scholarly journals Molecular Mechanisms of Eosinophilic Esophagitis

2021 ◽  
Vol 22 (24) ◽  
pp. 13183
Author(s):  
Yury V. Zhernov ◽  
Sonya O. Vysochanskaya ◽  
Vitaly A. Sukhov ◽  
Olga K. Zaostrovtseva ◽  
Denis S. Gorshenin ◽  
...  
Keyword(s):  
Eosinophilic Esophagitis ◽  
Molecular Mechanisms ◽  
Molecular Genetic ◽  
Food Hypersensitivity ◽  
Cytokine Signaling ◽  
Molecular Features ◽  
Modern Classification ◽  
Ige Mediated ◽  
Transcriptomic Changes ◽  
Allergic Disorders

Food hypersensitivity is a group of diseases arising from a specific immune response that reproduces on exposure to a given food. The current understanding of molecular mechanisms and immunopathology of non-IgE-mediated/mixed food hypersensitivity, e.g., eosinophilic esophagitis, contains many gaps in knowledge. This review aims to provide a modern classification and identify the primary diseases of non-IgE-mediated/mixed food hypersensitivity reactions, delineate the distinctive molecular features, and discuss recent findings in the immunopathology of eosinophilic esophagitis that may become a basis to develop valid biomarkers and novel therapies for this disease. Eosinophilic esophagitis is a recently recognized allergic-mediated disease with eosinophil-predominant esophagus inflammation. Its pathogenesis is a complicated network of interactions and signaling between epithelial, mesenchymal, and immune cells on molecular and intercellular levels. Alterations produced by overactivation of some cytokine signaling pathways, e.g., IL-13 or thymic stromal lymphopoietin (TSLP), were evolved and observed in this review from the viewpoints of molecular, genetic, epigenetic, and transcriptomic changes. Despite substantial experimental data, the reliable and representative mechanism of eosinophilic esophagitis pathogenesis has yet to show itself. So, the place of esophagitis between mixed and non-IgE-mediated allergic disorders and between eosinophilic gastrointestinal disorders currently seems vague and unclear.

scholarly journals Cellular and molecular mechanisms of the demyelination in the central nervous system and cell therapy approaches

2017 ◽  
Vol 5 (1) ◽  
pp. 74-78
Author(s):  
V. Tsymbaliuk ◽  
V. Semenova ◽  
L. Pichkur ◽  
O. Velychko ◽  
D. Egorova
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cell Therapy ◽  
Molecular Mechanisms ◽  
Molecular Genetic ◽  
Light And Electron Microscopy ◽  
Cellular Level ◽  
Molecular Features ◽  
The Central Nervous System ◽  
Demyelinating Disorders

The review summarizes the current concepts of cell-tissue and molecular features of development of demyelinating processes in the central nervous system related to multiple sclerosis and its animal model – allergic encephalomyelitis. An analysis of recently published studies of this pathology, carried out with light and electron microscopy and immunohistochemical and molecular genetic methods, is given. New methodological approaches to the study of the pathomorhological aspects of demyelinating disorders allowed receiving in-depth understanding of the etiology and mechanisms of demyelination processes in the brain and spinal cord tissues at the cellular level and identifying the ways to develop effective modern methods of pathogenetic treatment of these diseases using cell therapy.

scholarly journals Updates on Food Allergy, Increasingly Prevalent Challenge

2018 ◽  
Vol 10 (3) ◽  
pp. 152
Author(s):  
Tonny Tanus ◽  
Sunny Wangko
Keyword(s):  
Atopic Dermatitis ◽  
Food Allergy ◽  
Eosinophilic Esophagitis ◽  
Immunoglobulin E ◽  
Pediatric Population ◽  
Food Allergies ◽  
Food Protein ◽  
Safety Issues ◽  
Ige Mediated ◽  
Allergic Disorders

