24,732 results match your criteria systemic signaling


The IL-1 Receptor Is Required to Maintain Neutrophil Viability and Function During Airway Infection.

Front Immunol 2021 12;12:675294. Epub 2021 Jul 12.

Department of Microbiology and Immunology, McGill University, Montréal, QC, Canada.

airway infections are associated with increased rates of hospitalizations and declining lung function in patients with chronic lung disease. While the pathogenesis of invasive infections is well studied, little is known about the development and progression of airway infections. Previous studies have demonstrated a critical role for the IL-1 cytokines, IL-1α and IL-1β in enhancing pulmonary neutrophil recruitment during invasive aspergillosis. Read More

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Notch1 signaling enhances collagen expression and fibrosis in mouse uterus.

Biofactors 2021 Jul 28. Epub 2021 Jul 28.

College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.

Fibrosis is a pathological process characterized by abnormal activation of fibroblasts with increased synthesis of extracellular matrix components, including collagens. It may lead to loss of proper tissue architecture and organ function in clinical diseases such as systemic sclerosis and liver fibrosis. Excess accumulation of collagens is considered the primary indicator of fibrosis. Read More

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Glioblastoma Therapy: Rationale for a Mesenchymal Stem Cell-based Vehicle to Carry Recombinant Viruses.

Stem Cell Rev Rep 2021 Jul 28. Epub 2021 Jul 28.

School of Life Science, Beijing Institute of Technology, Beijing, 100811, China.

Evasion of growth suppression is among the prominent hallmarks of cancer. Phosphatase and tensin homolog (PTEN) and p53 tumor-suppressive pathways are compromised in most human cancers, including glioblastoma (GB). Hence, these signaling pathways are an ideal point of focus for novel cancer therapeutics. Read More

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STING suppresses bone cancer pain via immune and neuronal modulation.

Nat Commun 2021 07 27;12(1):4558. Epub 2021 Jul 27.

Center for Translational Pain Medicine, Department of Anesthesiology, Duke University Medical Center, Durham, NC, USA.

Patients with advanced stage cancers frequently suffer from severe pain as a result of bone metastasis and bone destruction, for which there is no efficacious treatment. Here, using multiple mouse models of bone cancer, we report that agonists of the immune regulator STING (stimulator of interferon genes) confer remarkable protection against cancer pain, bone destruction, and local tumor burden. Repeated systemic administration of STING agonists robustly attenuates bone cancer-induced pain and improves locomotor function. Read More

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Short stature and combined immunodeficiency associated with mutations in RGS10.

Sci Signal 2021 07 27;14(693). Epub 2021 Jul 27.

Lung and Vascular Inflammation Section, Laboratory of Allergic Diseases, NIAID/NIH Bethesda, MD 20892, USA.

We report the clinical and molecular phenotype of three siblings from one family, who presented with short stature and immunodeficiency and carried uncharacterized variants in (c.489_491del:p.E163del and c. Read More

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2-Aminoethyl diphenylborinate inhibits bleomycin-induced skin and pulmonary fibrosis via interrupting intracellular Ca regulation.

J Dermatol Sci 2021 Jul 13. Epub 2021 Jul 13.

Department of Dermatology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Cosmetic Science, Chang Gung University of Science and Technology, Taoyuan, Taiwan. Electronic address:

Background: Systemic sclerosis (SSc) causes progressive fibrosis of multiple organs with the low efficacy of immunosuppressive therapies. Our previous study indicated the SSc pathological pathways are closely correlated with Ca signals, and blockage of the intracellular Ca elevation facilitates inhibition of SSc pathogenesis.

Objective: Transforming growth factor β (TGF-β)-modulated SMAD signaling is crucial in regulating SSc pathogenesis. Read More

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IRE1 and PERK signaling regulates inflammatory responses in a murine model of contact hypersensitivity.

Allergy 2021 Jul 27. Epub 2021 Jul 27.

Allergy Research Group, Department of Dermatology, Medical Center, University of Freiburg, Faculty of Medicine, University of Freiburg, Germany.

