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Neuronal Signaling

Anti-myeloma effect of pharmacological inhibition of Notch/gamma-secretase with RO4929097 is mediated by modulation of tumor microenvironment

6 | Dec 02 2019

Pisklakova A et al. indicated that targeting Notch may be considered as a new strategy to be tested for MM therapy. [Read the Full Post]

Exogenous mesenchymal stem cells affect the function of endogenous lung stem cells (club cells) in phosgene-induced lung injury

0 | Oct 21 2019

Ye K et al. showed that MSCs reduced the secretion of club cells. And MSCs enhanced the proliferation of club cells partly via activating the Notch signaling pathway, which promoted lung injury repair. [Read the Full Post]

The BACE1 inhibitor verubecestat (MK-8931) reduces CNS β-amyloid in animal models and in Alzheimer's disease patients

79 | Aug 27 2019

Kennedy ME indicated the human data were fit to an amyloid pathway model that provided insight into the Aβ pools affected by BACE1 inhibition and guided the choice of doses for subsequent clinical trials. [Read the Full Post]

Notch signaling pathway is a potential therapeutic target for extracranial vascular malformations

97 | Aug 18 2019

Davis RB et al. showed that two gamma secretase inhibitors (GSIs), DAPT (GSI-IX) and RO4929097, cause dose-dependent inhibition of Notch target gene expression (Hey1) and rate of migration of monolayer cultures of lymphatic endothelial cells (hLECs) and blood endothelial cells (HUVEC). GSIs also inhibit HUVEC network formation. hLECs are more sensitive to GSIs compared to HUVEC. GSIs have been found to be safe in clinical trials in patients with Alzheimer's disease or cancer. Our results provide further rationale to support testing of Notch inhibitors in patients with extracranial vascular malformations. [Read the Full Post]

Clinical relevance of ticagrelor monotherapy following 1-month dual antiplatelet therapy after bifurcation percutaneous coronary intervention: Insight from GLOBAL LEADERS trial

88 | Aug 16 2019

Kogame N et al. found that after PCI for bifurcation lesions using 1-month of DAPT followed by ticagrelor monotherapy for 23 months did not demonstrate explicit benefit regarding all-cause death or new Q-wave MI as in the overall trial. [Read the Full Post]

Use of Antiplatelet Therapy/DAPT for Post-PCI Patients Undergoing Noncardiac Surgery

91 | Aug 14 2019

Banerjee S et al. present3 commonly encountered clinical scenarios that lead into an evidence-based discussion of practical strategies for managing perioperative antiplatelet therapy in patients following percutaneous coronary intervention. [Read the Full Post]

Exogenous mesenchymal stem cells affect the function of endogenous lung stem cells (club cells) in phosgene-induced lung injury

98 | Jul 05 2019

Ye K et al. showed that MSCs reduced the secretion of club cells. And MSCs enhanced the proliferation of club cells partly via activating the Notch signaling pathway, which promoted lung injury repair. [Read the Full Post]

Chronic Verubecestat Treatment Suppresses Amyloid Accumulation in Advanced Aged Tg2576-AβPPswe Mice Without Inducing Microhemorrhage

139 | Jul 02 2019

Villarreal S et al. showed the absence of elevated ARIA events in verubecestat-treated mice was associated with a significant reduction in the level of accumulated CNS amyloid pathology and brain Aβ peptides; effects consistent with the desired therapeutic mechanism of verubecestat in AD patients. These data will be compared with longitudinal MRI profiles from ongoing clinical trials. [Read the Full Post]

Efficacy of Ramelteon for delirium after lung cancer surgery

90 | Jun 20 2019

Miyata R et al. showed that Ramelteon is likely to reduce the incidence and intensity of delirium after surgery for lung cancer in elderly patients. [Read the Full Post]

Ultraviolet A eye irradiation ameliorates colon carcinoma induced by azoxymethane and dextran sodium sulfate through β-endorphin and methionine-enkephalin

0 | Mar 16 2019

Hiramoto K et al. suggested that UVA eye irradiation exerts major effects on AOM + DSS-induced colon carcinoma. [Read the Full Post]

Inhibition of the NOTCH pathway using γ-secretase inhibitor RO4929097 has limited antitumor activity in established glial tumors

904 | Feb 05 2019

Dantas-Barbosa C et al. indicated that RO4929097-mediated effects were independent of NOTCH1 mutation status or expression levels, but associated with low IL-6 levels. In established glial tumor models, NOTCH inhibition had limited effects as a single agent, but enhanced efficacy when combined with DNA-interfering agents. These preclinical data need to be considered for further clinical development of NOTCH inhibitors in glial tumors. [Read the Full Post]

Inhibition of γ-secretase activity synergistically enhances tumour necrosis factor-related apoptosis-inducing ligand induced apoptosis in T-cell acute lymphoblastic leukemia cells via upregulation of death receptor 5

152 | Jan 28 2019

Greene LM et al. found that DAPT/TRAIL apoptotic synergy was dependent on the extrinsic apoptotic pathway and was associated with a decrease in BH3 interacting-domain death agonist and x-linked inhibitor of apoptosis. In conclusion, γ-secretase inhibition represents a potential therapeutic strategy to overcome TRAIL resistance for the treatment of T-ALL. [Read the Full Post]

Ultraviolet A eye irradiation ameliorates colon carcinoma induced by azoxymethane and dextran sodium sulfate through β-endorphin and methionine-enkephalin

