scholarly journals Genetic and Epigenetic Aspects of Atopic Dermatitis

2020 ◽  
Vol 21 (18) ◽  
pp. 6484 ◽  
Author(s):  
Bogusław Nedoszytko ◽  
Edyta Reszka ◽  
Danuta Gutowska-Owsiak ◽  
Magdalena Trzeciak ◽  
Magdalena Lange ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Treatment Strategies ◽  
Structural Proteins ◽  
Epigenetic Changes ◽  
Epigenetic Alterations ◽  
Adaptive Immune ◽  
Genes Encoding ◽  
Inflammatory Processes ◽  
Non Coding Rnas

Atopic dermatitis is a heterogeneous disease, in which the pathogenesis is associated with mutations in genes encoding epidermal structural proteins, barrier enzymes, and their inhibitors; the role of genes regulating innate and adaptive immune responses and environmental factors inducing the disease is also noted. Recent studies point to the key role of epigenetic changes in the development of the disease. Epigenetic modifications are mainly mediated by DNA methylation, histone acetylation, and the action of specific non-coding RNAs. It has been documented that the profile of epigenetic changes in patients with atopic dermatitis (AD) differs from that observed in healthy people. This applies to the genes affecting the regulation of immune response and inflammatory processes, e.g., both affecting Th1 bias and promoting Th2 responses and the genes of innate immunity, as well as those encoding the structural proteins of the epidermis. Understanding of the epigenetic alterations is therefore pivotal to both create new molecular classifications of atopic dermatitis and to enable the development of personalized treatment strategies.

Virome and Inflammasomes, a Finely Tuned Balance with Important Consequences for the Host Health

2019 ◽  
Vol 26 (6) ◽  
pp. 1027-1044 ◽  
Author(s):  
Giulia Freer ◽  
Fabrizio Maggi ◽  
Mauro Pistello
Keyword(s):  
Immune System ◽  
Human Beings ◽  
Review Of The Literature ◽  
Adaptive Immune ◽  
Downstream Effects ◽  
Host Health ◽  
Inflammatory Processes ◽  
Human Immune ◽  
Immune Defences

Background:The virome is a network of viruses normally inhabiting humans. It forms a conspicuous portion of the so-called microbiome, once generically referred to as resident flora. Indeed, viruses infecting humans without leading to clinical disease are increasingly recognized as part of the microbiome and have an impact on the development of our immune system. In addition, they activate inflammasomes, multiprotein complexes that assemble in cells and that are responsible for the downstream effects of sensing pathogens.Objective:This review aims at summarizing the evidence on the role of the virome in modulating inflammation and emphasizes evidence for Anelloviruses as useful molecular markers to monitor inflammatory processes and immune system competence.Method:We carried out a review of the literature published in the last 5 years and summarized older literature to take into account ground-breaking discoveries concerning inflammasome assembly and virome.Results:A massive amount of data recently emerging demonstrate that the microbiome closely reflects what we eat, and many other unexpected variables. Composition, location, and amount of the microbiome have an impact on innate and adaptive immune defences. Viruses making up the virome contribute to shaping the immune system. Anelloviruses, the best known of such viruses, are present in most human beings, persistently without causing apparent disease. Depending on their interplay with such viruses, inflammasomes instruct host defences to tolerate or forfeit a specific microorganism.Conclusion:The virome plays an important role in shaping human immune defences and contributes to inflammatory processes by quenching or increasing them.

scholarly journals Drug Resistance in Osteosarcoma: Emerging Biomarkers, Therapeutic Targets and Treatment Strategies

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2878
Author(s):  
Claudia Maria Hattinger ◽  
Maria Pia Patrizio ◽  
Leonardo Fantoni ◽  
Chiara Casotti ◽  
Chiara Riganti ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Therapeutic Targets ◽  
Treatment Strategies ◽  
Cure Rate ◽  
Acquired Drug Resistance ◽  
Unselected Patient ◽  
Dismal Prognosis ◽  
Non Coding Rnas ◽  
High Grade Osteosarcoma