Background: Contact sensitizers may interfere with correct protein folding. Generation of un-/misfolded proteins can activate the IRE-1 or PERK-signaling pathways initiating the unfolded protein response (UPR) and thereby determine inflammatory immune responses. We have analyzed the effect of sensitizers with different potencies on the induction of UPR activation/inhibition and the subsequent generation of a pro-inflammatory micromilieu in vitro as well as the effect of UPR modulation on the inflammatory response in the murine contact hypersensitivity (CHS) in vivo. Read More

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Crosstalk between AdipoR1/AdipoR2 and Nrf2/HO-1 signal pathways activated by β-caryophyllene suppressed the compound 48/80 induced pseudo-allergic reactions.

Clin Exp Pharmacol Physiol 2021 Jul 27. Epub 2021 Jul 27.

Division of Pharmaceutical Technology. Defence Research Laboratory, Tezpur, India.

Mast cell activation is initiated by two signaling pathways: Immunoglobulin E (IgE) dependent and IgE independent pathway. It is reported that the IgE-independent type or pseudo-allergy pathway gets activated by G-protein-dependent activation of the mast cell. Recently, adiponectin (APN) receptors, AdipoR1, and AdipoR2 are identified as G-protein-coupled receptors (GPCRs). Read More

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Blood Biomarkers Reflect the Effects of Obesity and Inflammation on the Human Breast Transcriptome.

Carcinogenesis 2021 Jul 27. Epub 2021 Jul 27.

Retired, Department of Medicine, Weill Cornell Medical College, New York, New York.

Obesity is a risk factor for the development of post-menopausal breast cancer. Breast white adipose tissue (WAT) inflammation, which is commonly found in women with excess body fat, is also associated with increased breast cancer risk. Both local and systemic effects are likely to be important for explaining the link between excess body fat, adipose inflammation and breast cancer. Read More

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Cf-02, a novel benzamide-linked small molecule, blunts NF-κB activation and NLRP3 inflammasome assembly and improves acute onset of accelerated and severe lupus nephritis in mice.

FASEB J 2021 08;35(8):e21785

Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.

In the present study, acute onset of severe lupus nephritis was successfully treated in mice using a new, benzamide-linked, small molecule that targets immune modulation and the NLRP3 inflammasome. Specifically, 6-(2,4-difluorophenyl)-3-(3-(trifluoromethyl)phenyl)-2H-benzo[e][1,3]oxazine-2,4(3H)-dione (Cf-02) (a) reduced serum levels of IgG anti-dsDNA, IL-1β, IL-6, and TNF-α, (b) inhibited activation of dendritic cells and differentially regulated T cell functions, and (c) suppressed the NF-κB/NLRP3 inflammasome axis, targeting priming and activating signals of the inflammasome. Moreover, treatment with Cf-02 significantly inhibited secretion of IL-1β in lipopolysaccharide-stimulated macrophages, but this effect was abolished by autophagy induction. Read More

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Hyperuricemia-induced endothelial insulin resistance: the nitric oxide connection.

Pflugers Arch 2021 Jul 27. Epub 2021 Jul 27.

Endocrine Physiology Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, No. 24, Parvaneh Street, P.O. Box: 19395-4763, VelenjakTehran, Iran.

Hyperuricemia, defined as elevated serum concentrations of uric acid (UA) above 416 µmol L, is related to the development of cardiometabolic disorders, probably via induction of endothelial dysfunction. Hyperuricemia causes endothelial dysfunction via induction of cell apoptosis, oxidative stress, and inflammation; however, it's interfering with insulin signaling and decreased endothelial nitric oxide (NO) availability, resulting in the development of endothelial insulin resistance, which seems to be a major underlying mechanism for hyperuricemia-induced endothelial dysfunction. Here, we elaborate on how hyperuricemia induces endothelial insulin resistance through the disruption of insulin-stimulated endothelial NO synthesis. Read More

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Tofacitinib in the treatment of skin and musculoskeletal involvement in patients with systemic sclerosis, evaluated by ultrasound.

Rheumatol Int 2021 Jul 27. Epub 2021 Jul 27.

Department of Internal Diseases, Medical University of Plovdiv, Plovdiv, Bulgaria.

Systemic sclerosis (SSc) is a rare autoimmune connective tissue disease characterized by fibrosis of the skin and internal organs, autoimmunity-driven damage and vasculopathy. The current approved disease-modifying treatments have limited efficacy, and treatment is guided toward alleviating organ complications. Thus, there is an unmet need for discovering new effective treatment options. Read More

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BAFF receptor polymorphisms and deficiency in humans.

Curr Opin Immunol 2021 Jul 23;71:103-110. Epub 2021 Jul 23.