321 | Jan 25 2019

Hiramoto K et al. suggested that UVA eye irradiation exerts major effects on AOM + DSS-induced colon carcinoma. [Read the Full Post]

Boosting Endogenous Resistance of Brain to Ischemia

0 | Jan 20 2019

Sun F et al. indicated the therapeutic activation of α7 nAChRs after cerebral ischemia may serve as an important physiological responsibility of these ubiquitous receptors and holds a significant translational potential. [Read the Full Post]

The pharmacokinetics and metabolism of lumiracoxib in chimeric humanized and murinized FRG mice

256 | Jan 06 2019

Dickie AP et al. showed taht comparison of the metabolic profiles obtained from the present study with previously published data from C57bl/6J mice and humans, revealed a greater though not complete match between chimeric humanized mice and humans, such that the liver-humanized FRG model may represent a useful approach to assessing the biotransformation of such compounds in humans. [Read the Full Post]

Tracking gastrointestinal transit of solids in aged rats as pharmacological models of chronic dysmotility

0 | Dec 28 2018

Dalziel JE et al. demonstrated that loperamide slowed overall transit in aged rats, while prucalopride increased stomach emptying and accelerates colonic transit. [Read the Full Post]

Procaine Attenuates Pain Behaviors of Neuropathic Pain Model Rats Possibly via Inhibiting JAK2/STAT3

0 | Dec 28 2018

Li D et al. indicated that procaine is capable of attenuating NPP, suggesting procaine is a potential therapeutic strategy for treating NPP. Its role may be associated with the inhibition on JAK2/STAT3 signaling. [Read the Full Post]

FBW7 mutations mediate resistance of colorectal cancer to targeted therapies by blocking Mcl-1 degradation

0 | Dec 19 2018

Tong J et al. demonstrated FBW7 mutational status as a key genetic determinant of CRC response to targeted therapies, and Mcl-1 as an attractive therapeutic target. [Read the Full Post]

Spinal Glutamate Transporters Are Involved in the Development of Electroacupuncture Tolerance

273 | Dec 16 2018

Cui L et al. indicated the participation of the spinal GTs in EAT. [Read the Full Post]

HDAC10 promotes lung cancer proliferation via AKT phosphorylation

241 | Dec 12 2018

Yang Y et al. demonstrated that HDAC10 localizes and functions in the cytoplasm of lung cancer cells, thereby underscoring its potential role in the diagnosis and treatment of lung cancer. [Read the Full Post]

5-HT4 receptors facilitate cholinergic neurotransmission throughout the murine gastrointestinal tract

391 | Dec 11 2018

Pauwelyn V et al. showed that in the murine gastrointestinal tract, activation of 5-HT4 receptors with prucalopride enhances cholinergic contractions, illustrating facilitation of myenteric cholinergic neurotransmission. The degree of enhancement with prucalopride is of similar magnitude as previously reported in other species, but the effective concentrations are lower than those needed in the gastrointestinal tract of other species. [Read the Full Post]

Levo-Tetrahydroberberrubine Produces Anxiolytic-Like Effects in Mice through the 5-HT1A Receptor

298 | Nov 30 2018

Mi G et al. suggested that l-THBr may produce potent anxiolytic-like effects mainly through serotonin receptors. [Read the Full Post]

Drug-protein hydrogen bonds govern the inhibition of the ATP hydrolysis of the multidrug transporter P-glycoprotein

0 | Nov 20 2018

Chufan EE et al. revealed that screening chemical compounds for their ability to inhibit the basal ATP hydrolysis can be a reliable tool to identify modulators with high affinity for P-gp. [Read the Full Post]

An RNA interference screen identifies new avenues for nephroprotection

294 | Oct 05 2018

Zynda ER et al. shed new light on the mechanisms of stress response in mammalian cells, and open new avenues to reduce the morbidity and mortality associated with renal injury. [Read the Full Post]

Experimental observation of human bone marrow mesenchymal stem cell transplantation into rabbit intervertebral discs

408 | Sep 30 2018

Tao H et al. indicated that in the sections of specimens removed at 1, 2, 4, 6 and 8 weeks post-transplantation, no GFP-positive cells were observed in the control groups, whereas GFP-positive cells were apparent in the nucleus pulposus at all periods in the GFP-labeled human BMSCs group, and the cell density at 6 and 8 weeks was significantly less than that at 1, 2 and 4 weeks post-transplantation (P<0.001). [Read the Full Post]

Cyclic cis-Locked Phospho-Dipeptides Reduce Entry of AβPP into Amyloidogenic Processing Pathway

977 | Sep 24 2018

Fisher CL et al. suggested a model in which pCDP-diBzl and pCDP-diPOM act at a common point to inhibit entry of AβPP into the amyloidogenic AβPP processing pathway but through different targets, and provide important insights for the development of novel AD therapeutics. [Read the Full Post]

Downregulation of mitochondrial cyclooxygenase-2 inhibits the stemness of nasopharyngeal carcinoma by decreasing the activity of dynamin-related protein 1

405 | Sep 19 2018

Zhou TJ et al. suggested that mitochondrial COX-2 is a potential theranostic target for the CSCs in NPC. Inhibition of mitochondrial COX-2 could be an attractive therapeutic option for the effective clinical treatment of therapy-resistant NPC. [Read the Full Post]

