316,742 results match your criteria activation signaling


Koumine modulates spinal microglial M1 polarization and the inflammatory response through the Notch-RBP-Jκ signaling pathway, ameliorating diabetic neuropathic pain in rats.

Phytomedicine 2021 Jun 29;90:153640. Epub 2021 Jun 29.

Department of Pharmacology, College of Pharmacy, Fujian Medical University, Fuzhou, Fujian, P.R. China; Fujian Key Laboratory of Natural Medicine Pharmacology, College of Pharmacy, Fujian Medical University, Fuzhou, Fujian, P.R. China. Electronic address:

Background: Diabetic neuropathic pain (DNP), a complication of diabetes, has serious impacts on human health. As the pathogenesis of DNP is very complex, clinical treatments for DNP is limited. Koumine (KM) is an active ingredient extracted from Gelsemium elegans Benth. Read More

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Inhibition of TNFAIP1 ameliorates the oxidative stress and inflammatory injury in myocardial ischemia/reperfusion injury through modulation of Akt/GSK-3β/Nrf2 pathway.

Int Immunopharmacol 2021 Jul 27;99:107993. Epub 2021 Jul 27.

Department of Cardiology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. Electronic address:

Tumor necrosis factor α-induced protein 1 (TNFAIP1) has been documented as a vital regulator of apoptosis and oxidative stress under various pathological conditions. However, whether TNFAIP1 plays a role in myocardial ischemia/reperfusion (I/R) injury has not been well investigated. This work aimed to evaluate the possible role of TNFAIP1 in mediating myocardial I/R injury. Read More

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Dichotomous thinking about social groups: Learning about one group can activate opposite beliefs about another group.

Cogn Psychol 2021 Jul 27;129:101408. Epub 2021 Jul 27.

University of California, Davis, United States.

Across three studies (N = 607), we examined people's use of a dichotomizing heuristic-the inference that characteristics belonging to one group do not apply to another group-when making judgments about novel social groups. Participants learned information about one group (e.g. Read More

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N, N, dimethyl-hexadecylamine modulates Arabidopsis root growth through modifying the balance between stem cell niche and jasmonic acid-dependent gene expression.

Gene Expr Patterns 2021 Jul 27:119201. Epub 2021 Jul 27.

Instituto de Investigaciones Químico-Biológicas, Universidad Michoacana de San Nicolás de Hidalgo. Edificio B3, Ciudad Universitaria, Morelia, Michoacán, Mexico. Electronic address:

N, N, dimethyl-hexadecylamine (DMHDA) is released as part of blends emitted by plant probiotic bacteria and affects root architecture, defense and nutrition of plants. Here, we investigated the changes in gene expression of transcription factors responsible of maintenance of the root stem cell niche and jasmonic acid signaling in Arabidopsis seedlings in response to this volatile. Concentrations of DMHDA that repress primary root growth were found to alter cell size and division augmenting cell tissue layers in the meristem and causing root widening. Read More

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Selective progesterone receptor blockade prevents BRCA1-associated mouse mammary tumors through modulation of epithelial and stromal genes.

Cancer Lett 2021 Jul 27. Epub 2021 Jul 27.

Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. Electronic address:

Pharmacological approaches to breast cancer risk-reduction for BRCA1 mutation carriers would provide an alternative to mastectomy. BRCA1-deficiency dysregulates progesterone signaling, promoting tumorigenesis. Selective progesterone receptor (PR) modulators (SPRMs) are therefore candidate prevention agents. Read More

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Cytokine Stimulation via MRGPRX2 Occurs with Lower Potency than by FcεRI-aggregation but with Similar Dependence on the ERK1/2 Module in Human Skin Mast Cells.

J Invest Dermatol 2021 Jul 27. Epub 2021 Jul 27.

Department of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. Electronic address:

Skin mast cells (MCs) contribute to chronic dermatoses that partially rely on MC-derived cytokines. The discovery of MRGPRX2 explains MC-dependent symptoms independently of FcεRI-activation. Here, we investigated whether MRGPRX2 can elicit cytokines, determined its relative potency versus FcεRI and addressed the underlying mechanisms. Read More

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Cynandione A causes a dynamic change in SIRT1 nuclear trafficking via PKA signaling and beige adipocyte differentiation in 3T3-L1 cells.

Eur J Pharmacol 2021 Jul 27:174382. Epub 2021 Jul 27.

