitro models for testing of pharmacologic agents. In this review, we discuss three main classes of bioreactors: cell expansion bioreactors, tissue engineering bioreactors, and lab-on-a-chip systems...
2018: F1000Research
https://www.readbyqxmd.com/read/29768709/comprehensive-multi-modal-characterization-of-an-imiquimod-induced-human-skin-inflammation-model-for-drug-development
#17
Tessa van der Kolk, Salma Assil, Rianne Rijneveld, Erica S Klaassen, Gary Feiss, Edwin Florencia, Errol P Prens, Jacobus Burggraaf, Matthijs Moerland, Robert Rissmann, Martijn B A van Doorn
Imiquimod (IMQ) is often used as topical challenge agent to provoke local skin inflammation. The objective of this study was to develop and refine a rapid, temporary and reversible human skin inflammation model with IMQ for application in clinical drug development. A randomized, vehicle-controlled, open-label, dose-ranging study was conducted in 16 healthy male subjects. IMQ (5 mg) was applied once daily for 72h under occlusion to intact skin (n = 8) or tape stripped (TS) skin (n = 8). Although IMQ alone induced limited effects, TS+IMQ treatment showed larger responses in several domains including erythema and perfusion (p<0...
May 16, 2018: Clinical and Translational Science
https://www.readbyqxmd.com/read/29768498/genomic-variants-in-an-inbred-mouse-model-predict-mania-like-behaviors
#18
Michael C Saul, Sharon A Stevenson, Changjiu Zhao, Terri M Driessen, Brian E Eisinger, Stephen C Gammie
Contemporary rodent models for bipolar disorders split the bipolar spectrum into complimentary behavioral endophenotypes representing mania and depression. Widely accepted mania models typically utilize single gene transgenics or pharmacological manipulations, but inbred rodent strains show great potential as mania models. Their acceptance is often limited by the lack of genotypic data needed to establish construct validity. In this study, we used a unique strategy to inexpensively explore and confirm population allele differences in naturally occurring candidate variants in a manic rodent strain, the Madison (MSN) mouse strain...
2018: PloS One
https://www.readbyqxmd.com/read/29768349/comparison-of-multiple-interventions-for-older-adults-with-alzheimer-disease-or-mild-cognitive-impairment-a-prisma-compliant-network-meta-analysis
#19
Jing-Hong Liang, Yong Xu, Lu Lin, Rui-Xia Jia, Hong-Bo Zhang, Lei Hang
BACKGROUND: The increasing prevalence of Alzheimer disease (AD) emphasizes the need for effective treatments. Both pharmacological therapies such as nutrition therapy (NT) and nonpharmacologic therapies including traditional treatment or personalized treatment (e.g., physical exercise, music therapy, computerized cognitive training) have been approved for the treatment of AD or mild cognitive impairment (MCI) in numerous areas. METHODS: The aim of this study was to compare 4 types of interventions, physical exercise (PE), music therapy (MT), computerized cognitive training (CCT), and NT, in older adults with mild to moderate AD or MCI and identify the most effective intervention for their cognitive function...
May 2018: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29767298/-complications-and-side-effects-of-conservative-treatment-of-rhinological-diseases
#20
REVIEW
I Küster, C Rudack, A Beule
BACKGROUND: The spectrum of rhinological diseases is wide, as is that of their drug-based treatment. Only 1272 compounds coded R01 (nasal preparations) are listed in the ATC group (Anatomical Therapeutic Chemical Classification). Conservative therapy of rhinological diseases additionally includes systemic (often oral) application of corticosteroids, antibiotics and immunomodulators. OBJECTIVE: The aim of this paper is to outline possible complications of medication (subdivided into classes of ingredients) commonly used to treat rhinological diseases in hospitals...
May 16, 2018: HNO
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