1,026,258 results match your criteria signaling

Aldosterone and Mineralocorticoid Receptor Signaling as Determinants of Cardiovascular and Renal Injury: From Hans Selye to the Present.

Murray Epstein

Am J Nephrol 2021 Apr 15:1-8. Epub 2021 Apr 15.

University of Miami School of Medicine, Miami, Florida, USA.

Background: A full understanding of the mechanisms of action of aldosterone and its interaction with the mineralocorticoid receptor (MR) allows a theoretical framework to predict the therapeutic potential of MR antagonists (MRAs) in CKD, and heart failure with reduced ejection fraction.

Summary: The initial focus on the mechanisms of action of aldosterone was directed primarily on its role in modulating renal excretory function. In contrast, many recent studies have demonstrated a wider and expanded role for aldosterone in modulating inflammation, collagen formation, fibrosis, and necrosis. Read More

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Randomised clinical trial: Efficacy and safety of Qing-Chang-Hua-Shi granules in a multicenter, randomized, and double-blind clinical trial of patients with moderately active ulcerative colitis.

Biomed Pharmacother 2021 Apr 12;139:111580. Epub 2021 Apr 12.

Affiliated Hospital of Nanjing University of Chinese Medicine (Jiangsu Province Hospital of Chinese Medicine), Nanjing 210029, China. Electronic address:

Qing-Chang-Hua-Shi (QCHS) is a Chinese herbal formula, which is composed of 11 herbs. Studies have also shown that QCHS granules can alleviate colitis in animal models by preventing inflammatory responses and suppressing apoptosis through the MEK/ERK signaling pathway. To determine the efficacy and safety of QCHS granules in patients with moderately active UC. Read More

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Screening and validation of candidate genes involved in the regulation of egg yolk deposition in chicken.

Poult Sci 2021 Mar 1;100(6):101077. Epub 2021 Mar 1.

National Engineering Laboratory for Animal Breeding and Key Laboratory of Animal Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affairs, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China. Electronic address:

Eggs with the same total weight may have considerable differences in yolk weight. Eggs with a high percentage of yolk have a higher nutritional value, more flavor, and are more desirable to consumers. However, a large yolk proportion means more dry matter in the eggs, which reduces the feed efficiency. Read More

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DNA methylation and protein expression of Wnt pathway markers in progressive glioblastoma.

Pathol Res Pract 2021 Apr 5;222:153429. Epub 2021 Apr 5.

Department of Laboratory Medicine, University of Pecs, School of Medicine, Pecs, Hungary; Szentagothai Research Center, University of Pecs, Pecs, Hungary. Electronic address:

Background: Wnt signaling plays important roles in tumorigenesis, invasiveness and therapeutic resistance of glioblastoma (GBM).

Methods: We simultaneously investigated six Wnt pathway markers (Wnt5a, Fzd-2, beta-catenin, Wnt3a, Wnt7b, Fzd-10) at epigenetic and protein levels in 21 sequential formalin-fixed paraffin-embedded GBM pairs and controls.

Results: Expression levels of Wnt5a, beta-catenin and Wnt3a proteins either moderately or significantly increased, while those of Fzd-2, Wnt7b and Fzd-10 decreased in the primary (GBM-P) and recurrent (GBM-R) tumors compared to the controls. Read More

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MHTP, a synthetic alkaloid, attenuates combined allergic rhinitis and asthma syndrome through downregulation of the p38/ERK1/2 MAPK signaling pathway in mice.

Int Immunopharmacol 2021 Apr 12;96:107590. Epub 2021 Apr 12.

Laboratory of Immunopharmacology, Postgraduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraíba, João Pessoa, PB, Brazil; Department of Physiology and Pathology, Federal University of Paraíba, João Pessoa, PB, Brazil. Electronic address:

The combined allergic rhinitis and asthma syndrome (CARAS) is a chronic airway inflammation of allergic individuals, with a type 2 immune response. Pharmacotherapy is based on drugs with relevant side effects. Thus, the goal of this study was to evaluate the synthetic alkaloid, MHTP in the experimental model of CARAS. Read More

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Skeletal muscle-specific Keap1 disruption modulates fatty acid utilization and enhances exercise capacity in female mice.

Redox Biol 2021 Apr 5;43:101966. Epub 2021 Apr 5.