Abstrak: Prevalensi alergi makanan makin meningkat di seluruh dunia dan mengenai semua usia. Keparahan dan kompleksitas penyakit juga meningkat terlebih pada populasi anak. Terdapat beberapa jenis reaksi alergi yang dibahas: immunoglobulin E (IgE) mediated allergies and anaphylaxis, food triggered atopic dermatitis, eosinophilic esophagitis, dan non IgE mediated gastrointestinal food allergic disorders seperti food protein induced enterocolitis syndrome (FPIEs). Tes alergi, baik melalui kulit maupun IgE yang telah dikerjakan sekian lama masih dibebani dengan hasil positif palsu dan negatif palsu yang bermakna dengan manfaat terbatas pada beberapa alergi makanan. Selain menghindari, tidak terdapat terapi yang ampuh untuk alergi makanan. Berbagai imunoterapi telah dipelajari melalui jalur, subkutan, epikutan, oral dan sublingual yang hanya menghasilkan desensitisasi sementara dan dibebani dengan berbagai isu mengenai keamanannya. Agen biologik yang menghambat sitokin/interleukin (IL) dan molekul pada reaksi alergi makanan tampaknya merupakan pilihan yang menjanjikan. Anti IgE telah dipergunakan pada asma dan urtikaria kronis. Anti IL-4 dan IL-13 yang menghambat produksi IgE diindikasikan untuk dermatitis atopik. Anti eosinofil anti IL-5 berhasil menurunkan eksaserbasi asma. Berbagai agen biologik telah dipelajari untuk berbagai kondisi alergik dan imunologik, tetapi efektivitas dan kepraktisan terapi yang mahal ini untuk alergi makanan masih menjadi tanda tanya.Kata kunci: alergi makanan, reaksi alergi, terapi alergi makananAbstract: Food allergies have been increasing in prevalence for years affecting all ages. Disease severity and complexity have also increased, especially in the pediatric population. There are several types of reactions including: immunoglobulin-E (IgE) mediated allergies and anaphylaxis, food-triggered atopic dermatitis, eosinophilic esophagitis, and non IgE mediated gastrointestinal food allergic disorders such as FPIEs. Though allergy testing has been around for years, both skin and IgE testing are burdened by significant false positives and negatives, and are only useful in some food allergies. Avoidance is the sole therapy for food allergy. A variety of immunotherapies have been studied; subcutaneous, epicutaneous, oral, and sublingual. At best they only produce a temporary state of desensitization and have many safety issues. Examples of biologicals which block critical cytokines/interleukins (IL) in allergic conditions are Anti IgE, anti IL-4 and IL-13, and Anti eosinophils, Anti IL-5. Other biologicals are being studied for allergic conditions, but whether these expensive future treatments will be proven effective and practical in food allergy is unknown.Keywords: food allergy, allergic reaction, food allergy therapy

scholarly journals Eosinophilic esophagitis is characterized by a non-IgE-mediated food hypersensitivity

Allergy ◽  
2016 ◽  
Vol 71 (5) ◽  
pp. 611-620 ◽  
Author(s):  
D. Simon ◽  
A. Cianferoni ◽  
J. M. Spergel ◽  
S. Aceves ◽  
M. Holbreich ◽  
...  
Keyword(s):  
Eosinophilic Esophagitis ◽  
Food Hypersensitivity ◽  
Ige Mediated

Molecular Basis and Clinical Aspects of Hereditary Megakaryocyte and Platelet Membrane Glycoprotein Disorders

1996 ◽  
Vol 16 (02) ◽  
pp. 114-138 ◽  
Author(s):  
R. E. Scharf
Keyword(s):  
Genetic Basis ◽  
Molecular Mechanisms ◽  
Molecular Genetic ◽  
Platelet Membrane ◽  
Clinical Aspects ◽  
Membrane Glycoprotein ◽  
Membrane Glycoproteins ◽  
Membrane Expression ◽  
Receptor Complexes ◽  
Platelet Membrane Glycoprotein

SummarySpecific membrane glycoproteins (GP) expressed by the megakaryocyte-platelet system, including GPIa-lla, GPIb-V-IX, GPIIb-llla, and GPIV are involved in mediat-ing platelet adhesion to the subendothelial matrix. Among these glycoproteins, GPIIb-llla plays a pivotal role since platelet aggregation is exclusively mediated by this receptor and its interaction with soluble macromolecular proteins. Inherited defects of the GPIIb-llla or GPIb-V-IX receptor complexes are associated with bleeding disorders, known as Glanzmann's thrombasthenia, Bernard-Soulier syndrome, or platelet-type von Willebrand's disease, respectively. Using immuno-chemical and molecular biology techniques, rapid advances in our understanding of the molecular genetic basis of these disorders have been made during the last few years. Moreover, analyses of patients with congenital platelet membrane glycoprotein abnormalities have provided valuable insights into molecular mechanisms that are required for structural and functional integrity, normal biosynthesis of the glycoprotein complexes and coordinated membrane expression of their constituents. The present article reviews the current state of knowledge of the major membrane glycoproteins in health and disease. The spectrum of clinical bleeding manifestations and established diagnostic criteria for each of these dis-orders are summarized. In particular, the variety of molecular defects that have been identified so far and their genetic basis will be discussed.