Department of Pharmaceutical Pharmacology, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime, 790-8578, Japan. Electronic address:

Inducible brown-like adipocytes, also known as beige adipocytes, dissipate energy through thermogenesis. Although recent reports suggest that silent information regulator 2 homolog 1 (SIRT1) promotes beige adipocyte differentiation (beiging), the activation mechanism of SIRT1 remains unknown. Here, we report that cynandione A (CA), a major component of Cynanchum wilfordii, causes dynamic changes in SIRT1 nuclear trafficking via protein kinase cAMP-dependent (PKA) signaling and induces the beiging process in adipocyte lineage cells. Read More

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A BMP4-p38 MAPK signaling axis controls ISL1 protein stability and activity during cardiogenesis.

Stem Cell Reports 2021 Jul 12. Epub 2021 Jul 12.

Department of Anatomy and Developmental Biology, European Center for Angioscience (ECAS), Medical Faculty Mannheim, Heidelberg University, Ludolf-Krehl-Street 7-11, 68167 Mannheim, Germany; Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, Mannheim, Germany. Electronic address:

During development, cells respond rapidly to intra- and intercellular signals, which induce signaling cascades regulating the activity of transcription factors at the transcriptional and/or post-translational level. The transcription factor ISL1 plays a key role in second heart field development and cardiac differentiation, and its mRNA levels are tightly regulated during cardiogenesis. Here, we show that a BMP-p38 MAPK signaling axis controls ISL1 protein function at the post-translational level. Read More

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The Small GTPase OsRac1 Forms Two Distinct Immune Receptor Complexes Containing the PRR OsCERK1 and the NLR Pit.

Plant Cell Physiol 2021 Jul 31. Epub 2021 Jul 31.

Graduate School of Biological Sciences, Nara Institute of Science and Technology, Nara 630-0192, Japan.

Plants employ two different types of immune receptors, cell surface pattern recognition receptors (PRRs) and intracellular nucleotide-binding and leucine-rich repeat-containing proteins (NLRs), to cope with pathogen invasion. Both immune receptors often share similar downstream components and responses but it remains unknown whether a PRR and an NLR assemble into the same protein complex or two distinct receptor complexes. We have previously found that the small GTPase OsRac1 plays key roles in the signaling of OsCERK1, a PRR for fungal chitin, and of Pit, an NLR for rice blast fungus, and associates directly and indirectly with both of these immune receptors. Read More

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Jasmonate inhibits adventitious root initiation through repression of CKX1 and activation of RAP2.6L transcription factor in Arabidopsis.

J Exp Bot 2021 Jul 30. Epub 2021 Jul 30.

Umeå Plant Science Centre, Department of Plant Physiology, Umeå University, SE-90736 Umeå, Sweden.

Adventitious rooting is a de novo organogenesis process that enables plants to propagate clonally and cope with environmental stresses. Adventitious root initiation (ARI) is controlled by interconnected transcriptional and hormonal networks, but there is little knowledge of the genetic and molecular programs orchestrating these networks. Thus, we have applied genome-wide transcriptome profiling to elucidate the profound transcriptional reprogramming events preceding ARI. Read More

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The secreted tyrosine kinase VLK is essential for normal platelet activation and thrombus formation.

Blood 2021 Jul 30. Epub 2021 Jul 30.

Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States.

Tyrosine phosphorylation of extracellular proteins is observed in cell cultures and in vivo, but little is known about the functional roles of tyrosine phosphorylation of extracellular proteins. Vertebrate Lonesome Kinase (VLK) is a broadly expressed secretory pathway tyrosine kinase present in platelet ɑ-granules. It is released from platelets upon activation and phosphorylates substrates extracellularly. Read More

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Regulation of the IGF1 signaling pathway is involved in idiopathic pulmonary fibrosis induced by alveolar epithelial cell senescence and core fucosylation.

Aging (Albany NY) 2021 Jul 30;13(undefined). Epub 2021 Jul 30.

Department of Respiratory and Critical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Idiopathic pulmonary fibrosis (IPF) mainly occurs in elderly people over the age of sixty. IPF pathogenesis is associated with alveolar epithelial cells (AECs) senescence. Activation of PI3K/AKT signaling induced by insulin-like growth factor 1 (IGF1) participates in AEC senescence and IPF by releasing CTGF, TGF-β1, and MMP9. Read More

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Integration of data from the cell-based ERK1/2 ELISA and the Comparative Toxicogenomics Database deciphers the potential mode of action of bisphenol A and benzo[a]pyrene in lung neoplasm.

Chemosphere 2021 Jul 14;285:131527. Epub 2021 Jul 14.