Department of Gene Expression Regulation, IDAC, Tohoku University, Sendai, 980-8575, Japan. Electronic address:

Skeletal muscle health is important for the prevention of various age-related diseases. The loss of skeletal muscle mass, which is known as sarcopenia, underlies physical disability, poor quality of life and chronic diseases in elderly people. The transcription factor NRF2 plays important roles in the regulation of the cellular defense against oxidative stress, as well as the metabolism and mitochondrial activity. Read More

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Targeted nanomedicine modalities for prostate cancer treatment.

Drug Resist Updat 2021 Mar 19;56:100762. Epub 2021 Mar 19.

The Fred Wyszkowski Cancer Research Laboratory, Department of Biology, Technion - Israel Institute of Technology, Haifa, 3200003, Israel. Electronic address:

Prostate cancer (PC) is the second most common cause of death amongst men in the USA. Therapy of PC has been transformed in the past decade by introducing novel therapeutics, advanced functional imaging and diagnostic approaches, next generation sequencing, as well as improved application of existing therapies in localized PC. Treatment of PC at the different stages of the disease may include surgery, androgen deprivation therapy (ADT), chemotherapy and radiation therapy. Read More

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Loss of tumor suppressive properties of lipid metabolism enzyme CPT2 in ovarian carcinoma: Comment on "CPT2 down-regulation promotes tumor growth and metastasis through inducing ROS/NFκB pathway in ovarian cancer" by Zhang et al.

Transl Oncol 2021 Apr 12;14(7):101067. Epub 2021 Apr 12.

Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine, 520 East 70th street, New York, NY 10021, USA. Electronic address:

Lipid metabolism is an essential process in cancer growth and progression. It is highly relevant in tumors with an adipocyte-rich microenvironment, such as ovarian carcinoma (OC). Carnitine palmitoyltransferase 2 (CPT2) is a key enzyme in fatty acid oxidation (FAO) that functions as a tumor suppressor in OC. Read More

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Apoptosis Signal-Regulating Kinase 1 (ASK1) Inhibition Reduces Endothelial Cytokine Production without Improving Permeability after Toll-like Receptor 4 (TLR4) Challenge.

Transl Res 2021 Apr 12. Epub 2021 Apr 12.

Department of 1Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232. Electronic address:

Sepsis represents a life-threatening event often mediated by the host's response to pathogens such as gram-negative organisms, which release the pro-inflammatory lipopolysaccharide (LPS). Within the endothelium, the mitogen-activated protein kinase (MAPK) pathway is an important driver of endothelial injury during sepsis, of which oxidant-sensitive apoptosis signal-regulating kinase 1 (ASK1) is postulated to be a critical upstream regulator. We hypothesized that ASK1 would play a key role in endothelial inflammation during bacterial challenge. Read More

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Heart Rhythm 2021 Apr 12. Epub 2021 Apr 12.

Cardiovascular Pathology and Cardiology Units, Department of Cardiac-Thoracic-Vascular Sciences and Public Health, University of Padua, Padua, Italy.

Background: Arrhythmogenic cardiomyopathy (AC) is a myocardial disease due to desmosomal mutations, whose pathogenesis remains incompletely understood.

Objective: To identify molecular pathways underlying early AC by gene expression profiling in both humans and animal models.

Methods: RNA sequencing for differentially expressed genes (DEGs) was performed on the myocardium of transgenic mice over-expressing the Desmoglein2-N271S mutation before phenotype onset. Read More

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Sodium fluoride activates the extrinsic apoptosis via regulating NOX4/ROS-mediated p53/DR5 signaling pathway in lung cells both in vitro and in vivo.

Free Radic Biol Med 2021 Apr 12. Epub 2021 Apr 12.

Zhengzhou Key Laboratory of Animal Nutrition Metabolic and Poisoning Diseases, College of Veterinary Medicine, Henan University of Animal Husbandry and Economy, Zhengzhou, 450000, Henan, China; Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, 030801, Shanxi, China. Electronic address:

An extensive body of research has demonstrated that pulmonary toxicity induced by fluoride is related to cell apoptosis. Although induction of death receptor-initiated extrinsic apoptosis by sodium fluoride (NaF) has been reported, its mechanism of action is still not clearly defined. Herein, we found that NaF treatment induced activation of caspase-8 in BEAS-2B cells, resulting in apoptosis, which was markedly reduced by blocking caspase-8 using small interfering RNA (siRNA). Read More

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Functions of the extracellular matrix in development: Lessons from Caenorhabditis elegans.