A regulatory circuit of miR-125b/miR-20b and Wnt signalling controls glioblastoma phenotypes through FZD6-modulated pathways

547 | Sep 19 2018

Huang T et al. confirmed by targeting differentially enriched pathways in PN versus MES GBM that results in inhibition of distinct GBM subtypes. Correlative expressions of the components of this circuit are prognostic relevant for clinical GBM. Our findings provide insights for understanding GBM pathogenesis and for improving treatment of GBM. [Read the Full Post]

The Effects of Ultraviolet Eye Irradiation on Dextran Sodium Sulfate-Induced Ulcerative Colitis in Mice

618 | Sep 15 2018

Hiramoto K et al. suggested that UV eye irradiation plays an important role in DSS-induced ulcerative colitis. [Read the Full Post]

Boosting Endogenous Resistance of Brain to Ischemia

326 | Sep 14 2018

Sun F et al. found that the therapeutic activation of α7 nAChRs after cerebral ischemia may serve as an important physiological responsibility of these ubiquitous receptors and holds a significant translational potential. [Read the Full Post]

Dihydromyricetin promotes autophagy and apoptosis through ROS-STAT3 signaling in head and neck squamous cell carcinoma

615 | Sep 13 2018

Fan TF et al. found that inhibiting autophagy could enhance DHM-induced apoptosis in head and neck squamous cell carcinoma. [Read the Full Post]

Identification of ACTG2 functions as a promoter gene in hepatocellular carcinoma cells migration and tumor metastasis

623 | Sep 11 2018

Wu Y et al. revealed a critical role of ACTG2 in HCC tumor metastasis, and renders it a novel target for the treatment of HCC. [Read the Full Post]

Fascin Is Critical for the Maintenance of Breast Cancer Stem Cell Pool Predominantly via the Activation of the Notch Self-Renewal Pathway

687 | Sep 11 2018

Barnawi R et al. demonstrated fascin as a critical regulator of breast CSC pool at least partially via activation of the Notch self-renewal signaling pathway and modification of the expression embryonic transcriptional factors. Targeting fascin may halt CSCs and thus presents a novel therapeutic approach for effective treatment of breast cancer. [Read the Full Post]

Disruption of clathrin-dependent trafficking results in the failure of grass carp reovirus cellular entry

594 | Sep 08 2018

Wang H et al. suggested that GCRV might enter CIK cells via clathrin-mediated endocytosis in a pH-dependent manner. Additionally, dynamin is critical for efficient viral entry. [Read the Full Post]

The Nonmetabolized β-Blocker Nadolol Is a Substrate of OCT1, OCT2, MATE1, MATE2-K, and P-Glycoprotein, but Not of OATP1B1 and OATP1B3

1245 | Sep 05 2018

Misaka S et al. indicated that these data will aid future in vivo studies on potential transporter-mediated drug-drug or drug-food interactions with involvement of nadolol. [Read the Full Post]

CRISPR/Cas-Mediated Knockin in Human Pluripotent Stem Cells

562 | Aug 17 2018

The transfection procedures described could also be used for additional applications, such as overexpression or lineage tracing studies. [Read the Full Post]

BMS-708163 and Nilotinib restore synaptic dysfunction in human embryonic stem cell-derived Alzheimer's disease models

889 | Aug 07 2018

Nishioka H et al. suggested that the AD models we developed are promising materials for the discovery of AD drugs that target the expression of pre-synaptic proteins and synaptic function. [Read the Full Post]

Cellular Prion Protein Mediates Pancreatic Cancer Cell Survival and Invasion through Association with and Enhanced Signaling of Notch1

735 | Jul 29 2018

Wang Y et al. unraveled a novel molecular pathway driven by interactions between PrP and Notch1 in the progression of PDAC, supporting a critical tumor-promoting role of Notch1 in PrP-expressing PDAC tumors. [Read the Full Post]

Notch and Hedgehog in the thymus/parathyroid common primordium: Crosstalk in organ formation

731 | Jul 27 2018

Figueiredo M et al. offered novel evidence on the role of Notch signalling in T/PT common primordium development, in an Hh-dependent manner. [Read the Full Post]

Thyroid Hormone-Induced Activation of Notch Signaling is Required for Adult Intestinal Stem Cell Development During Xenopus Laevis Metamorphosis

770 | Jul 27 2018

Hasebe T et al. provided evidence for evolutionarily conserved role of Notch signaling in intestinal cell fate determination but more importantly reveal, for the first time, an important role of Notch pathway in the formation of adult intestinal stem cells during vertebrate development. Stem Cells 2017;35:1028-1039. [Read the Full Post]

Aberrant Notch Signaling in the Bone Marrow Microenvironment of Acute Lymphoid Leukemia Suppresses Osteoblast-Mediated Support of Hematopoietic Niche Function

878 | Jul 25 2018

Wang W et al. suggested that therapeutically targeting the leukemia-infiltrated hematopoietic niche may restore HSPC homeostasis and improve the outcome of ALL patients. [Read the Full Post]

Drug-protein hydrogen bonds govern the inhibition of the ATP hydrolysis of the multidrug transporter P-glycoprotein

557 | Jul 06 2018

Chufan EE et al. reveal that screening chemical compounds for their ability to inhibit the basal ATP hydrolysis can be a reliable tool to identify modulators with high affinity for P-gp. [Read the Full Post]

