scholarly journals Dysregulated neutrophil responses and neutrophil extracellular trap formation and degradation in PAPA syndrome

2018 ◽  
Vol 77 (12) ◽  
pp. 1825-1833 ◽  
Author(s):  
Pragnesh Mistry ◽  
Carmelo Carmona-Rivera ◽  
Amanda K Ombrello ◽  
Patrycja Hoffmann ◽  
Nickie L Seto ◽  
...  
Keyword(s):  
Neutrophil Extracellular Trap ◽  
Therapeutic Approaches ◽  
Gene Signatures ◽  
New Therapeutic Approaches ◽  
Papa Syndrome ◽  
Healthy Control ◽  
Skin Biopsies ◽  
Neutrophil Infiltrate

ObjectivesPyogenic arthritis, pyoderma gangrenosum and acne (PAPA) syndrome is characterised by flares of sterile arthritis with neutrophil infiltrate and the overproduction of interleukin (IL)-1β. The purpose of this study was to elucidate the potential role of neutrophil subsets and neutrophil extracellular traps (NET) in the pathogenesis of PAPA.MethodsNeutrophils and low-density granulocytes (LDG) were quantified by flow cytometry. Circulating NETs were measured by ELISA and PAPA serum was tested for the ability to degrade NETs. The capacity of NETs from PAPA neutrophils to activate macrophages was assessed. Skin biopsies were analysed for NETs and neutrophil gene signatures.ResultsCirculating LDGs are elevated in PAPA subjects. PAPA neutrophils and LDGs display enhanced NET formation compared with control neutrophils. PAPA sera exhibit impaired NET degradation and this is corrected with exogenous DNase1. Recombinant human IL-1β induces NET formation in PAPA neutrophils but not healthy control neutrophils. NET formation in healthy control neutrophils is induced by PAPA serum and this effect is inhibited by the IL-1 receptor antagonist, anakinra. NETs from PAPA neutrophils and LDGs stimulate IL-6 release in healthy control macrophages. NETs are detected in skin biopsies of patients with PAPA syndrome in association with increased tissue IL-1β, IL-8 and IL-17. Furthermore, LDG gene signatures are detected in PAPA skin.ConclusionsPAPA syndrome is characterised by an imbalance of NET formation and degradation that may enhance the half-life of these structures in vivo, promoting inflammation. Anakinra ameliorates NET formation in PAPA and this finding supports a role for IL-1 signalling in exacerbated neutrophil responses in this disease. The study also highlights other inflammatory pathways potentially pathogenic in PAPA, including IL-17 and IL-6, and these results may help guide new therapeutic approaches in this severe and often treatment-refractory condition.

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

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

Cancer metabolism

2019 ◽  
pp. 221-238
Author(s):  
Almut Schulze ◽  
Karim Bensaad ◽  
Adrian L. Harris
Keyword(s):  
Cancer Metabolism ◽  
Krebs Cycle ◽  
Cell Types ◽  
Oxygen Limitation ◽  
Genetic Changes ◽  
New Therapeutic Approaches ◽  
Rare Mutations ◽  
Metabolic Adaptations

Abnormalities in cancer metabolism have been noted since Warburg first described the phenomenon of glycolysis in normoxic conditions. This chapter reviews the major pathways in metabolism known to be modified in cancer, including glycolysis and the Krebs cycle, the pentose shunt, and new data implicating the role of different metabolic adaptations, including oncometabolism. It highlights the genetic changes that effect metabolism including many of the commonly occurring oncogenes but also rare mutations that specifically target metabolism. Nutrient and oxygen limitation and proliferation create the microenvironmental selective stress for modifications in hypoxic metabolism, but also affect other cell types such as endothelial cells and macrophages. This range of changes provides many new therapeutic approaches. It also describes the potential value of targeting these adaptations and approaches to monitoring in vivo effects in patients to monitor therapeutic activity.

MHO_0730 as a Surface-Exposed Calcium-Dependent Nuclease of Mycoplasma hominis Promoting Neutrophil Extracellular Trap Formation and Escape

2019 ◽  
Vol 220 (12) ◽  
pp. 1999-2008 ◽  
Author(s):  
Carla Cacciotto ◽  
Daniele Dessì ◽  
Tiziana Cubeddu ◽  
Anna Rita Cocco ◽  
Andrea Pisano ◽  
...  
Keyword(s):  
Natural Infection ◽  
Mycoplasma Hominis ◽  
Neutrophil Extracellular Trap ◽  
Host Immune System ◽  
Potent Inducer ◽  
Calcium Dependent ◽  
Relevant Role ◽  
Extracellular Trap

Abstract Mycoplasma lipoproteins play a relevant role in pathogenicity and directly interact with the host immune system. Among human mycoplasmas, Mycoplasma hominis is described as a commensal bacterium that can be associated with a number of genital and extragenital conditions. Mechanisms of M. hominis pathogenicity are still largely obscure, and only a limited number of proteins have been associated with virulence. The current study focused on investigating the role of MHO_0730 as a virulence factor and demonstrated that MHO_0730 is a surface lipoprotein, potentially expressed in vivo during natural infection, acting both as a nuclease with its amino acidic portion and as a potent inducer of Neutrophil extracellular trapsosis with its N-terminal lipid moiety. Evidence for M. hominis neutrophil extracellular trap escape is also presented. Results highlight the relevance of MHO_0730 in promoting infection and modulation and evasion of innate immunity and provide additional knowledge on M. hominis virulence and survival in the host.

