696,288 results match your criteria signal pathway

Effect of Inhibition of the JAK2/STAT3 Signaling Pathway on the Th17/IL-17 Axis in Acute Cellular Rejection After Heart Transplantation in Mice.

J Cardiovasc Pharmacol 2021 Apr 7;77(5):614-620. Epub 2021 Apr 7.

Department of Thoracic and Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People's Republic of China.

Abstract: Acute immune rejection is one of the most serious complications of heart transplantation, and its mechanism has always been a hot spot. Th17 cells and cytokine interleukin-17 (IL-17) have been proved to be involved in acute immune rejection, and the signaling pathway mechanism has attracted our interest. It has been confirmed that the Janus kinase 2-signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway is involved in the differentiation of CD4+ T cells, so we focus on whether the JAK2/STAT3 signaling pathway is involved in the occurrence of acute immune rejection by regulating the Th17/IL-17 axis. Read More

View Article and Full-Text PDF

Two bHLH transcription factors, bHLH48 and bHLH60, associate with phytochrome interacting factor 7 to regulate hypocotyl elongation in Arabidopsis.

Cell Rep 2021 May;35(5):109054

State Key Laboratory of Genetic Engineering and Institute of Plant Biology, School of Life Sciences, Fudan University, Shanghai 200438, People's Republic of China. Electronic address:

The basic helix-loop-helix (bHLH) transcription factor PHYTOCHROME-INTERACTING FACTOR 7 (PIF7) is a central regulator that promotes stem growth by activating growth-related gene expression during shade-avoidance responses. Studying the co-factors of PIF7 can facilitate understanding of the mechanism of PIFs and light signal transduction. Here, we describe the identification of two bHLH transcription factors, bHLH48 and bHLH60 (bHLH48/bHLH60), as essential partners for PIF7-dependent modulation of hypocotyl elongation and function downstream of phytochrome B. Read More

View Article and Full-Text PDF

Carnosol and its analogues attenuate muscle atrophy and fat lipolysis induced by cancer cachexia.

J Cachexia Sarcopenia Muscle 2021 May 5. Epub 2021 May 5.

Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China.

Background: Cancer cachexia is a multifactorial debilitating syndrome that directly accounts for more than 20% of cancer deaths while there is no effective therapeutic approach for treatment of cancer cachexia. Carnosol (CS) is a bioactive diterpene compound present in Lamiaceae spp., which has been demonstrated to have antioxidant, anti-inflammatory, and anticancer properties. Read More

View Article and Full-Text PDF

HSP17.4 mediates salicylic acid and jasmonic acid pathways in the regulation of resistance to Colletotrichum gloeosporioides in strawberry.

Mol Plant Pathol 2021 May 5. Epub 2021 May 5.

Institute of Forestry and Pomology, Shanghai Academy of Agricultural Sciences, Shanghai, China.

In this study, we used virus-mediated gene silencing technology and found that the HSP17.4 gene-silenced cultivar Sweet Charlie plants were more susceptible to Colletotrichum gloeosporioides than the wild-type Sweet Charlie, and the level of infection was even higher than that of the susceptible cultivar Benihopp. The results of differential quantitative proteomics showed that after infection with the pathogen, the expression of the downstream response genes NPR1, TGA, and PR-1 of the salicylic acid (SA) signalling pathway was fully up-regulated in the wild-type Sweet Charlie, and the expression of the core transcription factor MYC2 of the jasmonic acid (JA) pathway was significantly down-regulated. Read More

View Article and Full-Text PDF

Relative Quantification of Phosphorylated and Glycosylated Peptides from the Same Sample Using Isobaric Chemical Labelling with a Two-Step Enrichment Strategy.

Methods Mol Biol 2021 ;2228:185-203

Bioanalytical Mass Spectrometry Group, Max Planck Institute for Biophysical Chemistry, Goettingen, Germany.

Post-translational modifications (PTMs) are essential for the regulation of all cellular processes. The interplay of various PTMs on a single protein or different proteins comprises a complexity that we are far from understanding in its entirety. Reliable strategies for the enrichment and accurate quantification of PTMs are needed to study as many PTMs on proteins as possible. Read More

View Article and Full-Text PDF
January 2021

Application of SILAC Labeling in Phosphoproteomics Analysis.

Methods Mol Biol 2021 ;2228:167-183

Medizinisches Proteom-Center (MPC), Medical Faculty, Ruhr-Universität Bochum, Bochum, Germany.