Inhibition of eEF-2 kinase sensitizes human nasopharyngeal carcinoma cells to lapatinib-induced apoptosis through the Src and Erk pathways

353 | May 30 2018

Liu L et al. suggested that targeting eEF-2 kinase may improve the efficacy of therapeutic interventions such as lapatinib in NPC cells. [Read the Full Post]

Gp130-mediated STAT3 activation by S-propargyl-cysteine, an endogenous hydrogen sulfide initiator, prevents doxorubicin-induced cardiotoxicity

652 | May 11 2018

Wu J et al. offered a novel molecular basis and therapeutic strategy of H2S donor for the treatment of heart failure. [Read the Full Post]

A Platelet/CMC coupled with offline UPLC-QTOF-MS/MS for screening antiplatelet activity components from aqueous extract of Danshen

479 | Apr 30 2018

Chen Y et al. suggested their retention time was closely related to the antiplatelet aggregation activities. This study provides a rapid, effective and novel method for screening the potential antiplatelet activity components from Chinese herb medicines. [Read the Full Post]

Lumiracoxib metabolism in male C57bl/6J mice: characterisation of novel in vivo metabolites

692 | Apr 25 2018

P Dickie A et al. found that while there was significant overlap with reported human metabolites, a number of unique mouse metabolites were detected, particularly taurine conjugates of lumiracoxib and its oxidative metabolites. [Read the Full Post]

Evaluation of cardioprotective effect of aqueous extract of Garcinia indica Linn. fruit rinds on isoprenaline-induced myocardial injury in Wistar albino rats

681 | Apr 18 2018

Patel KJ et al. found that the aqueous extract of G. indica was not found to be cardioprotective against myocardial injury. [Read the Full Post]

Relative cytotoxic potencies and cell death mechanisms of α1 -adrenoceptor antagonists in prostate cancer cell lines

0 | Mar 17 2018

Forbes A et al. demonstrated cytotoxic actions on both castration-resistant PC-3 and androgen-sensitive LNCap prostate cancer cells. [Read the Full Post]

IgG subclasses determine pathways of anaphylaxis in mice

0 | Mar 09 2018

Beutier H et al. proposed that the differential expression of inhibitory FcγRIIB on myeloid cells and its differential binding of IgG subclasses controls the contributions of mast cells, basophils, neutrophils, and macrophages to IgG subclass-dependent anaphylaxis. [Read the Full Post]

Epigenetic Regulation of Interleukin 6 by Histone Acetylation in Macrophages and Its Role in Paraquat-Induced Pulmonary Fibrosis

1807 | Feb 06 2018

Hu L et al. indicated IL-6 functioning through EMT in PQ-induced pulmonary fibrosis was regulated dynamically by HDAC and HAT both in vitro and in vivo via epigenetically regulating chromatin accessibility. [Read the Full Post]

Prospective identification of resistance mechanisms to HSP90 inhibition in KRAS mutant cancer cells

850 | Jan 20 2018

Rouhi A et al. identified potential mechanisms of acquired resistance to small molecules targeting HSP90 that may warrant proactive screening for additional HSP90 inhibitors or rational combination therapies. [Read the Full Post]

Melatonin alleviates inflammasome-induced pyroptosis through inhibiting NF-κB/GSDMD signal in mice adipose tissue

934 | Dec 13 2017

Liu Z et al. revealed a novel function of melatonin on adipocyte pyroptosis, suggesting a new potential therapy for melatonin to prevent and treat obesity caused systemic inflammatory response. [Read the Full Post]

The HDAC Inhibitor LAQ824 Enhances Epigenetic Reprogramming and In Vitro Development of Porcine SCNT Embryos.

829 | Dec 13 2017

Optimum exposure (100 nM for 24 h) to LAQ824 post-activation improved the in vitro development of porcine SCNT embryos by enhancing levels of H3K9 and H4K12, reducing 5-mC, and regulating gene expression. [Read the Full Post]

Differential expression of cyclooxygenase-2 in metastatic melanoma affects progression free survival

1033 | Nov 13 2017

Panza E et al. suggested that COX-2 expression may become an useful diagnostic tool in defining melanoma malignancy as well as argue for a possible therapeutic use of NSAID as add on therapy in selected cases. [Read the Full Post]

COX-2 expression positively correlates with PD-L1 expression in human melanoma cells

980 | Nov 13 2017

Botti G et al. showed that COX-2 expression correlates with and modulates PD-L1 expression in melanoma cells. These findings have clinical relevance since they provide a rationale to implement novel clinical trials to test COX-2 inhibition as a potential treatment to prevent melanoma progression and immune evasion as well as to enhance the anti-tumor activity of PD-1/PD-L1 based immunotherapy for the treatment of melanoma patients with or without BRAF/NRAS mutations. [Read the Full Post]

Targeting the Notch-regulated non-coding RNA TUG1 for glioma treatment

1631 | Oct 24 2017

Katsushima K et al. showed that highlight the importance of the Notch-lncRNA axis in regulating self-renewal of glioma cells and provide a strong rationale for targeting TUG1 as a specific and potent therapeutic approach to eliminate the GSC population. [Read the Full Post]

Procaine Attenuates Pain Behaviors of Neuropathic Pain Model Rats Possibly via Inhibiting JAK2/STAT3

1337 | Sep 21 2017

Li D et al. indicated that procaine is capable of attenuating NPP, suggesting procaine is a potential therapeutic strategy for treating NPP. Its role may be associated with the inhibition on JAK2/STAT3 signaling. [Read the Full Post]

