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https://www.readbyqxmd.com/read/29150942/a-novel-epididymal-quiescence-factor-inhibits-sperm-motility-by-modulating-nos-activity-and-intracellular-no-cgmp-pathway
#1
Prasanta Ghosh, Sandipan Mukherjee, Arpita Bhoumik, Sandhya Rekha Dungdung
Mature and potentially motile spermatozoa stored in cauda epididymis in an inactive state for approximately 30 days; however during ejaculation they regain motility. To understand the actual molecular mechanism of the sperm quiescence during caudal stay, a proteinaceous quiescence factor (QF) has been purified from caprine epididymal plasma to apparent homogeneity. In the present study complete purification, detailed characterization as well as mechanistic pathway of QF has been described. QF was purified to 215 fold with 45% activity recovery...
November 18, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29150937/cgmp-production-and-analysis-of-bg505-sosip-664-an-extensively-glycosylated-trimeric-hiv-1-envelope-glycoprotein-vaccine-candidate
#2
Antu K Dey, Albert Cupo, Gabriel Ozorowski, Vaneet K Sharma, Anna-Janina Behrens, Eden P Go, Thomas J Ketas, Anila Yasmeen, Per J Klasse, Eddy Sayeed, Heather Desaire, Max Crispin, Ian A Wilson, Rogier W Sanders, Thomas Hassell, Andrew Ward, John P Moore
We describe the properties of BG505 SOSIP.664 HIV-1 envelope glycoprotein trimers produced under current Good Manufacturing Practice (cGMP) conditions. These proteins are the first of a new generation of native-like trimers that are the basis for many structure-guided immunogen development programs aimed at devising how to induce broadly neutralizing antibodies (bNAbs) to HIV-1 by vaccination. The successful translation of this prototype demonstrates the feasibility of producing similar immunogens on an appropriate scale and of an acceptable quality for Phase I experimental medicine clinical trials...
November 18, 2017: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29150923/pkg-ii-effectively-reversed-egf-induced-protein-expression-alterations-in-human-gastric-cancer-cell-lines
#3
Hai Qian, Yan Tao, Lu Jiang, Ying Wang, Ting Lan, Min Wu, Ji Pang, Kwaku Appiah-Kubi, Yongchang Chen, Yan Wu
Epidermal growth factor receptor (EGFR) plays an important role in gastric cancer (GC) progression. Our previous data demonstrated that type II cGMP-dependent protein kinase (PKG II) could block the EGF-EGFR axis as well as down-stream signaling pathways for example, MAPK, PI3K and PLC in gastric cancer cells. However, the exact mechanisms of PKG II against cancer remain unclear. Therefore, the present work was to address the above question. Human gastric cancer cell line AGS was infected with adenoviral construct encoding cDNA of PKG II (Ad-PKG II) to up-regulate PKG II and then treated with 8-pCPT-cGMP...
November 18, 2017: Cell Biology International
https://www.readbyqxmd.com/read/29150274/neuroprotective-potential-of-high-dose-biotin
#4
Mark F McCarty, James J DiNicolantonio
A recent controlled trial has established that high-dose biotin supplementation - 100 mg, three times daily - has a stabilizing effect on progression of multiple sclerosis (MS). Although this effect has been attributed to an optimization of biotin's essential cofactor role in the brain, a case can be made that direct stimulation of soluble guanylate cyclase (sGC) by pharmacological concentrations of biotin plays a key role in this regard. The utility of high-dose biotin in MS might reflect an anti-inflammatory effect of cGMP on the cerebral microvasculature, as well on oligodendrocyte differentiation and on Schwann cell production of neurotrophic factors thought to have potential for managing MS...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29138480/nitric-oxide-contributes-to-high-salt-perception-in-a-blood-sucking-insect-model
#5
Agustina Cano, Gina Pontes, Valeria Sfara, Diego Anfossi, Romina B Barrozo
In all organisms, salts produce either appetitive or aversive responses depending on the concentration. While low-salt concentration in food elicits positive responses to ingest, high-salt triggers aversion. Still the mechanisms involved in this dual behavior have just started to be uncovered in some organisms. In Rhodnius prolixus, using pharmacological and behavioral assays, we demonstrated that upon high-salt detection in food a nitric oxide (NO) dependent cascade is activated. This activation involves a soluble guanylate cyclase (sGC) and the production of cyclic guanosine monophosphate (cGMP)...