Dept. of Rheumatology and Clinical Immunology and Center for Chronic Immunodeficiency, Medical Center, University of Freiburg, Freiburg, Germany. Electronic address:

The BAFF-receptor (BAFFR) is a member of the TNF-receptor family. It is expressed only by B cells and binds BAFF as single ligand, which activates key signaling pathways regulating essential cellular functions, including survival, protein synthesis, and metabolic fitness. In humans, BAFFR deficiency interrupts B cell development at the transition from immature to mature B cells and causes B lymphopenia, hypogammaglobulinemia, and impaired humoral immune responses. Read More

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Heparan sulfate promotes differentiation of white adipocytes to maintain insulin sensitivity and glucose homeostasis.

J Biol Chem 2021 Jul 23:101006. Epub 2021 Jul 23.

Department of Pharmacology, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan. Electronic address:

Heparan sulfate (HS), a highly sulfated linear polysaccharide, is involved in diverse biological functions in various tissues. Although previous studies have suggested a possible contribution of HS to the differentiation of white adipocytes, there has been no direct evidence supporting this. Here, we inhibited the synthesis of HS chains in 3T3-L1 cells using CRISPR/Cas9 technology, resulting in impaired differentiation of adipocytes with attenuated BMP4 (bone morphogenetic protein 4)/FGF1 (fibroblast growth factor 1) signaling pathways. Read More

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Micro-RNA 133a-3p induces repolarization abnormalities in atrial myocardium and modulates ventricular electrophysiology affecting I and Ito currents.

Eur J Pharmacol 2021 Jul 24;908:174369. Epub 2021 Jul 24.

Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK; Heart Embryology and Anatomy Research Team, Department of Anatomy, Jagiellonian University Medical College, Cracow, Poland.

Mir-133a-3p is the most abundant myocardial microRNA. The impact of mir-133a-3p on cardiac electrophysiology is poorly explored. In this study, we investigated the effects of mir-133a-3p on the main ionic currents critical for action potential (AP) generation and electrical activity of the heart. Read More

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The impact of atezolizumab and bevacizumab in hepatocellular carcinoma with activated ß-catenin signaling.

Cancer Rep (Hoboken) 2021 Jul 26:e1493. Epub 2021 Jul 26.

Department of Internal Medicine I, Martin-Luther University Halle-Wittenberg, Halle (Saale), Germany.

Background: To date, no biomarkers exist to predict response or resistance to immunotherapy in hepatocellular carcinoma (HCC). Recent approaches to classify HCC into different immunological states revealed a negative correlation between Wnt/ß-catenin activation and immunogenicity and T-cell infiltration. If these "cold" tumors with primary resistance to checkpoint inhibition (CPI) may benefit from dual treatment of CPI and anti-angiogenic therapy has not been proved. Read More

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Case Report: Hodgkin Lymphoma and Refractory Systemic Lupus Erythematosus Unveil Activated Phosphoinositide 3-Kinase-δ Syndrome 2 in an Adult Patient.

Front Pediatr 2021 8;9:702546. Epub 2021 Jul 8.

Pediatric Unit, Istituti di Ricovero e Cura a Carattere Scientifico Azienda Ospedaliero-Universitaria di Bologna, University of Bologna, Bologna, Italy.

Activated phosphoinositide 3-kinase-δ syndrome 2 (APDS2) is a rare primary immune regulatory disorder caused by heterozygous gain of function mutation in the gene encoding PI3Kδ regulatory p85α subunit and resulting in PI3Kδ hyperactivation. Clinical features range from recurrent infections to manifestations of immune dysregulation like autoimmunity, inflammation, systemic lymphoproliferation, and increased risk of cancer. We describe a new dominant mutation causing APDS2 presenting with lymphoma and systemic refractory autoimmunity. Read More

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Associated genetic polymorphisms and clinical manifestations in systemic lupus erythematosus in Asian populations - A systematic literature review.

Med J Malaysia 2021 Jul;76(4):541-550

Universiti Kebangsaan Malaysia (UKM), UKM Medical Molecular Biology Institute (UMBI), Cheras, Kuala Lumpur, Malaysia.