Cell Signal 2021 Apr 12:110006. Epub 2021 Apr 12.

Development and Stem Cells Program, Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria 3800, Australia; Department of Experimental Medical Science, Lund University, Lund, Sweden. Electronic address:

Cell-extracellular matrix interactions are crucial for the development of an organism from the earliest stages of embryogenesis. The main constituents of the extracellular matrix are collagens, laminins, proteoglycans and glycosaminoglycans that form a network of interactions. The extracellular matrix and its associated molecules provide developmental cues and structural support from the outside of cells during development. Read More

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Laminins in metabolic tissues.

Metabolism 2021 Apr 12:154775. Epub 2021 Apr 12.

Committee on Molecular Metabolism and Nutrition, The University of Chicago, 900 East 57(th) St, Chicago, IL 60637, USA; Section of Endocrinology, Diabetes, and Metabolism, The University of Chicago, 5841 South Maryland Ave, Chicago, IL 60637, USA. Electronic address:

Laminins are extracellular matrix proteins that reside in the basement membrane and provide structural support in addition to promoting cellular adhesion and migration. Through interactions with cell surface receptors, laminins stimulate intracellular signaling cascades which direct specific survival and differentiation outcomes. In metabolic tissues such as the pancreas, adipose, muscle, and liver, laminin isoforms are expressed in discrete temporal and spatial patterns suggesting that certain isoforms may support the development and function of particular metabolic cell types. Read More

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Pyrazoles as novel protein tyrosine phosphatase 1B (PTP1B) inhibitors: An in vitro and in silico study.

Int J Biol Macromol 2021 Apr 12. Epub 2021 Apr 12.

LAQV-REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal. Electronic address:

Type 2 diabetes mellitus (DM) is a complex chronic disorder and a major global health problem. Insulin resistance is the primary detectable abnormality and the main characteristic feature in individuals with type 2 DM. Protein tyrosine phosphatase 1B (PTP1B) is a key negative regulator of the insulin signaling pathway, which dephosphorylates insulin receptor and insulin receptor substrates, suppressing the insulin signaling cascade. Read More

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PMEPA1 stimulates the proliferation, colony formation of pancreatic cancer cells via the MAPK signaling pathway.

Am J Med Sci 2021 Apr 12. Epub 2021 Apr 12.

Department of Hepatobiliary and Pancreatic Surgery, the Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, 266003, China. Electronic address:

Background: Prostate transmembrane protein androgen-induced 1 (PMEPA1) is reportedly highly expressed in pancreatic cancer (PC). However, its biological role and associated mechanisms have not been addressed in PC progression.

Methods: PMEPA1 mRNA expression and survival outcome of PC patients were evaluated via the GEPIA website. Read More

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USP9X deubiquitinates connexin43 to prevent high glucose-induced epithelial-to-mesenchymal transition in NRK-52E cells.

Biochem Pharmacol 2021 Apr 12:114562. Epub 2021 Apr 12.

Laboratory of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Sun Yat-sen University, Guangzhou 510006, China. Electronic address:

Epithelial-to-mesenchymal transition (EMT) plays an important role in diabetic nephropathy (DN). Ubiquitin-specific protease 9X (USP9X/FAM) is closely linked to TGF-β and fibrosis signaling pathway. However, it remains unknown whether USP9X is involved in the process of EMT in DN. Read More

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Investigation of n-3 Polyunsaturated Fatty Acid Biological Activity in a Tissue-Engineered Skin Model Involving Psoriatic cells: Omega-3 and psoriatic skin.

J Invest Dermatol 2021 Apr 12. Epub 2021 Apr 12.

Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Axe médecine régénératrice, Centre de recherche du CHU de Québec-Université Laval, Québec, QC, Canada; Faculté de pharmacie de l'Université Laval, Québec, QC, Canada. Electronic address:

Clinical studies have shown that diets enriched with omega-3 polyunsaturated fatty acids (n-3 PUFAs) could relieve the symptoms of psoriatic patients. However, the mechanisms involved remain poorly understood. The aim of this study was to investigate the effects of α-linolenic acid (ALA) on the proliferation and differentiation of psoriatic keratinocytes in a 3D skin model. Read More

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Sarcoplasmic reticulum-mitochondria communication; implications for cardiac arrhythmia.

J Mol Cell Cardiol 2021 Apr 12. Epub 2021 Apr 12.

