Neutrophils are key mediators in crescentic glomerulonephritis and targets for new therapeutic approaches

2020 ◽  
Author(s):  
Marilina Antonelou ◽  
Rhys D R Evans ◽  
Scott R Henderson ◽  
Alan D Salama
Keyword(s):  
Serine Proteases ◽  
Crescentic Glomerulonephritis ◽  
Antigen Expression ◽  
Therapeutic Approaches ◽  
Extracellular Traps ◽  
New Therapeutic Approaches ◽  
Self Tolerance ◽  
Wide Range ◽  
Neutrophil Degranulation

Abstract Crescentic glomerulonephritis (CGN) results from a diverse set of diseases associated with immune dysregulation and the breakdown of self-tolerance to a wide range of autoantigens, some known and some that remain unknown. Experimental data demonstrate that neutrophils have an important role in the pathogenesis of CGN. Upon activation, neutrophils generate reactive oxygen species, release serine proteases and form neutrophil extracellular traps (NETs), all of which can induce direct tissue damage. In addition, serine proteases such as myeloperoxidase and proteinase 3, presented on NETs, can be processed and recognized as autoantigens, leading to the generation and maintenance of autoimmune responses in susceptible individuals. The basis of the specificity of autoimmune responses in different patients to NET proteins is unclear, but relates at least in part to differences in human leucocyte antigen expression. Conditions associated with CGN are often characterized by aberrant neutrophil activation and NETosis and, in some, impaired NET degradation. Targeting neutrophil degranulation and NETosis is now possible using a variety of novel compounds and may provide a promising therapeutic alternative to glucocorticoid use, which has been a mainstay of management in CGN for decades and is associated with significant adverse effects. In this review, we discuss the evidence supporting the role of neutrophils in the development of CGN and the pathways identified in neutrophil degranulation and NETosis that may translate to novel therapeutic applications.

scholarly journals The PI3K/AKT/mTOR pathway in the pathophysiology and treatment of pituitary adenomas

2014 ◽  
Vol 21 (4) ◽  
pp. R331-R344 ◽  
Author(s):  
Eric Monsalves ◽  
Kyle Juraschka ◽  
Toru Tateno ◽  
Sameer Agnihotri ◽  
Sylvia L Asa ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Human Cancer ◽  
Tumor Biology ◽  
Pituitary Tumors ◽  
Mass Effect ◽  
Therapeutic Approaches ◽  
Hormone Production ◽  
New Therapeutic Approaches ◽  
Wide Range

Pituitary adenomas are common intracranial neoplasms. Patients with these tumors exhibit a wide range of clinically challenging problems, stemming either from results of sellar mass effect in pituitary macroadenoma or the diverse effects of aberrant hormone production by adenoma cells. While some patients are cured/controlled by surgical resection and/or medical therapy, a proportion of patients exhibit tumors that are refractory to current modalities. New therapeutic approaches are needed for these patients. Activation of the AKT/phophotidylinositide-3-kinase pathway, including mTOR activation, is common in human neoplasia, and a number of therapeutic approaches are being employed to neutralize activation of this pathway in human cancer. This review examines the role of this pathway in pituitary tumors with respect to tumor biology and its potential role as a therapeutic target.

scholarly journals An Emerging Role for Serine Protease Inhibitors in T Lymphocyte Immunity and Beyond

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Philip G. Ashton-Rickardt
Keyword(s):  
T Lymphocytes ◽  
Serine Protease ◽  
Serine Proteases ◽  
Cellular Viability ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Survival And Development ◽  
Serine Proteases Inhibitors ◽  
Lymphocyte Immunity

The serine proteases of T lymphocytes provide immunity to infection. Serine Proteases Inhibitors (serpins) control the recognition of antigen, effector function, and homeostatic control of T lymphocytes through the inhibition of serine protease targets. Serpins are important promoters of cellular viability through their inhibition of executioner proteases, which affects the survival and development of long-lived memory T cells. The potent antiapoptotic properties of serpins can also work against cellular immunity by protecting viruses and tumors from eradication by T lymphocytes. Recent insights from knockout mouse models demonstrate that serpins also are required for hematological progenitor cells and so are critical for the development of lineages other than T lymphocytes. Given the emerging role of serpins in multiple aspects of lymphocyte immunity and blood development, there is much potential for new therapeutic approaches based directly on serpins or knowledge gained from identifying their physiologically relevant protease targets.

scholarly journals The emerging role of mechanical and topographical factors in the development and treatment of nervous system disorders: dark and light sides of the force

2021 ◽  
Author(s):  
Natalia Bryniarska-Kubiak ◽  
Andrzej Kubiak ◽  
Małgorzata Lekka ◽  
Agnieszka Basta-Kaim
Keyword(s):  
Nervous System ◽  
Physical Factors ◽  
Nervous System Diseases ◽  
Therapeutic Approaches ◽  
System Disease ◽  
New Therapeutic Approaches ◽  
The Subject ◽  
Topographical Factors ◽  
New Treatment