Paeoniflorin protects diabetic mice against myocardial ischemic injury via the transient receptor potential vanilloid 1/calcitonin gene-related peptide pathway

0 | Sep 16 2017

Han F et al. demonstrated that PF protects diabetic mice against MI at least partially via the TRPV1/CaMK/CREB/CGRP signaling pathway. [Read the Full Post]

miR-203 inhibits arecoline-induced epithelial-mesenchymal transition by regulating secreted frizzled-related protein 4 and transmembrane-4 L six family member 1 in oral submucous fibrosis

764 | Sep 12 2017

Zheng L et al. provideD evidence to illustrate that miR-203 plays a role in the pathogenesis of OSF, which may be a target for OSF management. [Read the Full Post]

Intrathecal Intermittent Orexin-A Causes Sympathetic Long-Term Facilitation and Sensitizes the Peripheral Chemoreceptor Response to Hypoxia in Rats

1102 | Sep 12 2017

Kim SJ et al. revealed that the activation of spinal orexin receptors is critical to enhance peripheral chemoreceptor responses to hypoxia after AIH. [Read the Full Post]

Tracking gastrointestinal transit of solids in aged rats as pharmacological models of chronic dysmotility

1347 | Sep 11 2017

Dalziel JE et al. demonstrated that loperamide slowed overall transit in aged rats, while prucalopride increased stomach emptying and accelerates colonic transit. [Read the Full Post]

Riluzole partially rescues age-associated, but not LPS-induced, loss of glutamate transporters and spatial memory

1126 | Sep 11 2017

Brothers HM et al. showed that highlight the therapeutic potential of reducing glutamatergic function upon memory impairment in neurodegenerative diseases associated with aging. [Read the Full Post]

Essential role of Notch4/STAT3 signaling in epithelial-mesenchymal transition of tamoxifen-resistant human breast cancer

1763 | Jul 25 2017

Bui QT et al. concluded Notch4 could be a potential target to prevent metastasis in TAM-resistant breast cancer. [Read the Full Post]

Endosulfan inhibits proliferation through the Notch signaling pathway in human umbilical vein endothelial cells

1696 | Jul 25 2017

Wei J et al. demonstrated that endosulfan inhibited proliferation through the Notch signaling pathway as a result of oxidative stress. In addition, endosulfan can damage the cytoskeleton and block mitosis, which may add another layer of toxic effects on endothelial cells. [Read the Full Post]

Jatrophane Diterpenoids as Modulators of P-Glycoprotein-Dependent Multidrug Resistance (MDR): Advances of Structure-Activity Relationships and Discovery of Promising MDR Reversal Agents

0 | Jun 24 2017

Zhu J et al. showed that modifications beyond just increasing the lipophilicity of this class of Pgp inhibitors are beneficial to the activity. [Read the Full Post]

An RNA interference screen identifies new avenues for nephroprotection

0 | Jun 05 2017

Zynda ER et al. found new light on the mechanisms of stress response in mammalian cells, and open new avenues to reduce the morbidity and mortality associated with renal injury. [Read the Full Post]

The gender differences in the inhibitory action of UVB-induced melanocyte activation by the administration of tranexamic acid

0 | Jun 04 2017

Hiramoto K et al. suggested that the suppression by tranexamic acid of the UVB-induced melanocyte activation (UVB sensitivity) is stronger in female mice than in male mice and that female hormones and β-endorphin play an important role in this sex difference. [Read the Full Post]

Mechanical stimulation orchestrates the osteogenic differentiation of human bone marrow stromal cells by regulating HDAC1

0 | Jun 01 2017

Wang J et al. found that mechanical stimulation orchestrates genes expression involved in the osteogenic differentiation of BMSCs via the direct regulation of HDAC1, and the therapeutic inhibition of HDAC1 may be an efficient strategy for enhancing bone formation under mechanical stimulation. [Read the Full Post]

Resveratrol protects CA1 neurons against focal cerebral ischemic reperfusion-induced damage via the ERK-CREB signaling pathway in rats

0 | Apr 10 2017

Li Z et al found that the NMDA receptor-mediated ERK-CREB signaling pathway might participates in Res-induced neuroprotection in rats with focal cerebral ischemia. [Read the Full Post]

Targeting the Neurokinin-1 Receptor Compromises Canonical Wnt Signaling in Hepatoblastoma

0 | Mar 30 2017

Ilmer M et al revealed important insight into the molecular mechanisms of the SP/NK1R complex as a critical component in a model of pediatric liver cancer and may support the development of novel therapeutic interventions for HB and other Wnt-activated cancers. [Read the Full Post]

An RNA interference screen identifies new avenues for nephroprotection

0 | Mar 29 2017

Zynda ER et al shed new light on the mechanisms of stress response in mammalian cells, and open new avenues to reduce the morbidity and mortality associated with renal injury. [Read the Full Post]

The gender differences in the inhibitory action of UVB-induced melanocyte activation by the administration of tranexamic acid

0 | Mar 28 2017

Hiramoto K et al suggested that the suppression by tranexamic acid of the UVB-induced melanocyte activation (UVB sensitivity) is stronger in female mice than in male mice and that female hormones and β-endorphin play an important role in this sex difference. [Read the Full Post]

FBW7 mutations mediate resistance of colorectal cancer to targeted therapies by blocking Mcl-1 degradation