November 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29138357/tadalafil-a-long-acting-phosphodiesterase-inhibitor-promotes-bone-marrow-stem-cell-survival-and-their-homing-into-ischemic-myocardium-for-cardiac-repair
#6
Ibrahim Elmadbouh, Muhammad Ashraf
The aim was to evaluate the tadalafil-mediated effects at molecular level on bone marrow-derived mesenchymal stem cells (MSCs) survival and their homing into the infarcted hearts to promote cardiac repair and improve function. MSCs were pretreated in vitro with inhibitors of PKG, MAPK, FasL, nitric oxide synthase (NOS) (L-NAME), CXCR4 (AMD3100), or miR-21 inhibitors (+/-luciferase construction +/-Fas) prior to tadalafil treatment for 2 h. These MSCs were then subjected to H2O2 stress to assess their injury...
November 2017: Physiological Reports
https://www.readbyqxmd.com/read/29138269/irreversible-activation-and-stabilization-of-soluble-guanylate-cyclase-by-the-protoporphyrin-ix-mimetic-cinaciguat
#7
Alexander Kollau, Marissa Opelt, Gerald Wölkart, Antonius C F Gorren, Michael Russwurm, Doris Koesling, Bernd Mayer, Astrid Schrammel
Belonging to the class of so-called sGC activators, cinaciguat and BAY 60-2770 are interesting therapeutic tools for the treatment of various cardiovascular pathologies. The drugs are supposed to preferentially stimulate oxidized or heme-depleted but not native sGC. Since this concept has been challenged by studies demonstrating complete relaxation of non-diseased vessels, this study was designed to re-investigate the mode of action in greater detail. To this purpose, the effect of cinaciguat was studied on vessel tone of porcine coronary arteries and rat thoracic aortas...
November 14, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/29136777/anti-hypertensive-and-vasodilatory-effects-of-amended-banxia-baizhu-tianma-tang
#8
Chu Shan Tan, Yean Chun Loh, Chiew Hoong Ng, Yung Sing Ch'ng, Mohd Zaini Asmawi, Mariam Ahmad, Mun Fei Yam
Although Banxia Baizhu Tianma Tang (BBT) has been long administered for hypertensive treatment in Traditional Chinese Medicine (TCM), the ratio of the herbal components that makes up the formulation has not been optimized with respect to the anti-hypertensive effect that it inherently possesses. A newly amended BBT (ABBT) formulation was developed using the evidence-based approach of orthogonal stimulus-response compatibility model. The ABBT showed enhanced therapeutic effect while maintaining its traditional theoretical approach rooted in TCM...
November 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29133940/stimulators-and-activators-of-soluble-guanylate-cyclase-for-urogenital-disorders
#9
REVIEW
Fabiola Z Mónica, Edson Antunes
Lower urinary tract symptoms (LUTS), comprising storage (such as urinary incontinence and urinary frequency), voiding, and postmicturition symptoms, are highly prevalent conditions that affect millions of people worldwide. LUTS have a profound effect on quality of life and are a considerable cost to health care systems. In men specifically, BPH commonly leads to LUTS. Clinical studies also show an association of LUTS with erectile dysfunction (ED). Nitric oxide (NO) has long been recognized as an important nonadrenergic, noncholinergic (NANC) transmitter in bladder, urethra, prostate, and corpus cavernosum smooth muscle...
November 14, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/29132129/administration-of-curcumin-protects-kidney-tubules-against-renal-ischemia-reperfusion-injury-riri-by-modulating-nitric-oxide-no-signaling-pathway
#10
Fuhe Liu, Wenjuan Ni, Jiajia Zhang, Guokang Wang, Fanzhu Li, Wenxia Ren
BACKGROUND/AIMS: To explore the protective effect of curcumin on renal ischemia-reperfusion injury (RIRI) in rats, and its influence on nephridial tissue's NO and cGMP levels as well as downstream signaling pathway, to elucidate the possible mechanism of curcumin on RIRI. METHODS: 36 Sprague Dawley rats (SD rats) were randomly divided into Sham group, Model group, curcumin (CUR +) Model group, 12 rats per group. They were all given RIRI model preparation by unilateral artery occlusion method...