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.

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.

scholarly journals Emerging role of circadian clock disruption in alcohol-induced liver disease

2018 ◽  
Vol 315 (3) ◽  
pp. G364-G373 ◽  
Author(s):  
Shannon M. Bailey
Keyword(s):  
Liver Disease ◽  
Circadian Clock ◽  
Therapeutic Approaches ◽  
Excessive Alcohol Consumption ◽  
Peripheral Tissues ◽  
New Therapeutic Approaches ◽  
Timing System ◽  
Excessive Alcohol ◽  
The Impact

The detrimental health effects of excessive alcohol consumption are well documented. Alcohol-induced liver disease (ALD) is the leading cause of death from chronic alcohol use. As with many diseases, the etiology of ALD is influenced by how the liver responds to other secondary insults. The molecular circadian clock is an intrinsic cellular timing system that helps organisms adapt and synchronize metabolism to changes in their environment. The clock also influences how tissues respond to toxic, environmental, and metabolic stressors, like alcohol. Consistent with the essential role for clocks in maintaining health, genetic and environmental disruption of the circadian clock contributes to disease. While a large amount of rich literature is available showing that alcohol disrupts circadian-driven behaviors and that circadian clock disruption increases alcohol drinking and preference, very little is known about the role circadian clocks play in alcohol-induced tissue injuries. In this review, recent studies examining the effect alcohol has on the circadian clock in peripheral tissues (liver and intestine) and the impact circadian clock disruption has on development of ALD are presented. This review also highlights some of the rhythmic metabolic processes in the liver that are disrupted by alcohol and potential mechanisms through which alcohol disrupts the liver clock. Improved understanding of the mechanistic links between the circadian clock and alcohol will hopefully lead to the development of new therapeutic approaches for treating ALD and other alcohol-related organ pathologies.

scholarly journals RNA-Mediated Gene Silencing in Hematopoietic Cells

2006 ◽  
Vol 2006 ◽  
pp. 1-13 ◽  
Author(s):  
Letizia Venturini ◽  
Matthias Eder ◽  
Michaela Scherr
Keyword(s):  
Gene Silencing ◽  
Mrna Translation ◽  
Therapeutic Approaches ◽  
Double Stranded Rna ◽  
Eukaryotic Gene Expression ◽  
Eukaryotic Gene ◽  
Specific Degradation

In the past few years, the discovery of RNA-mediated gene silencing mechanisms, like RNA interference (RNAi), has revolutionized our understanding of eukaryotic gene expression. These mechanisms are activated by double-stranded RNA (dsRNA) and mediate gene silencing either by inducing the sequence-specific degradation of complementary mRNA or by inhibiting mRNA translation. RNAi now provides a powerful experimental tool to elucidate gene function in vitro and in vivo, thereby opening new exciting perspectives in the fields of molecular analysis and eventually therapy of several diseases such as infections and cancer. In hematology, numerous studies have described the successful application of RNAi to better define the role of oncogenic fusion proteins in leukemogenesis and to explore therapeutic approaches in hematological malignancies. In this review, we highlight recent advances and caveats relating to the application of this powerful new methodology to hematopoiesis.

Comorbidity of Migraine and Epilepsy in Pediatrics: A Review

2018 ◽  
Vol 33 (12) ◽  
pp. 801-808 ◽  
Author(s):  
Jasna Jancic ◽  
Vesna Djuric ◽  
Boris Hencic ◽  
John N. van den Anker ◽  
Janko Samardzic
Keyword(s):  
Genetic Basis ◽  
Treatment Options ◽  
Dietary Therapy ◽  
Channel Blockers ◽  
Therapeutic Approaches ◽  
Randomized Controlled Clinical Trials ◽  
Randomized Controlled ◽  
New Therapeutic Approaches ◽  
Neurologic Disorders

Migraine and epilepsy are classified as chronic paroxysmal neurologic disorders sharing many clinical features, as well as possible treatment options. This review highlights the similarities between migraine and epilepsy in pediatrics, focusing on epidemiologic, pathophysiological, genetic, clinical, and pharmacologic aspects. Despite the fact that several syndromes share symptoms of both migraine and epilepsy, further research is needed to clarify the pathophysiological and genetic basis of their comorbidity. Drugs used for prophylactic therapy of migraine and epilepsy have similar pharmacologic properties. The role of epileptic pharmacotherapy in the prophylaxis of migraine is assessed, including the use of conventional antiepileptic drugs, calcium channel blockers, and nonpharmacologic methods such as dietary therapy, supplements, and vagal nerve stimulation. Further randomized, controlled clinical trials assessing pharmacologic and nonpharmacologic methods for the treatment of both disorders are essential, in order to initiate new therapeutic approaches.

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