scholarly journals Epigenetics in Food Allergy and Immunomodulation

Nutrients ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 4345
Author(s):  
José A. Cañas ◽  
Rafael Núñez ◽  
Anyith Cruz-Amaya ◽  
Francisca Gómez ◽  
María J. Torres ◽  
...  
Keyword(s):  
Food Allergy ◽  
Treatment Options ◽  
Allergic Diseases ◽  
Developed Countries ◽  
Epigenetic Mechanism ◽  
Diagnostic Tools ◽  
Epigenetic Mechanisms ◽  
Immune Genes ◽  
Dietary Components

Food allergy (FA) is an increasing problem worldwide and, over recent years, its prevalence is rising in developed countries. Nowadays, the immunological and cellular processes that occur in the allergic reactions are not fully understood, which hampers the development of in vitro diagnostic tools and further treatment options. Moreover, allergic diseases could be reinforced by environmental exposure and genetic modifications. Gene expression can be controlled by different epigenetic mechanisms like DNA methylation, histone modifications, and microRNAs. In addition, several environmental factors such as dietary components (vitamin D, butyrate, folic acid) are able to regulate this epigenetic mechanism. All these factors produce modifications in immune genes that could alter the development and function of immune cells, and therefore the etiology of the disease. Furthermore, these epigenetic mechanisms have also an influence on immunomodulation, which could explain sustained responsiveness or unresponsiveness during immunotherapy due to epigenetic modifications in key genes that induce tolerance in several FA. Thus, in this review we focus on the different epigenetic mechanisms that occur in FA and on the influence of several dietary components in these gene modifications.

scholarly journals Solid Food Introduction and the Development of Food Allergies

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1790 ◽  
Author(s):  
Carlo Caffarelli ◽  
Dora Di Mauro ◽  
Carla Mastrorilli ◽  
Paolo Bottau ◽  
Francesca Cipriani ◽  
...  
Keyword(s):  
Food Allergy ◽  
Allergic Diseases ◽  
Developed Countries ◽  
World Health ◽  
Food Allergies ◽  
Current Evidence ◽  
Healthy Children ◽  
Egg Allergy ◽  
Complementary Foods ◽  
Severe Eczema

The rise of food allergy in childhood, particularly among developed countries, has a significant weight on public health and involves serious implications for patients’ quality of life. Even if the mechanisms of food tolerance and the complex interactions between the immune system and environmental factors are still mainly unknown, pediatricians have worldwide implemented preventive measures against allergic diseases. In the last few decades, the prevention of food allergy has tracked various strategies of complementary feeding with a modification of international guidelines from delayed introduction to early weaning. Current evidence shows that complementary foods, including allergenic ones, should be introduced into diet after four months, or even better, following World Health Organization advice, around six months irrespective of risk for allergy of the individual. The introduction of peanut is recommended before 12 months of age among infants affected by severe eczema and/or egg allergy to diminish the occurrence of peanut allergy in countries with high peanut consumption. The introduction of heated egg at 6–8 months of age may reduce egg allergy. Infants at high risk of allergy similarly to healthy children should introduce complementary foods taking into account family and cultural preferences.

scholarly journals SARS-CoV-2-mediated dysregulation of metabolism and autophagy uncovers host-targeting antivirals

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nils C. Gassen ◽  
Jan Papies ◽  
Thomas Bajaj ◽  
Jackson Emanuel ◽  
Frederik Dethloff ◽  
...  
Keyword(s):  
Disease Duration ◽  
Treatment Options ◽  
Cellular Metabolism ◽  
Hamster Model ◽  
Immune Genes ◽  
Single Cell Sequencing ◽  
Human Lung Cells ◽  
Infected Cells ◽  
Single Nucleus

AbstractViruses manipulate cellular metabolism and macromolecule recycling processes like autophagy. Dysregulated metabolism might lead to excessive inflammatory and autoimmune responses as observed in severe and long COVID-19 patients. Here we show that SARS-CoV-2 modulates cellular metabolism and reduces autophagy. Accordingly, compound-driven induction of autophagy limits SARS-CoV-2 propagation. In detail, SARS-CoV-2-infected cells show accumulation of key metabolites, activation of autophagy inhibitors (AKT1, SKP2) and reduction of proteins responsible for autophagy initiation (AMPK, TSC2, ULK1), membrane nucleation, and phagophore formation (BECN1, VPS34, ATG14), as well as autophagosome-lysosome fusion (BECN1, ATG14 oligomers). Consequently, phagophore-incorporated autophagy markers LC3B-II and P62 accumulate, which we confirm in a hamster model and lung samples of COVID-19 patients. Single-nucleus and single-cell sequencing of patient-derived lung and mucosal samples show differential transcriptional regulation of autophagy and immune genes depending on cell type, disease duration, and SARS-CoV-2 replication levels. Targeting of autophagic pathways by exogenous administration of the polyamines spermidine and spermine, the selective AKT1 inhibitor MK-2206, and the BECN1-stabilizing anthelmintic drug niclosamide inhibit SARS-CoV-2 propagation in vitro with IC50 values of 136.7, 7.67, 0.11, and 0.13 μM, respectively. Autophagy-inducing compounds reduce SARS-CoV-2 propagation in primary human lung cells and intestinal organoids emphasizing their potential as treatment options against COVID-19.