The analysis of disease-related changes in the phosphorylation status of cellular signal transduction networks is of major interest to biomedical researchers. Mass spectrometry-based proteomics allows the analysis of phosphorylation in a global manner. However, several technical challenges need to be addressed when the phosphorylation of proteins is analyzed. Read More

View Article and Full-Text PDF
January 2021

Response mechanism of ♀ Epinephelus fuscoguttatus × ♂ Epinephelus lanceolatus under low-temperature and waterless stresses using TMT proteomic analysis.

Protoplasma 2021 May 5. Epub 2021 May 5.

College of Food Science and Technology, Guangdong Ocean University, Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, Guangdong Provincial Engineering Technology Research Center of Marine Food, Key Laboratory of Advanced Processing of Aquatic Products of Guangdong Higher Education Institution, Zhanjiang, 524088, China.

♀Epinephelus fuscoguttatus × ♂Epinephelus lanceolatus, a hybrid grouper created from artificial breeding, has been widely developed over the past decades. However, the study focusing on lukewarm high-protein-content fish species using advanced techniques has rarely been reported. In this work, the TMT (tandem mass tag)-assisted technique was employed to explore its differentially expressed proteins and response mechanisms under low-temperature dormant and waterless stresses. Read More

View Article and Full-Text PDF

Aspergillus niger uses the peroxisomal CoA-dependent β-oxidative genes to degrade the hydroxycinnamic acids caffeic acid, ferulic acid, and p-coumaric acid.

Appl Microbiol Biotechnol 2021 May 5. Epub 2021 May 5.

Fungal Physiology, Westerdijk Fungal Biodiversity Institute & Fungal Molecular Physiology, Utrecht University, Utrecht, The Netherlands.

Aromatic compounds are important molecules which are widely applied in many industries and are mainly produced from nonrenewable sources. Renewable sources such as plant biomass are interesting alternatives for the production of aromatic compounds. Ferulic acid and p-coumaric acid, a precursor for vanillin and p-vinyl phenol, respectively, can be released from plant biomass by the fungus Aspergillus niger. Read More

View Article and Full-Text PDF

JAK1: Number one in the family; number one in inflammation?

Rheumatology (Oxford) 2021 May;60(Supplement_2):ii3-ii10

Translational Immunology Section, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA.

Several cytokines involved in inflammatory pathologies signal via the Janus kinase-signal transducer and activator of transcription pathway. Four JAKs are known: JAK1, JAK2, JAK3 and TYK2. The specific activation of JAKs and STATs determines the biological effects of each cytokine. Read More

View Article and Full-Text PDF

JAK1 selective inhibitors for the treatment of spondyloarthropathies.

Rheumatology (Oxford) 2021 May;60(Supplement_2):ii39-ii44

Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Science, University of Oxford, Oxford, UK.

As our understanding of the pathogenesis of SpA improves, focus has turned to the role janus kinase (JAK)-mediated signal transduction and inhibiting its actions as a therapeutic mechanism. Small molecule inhibitors of JAK exist, with variable selectivity for the different JAK isoforms. Less selective JAK inhibitors have variable efficacy and safety profiles, prompting the investigation of selective JAK1 inhibition. Read More

View Article and Full-Text PDF

Crystallographic analysis and phasing of iron-assimilating protein 1 (FEA1) from Chlamydomonas reinhardtii.

Acta Crystallogr F Struct Biol Commun 2021 May 28;77(Pt 5):134-139. Epub 2021 Apr 28.

Institute for Protein Research, Osaka University, Yamada-oka 3-2, Suita, Osaka 565-0871, Japan.

As an essential component of protein cofactors, iron is important for all photosynthetic organisms. In Chlamydomonas reinhardtii, iron levels are strictly controlled by proteins such as iron-assimilating protein 1 (FEA1). This periplasmic protein is expressed under conditions of iron deficiency, but its mechanisms of function remain unknown. Read More

View Article and Full-Text PDF

LncRNA AFAP1-AS1 regulates proliferation and apoptosis of endometriosis through activating STAT3/TGF-β/Smad signaling via miR-424-5p.

J Obstet Gynaecol Res 2021 May 4. Epub 2021 May 4.

Reproductive Center, The First People's Hospital of Yueyang, Yueyang, China.

Aim: Endometriosis is a common gynecological disorder characterized by chronic pelvic pain and infertility, which negatively affects women's health worldwide. AFAP1-AS1 has been implicated in endometriosis lesions recently, but its mechanism of endometriosis progression remains unclear.

Methods: Endometrial stromal cells (ESCs) were used to identify the role of AFAP1-AS1 in endometriosis. Read More

View Article and Full-Text PDF

Sonic hedgehog signaling is associated with resistance to zoledronic acid in CD133high/CD44high prostate cancer stem cells.