University of Novi Sad, Faculty of Sciences, Department of Biology and Ecology, Serbia. Electronic address:

Chemicals can activate a variety of signaling pathways, initiating changes in gene expression and cellular functions. Here, we combined experimental data on the chemical-induced extracellular signal-regulated kinase 1/2 (ERK1/2) activation with the Comparative Toxicogenomics Database (CTD) to connect signaling, genes, and phenotypes to reveal the potential chemical's mode of action (MOA) responsible for the disease state. Experimental data on ERK1/2 activation were derived from the cell-based phospho-ERK1/2 ELISA on human alveolar epithelial cells A549. Read More

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Structural basis for molecular recognition of G protein-coupled estrogen receptor by selected bisphenols.

Sci Total Environ 2021 Jun 22;793:148558. Epub 2021 Jun 22.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, PR China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100190, PR China; School of Environment, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310012, PR China. Electronic address:

Complicated ligand-dependent signaling pathways of bisphenol A (BPA) and its analogues involve not only intranuclear estrogen receptor but also membrane receptor G protein-coupled estrogen receptor (GPER). However, the structural basis for molecular recognition of GPER by the environmental chemicals remains unknown. To reveal the structural dependence of GPER recognition by bisphenols, a systematic molecular dynamics simulation study was performed for selected bisphenols with different electron hybrid orbitals and substituents on their C atoms connecting two phenol rings. Read More

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LINC00511 facilitates Temozolomide resistance of glioblastoma cells via sponging miR-126-5p and activating Wnt/β-catenin signaling.

J Biochem Mol Toxicol 2021 Jul 30:e22848. Epub 2021 Jul 30.

Department of Neurology, Xinxiang Central Hospital, Xinxiang, Henan province, China.

Temozolomide (TMZ) is the first-line chemotherapy drug for glioblastoma (GBM) but acquired TMZ resistance is frequently observed. Thus, a TMZ resistant GBM cell line U87-R was established to search for potential long noncoding RNAs (lncRNAs) used in TMZ resistance. In our study, LINC00511 was identified as a TMZ resistance-associated lncRNA in U87-R cells by transcriptome RNA sequencing. Read More

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CXCL10/CXCR3 signaling contributes to an inflammatory microenvironment and its blockade enhances progression of murine pancreatic precancerous lesions.

Elife 2021 Jul 30;10. Epub 2021 Jul 30.

Cancer Biology, Mayo Clinic, Jacksonville, United States.

The development of pancreatic cancer requires recruitment and activation of different macrophage populations. However, little is known about how macrophages are attracted to the pancreas after injury or an oncogenic event, and how they crosstalk with lesion cells or other cells of the lesion microenvironment. Here, we delineate the importance of CXCL10/CXCR3 signaling during the early phase of murine pancreatic cancer. Read More

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TIFA has dual functions in Helicobacter pylori-induced classical and alternative NF-κB pathways.

EMBO Rep 2021 Jul 30:e52878. Epub 2021 Jul 30.

Institute of Experimental Internal Medicine, Medical Faculty, Otto von Guericke University, Magdeburg, Germany.

Helicobacter pylori infection constitutes one of the major risk factors for the development of gastric diseases including gastric cancer. The activation of nuclear factor-kappa-light-chain-enhancer of activated B cells (NF-κB) via classical and alternative pathways is a hallmark of H. pylori infection leading to inflammation in gastric epithelial cells. Read More

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Liquiritigenin attenuates isoprenaline‑induced myocardial fibrosis in mice through the TGF‑β1/Smad2 and AKT/ERK signaling pathways.

Mol Med Rep 2021 Oct 30;24(4). Epub 2021 Jul 30.

Type‑B Ultrasonic Room, Heart Center, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang 310000, P.R. China.

Myocardial fibrosis is a pathological process characterized by excessive accumulation of extracellular matrix in myocardial interstitial spaces. Myocardial fibrosis is a fundamental process in ventricular remodeling and a primary contributor to the progression of heart failure. Liquiritigenin (LQ) is a flavanone compound with anti‑oxidative, anti‑carcinogenic, anti‑inflammatory and estrogenic properties. Read More

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October 2021

The meristem-associated endosymbiont Methylorubrum extorquens DSM13060 reprograms development and stress responses of pine seedlings.

Tree Physiol 2021 Jul 29. Epub 2021 Jul 29.

Ecology and Genetics, University of Oulu, PO Box 3000, FIN-90014 Oulu, Finland.

