scholarly journals CLASSIFICATION OF PRIMARY IMMUNODEFICIENCIES AS A REFLECTION OF MODERN IDEAS ABOUT THEIR PATHOGENESIS AND THERAPEUTIC APPROACHES

2017 ◽  
Vol 4 (3) ◽  
pp. 51-57 ◽  
Author(s):  
N. B. Kuzmenko ◽  
A. Yu. Shcherbina
Keyword(s):  
Primary Immunodeficiencies ◽  
Therapeutic Approaches

scholarly journals Practical classification of triple-negative breast cancer: intratumoral heterogeneity, mechanisms of drug resistance, and novel therapies

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Antonio Marra ◽  
Dario Trapani ◽  
Giulia Viale ◽  
Carmen Criscitiello ◽  
Giuseppe Curigliano
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Residual Disease ◽  
Therapeutic Approaches ◽  
Minimal Residual Disease Monitoring ◽  
Anticancer Treatment ◽  
Immune Contexture

Abstract Triple-negative breast cancer (TNBC) is not a unique disease, encompassing multiple entities with marked histopathological, transcriptomic and genomic heterogeneity. Despite several efforts, transcriptomic and genomic classifications have remained merely theoretic and most of the patients are being treated with chemotherapy. Driver alterations in potentially targetable genes, including PIK3CA and AKT, have been identified across TNBC subtypes, prompting the implementation of biomarker-driven therapeutic approaches. However, biomarker-based treatments as well as immune checkpoint inhibitor-based immunotherapy have provided contrasting and limited results so far. Accordingly, a better characterization of the genomic and immune contexture underpinning TNBC, as well as the translation of the lessons learnt in the metastatic disease to the early setting would improve patients’ outcomes. The application of multi-omics technologies, biocomputational algorithms, assays for minimal residual disease monitoring and novel clinical trial designs are strongly warranted to pave the way toward personalized anticancer treatment for patients with TNBC.

Advances in the Biology and Genetics of the Podocytopathies: Implications for Diagnosis and Therapy

2009 ◽  
Vol 133 (2) ◽  
pp. 201-216 ◽  
Author(s):  
Laura Barisoni ◽  
H. William Schnaper ◽  
Jeffrey B. Kopp
Keyword(s):  
Current Knowledge ◽  
Diffuse Mesangial Sclerosis ◽  
Therapeutic Approaches ◽  
Glomerular Diseases ◽  
Podocyte Injury ◽  
Collapsing Glomerulopathy ◽  
Novel Approach ◽  
Genes Encoding ◽  
Glomerular Morphology

AbstractContext.—Etiologic factors and pathways leading to altered podocyte phenotype are clearly numerous and involve the activity of different cellular function.Objective.—To focus on recent discoveries in podocyte biology and genetics and their relevance to these human glomerular diseases, named podocytopathies.Data Sources.—Genetic mutations in genes encoding for proteins in the nucleus, slit diaphragm, podocyte cytoplasm, and cell membrane are responsible for podocyte phenotype and functional abnormalities. Podocyte injury may also derive from secondary stimuli, such as mechanical stress, infections, or use of certain medications. Podocytes can respond to injury in a limited number of ways, which include (1) effacement, (2) apoptosis, (3) arrest of development, and (4) dedifferentiation. Each of these pathways results in a specific glomerular morphology: minimal change nephropathy, focal segmental glomerulosclerosis, diffuse mesangial sclerosis, and collapsing glomerulopathy.Conclusions.—Based on current knowledge of podocyte biology, we organized etiologic factors and morphologic features in a taxonomy of podocytopathies, which provides a novel approach to the classification of these diseases. Current and experimental therapeutic approaches are also discussed.

scholarly journals An Integrated View on Neuronal Subsets in the Peripheral Nervous System and Their Role in Immunoregulation