scholarly journals Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens

Genes ◽  
2018 ◽  
Vol 9 (9) ◽  
pp. 461 ◽  
Author(s):  
Ewa Ksiezopolska ◽  
Toni Gabaldón
Keyword(s):  
Drug Resistance ◽  
Fungal Infections ◽  
Current Knowledge ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Developed Countries ◽  
Antifungal Drugs ◽  
Opportunistic Pathogens ◽  
Evolutionary Mechanisms

Fungal infections, such as candidiasis caused by Candida, pose a problem of growing medical concern. In developed countries, the incidence of Candida infections is increasing due to the higher survival of susceptible populations, such as immunocompromised patients or the elderly. Existing treatment options are limited to few antifungal drug families with efficacies that vary depending on the infecting species. In this context, the emergence and spread of resistant Candida isolates are being increasingly reported. Understanding how resistance can evolve within naturally susceptible species is key to developing novel, more effective treatment strategies. However, in contrast to the situation of antibiotic resistance in bacteria, few studies have focused on the evolutionary mechanisms leading to drug resistance in fungal species. In this review, we will survey and discuss current knowledge on the genetic bases of resistance to antifungal drugs in Candida opportunistic pathogens. We will do so from an evolutionary genomics perspective, focusing on the possible evolutionary paths that may lead to the emergence and selection of the resistant phenotype. Finally, we will discuss the potential of future studies enabled by current developments in sequencing technologies, in vitro evolution approaches, and the analysis of serial clinical isolates.

scholarly journals Assessment of Current Gene Therapy Practices in Hepatocellular Carcinoma

2020 ◽  
Vol 2 (4) ◽  
pp. 469-480
Author(s):  
Bryan Mckiver ◽  
Mohamad Imad Damaj ◽  
Devanand Sarkar
Keyword(s):  
Hepatocellular Carcinoma ◽  
Gene Therapy ◽  
Late Stage ◽  
Viral Vectors ◽  
Primary Liver Cancer ◽  
Treatment Options ◽  
Diagnostic Tools ◽  
In Vivo Models

Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and the fifth most common cancer worldwide. HCC is recognized as the fourth most common cause of cancer related deaths worldwide due to the lack of effective early diagnostic tools, which often leads to individuals going undiagnosed until the cancer has reached late stage development. The current FDA approved treatments for late stage HCC provide a minimal increase in patient survival and lack tumor specificity, resulting in toxic systemic side effects. Gene therapy techniques, such as chimeric antigen receptor (CAR)-T Cells, viral vectors, and nanoparticles, are being explored as novel treatment options in various genetic diseases. Pre-clinical studies using gene therapy to treat in vitro and in vivo models of HCC have demonstrated potential efficacy for use in human patients. This review highlights genetic targets, techniques, and current clinical trials in HCC utilizing gene therapy.

scholarly journals macroH2A2 shapes chromatin accessibility at enhancer elements in glioblastoma to modulate a targetable self-renewal epigenetic network

2021 ◽  
Author(s):  
Ana Nikolic ◽  
Anna Bobyn ◽  
Francesca Maule ◽  
Katrina Ellestad ◽  
Xueqing Lun ◽  
...  
Keyword(s):  
Chromatin Accessibility ◽  
Epigenetic Mechanism ◽  
Epigenetic Mechanisms ◽  
Direct Role ◽  
Self Renewal ◽  
In Vivo Models ◽  
Chromatin Regulators ◽  
New Treatment

Self-renewal is a crucial property of glioblastoma cells and is enabled by the choreographed function of chromatin regulators and transcription factors. Identifying targetable epigenetic mechanisms of self-renewal could represent an important step toward developing new and effective treatments for this universally lethal cancer. Here we uncover a targetable epigenetic axis of self-renewal mediated by the histone variant macroH2A2. Using patient-derived in vitro and in vivo models, we show that macroH2A2 has a direct role in shaping chromatin accessibility at enhancer elements to antagonize transcriptional programs of self-renewal. Pharmaceutical inhibition of the chromatin remodeler Menin increased macroH2A2 levels and repressed self-renewal. Our results reveal a targetable epigenetic mechanism of self-renewal controlled by macroH2A2 and suggest new treatment approaches for glioblastoma patients.