AbstractNervous system diseases are the subject of intensive research due to their association with high mortality rates and their potential to cause irreversible disability. Most studies focus on targeting the biological factors related to disease pathogenesis, e.g. use of recombinant activator of plasminogen in the treatment of stroke. Nevertheless, multiple diseases such as Parkinson’s disease and Alzheimer’s disease still lack successful treatment. Recently, evidence has indicated that physical factors such as the mechanical properties of cells and tissue and topography play a crucial role in homeostasis as well as disease progression. This review aims to depict these factors’ roles in the progression of nervous system diseases and consequently discusses the possibility of new therapeutic approaches. The literature is reviewed to provide a deeper understanding of the roles played by physical factors in nervous system disease development to aid in the design of promising new treatment approaches. Graphic abstract

scholarly journals Development of cancer metabolism as a therapeutic target: new pathways, patient studies, stratification and combination therapy

2019 ◽  
Vol 122 (1) ◽  
pp. 1-3 ◽  
Author(s):  
Adrian L. Harris
Keyword(s):  
Metabolic Pathways ◽  
Trial Design ◽  
Cancer Metabolism ◽  
Aerobic Glycolysis ◽  
Critical Role ◽  
Therapeutic Approaches ◽  
Preclinical Models ◽  
Wide Range ◽  
Patient Studies

AbstractCancer metabolism has undergone a resurgence in the last decade, 70 years after Warburg described aerobic glycolysis as a feature of cancer cells. A wide range of techniques have elucidated the complexity and heterogeneity in preclinical models and clinical studies. What emerges are the large differences between tissues, tumour types and intratumour heterogeneity. However, synergies with inhibition of metabolic pathways have been found for many drugs and therapeutic approaches, and a critical role of window studies and translational trial design is key to success.

Insights into the role of components of the tumor microenvironment in oral carcinoma call for new therapeutic approaches

2014 ◽  
Vol 325 (2) ◽  
pp. 58-64 ◽  
Author(s):  
Tuula Salo ◽  
Marilena Vered ◽  
Ibrahim O. Bello ◽  
Pia Nyberg ◽  
Carolina Cavalcante Bitu ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Oral Carcinoma ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches

scholarly journals Neutrophil Extracellular Traps in Periodontitis

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1494 ◽  
Author(s):  
Antonio Magán-Fernández ◽  
Sarmad Muayad Rasheed Al-Bakri ◽  
Francisco O’Valle ◽  
Cristina Benavides-Reyes ◽  
Francisco Abadía-Molina ◽  
...  
Keyword(s):  
Current Knowledge ◽  
Decisive Role ◽  
Neutrophil Extracellular Traps ◽  
Gingival Tissue ◽  
Multifactorial Disease ◽  
Extracellular Traps ◽  
Wide Range ◽  
Neutrophil Response ◽  
Inflammatory Component

Neutrophils are key cells of the immune system and have a decisive role in fighting foreign pathogens in infectious diseases. Neutrophil extracellular traps (NETs) consist of a mesh of DNA enclosing antimicrobial peptides and histones that are released into extracellular space following neutrophil response to a wide range of stimuli, such as pathogens, host-derived mediators and drugs. Neutrophils can remain functional after NET formation and are important for periodontal homeostasis. Periodontitis is an inflammatory multifactorial disease caused by a dysbiosis state between the gingival microbiome and the immune response of the host. The pathogenesis of periodontitis includes an immune-inflammatory component in which impaired NET formation and/or elimination can be involved, contributing to an exacerbated inflammatory reaction and to the destruction of gingival tissue. In this review, we summarize the current knowledge about the role of NETs in the pathogenesis of periodontitis.

scholarly journals Clinical Significance of Circulating Tumor Cells in Gastrointestinal Carcinomas

Diagnostics ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 192
Author(s):  
Leonie Konczalla ◽  
Anna Wöstemeier ◽  
Marius Kemper ◽  
Karl-Frederik Karstens ◽  
Jakob Izbicki ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Clinical Application ◽  
Liquid Biopsy ◽  
Cancer Diagnostics ◽  
Therapeutic Approaches ◽  
Primary Tumors ◽  
New Therapeutic Approaches ◽  
Tumor Dissemination

The idea of a liquid biopsy to screen, surveil and treat cancer patients is an intensively discussed and highly awaited tool in the field of oncology. Despite intensive research in this field, the clinical application has not been implemented yet and further research has to be conducted. However, one component of the liquid biopsy is circulating tumor cells (CTCs) whose potential for clinical application is evaluated in the following. CTCs can shed from primary tumors to the peripheral blood at any time point during the progress of a malignant disease. Following, one single CTC can be the origin for distant metastasis at later cancer stage. Thus, CTCs have great potential to either be used in cancer diagnostics and patient stratification or to function as a target for new therapeutic approaches to stop tumor dissemination and metastasis at the very early beginning. Due to the biological fundamental role of CTCs in tumor progression, here, we provide an overview of CTCs in gastrointestinal cancers and their potential use in the clinical setting. In particular, we discuss the usage of CTC for screening and stratifying patients’ risk. Moreover, we will discuss the potential role of CTCs for treatment specification and treatment monitoring.