High-grade osteosarcoma (HGOS), the most common primary malignant tumor of bone, is a highly aggressive neoplasm with a cure rate of approximately 40–50% in unselected patient populations. The major clinical problems opposing the cure of HGOS are the presence of inherent or acquired drug resistance and the development of metastasis. Since the drugs used in first-line chemotherapy protocols for HGOS and clinical outcome have not significantly evolved in the past three decades, there is an urgent need for new therapeutic biomarkers and targeted treatment strategies, which may increase the currently available spectrum of cure modalities. Unresponsive or chemoresistant (refractory) HGOS patients usually encounter a dismal prognosis, mostly because therapeutic options and drugs effective for rescue treatments are scarce. Tailored treatments for different subgroups of HGOS patients stratified according to drug resistance-related biomarkers thus appear as an option that may improve this situation. This review explores drug resistance-related biomarkers, therapeutic targets and new candidate treatment strategies, which have emerged in HGOS. In addition to consolidated biomarkers, specific attention has been paid to the role of non-coding RNAs, tumor-derived extracellular vesicles, and cancer stem cells as contributors to drug resistance in HGOS, in order to highlight new candidate markers and therapeutic targets. The possible use of new non-conventional drugs to overcome the main mechanisms of drug resistance in HGOS are finally discussed.

scholarly journals Epigenetic Regulation of Endothelial Dysfunction and Inflammation in Pulmonary Arterial Hypertension

2021 ◽  
Vol 22 (22) ◽  
pp. 12098
Author(s):  
Jaylen Hudson ◽  
Laszlo Farkas
Keyword(s):  
Endothelial Dysfunction ◽  
Pulmonary Artery Hypertension ◽  
Metabolic Reprogramming ◽  
Pulmonary Vascular Disease ◽  
Epigenetic Changes ◽  
Apoptosis Resistance ◽  
Cell Dysfunction ◽  
Pulmonary Arterial ◽  
Non Coding Rnas

Once perceived as a disorder treated by vasodilation, pulmonary artery hypertension (PAH) has emerged as a pulmonary vascular disease with severe endothelial cell dysfunction. In the absence of a cure, many studies seek to understand the detailed mechanisms of EC regulation to potentially create more therapeutic options for PAH. Endothelial dysfunction is characterized by complex phenotypic changes including unchecked proliferation, apoptosis-resistance, enhanced inflammatory signaling and metabolic reprogramming. Recent studies have highlighted the role of epigenetic modifications leading to pro-inflammatory response pathways, endothelial dysfunction, and the progression of PAH. This review summarizes the existing literature on epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNAs, which can lead to aberrant endothelial function. Our goal is to develop a conceptual framework for immune dysregulation and epigenetic changes in endothelial cells in the context of PAH. These studies as well as others may lead to advances in therapeutics to treat this devastating disease.

scholarly journals The Osteoporosis/Microbiota Linkage: The Role of miRNA

2020 ◽  
Vol 21 (23) ◽  
pp. 8887 ◽  
Author(s):  
Massimo De Martinis ◽  
Lia Ginaldi ◽  
Alessandro Allegra ◽  
Maria Maddalena Sirufo ◽  
Giovanni Pioggia ◽  
...  
Keyword(s):  
Dynamic Equilibrium ◽  
Treatment Strategies ◽  
Therapeutic Agents ◽  
Osteoporosis Prevention ◽  
Regulate Gene Expression ◽  
Molecular Biotechnology ◽  
Non Coding Rnas ◽  
The Relationship ◽  
Complementary Mechanism

Hundreds of trillions of bacteria are present in the human body in a mutually beneficial symbiotic relationship with the host. A stable dynamic equilibrium exists in healthy individuals between the microbiota, host organism, and environment. Imbalances of the intestinal microbiota contribute to the determinism of various diseases. Recent research suggests that the microbiota is also involved in the regulation of the bone metabolism, and its alteration may induce osteoporosis. Due to modern molecular biotechnology, various mechanisms regulating the relationship between bone and microbiota are emerging. Understanding the role of microbiota imbalances in the development of osteoporosis is essential for the development of potential osteoporosis prevention and treatment strategies through microbiota targeting. A relevant complementary mechanism could be also constituted by the permanent relationships occurring between microbiota and microRNAs (miRNAs). miRNAs are a set of small non-coding RNAs able to regulate gene expression. In this review, we recapitulate the physiological and pathological meanings of the microbiota on osteoporosis onset by governing miRNA production. An improved comprehension of the relations between microbiota and miRNAs could furnish novel markers for the identification and monitoring of osteoporosis, and this appears to be an encouraging method for antagomir-guided tactics as therapeutic agents.