2055 | Mar 21 2017

Tong J et al. demonstrate FBW7 mutational status as a key genetic determinant of CRC response to targeted therapies, and Mcl-1 as an attractive therapeutic target. [Read the Full Post]

IgG subclasses determine pathways of anaphylaxis in mice

2138 | Feb 27 2017

Beutier H et al. proposed that the differential expression of inhibitory FcγRIIB on myeloid cells and its differential binding of IgG subclasses controls the contributions of mast cells, basophils, neutrophils, and macrophages to IgG subclass-dependent anaphylaxis. Collectively, our results unravel novel complexities in the involvement and regulation of cell populations in IgG-dependent reactions in vivo. [Read the Full Post]

Relative cytotoxic potencies and cell death mechanisms of α1 -adrenoceptor antagonists in prostate cancer cell lines

1675 | Feb 24 2017

Prazosin and doxazosin demonstrated cytotoxic actions on both castration-resistant PC-3 and androgen-sensitive LNCap prostate cancer cells. The mechanisms involved included changes in a number of proliferation and apoptosis regulatory proteins. The role of autophagy depended on the cell type, but contributed to cell death in PC3 cells. [Read the Full Post]

Targeting Wnt pathway in mantle cell lymphoma-initiating cells

0 | Feb 20 2017

Mathur R, et al.‘s’ results suggest that Wnt signaling is critical for the maintenance and survival of MCL-ICs, and effective MCL therapy should aim to eliminate MCL-ICs through Wnt signaling inhibitors. [Read the Full Post]

Cyclopiazonic acid, an inhibitor of calcium-dependent ATPases with antiviral activity against human respiratory syncytial virus

0 | Feb 10 2017

Cui R et al.‘s’ findings provide a new strategy for anti-RSV therapy via increasing intracellular calcium concentration. [Read the Full Post]

Human UDP-glucuronosyltransferase (UGT) 2B10: Validation of cotinine as a selective probe substrate, inhibition by UGT enzyme selective inhibitors and antidepressant and antipsychotic drugs, and structural determinants of enzyme inhibition

1817 | Feb 09 2017

Pattanawongsa A, et al.'s result indicates that these drugs may perpetrate inhibitory drug-drug interactions when coadministered with compounds that are cleared predominantly by UGT2B10. [Read the Full Post]

AKT and 14-3-3 Regulate Notch4 Nuclear Localization

2640 | Feb 06 2017

Ramakrishnan G, et al.'s findings provide a novel mechanism for Notch4-ICD regulation, suggesting a negative regulatory role for the PI3K-AKT pathway in Notch4 nuclear signaling. [Read the Full Post]

The gender differences in the inhibitory action of UVB-induced melanocyte activation by the administration of tranexamic acid.

2295 | Feb 01 2017

Hiramoto K et al. suggested that the suppression by tranexamic acid of the UVB-induced melanocyte activation (UVB sensitivity) is stronger in female mice than in male mice and that female hormones and β-endorphin play an important role in this sex difference. [Read the Full Post]

Targeting the Neurokinin-1 Receptor Compromises Canonical Wnt Signaling in Hepatoblastoma

1243 | Jan 31 2017

Ilmer M et al. revealed important insight into the molecular mechanisms of the SP/NK1R complex as a critical component in a model of pediatric liver cancer and may support the development of novel therapeutic interventions for HB and other Wnt-activated cancers. [Read the Full Post]

An RNA interference screen identifies new avenues for nephroprotection

1265 | Jan 31 2017

These data shed new light on the mechanisms of stress response in mammalian cells, and open new avenues to reduce the morbidity and mortality associated with renal injury. [Read the Full Post]

Targeting Wnt pathway in mantle cell lymphoma-initiating cells

3641 | Jan 10 2017

Mathur R, et al.'s results suggest that Wnt signaling is critical for the maintenance and survival of MCL-ICs, and effective MCL therapy should aim to eliminate MCL-ICs through Wnt signaling inhibitors. [Read the Full Post]

Human UDP-glucuronosyltransferase (UGT) 2B10: Validation of cotinine as a selective probe substrate, inhibition by UGT enzyme selective inhibitors and antidepressant and antipsychotic drugs, and structural determinants of enzyme inhibition

1680 | Jan 04 2017

In vitro-in vivo extrapolation of Pattanawongsa A, et al. indicates that these drugs may perpetrate inhibitory drug-drug interactions when coadministered with compounds that are cleared predominantly by UGT2B10. [Read the Full Post]

AKT and 14-3-3 Regulate Notch4 Nuclear Localization

2964 | Dec 29 2016

Ramakrishnan G, et al.'s findings provide a novel mechanism for Notch4-ICD regulation, suggesting a negative regulatory role for the PI3K-AKT pathway in Notch4 nuclear signaling. [Read the Full Post]

Jatrophane Diterpenoids as Modulators of P-Glycoprotein-Dependent Multidrug Resistance (MDR): Advances of Structure-Activity Relationships and Discovery of Promising MDR Reversal Agents

1920 | Dec 28 2016

Zhu J, et al found that compound 26, which exhibited a remarkable metabolic stability in vitro and a favorable antitumor effect in vivo, would serve as a promising lead for the development of new MDR reversal agents. [Read the Full Post]

Paeoniflorin protects diabetic mice against myocardial ischemic injury via the transient receptor potential vanilloid 1/calcitonin gene-related peptide pathway