2021 ◽  
Vol 12 ◽  
Author(s):  
Manuel O. Jakob ◽  
Michael Kofoed-Branzk ◽  
Divija Deshpande ◽  
Shaira Murugan ◽  
Christoph S. N. Klose
Keyword(s):  
Nervous System ◽  
Immune Responses ◽  
Peripheral Nervous System ◽  
Tissue Homeostasis ◽  
Therapeutic Approaches ◽  
Immune Reactions ◽  
Peripheral Neurons ◽  
Inflammatory Signals ◽  
Neuronal Regulation

The peripheral nervous system consists of sensory circuits that respond to external and internal stimuli and effector circuits that adapt physiologic functions to environmental challenges. Identifying neurotransmitters and neuropeptides and the corresponding receptors on immune cells implies an essential role for the nervous system in regulating immune reactions. Vice versa, neurons express functional cytokine receptors to respond to inflammatory signals directly. Recent advances in single-cell and single-nuclei sequencing have provided an unprecedented depth in neuronal analysis and allowed to refine the classification of distinct neuronal subsets of the peripheral nervous system. Delineating the sensory and immunoregulatory capacity of different neuronal subsets could inform a better understanding of the response happening in tissues that coordinate physiologic functions, tissue homeostasis and immunity. Here, we summarize current subsets of peripheral neurons and discuss neuronal regulation of immune responses, focusing on neuro-immune interactions in the gastrointestinal tract. The nervous system as a central coordinator of immune reactions and tissue homeostasis may predispose for novel promising therapeutic approaches for a large variety of diseases including but not limited to chronic inflammation.

scholarly journals Atg8-Family Proteins—Structural Features and Molecular Interactions in Autophagy and Beyond

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2008 ◽  
Author(s):  
Nicole Wesch ◽  
Vladimir Kirkin ◽  
Vladimir V. Rogov
Keyword(s):  
Protein Interactions ◽  
Membrane Trafficking ◽  
Structural Features ◽  
Structural Level ◽  
Interacting Proteins ◽  
Therapeutic Approaches ◽  
Basic Principles ◽  
Interaction Partners ◽  
Shed Light

Autophagy is a common name for a number of catabolic processes, which keep the cellular homeostasis by removing damaged and dysfunctional intracellular components. Impairment or misbalance of autophagy can lead to various diseases, such as neurodegeneration, infection diseases, and cancer. A central axis of autophagy is formed along the interactions of autophagy modifiers (Atg8-family proteins) with a variety of their cellular counter partners. Besides autophagy, Atg8-proteins participate in many other pathways, among which membrane trafficking and neuronal signaling are the most known. Despite the fact that autophagy modifiers are well-studied, as the small globular proteins show similarity to ubiquitin on a structural level, the mechanism of their interactions are still not completely understood. A thorough analysis and classification of all known mechanisms of Atg8-protein interactions could shed light on their functioning and connect the pathways involving Atg8-proteins. In this review, we present our views of the key features of the Atg8-proteins and describe the basic principles of their recognition and binding by interaction partners. We discuss affinity and selectivity of their interactions as well as provide perspectives for discovery of new Atg8-interacting proteins and therapeutic approaches to tackle major human diseases.

Endometriotic lesions

2019 ◽  
Vol 11 (2) ◽  
pp. 62-76
Author(s):  
Sri PK Maharajaa ◽  
Razan Asally ◽  
Robert Markham ◽  
Frank Manconi
Keyword(s):  
Immune Cell ◽  
Histopathological Examination ◽  
Abdominal Cavity ◽  
Reproductive Age ◽  
Deep Infiltrating Endometriosis ◽  
Therapeutic Approaches ◽  
Nerve Fibres ◽  
Pain Mechanisms ◽  
Unmyelinated Nerve