Mol Biol Rep 2021 May 4. Epub 2021 May 4.

Department of Histology and Embryology, Faculty of Medicine, Ege University, Izmir, 35080, Turkey.

Cancer stem cells (CSCs) are a unique population that has been linked to drug resistance and metastasis and recurrence of prostate cancer. The sonic hedgehog (SHH) signal regulates stem cells in normal prostate epithelium by affecting cell behavior, survival, proliferation, and maintenance. Aberrant SHH pathway activation leads to an unsuitable expansion of stem cell lineages in the prostate epithelium and the transformation of prostate CSCs (PCSCs). Read More

View Article and Full-Text PDF

Targeted Quantification of Phosphorylation Sites Identifies STRIPAK-Dependent Phosphorylation of the Hippo Pathway-Related Kinase SmKIN3.

mBio 2021 May 4;12(3). Epub 2021 May 4.

Allgemeine und Molekulare Botanik, Ruhr-Universität, Bochum, Germany

We showed recently that the erminal enter inase III (GCKIII) SmKIN3 from the fungus is involved in sexual development and hyphal septation. Our recent extensive global proteome and phosphoproteome analysis revealed that SmKIN3 is a target of the iatin-nteracting hosphatase nd inase (STRIPAK) multisubunit complex. Here, using protein samples from the wild type and three STRIPAK mutants, we applied absolute quantification by arallel-eaction onitoring (PRM) to analyze phosphorylation site occupancy in SmKIN3 and other eptation nitiation etwork (SIN) components, such as CDC7 and DBF2, as well as BUD4, acting downstream of SIN. Read More

View Article and Full-Text PDF

Viral Evolution Identifies a Critical Residue in the Alphaherpesvirus Fusion Glycoprotein B Ectodomain That Controls gH/gL-Independent Entry.

mBio 2021 May 4;12(3). Epub 2021 May 4.

Institute of Molecular Virology and Cell Biology, Friedrich-Loeffler-Institut, Greifswald-Insel Riems, Germany

Herpesvirus entry and spread requires fusion of viral and host cell membranes, which is mediated by the conserved surface glycoprotein B (gB). Upon activation, gB undergoes a major conformational change and transits from a metastable prefusion to a stable postfusion conformation. Although gB is a structural homolog of low-pH-triggered class III fusogens, its fusion activity depends strictly on the presence of the conserved regulatory gH/gL complex and nonconserved receptor binding proteins, which ensure that fusion occurs at the right time and space. Read More

View Article and Full-Text PDF

The Landscape of Cell-free HBV Integrations and Mutations in Cirrhosis and Hepatocellular Carcinoma Patients.

Clin Cancer Res 2021 May 4. Epub 2021 May 4.

Berry Oncology Corporation, Beijing, China.

Purpose: Intratumoral hepatitis B virus (HBV) integrations and mutations are related to hepatocellular carcinoma (HCC) progression. Circulating cell-free DNA (cfDNA) has shown itself as a powerful non-invasive biomarker for cancer. However, the HBV integration and mutation landscape on cfDNA remains unclear. Read More

View Article and Full-Text PDF

Investigation of Neuropathology after Nerve Release in Chronic Constriction Injury of Rat Sciatic Nerve.

Int J Mol Sci 2021 Apr 29;22(9). Epub 2021 Apr 29.

Division of Plastic and Reconstructive Surgery, Department of Surgery, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan.

Peripheral compressive neuropathy causes significant neuropathic pain, muscle weakness and prolong neuroinflammation. Surgical decompression remains the gold standard of treatment but the outcome is suboptimal with a high recurrence rate. From mechanical compression to chemical propagation of the local inflammatory signals, little is known about the distinct neuropathologic patterns and the genetic signatures after nerve decompression. Read More

View Article and Full-Text PDF

Proteolytic Cleavage of Receptor Tyrosine Kinases.

Hao Huang

Biomolecules 2021 Apr 29;11(5). Epub 2021 Apr 29.

Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.

The receptor tyrosine kinases (RTKs) are a large family of cell-surface receptors, which are essential components of signal transduction pathways. There are more than fifty human RTKs that can be grouped into multiple RTK subfamilies. RTKs mediate cellular signaling transduction, and they play important roles in the regulation of numerous cellular processes. Read More

View Article and Full-Text PDF

Elevated Sporulation Efficiency in Fission Yeast Strains Isolated from .

J Fungi (Basel) 2021 Apr 29;7(5). Epub 2021 Apr 29.

Center for Biosystems Dynamics Research, RIKEN, 6-2-3 Furuedai, Suita, Osaka 565-0874, Japan.

