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  • ||||||||||  GTS21 / CoMentis
    Journal:  Vagal-α7nAChR signaling promotes lung stem cells regeneration via fibroblast growth factor 10 during lung injury repair. (Pubmed Central) -  Jun 22, 2021   
    These results demonstrated that low-dose ketamine could produce neuroprotective effects by activating the α7nAChR-mediated cholinergic anti-inflammatory pathway (CAP) in depression, resulting in a rapid antidepressant effect. The vagus nerve deploys α7nAChR to enhance LSCs proliferation and transdifferentiation and promote lung repair in an FGF10-dependent manner during LPS-induced lung injury.
  • ||||||||||  Actemra IV (tocilizumab) / Roche, JW Pharma
    Journal:  From nicotine to the cholinergic anti-inflammatory reflex - Can nicotine alleviate the dysregulated inflammation in COVID-19? (Pubmed Central) -  May 1, 2021   
    Nicotine can activate the cholinergic anti-inflammatory reflex, which attenuates the up-regulation and the excessive release of pro-inflammatory cytokines/chemokines. Therefore, we hypothesize that low molecular weight compounds that activate the cholinergic anti-inflammatory reflex, such as nicotine or GTS-21, may represent a potential therapeutic approach to attenuate the dysregulated inflammatory responses in patients with severe COVID-19.
  • ||||||||||  GTS21 / CoMentis
    Journal:  Activation of the Cholinergic Anti-inflammatory Pathway Attenuated Angiotension II-Dependent Hypertension and Renal Injury. (Pubmed Central) -  Apr 7, 2021   
    In vitro, GTS-21 suppressed NF-κB activation, attenuated AngII-induced epithelial-mesenchymal transition and reduced inflammation and fibrosis in NRK-52E cells; α-bungarotoxin (α-Bgt, an α7-nAChR selective antagonist) partly inhibited these effects. CAP protected against AngII-induced hypertension via improvement in autonomic control, suppression of NF-κB activation, and reduction of renal fibrosis and inflammatory response.
  • ||||||||||  GTS21 / CoMentis
    [VIRTUAL] GTS-21 Attenuates the Inflammation of AKI Independent of α7 Nicotinic Acetylcholine Receptor (On-Demand) -  Oct 11, 2020 - Abstract #KIDNEYWEEK2020KIDNEY_WEEK_804;    
    Therefore, the α7nAChR represents a possible pharmacological target to improve the clinical outcome of patients on ventilators by augmenting host defense against bacterial infections. These results suggest that nicotine or GTS-21 might suppress the inflammation independent of α7nAChR in macrophages in vivo and in vitro.
  • ||||||||||  GTS21 / CoMentis
    Journal:  Distinct Roles of α7 nAChRs in Antigen-Presenting Cells and CD4 T Cells in the Regulation of T Cell Differentiation. (Pubmed Central) -  Aug 23, 2020   
    In addition, during antigen-nonspecific, APC-independent anti-CD3/CD28 antibody-induced CD4 polyclonal T cell activation in the presence of respective polarizing cytokines, GTS-21 promoted development of all lineages, which indicates that GTS-21 also acts via α7 nAChRs on T cells. These results suggest 1) that α7 nAChRs on APCs suppress CD4 T cell activation by interfering with antigen presentation through inhibition of antigen processing; 2) that α7 nAChRs on CD4 T cells up-regulate development of Tregs and effector T cells; and that α7 nAChR agonists and antagonists could be potentially useful agents for immune response modulation and enhancement.
  • ||||||||||  GTS21 / CoMentis
    Journal:  The cholinergic anti-inflammatory pathway alleviates acute lung injury. (Pubmed Central) -  Jul 15, 2020   
    This comprehension was recently reinforced by results reported in Molecular Medicine by Sitapara and coworkers demonstrating that administration of an α7 nicotinic acetylcholine receptor agonist attenuated hyperoxia-induced acute inflammatory lung injury by alleviating the accumulation of HMGB1 in the airways and the circulation. Activating the cholinergic antiinflammatory path might be considered to alleviate severe COVID-19 with or without concurrent oxygen-induced lung injury.