Department of Physiology and Cell Biology, Davis Heart and Lung Research Institute, Wexner Medical Center, The Ohio State University, Columbus, OH, United States of America. Electronic address:

Sudden cardiac death due to ventricular tachyarrhythmias remains the major cause of mortality in the world. Heart failure, diabetic cardiomyopathy, old age-related cardiac dysfunction and inherited disorders are associated with enhanced propensity to malignant cardiac arrhythmias. Both defective mitochondrial function and abnormal intracellular Ca homeostasis have been established as the key contributing factors in the pathophysiology and arrhythmogenesis in these conditions. Read More

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Cardiomyocyte heterogeneity during zebrafish development and regeneration.

Dev Biol 2021 Apr 12. Epub 2021 Apr 12.

Department of Developmental Genetics, Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany. Electronic address:

Contrary to adult mammals, zebrafish are able to regenerate their heart after cardiac injury. This regenerative response relies, in part, on the endogenous ability of cardiomyocytes (CMs) to dedifferentiate and proliferate to replenish the lost muscle. However, CM heterogeneity and population dynamics during development and regeneration require further investigation. Read More

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CDKL kinase regulates the length of the ciliary proximal segment.

Curr Biol 2021 Apr 8. Epub 2021 Apr 8.

Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada; Centre for Cell Biology, Development, and Disease, Simon Fraser University, 8888 University Drive, Burnaby, BC V5A 1S6, Canada. Electronic address:

Cilia are organelles found throughout most unicellular eukaryotes and different metazoan cell types. To accomplish their essential roles in cell motility, fluid flow, and signaling, cilia are divided into subcompartments with variable structures, compositions, and functions. How these specific subcompartments are built remains almost completely unexplored. Read More

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Glioblastomas acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion.

Cell 2021 Apr 9. Epub 2021 Apr 9.

Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, UK; CRUK Edinburgh Centre, Institute of Genetics and Molecular Medicine, Crewe Road South, University of Edinburgh, Edinburgh EH42XR, UK. Electronic address:

Glioblastoma multiforme (GBM) is an aggressive brain tumor for which current immunotherapy approaches have been unsuccessful. Here, we explore the mechanisms underlying immune evasion in GBM. By serially transplanting GBM stem cells (GSCs) into immunocompetent hosts, we uncover an acquired capability of GSCs to escape immune clearance by establishing an enhanced immunosuppressive tumor microenvironment. Read More

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Il4ra-independent vaginal eosinophil accumulation following helminth infection exacerbates epithelial ulcerative pathology of HSV-2 infection.

Cell Host Microbe 2021 Apr;29(4):579-593.e5

Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), Institute of Infectious Disease and Molecular Medicine (IDM), Department of Pathology, Division of Immunology, Faculty of Health Science, University of Cape Town, Cape Town 7925, South Africa; Laboratory of Experimental and Molecular Immunology and Neurogenetics (INEM), UMR 7355 CNRS-University of Orléans, 45000 Orléans, France; Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK. Electronic address:

How helminths influence the pathogenesis of sexually transmitted viral infections is not comprehensively understood. Here, we show that an acute helminth infection (Nippostrongylus brasiliensis [Nb]) induced a type 2 immune profile in the female genital tract (FGT). This leads to heightened epithelial ulceration and pathology in subsequent herpes simplex virus (HSV)-2 infection. Read More

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How can we turn the PI3K/AKT/mTOR pathway down? Insights into inhibition and treatment of cancer.

Expert Rev Anticancer Ther 2021 Apr 15. Epub 2021 Apr 15.

Department of Biotechnology and Drug Discovery, Graduate School of Interdisciplinary Science and Engineering in Health Systems, Okayama University, Okayama, 700-8530, Japan.

Introduction: The phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway is a fundamental regulator of cell proliferation and survival. Dysregulation in this pathway leads to the development of cancer. Accumulating evidence indicates that dysregulation in this pathway is involved in cancer initiation, progression, and recurrence. Read More

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Pilot Analyses of Interferon Subtype Expression Profiles in Patients with Herpes Zoster or Postherpetic Neuralgia.

Viral Immunol 2021 Apr 15. Epub 2021 Apr 15.

Department of Pharmaceutical Sciences, School of Pharmacy and Health Professions, University of Maryland Eastern Shore, Princess Anne, Maryland, USA.