November 13, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29132113/fluorometric-detection-of-protein-ligand-engagement-the-case-of-phosphodiesterase5
#11
Giulia Di Rocco, Ilaria Martinelli, Salvatore Pacifico, Remo Guerrini, Elena Cichero, Paola Fossa, Silvia Franchini, Silvia Cardarelli, Mauro Giorgi, Marco Sola, Glauco Ponterini
Phosphodiesterases (PDEs) regulate the intracellular levels of cAMP and cGMP. The great clinical success of the PDE5 inhibitors, Sildenafil (Viagra), Vardenafil (Levitra) and Tadalafil (Cialis) has led to an increasing interest for this class of enzymes. Recent studies have shown a correlation between tumor growth and PDE5 overexpression, making PDE5-selective inhibitors promising candidates for cancer treatment. The search for such inhibitors rests today on radioactive assays. In this work, we exploit the conserved catalytic domain of the enzyme and propose a faster and safer method for detecting the binding of ligands and evaluate their affinities...
November 10, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/29130591/familial-choreoathetosis-due-to-novel-heterozygous-mutation-in-pde10a
#12
Dhanya L Narayanan, Dipti Deshpande, Aneek Das Bhowmik, Dandu R Varma, Ashwin Dalal
PDE10A encodes a dual cAMP-cGMP phosphodiesterase that is enriched in the medium spiny neurons of the corpus striatum in the brain and plays an important role in basal ganglia circuitry. Three unrelated patients with childhood onset chorea and striatal abnormalities on MRI brain with heterozygous de novo variants in PDE10A have been described previously. Two families with eight affected individuals with biallelic mutations in PDE10A have also been described previously. We report a family with multiple affected individuals with childhood onset chorea, striatal abnormalities, and a novel heterozygous mutation, c...
November 12, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/29130351/the-gene-therapy-resource-program-a-decade-of-dedication-to-translational-research-by-the-national-heart-lung-and-blood-institute
#13
Terence R Flotte, Eric Daniels, Janet Benson, Jenee M Bevett-Rose, Kenneth Cornetta, Margaret Diggins, Julie Johnston, Susan Sepelak, Johannes Van Der Loo, James M Wilson, Cheryl L McDonald
Over a ten-year period, the Gene Therapy Resource Program (GTRP) of the National Heart Lung and Blood Institute (NHLBI) has provided a set of core services to investigators to facilitate the clinical translation of gene therapy. These services have included a preclinical (research-grade) vector production core; current Good Manufacturing Practice (cGMP) clinical-grade vector cores for recombinant adeno-associated virus (rAAV) and lentivirus vectors; a pharmacology and toxicology core; and a coordinating center to manage program logistics and to provide regulatory and financial support to early phase clinical trials...
November 12, 2017: Human Gene Therapy. Clinical Development
https://www.readbyqxmd.com/read/29126066/formaldehyde-regulates-vascular-tensions-through-nitric-oxide-cgmp-signaling-pathway-and-ion-channels
#14
Quanxi Zhang, Peiru Tian, Miaomiao Zhai, Xiaodong Lei, Zhenhua Yang, Yan Liu, Mengting Liu, Hao Huang, Xiri Zhang, Xu Yang, Yun Zhao, Ziqiang Meng
Formaldehyde (FA) has been linked to the detrimental cardiovascular effects. Here, we explored the effects and mechanisms of FA on rat aortas both in vivo and in vitro. The results presented that FA evidently lowered the blood pressures of rats. The expression levels of BKCa subunits α and β1 and iNOS of the aortas were up-regulated by FA in vivo. However, FA markedly reduced the levels of Cav1.2 and Cav1.3, which are the subunits of L-Ca(2+) channel. Furthermore, the contents of NO, cGMP and iNOS in the aortas were augmented by FA...
November 4, 2017: Chemosphere
https://www.readbyqxmd.com/read/29122629/long-term-cilostazol-administration-prevents-age-related-decline-of-hippocampus-dependent-memory-in-mice
#15
Shuichi Yanai, Hideki Ito, Shogo Endo
Phosphodiesterases (PDEs) are enzymes that hydrolyze and inactivate 3', 5'-cyclic adenosine monophosphate (cAMP) and/or 3', 5'-cyclic guanosine monophosphate (cGMP). The regulation of intracellular signaling pathways mediated by cyclic nucleotides is imperative to synaptic plasticity and memory in animals. Because PDEs play an important role in this regulation, PDE inhibitors are considered as candidate compounds for treating cognitive and memory disorders. In the present study, we tested whether cilostazol, a selective PDE3 inhibitor, prevents the cognitive deterioration that occurs during the course of normal aging in mice...