scholarly journals Epigenetic targeting and personalized approaches for AML

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 44-51 ◽  
Author(s):  
Gail J. Roboz
Keyword(s):  
Molecular Genetic ◽  
Treatment Strategies ◽  
Regulation Of Transcription ◽  
Hematopoietic Stem ◽  
Genetic Characteristics ◽  
Sequencing Technologies ◽  
Recurrent Mutations ◽  
Genes Encoding ◽  
Cell Disorder

Abstract Acute myeloid leukemia (AML) is a genetically heterogeneous clonal hematopoietic stem cell disorder and the majority of patients with AML die from their disease. The treatment paradigms for AML were developed decades ago and, although there have been improvements in the outcomes of selected younger patients and those with specific cytogenetic and molecular genetic characteristics, the overall survival for older patients remains dismal. Over the last few years, next-generation sequencing technologies have identified recurrent mutations in genes encoding proteins involved in the epigenetic regulation of transcription in most patients with AML. This discovery has led to new insights into the role of the epigenome in AML and opens the possibility of epigenetically targeted therapies. This chapter describes how epigenetic dysregulation plays a role in AML and highlights current and future treatment strategies that attempt to exploit epigenetic targets.

scholarly journals Epigenetic Regulation of the Human Papillomavirus Life Cycle

Pathogens ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 483 ◽  
Author(s):  
Michelle Mac ◽  
Cary A. Moody
Keyword(s):  
Life Cycle ◽  
Hpv Infection ◽  
Epigenetic Modifications ◽  
Human Papillomaviruses ◽  
Epigenetic Changes ◽  
Epigenetic Alterations ◽  
Malignant Phenotype ◽  
Public Health Burden ◽  
Damage Response

Persistent infection with certain types of human papillomaviruses (HPVs), termed high risk, presents a public health burden due to their association with multiple human cancers, including cervical cancer and an increasing number of head and neck cancers. Despite the development of prophylactic vaccines, the incidence of HPV-associated cancers remains high. In addition, no vaccine has yet been licensed for therapeutic use against pre-existing HPV infections and HPV-associated diseases. Although persistent HPV infection is the major risk factor for cancer development, additional genetic and epigenetic alterations are required for progression to the malignant phenotype. Unlike genetic mutations, the reversibility of epigenetic modifications makes epigenetic regulators ideal therapeutic targets for cancer therapy. This review article will highlight the recent advances in the understanding of epigenetic modifications associated with HPV infections, with a particular focus on the role of these epigenetic changes during different stages of the HPV life cycle that are closely associated with activation of DNA damage response pathways.

scholarly journals Role of microRNAs in the Regulation of Dendritic Cell Generation and Function

2020 ◽  
Vol 21 (4) ◽  
pp. 1319 ◽  
Author(s):  
Viviana Scalavino ◽  
Marina Liso ◽  
Grazia Serino
Keyword(s):  
Adaptive Systems ◽  
Intrinsic Factors ◽  
Inflammatory Conditions ◽  
Inflammatory Processes ◽  
Plasmacytoid Dcs ◽  
Non Coding Rnas ◽  
And Function ◽  
Antigen Presenting ◽  
Mirna Deregulation

Dendritic cells (DCs) are antigen-presenting cells with a key role in immune responses. They act as a link between the innate and adaptive systems and they can induce and maintain immunologic tolerance. DCs are subdivided into conventional and plasmacytoid DCs. These cell subsets originate from the same bone marrow precursors and their differentiation process is determined by several extrinsic and intrinsic factors, such as cytokines, transcription factors, and miRNAs. miRNAs are small non-coding RNAs that play a crucial role in modulating physiological and pathological processes mediated by DCs. miRNA deregulation affects many inflammatory conditions and diseases. The aim of this review was to underline the importance of miRNAs in inflammatory processes mediated by DCs in physiological and pathological conditions and to highlight their potential application for future therapies.