1090 | Nov 29 2016

Han F et al.’s findings demonstrate that PF protects diabetic mice against MI at least partially via the TRPV1/CaMK/CREB/CGRP signaling pathway. [Read the Full Post]

Cyclopiazonic acid, an inhibitor of calcium-dependent ATPases with antiviral activity against human respiratory syncytial virus

2980 | Nov 03 2016

Cui R et al. provided a new strategy for anti-RSV therapy via increasing intracellular calcium concentration. [Read the Full Post]

Mechanical stimulation orchestrates the osteogenic differentiation of human bone marrow stromal cells by regulating HDAC1

4483 | Oct 27 2016

Wang J et al. found that mechanical stimulation orchestrates genes expression involved in the osteogenic differentiation of BMSCs via the direct regulation of HDAC1, and the therapeutic inhibition of HDAC1 may be an efficient strategy for enhancing bone formation under mechanical stimulation. [Read the Full Post]

Resveratrol protects CA1 neurons against focal cerebral ischemic reperfusion-induced damage via the ERK-CREB signaling pathway in rats

1392 | Sep 13 2016

Li Z, et al. showed that the NMDA receptor-mediated ERK-CREB signaling pathway might participates in Res-induced neuroprotection in rats with focal cerebral ischemia. [Read the Full Post]

Unexpected role of Notch signaling on directing the trophectoderm lineage in the mouse blastocyst

5495 | Jan 30 2015

Rayon et al. showed that Notch signaling plays a key role in mediating TE-specific expression of Cdx2, though interaction with the transcription factor TEAD4. [Read the Full Post]

The Notch signaling controls maintenance of memory CD4+ T cells

8552 | Dec 16 2014

Recently, Maekawa et al. demonstrated Notch signaling is important for the survival of memory CD4+ T cells by regulating glucose uptake. [Read the Full Post]

MeCP2 S421 phosphorylation mediates neurogenesis via Notch signaling pathway

7486 | Dec 04 2014

Li et al. identified the Notch signaling is involved in the regulation of MeCP2 S421 phosphorylation other than neuronal activity. [Read the Full Post]

Two strategies to overcome eribulin resistance: pharmacokinetic imaging and nanoparticle delivery system

4536 | Nov 17 2014

Laughney et al. developed strategies of pharmacokinetic for to reveal drug-resistant mechanisms, and nanoparticle system to overcome the resistance. [Read the Full Post]

A new neurogenic receptor activator of P2Y1——Up4A

3852 | Nov 13 2014

Recently, researchers from Nevada School of Medicine found a novel factor, Up4A, may contribute in mediating enteric inhibitory neurotransmission of the intestines, acts through P2Y1 receptors and apamin-sensitive small-conductance SK channels. [Read the Full Post]

Notch signaling acts as a key regulator in generation of neurons from neural precursor cells

4849 | Oct 23 2014

Notch signaling plays a central role before asymmetric division and in the fate of Drosophila melanogaster neural precursor cells. It also acts as a critical factor in Numb distribution in neural precursor cells before cleavage. [Read the Full Post]

Tariquidar is a P glycoprotein inhibitor undergoing research

3635 | Jan 27 2014

Tariquidar (XR9576) is a potent and selective noncompetitive inhibitor of P-glycoprotein with Kd of 5.1 nM, reverses drug resistance in MDR cell Lines. [Read the Full Post]

Tariquidar is a P glycoprotein inhibitor undergoing research

3745 | Dec 30 2013

Tariquidar displays high-affinity binding to P-gp with Bmax of 275 pmol/mg. [Read the Full Post]

Zosuquidar is a compound of antineoplastic drug

3646 | Dec 30 2013

Zosuquidar (LY335979) is a potent modulator of P-glycoprotein-mediated multi-drug resistance with Ki of 60 nM. [Read the Full Post]

LY335979 is a potent inhibitor that contains a cyclopropyldibenzosuberane moiety

3908 | Dec 16 2013

LY335979 competitively inhibits equilibrium binding of vinblastine to Pgp by blocking azidopine photoaffinity labeling of the Pgp in CEM/VLB100 plasma membranes. [Read the Full Post]

Tariquidar is a P glycoprotein inhibitor undergoing research as an adjuvant

3524 | Oct 23 2013

Tariquidar is a potent and selective noncompetitive inhibitor of P-glycoprotein with Kd of 5.1 nM, reverses drug resistance in MDR cell Lines. [Read the Full Post]

MRS2578 is a selective antagonist of P2Y6 nucleotide receptors

2433 | Jul 29 2013

MRS 2578 (10 μM) significant reduces TNF-α–induced proinflammatory gene expression in HMEC-1 cells. [Read the Full Post]

MK 801 has a great deal of potential to be used in research in creating animal models of schizophrenia

3251 | May 10 2013

MK-801 has a great deal of potential to be used in research in creating animal models of schizophrenia. Unlike dopaminergic agonists, which mimic only the positive symptoms of schizophrenia, a single injection of MK801 was successful in modelling both the positive and negative symptoms of schizophrenia. [Read the Full Post]

Bufexamac is a drug used as an anti inflammatory agent on the skin

3519 | Jan 21 2013

The Bufexamac importance of the HGF/c-MET pathway in the control of tissue homeostasis is supported by the well established protective activity of HGF in several degenerative diseases, including progressive nephropathies , liver cirrhosis and lung fibrosis. [Read the Full Post]