scholarly journals Nuclear Receptors as Therapeutic Targets for Neurodegenerative Diseases: Lost in Translation

2019 ◽  
Vol 59 (1) ◽  
pp. 237-261 ◽  
Author(s):  
Miguel Moutinho ◽  
Juan F. Codocedo ◽  
Shweta S. Puntambekar ◽  
Gary E. Landreth
Keyword(s):  
Animal Models ◽  
Neurodegenerative Diseases ◽  
Nuclear Receptors ◽  
Motor Impairment ◽  
Therapeutic Approaches ◽  
New Findings ◽  
Wide Range ◽  
Preclinical And Clinical Studies ◽  
Lost In Translation

Neurodegenerative diseases are characterized by a progressive loss of neurons that leads to a broad range of disabilities, including severe cognitive decline and motor impairment, for which there are no effective therapies. Several lines of evidence support a putative therapeutic role of nuclear receptors (NRs) in these types of disorders. NRs are ligand-activated transcription factors that regulate the expression of a wide range of genes linked to metabolism and inflammation. Although the activation of NRs in animal models of neurodegenerative disease exhibits promising results, the translation of this strategy to clinical practice has been unsuccessful. In this review we discuss the role of NRs in neurodegenerative diseases in light of preclinical and clinical studies, as well as new findings derived from the analysis of transcriptomic databases from humans and animal models. We discuss the failure in the translation of NR-based therapeutic approaches and consider alternative and novel research avenues in the development of effective therapies for neurodegenerative diseases.

Corrigendum

2019 ◽  
Vol 26 (3) ◽  
pp. 235-235
Keyword(s):  
Review Article ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches

In the Review Article entitled “An Emerging Role of Endometrial Inflammasome in Reproduction: New Therapeutic Approaches” published in Protein & Peptides Letters, 2018, Vol. 26, No. 5, the affiliations of authors are revised due to recent restructuring that took place within the Institution for which the authors work for. The revised affiliation is as follows: </p><p> Fiorella Di Nicuoloa,b,*, Monia Specchiac, Lorenza Trentavizic, Alfredo Pontecorvid, Giovanni Scambiacc,e and Nicoletta Di Simoneb,c </p><p> aIstituto Scientifico Internazionale Paolo VI, ISI, Università Cattolica del Sacro Cuore, Rome, Italia; bFondazione Policlinico Universitario A. Gemelli IRCCS, U.O.C. di Ostetricia e Patologia Ostetrica, Dipartimento di Scienze della Salute della Donna e del Bambino, Roma, Italia; cUniversità Cattolica del Sacro Cuore, Istituto di Clinica Ostetrica e Ginecologica, Roma, Italia; dFondazione Policlinico Universitario A. Gemelli IRCCS, Dipartimento di Scienze Gastroenterologiche, Endocrino- Metaboliche e Nefro-Urologiche, Roma, Italia; eFondazione Policlinico Universitario A. Gemelli IRCCS, U.O.C. di Ginecologia Oncologica, Dipartimento di Scienze della Salute della Donna e del Bambino, Roma, Italia

scholarly journals Personalized Dentistry: Approaching a New Way for Diagnosis and Treatment of Oral Diseases

2020 ◽  
Vol 10 (2) ◽  
pp. 35
Author(s):  
Romeo Patini
Keyword(s):  
In Vivo Studies ◽  
Oral Microbiota ◽  
Oral Diseases ◽  
Therapeutic Approaches ◽  
Bacterial Populations ◽  
Treatment Techniques ◽  
Wide Range ◽  
Analysis Of Results

For years, it has been thought that the field of dentistry was referring exclusively to some diseases that strictly affect the oral cavity. Dental caries, periodontal disease, and pathologies associated with their worsening were considered almost the only interest in scientific research in dentistry. Recent studies have begun to shed light on the effect of the oral microbiota on general health and on the crucial role of dentistry in its maintenance. In this way, we came to understand that the bacterial populations that make up the oral microbiota can vary profoundly between individuals and that contribute in a fundamental way to outlining the so-called “oral signature”. This characteristic is called into question to evaluate the susceptibility, or lack thereof, of the subject to the contraction of a wide range of pathologies, apparently not connected with oral health. From this evidence, it will also be possible to study therapeutic approaches aimed at the eradication of species considered at risk or colonization with species considered protective; thus, giving life to so-called “personalized dentistry”. Therefore, this Special Issue is aimed at spreading the scientific knowledge over the current limits in terms of new molecular and culturomic approaches towards the diagnosis of oral microbiota and the treatment techniques of eventually associated systemic diseases. In vivo studies and systematic literature reviews with quantitative analysis of results, when possible, will be given a high priority.

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