scholarly journals Adaptive Immune Responses in Primary Cutaneous Sarcoidosis

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Matteo Bordignon ◽  
Paola Rottoli ◽  
Carlo Agostini ◽  
Mauro Alaibac
Keyword(s):  
Dendritic Cells ◽  
Treatment Strategies ◽  
Immunological Response ◽  
Inflammatory Disorder ◽  
Cutaneous Sarcoidosis ◽  
Cutaneous Lesions ◽  
Adaptive Immune ◽  
Immunological Mechanisms ◽  
Adaptive Immune Systems

Sarcoidosis is a multisystemic inflammatory disorder with cutaneous lesions present in about one-quarter of the patients. Cutaneous lesions have been classified as specific and nonspecific, depending on the presence of nonnecrotizing epithelial cell granulomas on histologic studies. The development and progression of specific cutaneous sarcoidosis involves a complex interaction between cells of the adaptive immune systems, notably T-lymphocytes and dendritic cells. In this paper, we will discuss the role of T-cells and skin dendritic cells in the development of primary cutaneous sarcoidosis and comment on the potential antigenic stimuli that may account for the development of the immunological response. We will further explore the contributions of selected cytokines to the immunopathological process. The knowledge of the adaptive immunological mechanisms operative in cutaneous sarcoidosis may subsequently be useful for identifying prevention and treatment strategies of systemic sarcoidosis.

scholarly journals NcRNAs in Vascular and Valvular Intercellular Communication

2021 ◽  
Vol 8 ◽  
Author(s):  
Benedikt Bartsch ◽  
Philip Roger Goody ◽  
Mohammed Rabiul Hosen ◽  
Denise Nehl ◽  
Neda Mohammadi ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Endothelial Dysfunction ◽  
Intercellular Communication ◽  
Treatment Strategies ◽  
Valvular Diseases ◽  
Disease Entities ◽  
Non Coding Rnas ◽  
Disease Pathways

Non-coding RNAs have been shown to be important biomarkers and mediators of many different disease entities, including cardiovascular (CV) diseases like atherosclerosis, aneurysms, and valvulopathies. Growing evidence suggests a central role of ncRNAs as regulators of different pathological pathways involved in endothelial dysfunction, cardiovascular inflammation, cell differentiation, and calcification. This review will discuss the role of protein-bound and extracellular vesicular-bound ncRNAs as biomarkers of vascular and valvular diseases, their role as intercellular communicators, and regulators of disease pathways and also highlights possible treatment strategies.

scholarly journals The Emerging Role of Succinate Dehyrogenase Genes (SDHx) in Tumorigenesis

2019 ◽  
Author(s):  
Elham Nazar ◽  
Fatemeh Khatami ◽  
Hiva Saffar ◽  
Seyed Mohammad Tavangar
Keyword(s):  
Normal Cell ◽  
Neoplastic Transformation ◽  
Genetic Alterations ◽  
Epigenetic Changes ◽  
Epigenetic Alterations ◽  
Mitochondrial Complex ◽  
Complex Ii ◽  
Hypoxic Conditions ◽  
Sdh Mutation

Transformation of a normal cell to cancerous one is dependent on the accumulation of several genetic and epigenetic alterations. One of the candidate driver genetic alterations can happen in succinate dehydrogenases (SDHx) coding gene include SDHA, SDHB, SDHC, SDHD, and SDHAF2.  The most important SDH mutation is in the SDHD gene, which encodes the smallest subunit of mitochondrial complex II (SDH). It has key function both in familial and non-familial hereditary paraganglioma/phaeochromocytoma syndrome (HPGL/PCC). SDHx genes mutations can have resulted in genetic and epigenetic changes like histone hypermethylation. These properties can lead to succinate-mediated inhibition of α-ketoglutarate-dependent dioxygenases. So hypoxic conditions can generate subsequent neoplastic transformation, and in this review, we are presenting the role of SDHx in several malignancies.

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