The fission yeast , comprising var. and var. varieties, has unique characteristics such as striking hyphal growth not seen in other species; however, information on its diversity and evolution, in particular mating and sporulation, remains limited. Read More

View Article and Full-Text PDF

The Multifaceted Roles of USP15 in Signal Transduction.

Int J Mol Sci 2021 Apr 29;22(9). Epub 2021 Apr 29.

Biomedical Research Institute, Korea Institute of Science and Technology, Seoul 02793, Korea.

Ubiquitination and deubiquitination are protein post-translational modification processes that have been recognized as crucial mediators of many complex cellular networks, including maintaining ubiquitin homeostasis, controlling protein stability, and regulating several signaling pathways. Therefore, some of the enzymes involved in ubiquitination and deubiquitination, particularly E3 ligases and deubiquitinases, have attracted attention for drug discovery. Here, we review recent findings on USP15, one of the deubiquitinases, which regulates diverse signaling pathways by deubiquitinating vital target proteins. Read More

View Article and Full-Text PDF

Wounding-Induced VOC Emissions in Five Tropical Agricultural Species.

Molecules 2021 Apr 29;26(9). Epub 2021 Apr 29.

Chair of Crop Science and Plant Biology, Institute of Agricultural and Environmental Sciences, Estonian University of Life Sciences, Kreutzwaldi 1, 51006 Tartu, Estonia.

Leaf mechanical wounding triggers a rapid release-within minutes-of a blend of volatile organic compounds. A wounding-induced VOC blend is mainly composed of oxygenated ubiquitous stress volatiles such as methanol and volatile products of lipoxygenase (LOX) pathway (mainly C5 and C6 alcohols and aldehydes and their derivatives), but also includes multiple minor VOCs that collectively act as infochemicals, inducing defences in non-damaged plant leaves and neighbouring plants and attracting herbivore enemies. At present, the interspecific variability of the rate of induction and magnitude of wounding-induced emissions and the extent to which plant structural traits and physiological activity alter these emissions are poorly known. Read More

View Article and Full-Text PDF

Reduced Expression in Lung Fibroblasts from Patients with IPF Is Not Mediated by Promoter Methylation or Mir155.

Biomedicines 2021 Apr 30;9(5). Epub 2021 Apr 30.

Institute for Respiratory Health, Nedland 6009, WA, Australia.

The interleukin (IL)-6 family of cytokines and exaggerated signal transducer and activator of transcription (STAT)3 signaling is implicated in idiopathic pulmonary fibrosis (IPF) pathogenesis, but the mechanisms regulating STAT3 expression and function are unknown. Suppressor of cytokine signaling (SOCS)1 and SOCS3 block STAT3, and low SOCS1 levels have been reported in IPF fibroblasts and shown to facilitate collagen production. Fibroblasts and lung tissue from IPF patients and controls were used to examine the mechanisms underlying SOCS1 down-regulation in IPF. Read More

View Article and Full-Text PDF

Integrated microRNA and mRNA Expression Profiling Identifies Novel Targets and Networks Associated with Ebstein's Anomaly.

Cells 2021 Apr 30;10(5). Epub 2021 Apr 30.

Department of Pediatric Cardiology, Saarland University Medical Center, 66421 Homburg/Saar, Germany.

Little is known about abundance level changes of circulating microRNAs (miRNAs) and messenger RNAs (mRNA) in patients with Ebstein's anomaly (EA). Here, we performed an integrated analysis to identify the differentially abundant miRNAs and mRNA targets and to identify the potential therapeutic targets that might be involved in the mechanisms underlying EA. A large panel of human miRNA and mRNA microarrays were conducted to determine the genome-wide expression profiles in the blood of 16 EA patients and 16 age and gender-matched healthy control volunteers (HVs). Read More

View Article and Full-Text PDF

Molecular Mechanism of Small-Molecule Inhibitors in Blocking the PD-1/PD-L1 Pathway through PD-L1 Dimerization.

Int J Mol Sci 2021 Apr 30;22(9). Epub 2021 Apr 30.

Key Laboratory for Bio-Based Materials and Energy of Ministry of Education, College of Materials and Energy, South China Agricultural University, Guangzhou 510630, China.

Programmed cell death-1 (PD-1), which is a molecule involved in the inhibitory signal in the immune system and is important due to blocking of the interactions between PD-1 and programmed cell death ligand-1 (PD-L1), has emerged as a promising immunotherapy for treating cancer. In this work, molecular dynamics simulations were performed on complex systems consisting of the PD-L1 dimer with (S)-BMS-200, (R)-BMS-200 and (MOD)-BMS-200 (i.e. Read More

View Article and Full-Text PDF

Correlated Motions of Conserved Polar Motifs Lay out a Plausible Mechanism of G Protein-Coupled Receptor Activation.