scholarly journals Degenerative Cervical Myelopathy: Insights into Its Pathobiology and Molecular Mechanisms

2021 ◽  
Vol 10 (6) ◽  
pp. 1214
Author(s):  
Ji Tu ◽  
Jose Vargas Castillo ◽  
Abhirup Das ◽  
Ashish D. Diwan
Keyword(s):  
Cervical Myelopathy ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Imaging Techniques ◽  
Disease Process ◽  
Classification Systems ◽  
Molecular Features ◽  
Formidable Challenge ◽  
Long Term Treatment ◽  
Degenerative Cervical Myelopathy

Degenerative cervical myelopathy (DCM), earlier referred to as cervical spondylotic myelopathy (CSM), is the most common and serious neurological disorder in the elderly population caused by chronic progressive compression or irritation of the spinal cord in the neck. The clinical features of DCM include localised neck pain and functional impairment of motor function in the arms, fingers and hands. If left untreated, this can lead to significant and permanent nerve damage including paralysis and death. Despite recent advancements in understanding the DCM pathology, prognosis remains poor and little is known about the molecular mechanisms underlying its pathogenesis. Moreover, there is scant evidence for the best treatment suitable for DCM patients. Decompressive surgery remains the most effective long-term treatment for this pathology, although the decision of when to perform such a procedure remains challenging. Given the fact that the aged population in the world is continuously increasing, DCM is posing a formidable challenge that needs urgent attention. Here, in this comprehensive review, we discuss the current knowledge of DCM pathology, including epidemiology, diagnosis, natural history, pathophysiology, risk factors, molecular features and treatment options. In addition to describing different scoring and classification systems used by clinicians in diagnosing DCM, we also highlight how advanced imaging techniques are being used to study the disease process. Last but not the least, we discuss several molecular underpinnings of DCM aetiology, including the cells involved and the pathways and molecules that are hallmarks of this disease.

scholarly journals Differential Morpho-Physiological and Transcriptomic Responses to Heat Stress in Two Blueberry Species

2021 ◽  
Vol 22 (5) ◽  
pp. 2481
Author(s):  
Jodi Callwood ◽  
Kalpalatha Melmaiee ◽  
Krishnanand P. Kulkarni ◽  
Amaranatha R. Vennapusa ◽  
Diarra Aicha ◽  
...  
Keyword(s):  
Heat Stress ◽  
Molecular Mechanisms ◽  
Stomatal Closure ◽  
Enrichment Analysis ◽  
Leaf Size ◽  
Vaccinium Corymbosum ◽  
Climatic Conditions ◽  
Differentially Expressed ◽  
Transcriptomic Changes ◽  
Go Terms

Blueberries (Vaccinium spp.) are highly vulnerable to changing climatic conditions, especially increasing temperatures. To gain insight into mechanisms underpinning the response to heat stress, two blueberry species were subjected to heat stress for 6 and 9 h at 45 °C, and leaf samples were used to study the morpho-physiological and transcriptomic changes. As compared with Vaccinium corymbosum, Vaccinium darrowii exhibited thermal stress adaptation features such as small leaf size, parallel leaf orientation, waxy leaf coating, increased stomatal surface area, and stomatal closure. RNAseq analysis yielded ~135 million reads and identified 8305 differentially expressed genes (DEGs) during heat stress against the control samples. In V. corymbosum, 2861 and 4565 genes were differentially expressed at 6 and 9 h of heat stress, whereas in V. darrowii, 2516 and 3072 DEGs were differentially expressed at 6 and 9 h, respectively. Among the pathways, the protein processing in the endoplasmic reticulum (ER) was the highly enriched pathway in both the species: however, certain metabolic, fatty acid, photosynthesis-related, peroxisomal, and circadian rhythm pathways were enriched differently among the species. KEGG enrichment analysis of the DEGs revealed important biosynthesis and metabolic pathways crucial in response to heat stress. The GO terms enriched in both the species under heat stress were similar, but more DEGs were enriched for GO terms in V. darrowii than the V. corymbosum. Together, these results elucidate the differential response of morpho-physiological and molecular mechanisms used by both the blueberry species under heat stress, and help in understanding the complex mechanisms involved in heat stress tolerance.