Introduction: Systemic lupus erythematosus (SLE) is a chronic and life-threatening autoimmune disease. Its prevalence and clinical manifestations are known to be particularly severe in the Asian populations. Although genetics is known to play an important role in SLE susceptibility and clinical manifestations, the specific polymorphisms associated with these phenotypes in Asia are unclear. Read More

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Dysregulation of host cell calcium signaling during viral infections: Emerging paradigm with high clinical relevance.

Mol Aspects Med 2021 Jul 22:101004. Epub 2021 Jul 22.

Laboratory of Calciomics and Systemic Pathophysiology, Regional Centre for Biotechnology (RCB), Faridabad-121001, Delhi-NCR, India. Electronic address:

Viral infections are one of the leading causes of human illness. Viruses take over host cell signaling cascades for their replication and infection. Calcium (Ca) is a versatile and ubiquitous second messenger that modulates plethora of cellular functions. Read More

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Biomarkers of systemic inflammation, soluble IL-2Rα and the multiple sclerosis-associated IL2RA SNP rs2104286 in healthy subjects and multiple sclerosis patients.

Mult Scler Relat Disord 2021 Jul 7;54:103140. Epub 2021 Jul 7.

Danish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Glostrup, Denmark; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

Soluble interleukin-2 (IL-2) receptor α (sIL-2Rα) antagonizes IL-2 signaling and is involved in the pathogenesis of several immune-mediated diseases including multiple sclerosis (MS). The level of sIL-2Rα is affected by the MS-associated single nucleotide polymorphism (SNP) rs2104286. By use of ELISA and electrochemiluminescence, we investigated if 26 biomarkers of systemic inflammation were associated with sIL-2Rα and rs2104286 in cohorts of healthy subjects and MS patients in serum and heparin plasma. Read More

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Hydrogen Sulfide: a Novel Immunoinflammatory Regulator in Rheumatoid Arthritis.

Adv Exp Med Biol 2021 ;1315:161-179

State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China.

Hydrogen sulfide (HS), an endogenous, gaseous, signaling transmitter, has been shown to have vasodilative, anti-oxidative, anti-inflammatory, and cytoprotective activities. Increasing evidence also indicates that HS can suppress the production of inflammatory mediators by immune cells, for example, T cells and macrophages. Inflammation is closely related to an immune response in several diseases such as rheumatoid arthritis (RA), multiple sclerosis (MS), systemic lupus erythematosus (SLE), and cancer. Read More

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Nitrate-functionalized patch confers cardioprotection and improves heart repair after myocardial infarction via local nitric oxide delivery.

Nat Commun 2021 07 23;12(1):4501. Epub 2021 Jul 23.

State key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials (Ministry of Education), College of Life Sciences, Nankai University, Tianjin, China.

Nitric oxide (NO) is a short-lived signaling molecule that plays a pivotal role in cardiovascular system. Organic nitrates represent a class of NO-donating drugs for treating coronary artery diseases, acting through the vasodilation of systemic vasculature that often leads to adverse effects. Herein, we design a nitrate-functionalized patch, wherein the nitrate pharmacological functional groups are covalently bound to biodegradable polymers, thus transforming small-molecule drugs into therapeutic biomaterials. Read More

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MYO1F regulates antifungal immunity by regulating acetylation of microtubules.

Proc Natl Acad Sci U S A 2021 Jul;118(30)

Key Laboratory of Molecular Biophysics of the Ministry of Education, National Engineering Research Center for Nanomedicine, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China;

Opportunistic fungal infections have become one of the leading causes of death among immunocompromised patients, resulting in an estimated 1.5 million deaths each year worldwide. The molecular mechanisms that promote host defense against fungal infections remain elusive. Read More

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Personalized profiles of antioxidant signaling pathway in patients with tuberculosis.

J Microbiol Immunol Infect 2021 Jul 17. Epub 2021 Jul 17.

Unit of Neuromuscular and Neurodegenerative Diseases, Department of Neuroscience, Children's Hospital Bambino Gesù, IRCCS, Rome, Italy. Electronic address:

Background/purpose: The non-protein thiol glutathione is protective against infection by Mycobacterium tuberculosis (MTB) and, together with the transcription factor NRF2 (the nuclear factor erythroid 2-related factor 2), plays a crucial role in counteracting MTB-induced redox imbalance. Many genes implicated in the antioxidant response belong to the NRF2-signalling pathway, whose central role in the pathogenesis of tuberculosis (TB) has been recently proposed.