  • ||||||||||  GTS21 / CoMentis
    Journal:  The cholinergic anti-inflammatory pathway in resistant hypertension treated with renal denervation. (Pubmed Central) -  Jul 7, 2020   
    RDN has an immediate effect on TNF in vivo and cytokine release ex vivo but seems to wane over time suggesting that current RDN techniques may not have long-lasting immunomodulatory effect. Repeated and extended stimulation of CAP in resistant hypertension by targeting neural circuits may be a potential therapeutic strategy for treatment of both hypertension and inflammation.
  • ||||||||||  GTS21 / CoMentis
    Review, Journal:  Minireview: Divergent roles of α7 nicotinic acetylcholine receptors expressed on antigen-presenting cells and CD4 T cells in the regulation of T cell differentiation. (Pubmed Central) -  Feb 23, 2020   
    Using spleen cells from ovalbumin (OVA)-specific T cell receptor transgenic DO11.10 mice and the α7 nAChR agonist GTS-21, investigation of (1) antigen processing-dependent and (2) -independent, antigen presenting cell (APC)-dependent, naïve CD4 T cell differentiation, as well as (3) non-specific APC-independent, anti-CD3/CD28 mAbs-induced CD4 T cell differentiation, revealed the differential roles of α7 nAChRs expressed on T cells and APCs in the regulation of CD4 T cell differentiation...Thus, the divergent roles of α7 nAChRs on APCs and T cells likely regulate the intensity of immune responses. These findings suggest the possibility of using α7 nAChR agonists to harvest greater numbers of Tregs and Th1 and Th2 cells for adoptive immune therapies for treatment of autoimmune diseases and cancers.
  • ||||||||||  GTS21 / CoMentis
    Trial completion:  DMXB-A: Phase 2 Trial of a Nicotinic Agonist in Schizophrenia (clinicaltrials.gov) -  Jan 29, 2020   
    P2,  N=29, Completed, 
    2014) is part of an investigation being conducted by the journal following the conclusions of an institutional enquiry at the University of Liverpool with respect to the quantitative mass spectrometry-generated results regarding acetylated and redox-modified HMGB1. Recruiting --> Completed
  • ||||||||||  GTS21 / CoMentis
    Journal:  GTS-21 has cell-specific anti-inflammatory effects independent of α7 nicotinic acetylcholine receptors. (Pubmed Central) -  Dec 25, 2019   
    Further, GTS-21 significantly inhibited LPS-induced IL6 and TNF secretion in macrophages isolated from knockout mice lacking α7 nAChRs. These data indicate that even though a discrete component of the anti-inflammatory effects of GTS-21 requires expression of α7 nAChRs in macrophages, GTS-21 also has anti-inflammatory effects independent of these receptors depending on the cellular context.
  • ||||||||||  ciprofloxacin / Generic Mfg.
    Deriving an Expanded Phenotypic Space for Cardiovascular Disease Using Whole Blood Perturbations (Zone 1, Science and Technology Hall) -  Nov 18, 2019 - Abstract #AHA2019AHA_10317;    
    We have established a framework for expansion of phenotypic space via whole blood perturbations, enabling rapid testing of novel disease-associations. Future work will include delineating the genetic basis of perturbation responses as well as using unsupervised learning approaches for disease subtyping via this multidimensional phenotypic readout.
  • ||||||||||  GTS21 / CoMentis
    Alpha-7 Nicotinic Receptor Agonist GTS-21 Ameliorates Contrast-Induced Nephropathy in Rats (Exhibit Hall, Walter E. Washington Convention Center) -  Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_3634;    
    In both contrast groups, an increase in IL-6 expression and a reduction in TGF-β expression were observed (p<0.05), but GTS-21 treatment increased TGF-β expression (p <0.05) and slightly depressed IL-6 expression. Conclusion GTS-21 improves renal dysfunction and provides a significant protection against contrast nephropathy via anti-oxidant and anti-inflammatory mechanisms.