Endometriosis is a complex gynaecological condition affecting women of reproductive age. It is characterised by the presence of lesions containing endometrial glands and stroma outside the uterus. The disease is typically associated with pelvic pain (including dysmenorrhoea and dyspareunia), infertility and bowel-related symptoms. Endometriotic lesions have a highly variable presentation and most commonly occur in the abdominal cavity. These lesions are broadly classified into peritoneal, ovarian and deep infiltrating endometriosis. There have been observations of increased density of nerve fibres and neurological molecules in the endometriotic lesions compared to the uninvolved peritoneum of women without endometriosis and the presence of unmyelinated nerve fibres were higher near the glands. The lesion sites are characterised by a range of immunological alterations, and specific immune cell populations have also been known to synthesise and secrete neurogenic factors. Endometriotic lesions are capable of producing prostaglandins which are direct generators of pain and are capable of inducing inflammation. Diagnosing the disease involves direct visualisation of the lesions through a laparoscopic or laparotomy, which is followed by histopathological examination of biopsied or excised lesions. The staging of endometriosis due to its complexity is highly variable as presentation and gaps in knowledge pose a great challenge in the classification of the disease. The medical management of endometriosis aims at providing adequate analgesia and suppression of the activity of the lesion. A better understanding of endometriotic lesion relationships between innervations and specific clinical characteristics may elucidate aspects of pain mechanisms and infertility in endometriosis and facilitate the development of novel therapeutic approaches.

On the classification of primary immunodeficiencies

1975 ◽  
Vol 86 (6) ◽  
pp. 988
Author(s):  
C. Pieraert ◽  
J.P. Farriaux ◽  
G. Fontaine
Keyword(s):  
Primary Immunodeficiencies

scholarly journals The method of diagnosis and classification of the gingival line defects of the teeth hard tissues

2017 ◽  
Vol 24 (2) ◽  
Author(s):  
Olena Bulbuk ◽  
Mykola Rozhko ◽  
Oleksandr Bulbuk
Keyword(s):  
Dental Treatment ◽  
Therapeutic Approaches ◽  
Hard Tissue ◽  
Dental Hard Tissues ◽  
Hard Tissues ◽  
Diagnosis And Classification ◽  
Clinical Variants ◽  
Line Defects ◽  
Tissue Defects

For solving the problem of diagnosis and treatment of hard tissue defects the significant role belongs to the choice of tactics for dental treatment of hard tissue defects located in the gingival line of any tooth.This work aims to study the problems of diagnosis and classification of gingival line defects of the teeth hard tissues. That will contribute to the objectification of differentiated diagnostic and therapeutic approaches in the dental treatment of various clinical variants of these defects localization.The objective of the study – is to develop the anatomical-functional classification for differentiated estimation of hard tissue defects in the gingival part, as the basis for the application of differential diagnostic-therapeutic approaches to the dental treatment of hard tissue defects disposed in the gingival part of any tooth.Materials and methods of investigation: There was conducted the examination of 48 patients with hard tissue defects located in the gingival part of any tooth. To assess the magnitude of gingival line destruction the periodontal probe and X-ray examination were used.Results. The result of the performed research the classification of the gingival line defects of the hard tissues was offered using exponent power. The value of this indicator is equal to an integer number expressed in millimeters of distance from the epithelial attachment to the cavity’s bottom of defect.Conclusions. The proposed classification fills an obvious gap in academic representations about hard tissue defects located in the gingival part of any tooth. Also it offers the prospects of consensus on differentiated diagnostic-therapeutic approaches in different clinical variants of location.  This classification builds methodological “bridge of continuity” between therapeutic and prosthetic dentistry in the field of treatment of the gingival line defects of dental hard tissues.

The nature of the semantic/episodic memory distinction: A missing piece of the “working through” process

2015 ◽  
Vol 38 ◽  
Author(s):  
Stanley B. Klein ◽  
Hans J. Markowitsch
Keyword(s):  
Episodic Memory ◽  
Autobiographical Memory ◽  
Memory Systems ◽  
Therapeutic Approaches ◽  
Working Through ◽  
Target Article ◽  
Two Systems

AbstractThe relations between the semantic and episodic-autobiographical memory systems are more complex than described in the target article. We argue that understanding the noetic/autonoetic distinction provides critical insights into the foundation of the delineation between the two memory systems. Clarity with respect to the criteria for classification of these two systems, and the evolving conceptualization of episodic memory, can further neuroscientifically informed therapeutic approaches.

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