Methods: In this study, we measured GSH levels in blood of patients with active TB and analysed the individual NRF2-mediated redox profile, in order to provide additional tools for discriminating the pathologic TB state and addressing therapeutic interventions. Read More

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Dysregulated Tear Film Proteins in Macular Edema Due to the Neovascular Age-Related Macular Degeneration Are Involved in the Regulation of Protein Clearance, Inflammation, and Neovascularization.

J Clin Med 2021 Jul 10;10(14). Epub 2021 Jul 10.

Department of Vitreoretinal Surgery, Medical University of Lublin, 20-079 Lublin, Poland.

Macular edema and its further complications due to the leakage from the choroidal neovascularization in course of the age-related macular degeneration (AMD) is a leading cause of blindness among elderly individuals in developed countries. Changes in tear film proteomic composition have been reported to occur in various ophthalmic and systemic diseases. There is an evidence that the acute form of neovascular AMD may be reflected in the tear film composition. Read More

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Retinoids as Chemo-Preventive and Molecular-Targeted Anti-Cancer Therapies.

Int J Mol Sci 2021 Jul 20;22(14). Epub 2021 Jul 20.

Center for Translational Cancer Research, Helen F. Graham Cancer Center & Research Institute, Newark, DE 19713, USA.

Retinoic acid (RA) agents possess anti-tumor activity through their ability to induce cellular differentiation. However, retinoids have not yet been translated into effective systemic treatments for most solid tumors. RA signaling is mediated by the following two nuclear retinoic receptor subtypes: the retinoic acid receptor (RAR) and the retinoic X receptor (RXR), and their isoforms. Read More

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Cigarette Smoke Stimulates SARS-CoV-2 Internalization by Activating AhR and Increasing ACE2 Expression in Human Gingival Epithelial Cells.

Int J Mol Sci 2021 Jul 18;22(14). Epub 2021 Jul 18.

Department of Biomedical Sciences, Arthur A. Dugoni School of Dentistry, University of the Pacific, San Francisco, CA 94103, USA.

A large body of evidence shows the harmful effects of cigarette smoke to oral and systemic health. More recently, a link between smoking and susceptibility to coronavirus disease 2019 (COVID-19) was proposed. COVID-19 is due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which uses the receptor ACE2 and the protease TMPRSS2 for entry into host cells, thereby infecting cells of the respiratory tract and the oral cavity. Read More

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Glycyrrhizin Attenuates Portal Hypertension and Collateral Shunting via Inhibition of Extrahepatic Angiogenesis in Cirrhotic Rats.

Int J Mol Sci 2021 Jul 17;22(14). Epub 2021 Jul 17.

Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei 11217, Taiwan.

Portal hypertension develops along with liver cirrhosis then induces the formation of portal-systemic collaterals and lethal complications. Extrahepatic angiogenesis plays an important role. Glycyrrhizin has been found to exhibit anti-angiogenic features, which leads to its extensive use. Read More

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Expression of DDX11 and DNM1L at the 12p11 Locus Modulates Systemic Lupus Erythematosus Susceptibility.

Int J Mol Sci 2021 Jul 16;22(14). Epub 2021 Jul 16.

Rheumatology Service, Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Reina Sofia Hospital, University of Cordoba, 14004 Cordoba, Spain.

Objectives: This study employed genetic and functional analyses using OASIS meta-analysis of multiple existing GWAS and gene-expression datasets to identify novel SLE genes.

Methods: Four hundred and ten genes were mapped using SNIPPER to 30 SLE GWAS loci and investigated for expression in three SLE GEO-datasets and the Cordoba GSE50395-dataset. Blood eQTL for significant SNPs in SLE loci and STRING for functional pathways of differentially expressed genes were used. Read More

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The Intrinsic Nutrient Sensing Adipokinetic Hormone Producing Cells Function in Modulation of Metabolism, Activity, and Stress.

Int J Mol Sci 2021 Jul 13;22(14). Epub 2021 Jul 13.

Department of Biology, Wake Forest University, Winston-Salem, NC 27109, USA.

All organisms confront the challenges of maintaining metabolic homeostasis in light of both variabilities in nutrient supplies and energetic costs of different physiologies and behaviors. While all cells are nutrient sensitive, only relative few cells within Metazoans are nutrient sensing cells. Nutrient sensing cells organize systemic behavioral and physiological responses to changing metabolic states. Read More

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