scholarly journals Oral Immunotherapy and Basophil and Mast Cell Reactivity in Food Allergy

2020 ◽  
Vol 11 ◽  
Author(s):  
Anuya Paranjape ◽  
Mindy Tsai ◽  
Kaori Mukai ◽  
Ramona A. Hoh ◽  
Shilpa A. Joshi ◽  
...  
Keyword(s):  
Food Allergy ◽  
Mast Cells ◽  
Oral Immunotherapy ◽  
Food Allergies ◽  
Diagnostic Tools ◽  
Blood Levels ◽  
Type I ◽  
Cell Reactivity ◽  
Specificity And Sensitivity

Basophil activation tests (BATs) can closely monitor, in vitro, a patient’s propensity to develop type I hypersensitivity reactions. Because of their high specificity and sensitivity, BATs have become promising diagnostic tools, especially in cases with equivocal clinical histories, skin prick test results, and/or levels of specific IgE to allergen extracts. BATs also are useful as tools for monitoring the effects of treatment, since oral immunotherapy (OIT) studies report a diminution in patients’ basophil responsiveness over the course of OIT. This review will discuss the BAT findings obtained before, during, and after OIT for food allergy. We will mainly focus on the association of basophil responsiveness, and alterations in basophil surface markers, with clinical outcomes and other clinical features, such as blood levels of specific IgG and IgE antibodies. The detailed analysis of these correlations will ultimately facilitate the use of BATs, along with other blood biomarkers, to differentiate short-term desensitization versus sustained unresponsiveness and to improve treatment protocols. Given the critical anatomic location of mast cells adjacent to the many IgE+ plasma cells found in the gastrointestinal tissues of allergic individuals, we will also discuss the role of gastrointestinal mast cells in manifestations of food allergies.

Abstract P375: Gender-based Cardio-protective Functional Dimorphism Of Bone Marrow Endothelial Progenitor Cells And Their Exosomes: Estrogen-independent Epigenetic Mechanisms

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Charan T Gurrala ◽  
Venkata Garikipati ◽  
Zhongjian Cheng ◽  
Vandana Mallaredy ◽  
Maria Cimini ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Capillary Density ◽  
Tube Formation ◽  
Ischemic Myocardium ◽  
Epigenetic Mechanism ◽  
Epigenetic Mechanisms ◽  
Endothelial Progenitor

Introduction: Estrogen or estrogen receptor-dependent mechanisms in enhancing the cardioprotective efficacy of bone marrow endothelial progenitor cells (BM-EPC) is well-established in preclinical studies. However, the efficacy of estrogen does not reflect in the data from randomized cardiovascular clinical trials, suggesting an estrogen-independent role of female BM-EPC in eliciting enhanced cardiac protection compared to males. Hypothesis: Epigenetic mechanisms may contribute to the sex-specific dimorphism of Sca-1 + /CD31 + BM-EPC in regulating cell-homing, pro-angiogenic and anti-inflammatory functions in the ischemic myocardium leading to enhanced reparative function of female progenitor cells. Methods & Results: Transplantation of GFP-BM-mononuclear cells from male and female GFP transgenic mice into the BM of lethally irradiated recipient male C57BL/6 mice resulted in the enhanced mobilization of female Sca-1 + CD31 + /GFP + BM-EPC into circulation post-MI. A higher number of female BM-EPC homed to the ischemic myocardium and significantly improved LV functions and capillary density post-MI compared to male BM-EPC. Female BM-EPC showed increased expression of bFGF, VEGFR2, SDF-1α, and IL-10 genes, thereby efficiently promoted endothelial tube formation in vitro compared to male BM-EPC. Transplantation of female BM-EPC and their exosomes into post-MI male mice improved LV cardiac function, reduced scar size, and improved capillary density compared to male BM-EPC and exosomes. Male BM-EPC showed an increased expression of G9a/Ehmt2, an H3K9me3 methyltransferase, and Dnmt3a DNA methyltransferase compared to female BM-EPC. In contrast, Kdm6b/JMJD3, H3K27me3 demethylase was highly expressed in female BM-EPC compared to males. Treatment of BM-EPC of both sexes with 17-β-estradiol did not alter the expression of Kdm6b/JMJD3. Male BM-EPC highly expressed repressive gene marks, H3K9me3, and H3K27me3 compared to females. Compared to the male, BM-EPC from female and ovariectomized (OXV) female mice showed equally high expression of angiogenic genes ANGPT-1, MDK, PLAU, Tie-2, and VEGFR2 and lower levels of inflammatory cytokines, TNFα, IFNγ, IL-1β, and CCL3. Conditioned medium from female and OVX BM-EPC equally promoted enhanced migration and tube formation of HUVEC in vitro, compared to male BM-EPC. Conclusions: An estrogen-independent epigenetic mechanism likely governs the enhanced cardiac reparative properties of female BM-EPC.