Postherpetic neuralgia (PHN) is a painful neuropathic complication resulting from herpes zoster (HZ). The pain manifests in peripheral nerves infected by herpesviruses, mostly from reactivation of latent varicella zoster virus. Mechanistic descriptions suggest that PHN develops because of disrupted immune system signaling and inflammation or peripheral nerve damage; however, the pathophysiology is not clear. Read More

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Development of Potent NEDD8-Activating Enzyme Inhibitors Bearing a Pyrimidotriazole Scaffold.

J Med Chem 2021 Apr 15. Epub 2021 Apr 15.

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China.

The ubiquitin-like protein NEDD8 is a critical signaling molecule implicated in the functional maintenance and homeostasis of cells. Dysregulation of this process is involved in a variety of human diseases, including cancer. Therefore, NEDD8-activating enzyme E1 (NAE), the only activation enzyme of the neddylation pathway, has been an emergent anticancer target. Read More

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Bacterial Extracellular Vesicles and the Gut-Microbiota Brain Axis: Emerging Roles in Communication and Potential as Therapeutics.

Adv Biol (Weinh) 2021 Apr 15:e2000540. Epub 2021 Apr 15.

Fischell Department of Bioengineering and Program in Molecular and Cell Biology, University of Maryland, 3116 A. James Clark Hall, College Park, MD, 20742, USA.

Bacterial extracellular vesicles (BEVs) have emerged as candidate signaling vectors for long-distance interkingdom communication within the gut-microbiota brain axis. Most bacteria release these nanosized vesicles, capable of signaling to the brain via their abundant protein and small RNA cargo, possibly directly via crossing the blood-brain barrier. BEVs have been shown to regulate brain gene expression and induce pathology at most stages of neuroinflammation and neurodegeneration, and thus they may play a causal role in diseases such as Alzheimer's, Parkinson's, and depression/anxiety. Read More

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Neuroimmune regulatory networks of the airway mucosa in allergic inflammatory disease.

J Leukoc Biol 2021 Apr 15. Epub 2021 Apr 15.

Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, USA.

Communication between the nervous and immune systems serves a key role in host-protective immunity at mucosal barrier sites including the respiratory tract. In these tissues, neuroimmune interactions operate in bidirectional circuits that can sense and respond to mechanical, chemical, and biologic stimuli. Allergen- or helminth-induced products can produce airway inflammation by direct action on nociceptive afferents and adjacent tissues. Read More

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K27-linked noncanonic ubiquitination in immune regulation.

J Leukoc Biol 2021 Apr 15. Epub 2021 Apr 15.

Department of Immunology, School of Basic Medical Sciences, NHC Key Laboratory of Medical Immunology (Peking University), Peking University Health Science Center, Beijing, China.

Ubiquitination is a common form of posttranslational modification that has been implicated in regulating considerable immune signaling pathways. The functions of canonic K48- and K63-linked ubiquitination have been well studied. However, the roles of noncanonic ubiquitination remain largely unexplored and require further investigations. Read More

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miRNA-Signature of Irradiated Ptch1+/- Mouse Lens is Dependent on Genetic Background.

Radiat Res 2021 Apr 15. Epub 2021 Apr 15.

Laboratory of Biomedical Technologies, Agenzia Nazionale per le Nuove Tecnologie, l'Energia e lo Sviluppo Economico Sostenibile (ENEA), Rome, Italy.

One harmful long-term effect of ionizing radiation is cataract development. Recent studies have been focused on elucidating the mechanistic pathways involved in this pathogenesis. Since accumulating evidence has established a role of microRNAs in ocular diseases, including cataract, the goal of this work was to determine the microRNA signature of the mouse lens, at short time periods postirradiation, to understand the mechanisms related to radio-induced cataractogenesis. Read More

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N- and C-terminal Gln3-Tor1 interaction sites: one acting negatively and the other positively to regulate nuclear Gln3 localization.

Genetics 2021 Apr;217(4)

Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN 38163, USA.

Gln3 activates Nitrogen Catabolite Repression, NCR-sensitive expression of the genes required for Saccharomyces cerevisiae to scavenge poor nitrogen sources from its environment. The global TorC1 kinase complex negatively regulates nuclear Gln3 localization, interacting with an α-helix in the C-terminal region of Gln3, Gln3656-666. In nitrogen replete conditions, Gln3 is sequestered in the cytoplasm, whereas when TorC1 is down-regulated, in nitrogen restrictive conditions, Gln3 migrates into the nucleus. Read More

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