Microbes living in plant tissues, endophytes, are mainly studied in crop plants where they typically colonize the root apoplast. Trees, a large carbon source with a high capacity for photosynthesis, provide a variety of niches for endophytic colonization. We have earlier identified a new type of plant-endophyte interaction in buds of adult Scots pine, where Methylorubrum species live inside the meristematic cells. Read More

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Effects of Naodesheng tablets on amyloid beta-induced dysfunction: A traditional Chinese herbal formula with novel therapeutic potential in Alzheimer's disease revealed by systems pharmacology.

Biomed Pharmacother 2021 Jul 22;141:111916. Epub 2021 Jul 22.

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; Beijing Key Laboratory of Drug Target Identification and Drug Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address:

Naodesheng (NDS) tablets have been widely used to treat ischemic stroke clinically. NDS relieves neurological function impairment and improve learning and memory in rats with focal cerebral ischemia, suggesting that NDS has potential for Alzheimer's disease (AD) treatment. However, there are no studies about its effective material basis and possible mechanisms. Read More

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Kaempferia parviflora extract inhibits TNF-α-induced release of MCP-1 in ovarian cancer cells through the suppression of NF-κB signaling.

Biomed Pharmacother 2021 Jul 12;141:111911. Epub 2021 Jul 12.

Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Research Center of Pharmaceutical Nanotechnology, Chiang Mai University, Thailand. Electronic address:

Ovarian clear cell carcinoma (OCCC) is an uncommon subtype of epithelial cell ovarian cancers (EOCs) that has poor response to conventional platinum-based therapy. Therefore, finding new potential therapeutic agents is required. Since inflammatory cytokine, tumor necrosis factor alpha (TNF-α), is strongly expressed in EOCs and associated with the level of tumor grade, disruption of this inflammation pathway may provide another potential target for OCCC treatment. Read More

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POU4F2 Promotes Colorectal Cancer Cell Migration and Invasion via Hedgehog-mediated Epithelial-Mesenchymal Transition.

Cancer Sci 2021 Jul 30. Epub 2021 Jul 30.

Department of Medical Oncology, The First Affiliated Hospital of Zhejiang Chinese Medical University, 310006, Zhejiang, China.

As a POU homeodomain transcription factor, POU4F2 has been implicated in regulating tumorigenic processes in various cancers. However, the role of POU4F2 in colorectal cancer remains unclear. Here, we revealed that POU4F2 functions as a tumor promotor in colorectal cancer. Read More

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Glycoprotein NMB functions with growth factor signaling to induce tumorigenesis through its serine phosphorylation.

Cancer Sci 2021 Jul 30. Epub 2021 Jul 30.

Department of Experimental Pathology, Faculty of Medicine, Ibaraki, Japan.

Breast cancer is the most common cancer among women. Glycoprotein NMB (GPNMB), a type I transmembrane protein that is highly expressed in many cancers, including breast cancer, has been shown to be a prognostic factor. We previously reported that GPNMB overexpression confers tumorigenic potential, as evidenced by invasive tumor growth in vivo, sphere formation, and cellular migration and invasion to non-tumorigenic mammary epithelial cells. Read More

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Reciprocal regulation of spontaneous synaptic vesicle fusion by Fragile X mental retardation protein and group I metabotropic glutamate receptors.

J Neurochem 2021 Jul 29. Epub 2021 Jul 29.

National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bengaluru, 560065, India.

Fragile X mental retardation protein (FMRP) is a neuronal protein mediating multiple functions, with its absence resulting in one of the most common monogenic causes of autism, Fragile X syndrome (FXS). Analyses of FXS pathophysiology have identified a range of aberrations in synaptic signaling pathways and plasticity associated with group I metabotropic glutamate (mGlu) receptors. These studies, however, have mostly focused on the postsynaptic functions of FMRP and mGlu receptor activation, and relatively little is known about their presynaptic effects. Read More

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Chronic angiotensin receptor activation promotes hepatic triacylglycerol accumulation during an acute glucose challenge in obese-insulin-resistant OLETF rats.

Endocrine 2021 Jul 29. Epub 2021 Jul 29.

School of Natural Sciences, University of California, Merced, CA, USA.

Purpose: Angiotensin receptor blockers (ARBs) can ameliorate metabolic syndrome (MetS)-associated dyslipidemia, hepatic steatosis, and glucose intolerance, suggesting that angiotensin receptor (AT1) over-activation contributes to impaired lipid and glucose metabolism, which is characteristic of MetS. The aim of this study was to evaluate changes in the lipid profile and proteins of fatty acid uptake, triacylglycerol (TAG) synthesis, and β-oxidation to better understand the links between AT1 overactivation and non-alcoholic fatty liver disease (NAFLD) during MetS.