  • ||||||||||  GTS21 / CoMentis
    Renal Protective Effect by Vagus Nerve Stimulation After Kidney Injury (Exhibit Hall, Walter E. Washington Convention Center) -  Oct 14, 2019 - Abstract #KIDNEYWEEK2019KIDNEY_WEEK_1103;    
    Because a7 nicotinic receptor plays an important role in the CAP, all of the cells were treated with a7nicotinic receptor agonist GTS-21 (50 mM for each) 4 and 6 hours after LPS administration, followed by assessment of the inflammatory status (TNF-α, IL-1β)...Conclusion CAP activation after injury could also exert organ protective effect. Funding Commercial Support
  • ||||||||||  GTS21 / CoMentis
    Preclinical, Journal:  Improved Outcomes of Cardiopulmonary Resuscitation in Rats Treated with Vagus Nerve Stimulation and its Potential Mechanism. (Pubmed Central) -  Aug 17, 2019   
    Forty animals were randomized into four groups and all underwent CPR (n = 10 each): CPR alone (control); VNS during CPR; α7nAChR antagonist methyllycaconitine citrate (MLA) with VNS; α7nAChR agonist 3-(2, 4-dimethoxybenzylidene) anabaseine (GTS-21 dihydrochloride) without VNS...In addition, VNS decreased the number of electrical shocks and the duration of CPR required. VNS improves multiple outcomes after CPR.
  • ||||||||||  GTS21 / CoMentis
    Trial initiation date, Trial primary completion date:  Effects of GTS-21 on Smoking Behavior and Neurocognitive Functions (clinicaltrials.gov) -  Jun 17, 2016   
    P2,  N=54, Not yet recruiting, 
    Phase classification: P1/2 --> P1b/2a | Recruiting --> Suspended Initiation date: Jul 2016 --> Dec 2016 | Trial primary completion date: Jul 2017 --> Dec 2018
  • ||||||||||  GTS21 / CoMentis
    Trial initiation date:  Effects of GTS-21 on Smoking Behavior and Neurocognitive Functions (clinicaltrials.gov) -  Nov 15, 2015   
    P2,  N=54, Not yet recruiting, 
    Recruiting --> Active, not recruiting | Trial primary completion date: May 2015 --> Jan 2016 Initiation date: Jul 2015 --> Jul 2016
  • ||||||||||  GTS21 / CoMentis
    Trial completion, Enrollment change, Trial primary completion date:  Nicotinic Receptors and Schizophrenia (clinicaltrials.gov) -  Jun 16, 2015   
    P2,  N=97, Completed, 
    Initiation date: Jul 2015 --> Jul 2016 Recruiting --> Completed | N=150 --> 97 | Trial primary completion date: Jun 2017 --> Jun 2015
  • ||||||||||  GTS21 / CoMentis
    Trial primary completion date:  DMXB-A: Phase 2 Trial of a Nicotinic Agonist in Schizophrenia (clinicaltrials.gov) -  Mar 12, 2015   
    P2,  N=36, Recruiting, 
    Recruiting --> Completed | N=150 --> 97 | Trial primary completion date: Jun 2017 --> Jun 2015 Trial primary completion date: Dec 2014 --> Dec 2015
  • ||||||||||  GTS21 / CoMentis
    Trial primary completion date:  Nicotinic Receptors and Schizophrenia (clinicaltrials.gov) -  Dec 9, 2014   
    P1,  N=10, Completed, 
    Trial primary completion date: Dec 2014 --> Dec 2015 Trial primary completion date: Jan 2013 --> Oct 2014
  • ||||||||||  GTS21 / CoMentis
    Trial primary completion date:  Nicotinic Receptors and Schizophrenia (clinicaltrials.gov) -  Dec 5, 2014   
    P2,  N=150, Recruiting, 
    Trial primary completion date: Jan 2013 --> Oct 2014 Trial primary completion date: Jun 2014 --> Jun 2017
  • ||||||||||  GTS21 / CoMentis
    Enrollment open:  Nicotinic Receptors and Schizophrenia (clinicaltrials.gov) -  Jan 30, 2013   
    P2,  N=150, Recruiting, 
    Trial primary completion date: Jun 2014 --> Jun 2017 Active, not recruiting --> Recruiting