November 6, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29119630/mycobacterium-tuberculosis-rv3651-is-a-triple-sensor-domain-protein
#16
Jan Abendroth, Andrew Frando, Isabelle Q Phan, Bart L Staker, Peter J Myler, Thomas E Edwards, Christoph Grundner
The genome of the human pathogen Mycobacterium tuberculosis (Mtb) encodes ∼4,400 proteins, but one third of them have unknown functions. We solved the crystal structure of Rv3651, a hypothetical protein with no discernible similarity to proteins with known function. Rv3651 has a three-domain architecture that combines one cGMP-specific phosphodiesterases, adenylyl cyclases and FhlA (GAF) domain and two Per-ARNT-Sim (PAS) domains. GAF and PAS domains are typically sensor domains that are linked to signaling effector molecules...
November 9, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/29119484/clinically-amendable-defined-and-rapid-induction-of-human-brain-organoids-from-induced-pluripotent-stem-cells
#17
Eva Tomaskovic-Crook, Jeremy M Crook
Human brain organoids provide opportunities to produce three-dimensional (3D) brain-like tissues for biomedical research and translational drug discovery, toxicology, and tissue replacement. Here we describe a protocol for rapid and defined induction of brain organoids from human induced pluripotent stem cells (iPSCs), using commercially available culture and differentiation media and a cheap, easy to handle and clinically approved semisynthetic hydrogel. Importantly, the methodology is uncomplicated, well-defined, and reliable for reproducible and scalable organoid generation, and amendable to principles of current good laboratory practice (cGLP), with the potential for prospective adaptation to current good manufacturing practice (cGMP) toward clinical compliance...
November 9, 2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29113064/inhibition-of-cyclic-adenosine-monophosphate-specific-phosphodiesterase-by-various-food-plant-derived-phytotherapeutic-agents
#18
Teresa Röhrig, Olga Pacjuk, Silvia Hernández-Huguet, Johanna Körner, Katharina Scherer, Elke Richling
Background: Phosphodiesterases (PDEs) play a major role in the regulation of cyclic adenosine monophosphate (cAMP)- and cyclic guanosine monophosphate (cGMP)-mediated pathways. Their inhibitors exhibit anti-inflammatory, vasodilatory and antithrombotic effects. Therefore, consumption of foods with PDE-inhibiting potential may possess beneficial influence on the risk of cardiovascular diseases. Methods: Four plant extracts (Arbutus unedo, Camellia sinensis, Cynara scolymus, Zingiber officinale) with promising ingredient profiles and physiological effects were tested for their ability to inhibit cAMP-specific PDE in vitro in a radioactive assay...
November 4, 2017: Medicines (Basel, Switzerland)
https://www.readbyqxmd.com/read/29111666/switching-cyclic-nucleotide-selective-activation-of-pka-holoenzyme-reveals-distinct-roles-of-tandem-cnb-domains
#19
Daniel He, Robin Lorenz, Choel Kim, Friedrich W Herberg, Chinten James Lim
The cAMP- and cGMP-dependent protein kinases (PKA and PKG) are key effectors of cyclic nucleotide signaling. Both share structural features that include tandem cyclic nucleotide-binding (CNB) domains, CNB-A and CNB-B, yet their functions are separated through preferential activation by either cAMP or cGMP. Based on structural studies and modeling, key CNB contact residues have been identified for both kinases. In this study, we explored the requirements for conversion of PKA activation from cAMP-dependent to cGMP-dependent...
November 7, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/29110463/8-nitro-cgmp-attenuates-the-interaction-between-snare-complex-and-complexin-through-s-guanylation-of-snap-25
#20
Yusuke Kishimoto, Kohei Kunieda, Atsushi Kitamura, Yuki Kakihana, Takaaki Akaike, Hideshi Ihara
8-Nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) is the second messenger in nitric oxide/reactive oxygen species redox signaling. This molecule covalently binds to protein thiol groups, called S-guanylation, and exerts various biological functions. Recently, we have identified synaptosomal-associated protein 25 (SNAP-25) as a target of S-guanylation, and demonstrated that S-guanylation of SNAP25 enhanced SNARE complex formation. In this study, we have examined the effects of S-guanylation of SNAP-25 on the interaction between the soluble SNARE complex and complexin (cplx), which binds to the SNARE complex with a high affinity...
November 7, 2017: ACS Chemical Neuroscience
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