LY2140023 is a novel investigational agent for the treatment of schizophrenia

3201 | Jan 18 2013

LY2140023 is a novel investigational agent for the treatment of schizophrenia. A member of a new class of antipsychotic drugs, LY2140023 is still in early stage clinical development. Nevertheless, analysts have hailed it as an exciting new medicine that may herald the arrival of third-generation antipsychotic drugs. [Read the Full Post]

Gamma secretase is a mult subunit protease complex

3053 | Jan 09 2013

The network of tumor blood vessels that perfuse a solid tumor plays a fundamental role in its growth and survival. Not only do the blood vessels feed the Gamma Secretase tumor with oxygen and nutrients through the blood, they also allow for the subsequent removal of cellular waste products. [Read the Full Post]

New and Potent COX receptor inhibitors are available

3274 | Dec 10 2012

PCR amplified cDNA COX Inhibitors fragment containing human EGFR kinase domain from amino acids 696 to 1022 was attached to the C-terminal coding region (3? region) of the glutathione S-transferase gene and the fused DNA fragment is cloned into a baculovirus expression vector pBacPAK8 (Clontech, Palo Alto, CA, USA). [Read the Full Post]

Gamma Secretase were grown in 5 ml of medium

4789 | Nov 28 2012

The cells were pelleted by centrifugation, the medium was Gamma Secretase removed with the drug, and the cells were washed washed with sterile PBS and centrifuged again. [Read the Full Post]

Celecoxib was observed in our in vitro

2906 | Oct 24 2012

EGFR somatic doublet mutations are potentially more frequent than previously understood, with majority of them representing driver driver mutations rather than driver passenger mutations [Read the Full Post]

RO4929097 – CHECKS NOTCH SIGNALING IN CANCERS

5252 | Mar 20 2012

RO4929097: A GAMMA SECRETASE INHIBITOR: Among well known proteases Gamma secretase is one which is made up of various subunits. This is present in the membrane hence is a protein in membrane which is also capable of cleaving certain transmembrane proteins therefore also known as the intramembrane protease. In case of Alzheimer’s disease amyloid plaques are formed in brain, these plaques are resulted due to the amyloid beta peptide and these peptides are produced due to the action of gamma secretase, this is one of the well known examples of this protease. Presently, we are focusing on the important role of gamma secretase in the Notch protein processing. In case of many cancers and tumors this Notch protein signaling is found to be abnormal, therefore the arresting of this pathway can be an authentic way to get rid of abnormal cell growth. In the light of this idea a novel RO4929097 gamma secretase inhibitor is discovered. The inhibitory effect of this inhibitor has been confirmed by various methods like western blotting. [Read the Full Post]

RO4929097 – TARGETING NOTCH SIGNALING IN CANCER

5736 | Mar 13 2012

RO4929097: INHIBIT GAMMA SECRETASE: Gamma secretase is famous protease consists of several subunits complex. This enzyme is also recognized as inter-membrane protease as it cuts trans-membrane proteins. The most eminent gamma secretase example is breakage of amyloid precursor, a protein to produce amyloid beta peptide which is involved in the formation of amyloid plaques in patient’s brain who suffer with Alzheimer’s disease. In the present situation though, we concentrate on the key role of gamma secretase in the Notch protein processing. It has been found as there is link between anomalous notch signaling and many cancers. Hence the idea of targeting those enzymes which are responsible for the processing of Notch protein became the reason of RO4929097 gamma secretase inhibitor discovery. The inhibiting Notch signaling by using RO4929097 GS inhibitor has been confirmed by protein estimation methods like Biuret method etc. [Read the Full Post]

RO4929097 – CONTROLLING NOTCH SIGNALING IN TUMORS

5987 | Mar 13 2012

Introduction: Gamma secretase Inhibition Gamma secretase is an internal protease enzyme that is a complex of a number of subunits. Its mode of action is to cleave proteins that lie within the membrane-spanning domain, these include the amyloid precursor protein (APP) and the Notch. The Notch signaling pathway processes four different Notch receptors (1, 2, 3 and 4) which span the cell membrane. Upon extracellular interaction with a substrate protein the internal domain is released. This section of the protein then induced a signaling cascade within the cell nucleus to alter gene expression. The function of the various NOTCH proteins is varied but in terms of cancer notch receptors have been demonstrated to be down regulated in basal cells carcinomas and cervical cancers. Notch 1 over-expression is associated with acute T cell leukemia and breast cancer, Notch 3 receptor is over-expressed in 20% of ovarian cancers [5-7] while overexpression of Notch 4 is evident in murine models of breast cancer. The field of research into NOTCH signaling is vast and beyond the scope of this document, simple put there existed evidence that inhibition of aberrant NOTCH over-expression would be an ideal target for chemotherapeutic activity. The development of inhibitors which would affect the action of NOTCH led to the targeting of the Gamma secretase enzyme. Developed by Roche the RO4929097 gamma secretase inhibitor represents a potent novel small molecule that is orally bioavailable. [Read the Full Post]

Yin, L., O. C. Velazquez, et al. (2010). "Notch signaling: emerging molecular targets for cancer therapy." Biochem Pharmacol 80(5): 690-701.

5138 | Jul 13 2011

This article is a review which give a presentation of Notch signal pathway and how the researchers target Notch signal pathway for a cancer therapy. [Read the Full Post]