Biomolecules 2021 Apr 30;11(5). Epub 2021 Apr 30.

Laboratory of Chemical Biology, Institute of Biochemistry, Biological Research Centre, Szeged, 62. Temesvári krt., H-6726 Szeged, Hungary.

Recent advancements in the field of experimental structural biology have provided high-resolution structures of active and inactive state G protein-coupled receptors (GPCRs), a highly important pharmaceutical target family, but the process of transition between these states is poorly understood. According to the current theory, GPCRs exist in structurally distinct, dynamically interconverting functional states of which populations are shifted upon binding of ligands and intracellular signaling proteins. However, explanation of the activation mechanism, on an entirely structural basis, gets complicated when multiple activation pathways and active receptor states are considered. Read More

View Article and Full-Text PDF

Short chain fatty acids delay the development of hepatocellular carcinoma in HBx transgenic mice.

Neoplasia 2021 May 1;23(5):529-538. Epub 2021 May 1.

Department of Biology, College of Science and Technology, Philadelphia, PA, USA. Electronic address:

Chronic infection with hepatitis B virus (HBV) is a major risk factor for the development of hepatocellular carcinoma (HCC). The HBV encoded oncoprotein, HBx, alters the expression of host genes and the activity of multiple signal transduction pathways that contribute to the pathogenesis of HCC by multiple mechanisms independent of HBV replication. However, it is not clear which pathways are the most relevant therapeutic targets in hepatocarcinogenesis. Read More

View Article and Full-Text PDF

The lncRNA and the transcription factor WRKY42 target common cell wall EXTENSIN encoding genes to trigger root hair cell elongation.

Plant Signal Behav 2021 May 4:1920191. Epub 2021 May 4.

Fundación Instituto Leloir and IIBBA-CONICET, Buenos Aires, CP, Argentina.

Plant long noncoding RNAs (lncRNAs) are key chromatin dynamics regulators, directing the transcriptional programs driving a wide variety of developmental outputs. Recently, we uncovered how the lncRNA () directly recognizes the locus encoding the root hair (RH) master regulator () modulating its transcriptional activation and leading to low temperature-induced RH elongation. We further demonstrated that interacts with the transcription factor WRKY42 in a novel ribonucleoprotein complex shaping epigenetic environment and integrating signals governing RH growth and development. Read More

View Article and Full-Text PDF

JAK inhibitors, Psoriatic Arthritis, and Axial Spondyloarthritis: a Critical Review of Clinical Trials.

Expert Rev Clin Immunol 2021 May 4. Epub 2021 May 4.

Division of Rheumatology, University of Alberta, Edmonton, Alberta, Canada.

Introduction: Psoriatic arthritis (PsA) and spondyloarthritis (SpA) are inflammatory arthritides associated with progressive damage, deformity and morbidity. Janus kinase (JAK) inhibitors block JAKs, cytoplasmic protein tyrosine kinases important in signal transduction and immune processes that are currently being studied as synthetic disease modifying anti-rheumatic drugs (tsDMARDs) in psoriatic arthritis and spondyloarthritis.

Areas Covered: This review evaluates published phase 2 and 3 clinical trial data for JAK kinase inhibitors for psoriatic arthritis and spondyloarthritis. Read More

View Article and Full-Text PDF

A novel lncRNA promotes myogenesis of bovine skeletal muscle satellite cells via PFN1-RhoA/Rac1.

J Cell Mol Med 2021 May 4. Epub 2021 May 4.

Tianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural University, Tianjin, China.

Myogenesis, the process of skeletal muscle formation, is a highly coordinated multistep biological process. Accumulating evidence suggests that long non-coding RNAs (lncRNAs) are emerging as a gatekeeper in myogenesis. Up to now, most studies on muscle development-related lncRNAs are mainly focussed on humans and mice. Read More

View Article and Full-Text PDF

Diagnostic and therapeutic potencies of miR-18a-5p in mixed-type gastric adenocarcinoma.

J Cell Biochem 2021 May 4. Epub 2021 May 4.

Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Mixed-type gastric adenocarcinoma (by Lauren Classification) has poor clinical outcomes with few targeted treatment options. The primary objective of this study was to find the prognostic factors, accurate treatment approaches, and effective postoperative adjuvant therapy strategies for patients with mixed-type gastric adenocarcinoma (GA). A microRNA sequencing data set and the corresponding clinical parameters of patients with gastric cancer were obtained from The Cancer Genome Atlas. Read More

View Article and Full-Text PDF