Treatment Options in COVID-19: The Role of Bioavailable Antiviral Ribonucleoside Analog on NHC in vitro

2020 ◽  
Author(s):  
Lara Bittmann
Keyword(s):  
World Health Organization ◽  
Clinical Picture ◽  
Treatment Options ◽  
World Health ◽  
Wuhan City ◽  
The World ◽  
Novel Coronavirus ◽  
Health Organization

On December 31, 2019, WHO was informed of cases of pneumonia of unknown cause in Wuhan City, China. A novel coronavirus was identified as the cause by Chinese authorities on January 7, 2020 and was provisionally named "2019-nCoV". This new Coronavirus causes a clinical picture which has received now the name COVID-19. The virus has spread subsequently worldwide and was explained on the 11th of March, 2020 by the World Health Organization to the pandemic.

Are Carbonic Anhydrases Suitable Targets to Fight Protozoan Parasitic Diseases?

2019 ◽  
Vol 25 (39) ◽  
pp. 5266-5278 ◽  
Author(s):  
Katia D'Ambrosio ◽  
Claudiu T. Supuran ◽  
Giuseppina De Simone
Keyword(s):  
Drug Resistance ◽  
Animal Models ◽  
Carbonic Anhydrase ◽  
Drug Target ◽  
Treatment Options ◽  
Parasitic Diseases ◽  
Carbonic Anhydrases ◽  
Extensive Drug Resistance ◽  
Protozoan Infections

Protozoans belonging to Plasmodium, Leishmania and Trypanosoma genera provoke widespread parasitic diseases with few treatment options and many of the clinically used drugs experiencing an extensive drug resistance phenomenon. In the last several years, the metalloenzyme Carbonic Anhydrase (CA, EC 4.2.1.1) was cloned and characterized in the genome of these protozoa, with the aim to search for a new drug target for fighting malaria, leishmaniasis and Chagas disease. P. falciparum encodes for a CA (PfCA) belonging to a novel genetic family, the η-CA class, L. donovani chagasi for a β-CA (LdcCA), whereas T. cruzi genome contains an α-CA (TcCA). These three enzymes were characterized in detail and a number of in vitro potent and selective inhibitors belonging to the sulfonamide, thiol, dithiocarbamate and hydroxamate classes were discovered. Some of these inhibitors were also effective in cell cultures and animal models of protozoan infections, making them of considerable interest for the development of new antiprotozoan drugs with a novel mechanism of action.

Targeting COVID-19 in Parkinson’s patients: Drugs repurposed.

2020 ◽  
Vol 27 ◽  
Author(s):  
Firoz Anwar ◽  
Salma Naqvi ◽  
Fahad A. Al-Abbasi ◽  
Nauroz Neelofar ◽  
Vikas Kumar ◽  
...  
Keyword(s):  
Day Treatment ◽  
Treatment Options ◽  
Developed Countries ◽  
Methyl Transferase ◽  
Comt Inhibitors ◽  
Mao B ◽  
Pharmacokinetic Properties ◽  
Us Fda ◽  
Approved Drugs ◽  
Fda Approved Drugs

: The last couple of months have witnessed the world in a state of virtual standstill. The SARS-CoV-2 virus has overtaken globe to economic and social lockdown. Many patients with COVID-19 have compromised immunity, especially in an aged population suffering from Parkinson disease (PD). Alteration in dopaminergic neurons or deficiency of dopamine in PD patients is the most common symptoms affecting 1% population above the age of 60 years. The compromised immune system and inflammatory manifestation in PD patients make them an easy target. The most common under trial drugs for COVID-19 are Remdesivir, Favipiravir, Chloroquine and Hydroxychloroquine, Azithromycin along with adjunct drugs like Amantadine with some monoclonal antibodies. : Presently, clinically US FDA approved drugs in PD includes Levodopa, catechol-O-methyl transferase (COMT) inhibitors, (Entacapone and Tolcapone), Dopamine agonists (Bromocriptine, Ropinirole, Pramipexole, and Rotigotine), Monoamine oxidase B (MAO-B) inhibitors (Selegiline and Rasagiline), Amantadine and Antimuscarinic drugs. The drugs have established mechanism of action on PD patients with known pharmacodynamics and pharmacokinetic properties along with dose and adverse effects. : Conclusion and relevance of this review focus on the drugs that can be tried for the PD patients with SAR CoV-2 infection, in particular, Amantadine approved by all developed countries a common drug possessing both antiviral properties by downregulation of CTSL, lysosomal pathway disturbance and change in pH necessary to uncoat the viral proteins and antiParkinson properties. The significant prognostic adverse effect of SARS-CoV-2 on PD and the present-day treatment options, clinical presentation and various mechanism is warrant need of the hour.

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