scholarly journals Listeria exploits IFITM3 to suppress antibacterial activity in phagocytes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Joel M. J. Tan ◽  
Monica E. Garner ◽  
James M. Regeimbal ◽  
Catherine J. Greene ◽  
Jorge D. Rojas Márquez ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Transmembrane Protein ◽  
Foodborne Pathogen ◽  
Systemic Infection ◽  
Cytokine Signaling ◽  
Type I ◽  
Type I Ifn ◽  
Antiviral Protein

AbstractThe type I interferon (IFN) signaling pathway has important functions in resistance to viral infection, with the downstream induction of interferon stimulated genes (ISG) protecting the host from virus entry, replication and spread. Listeria monocytogenes (Lm), a facultative intracellular foodborne pathogen, can exploit the type I IFN response as part of their pathogenic strategy, but the molecular mechanisms involved remain unclear. Here we show that type I IFN suppresses the antibacterial activity of phagocytes to promote systemic Lm infection. Mechanistically, type I IFN suppresses phagosome maturation and proteolysis of Lm virulence factors ActA and LLO, thereby promoting phagosome escape and cell-to-cell spread; the antiviral protein, IFN-induced transmembrane protein 3 (IFITM3), is required for this type I IFN-mediated alteration. Ifitm3−/− mice are resistant to systemic infection by Lm, displaying decreased bacterial spread in tissues, and increased immune cell recruitment and pro-inflammatory cytokine signaling. Together, our findings show how an antiviral mechanism in phagocytes can be exploited by bacterial pathogens, and implicate IFITM3 as a potential antimicrobial therapeutic target.

Misregulation of suppressors of cytokine signaling in eosinophilic esophagitis

2012 ◽  
Vol 48 (8) ◽  
pp. 910-920 ◽  
Author(s):  
Mª Paz Zafra ◽  
Natally Cancelliere ◽  
Pablo Rodríguez del Río ◽  
Mónica Ruiz-García ◽  
Laura Estévez ◽  
...  
Keyword(s):  
Eosinophilic Esophagitis ◽  
Cytokine Signaling ◽  
Suppressors Of Cytokine Signaling

scholarly journals How immunologic and genetic biomarkers impact Hodgkin lymphoma classification, diagnosis, and management: a huge potential that yet needs to be exploited

2017 ◽  
Vol 33 (2) ◽  
pp. 137-140 ◽  
Author(s):  
Antonino Carbone ◽  
Annunziata Gloghini
Keyword(s):  
Hodgkin Lymphoma ◽  
Molecular Genetic ◽  
Scientific Basis ◽  
Grey Zone ◽  
Molecular Virology ◽  
Barr Virus ◽  
Long Time ◽  
Modern Classification ◽  
Epstein Barr

“Ne è passata di acqua sotto i ponti.” It has been a long time since the diagnosis of Hodgkin lymphoma (HL) was exclusively based on the detection of typical Reed-Sternberg cells and the recognition of the characteristic morpho-histological background, as well as on the pathologist’s skill. The discovery of immunologic, molecular genetic and virologic biomarkers has provided an objective contribution to the diagnosis and a scientific basis for a modern classification of HL. Recent updates have clarified the nature of the so-called nodular lymphocyte predominant HL and its link to the T-cell/histiocyte-rich large B-cell lymphomas as well as its relationship with the lymphocyte-rich subset of classical HL (CHL). Molecular virology studies assessed a role for the Epstein-Barr virus in the pathogenesis of a fraction of CHL of the general population, and virtually in all cases of CHL occurring in people infected by HIV. Finally, immunologic and genetic findings corroborated the existence of grey zone lymphomas at the edges of CHL. Overall, these advances provided additional and useful information to address the treatment of patients affected by HL.

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