Methods: Four groups of 25-week-old-rats were used: (1) untreated LETO, (2) untreated OLETF, (3) OLETF + angiotensin receptor blocker (ARB; 10 mg olmesartan/kg/d × 8 weeks) and (4) OLETF ± ARB (MINUS; 10 mg olmesartan/kg/d × 4 weeks, then removed until dissection). Read More

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Exogenous Ca enhances antioxidant defense in rice to simulated acid rain by regulating ascorbate peroxidase and glutathione reductase.

Planta 2021 Jul 29;254(2):41. Epub 2021 Jul 29.

State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, 214122, China.

Main Conclusion: Exogenous calcium enhances rice tolerance to acid rain stress by regulating isozymes composition and transcriptional expression of ascorbate peroxidase and glutathione reductase. Calcium (Ca) participates in signal transduction in plants under abiotic stress, and addition of Ca is beneficial to alleviate damage of plants caused by acid rain. To clarify the effect of exogenous Ca on tolerance of plants to acid rain stress, we investigated regulation of Ca (5 mM) on activities, isozymes composition and transcriptional expression of ascorbate peroxidase (APX) and glutathione reductase (GR), redox state, and HO concentration and growth in rice leaves and roots under simulated acid rain (SAR) stress. Read More

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Influence of Nitric Oxide-Cyclic GMP and Oxidative STRESS on Amyloid-β Peptide Induced Decrease of Na,K-ATPase Activity in Rat Hippocampal Slices.

J Membr Biol 2021 Jul 29. Epub 2021 Jul 29.

Laboratory of Molecular Neuropharmacology, Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.

Amyloid-β peptide (Aβ) has been shown to cause synaptic dysfunction and can render neurons vulnerable to excitotoxicity and oxidative stress. Na,K-ATPase plays an important role to maintain cell ionic equilibrium and it can be modulated by N-methyl-D-aspartate (NMDA)-nitric oxide (NO)-cyclic GMP pathway. Disruption of NO synthase (NOS) activity and reactive oxygen species (ROS) production could lead to changes in Na,K-ATPase isoforms' activities that may be detrimental to the cells. Read More

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Visualization of Host Cell Kinase Activation by Viral Proteins Using GFP Fluorescence Complementation and Immunofluorescence Microscopy.

Bio Protoc 2021 Jul 5;11(13):e4068. Epub 2021 Jul 5.

Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA.

Non-receptor protein-tyrosine kinases regulate cellular responses to many external signals and are important drug discovery targets for cancer and infectious diseases. While many assays exist for the assessment of kinase activity , methods that report changes in tyrosine kinase activity in single cells have the potential to provide information about kinase responses at the cell population level. In this protocol, we combined bimolecular fluorescence complementation (BiFC), an established method for the assessment of protein-protein interactions, and immunofluorescence staining with phosphospecific antibodies to characterize changes in host cell tyrosine kinase activity in the presence of an HIV-1 virulence factor, Nef. Read More

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Neurovascular Coupling in Development and Disease: Focus on Astrocytes.

Front Cell Dev Biol 2021 12;9:702832. Epub 2021 Jul 12.

Department of Neurology, Jungers Center for Neurosciences Research, Oregon Health & Science University, Portland, OR, United States.

Neurovascular coupling is a crucial mechanism that matches the high energy demand of the brain with a supply of energy substrates from the blood. Signaling within the neurovascular unit is responsible for activity-dependent changes in cerebral blood flow. The strength and reliability of neurovascular coupling form the basis of non-invasive human neuroimaging techniques, including blood oxygen level dependent (BOLD) functional magnetic resonance imaging. Read More

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CXCL2 Impairs Functions of Bone Marrow Mesenchymal Stem Cells and Can Serve as a Serum Marker in High-Fat Diet-Fed Rats.

Front Cell Dev Biol 2021 13;9:687942. Epub 2021 Jul 13.

Research Center of Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

In modern society excessive consumption of a high-fat diet (HFD) is a significant risk factor for many diseases such as diabetes, osteoarthritis and certain cancers. Resolving cellular and molecular mechanisms underlying HFD-associated disorders is of great importance to human health. Mesenchymal stem cells (MSCs) are key players in tissue homeostasis and adversely affected by prolonged HFD feeding. Read More

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