scholarly journals “Let Food Be Thy Medicine”: Gluten and Potential Role in Neurodegeneration

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 756
Author(s):  
Aaron Lerner ◽  
Carina Benzvi
Keyword(s):  
Side Effects ◽  
Autoimmune Diseases ◽  
Neurodegenerative Disease ◽  
Potential Role ◽  
Molecular Mimicry ◽  
Narrative Review ◽  
Major Protein ◽  
Staple Food ◽  
Effect Relationship ◽  
Systemic Side Effects

Wheat is a most favored staple food worldwide and its major protein is gluten. It is involved in several gluten dependent diseases and lately was suggested to play a role in non-celiac autoimmune diseases. Its involvement in neurodegenerative conditions was recently suggested but no cause-and-effect relationship were established. The present narrative review expands on various aspects of the gluten-gut-brain axes events, mechanisms and pathways that connect wheat and gluten consumption to neurodegenerative disease. Gluten induced dysbiosis, increased intestinal permeabillity, enteric and systemic side effects, cross-reactive antibodies, and the sequence of homologies between brain antigens and gluten are highlighted. This combination may suggest molecular mimicry, alluding to some autoimmune aspects between gluten and neurodegenerative disease. The proverb of Hippocrates coined in 400 BC, “let food be thy medicine,” is critically discussed in the frame of gluten and potential neurodegeneration evolvement.

Immunoengineering approaches for cytokine therapy

2021 ◽  
Author(s):  
Aslan Mansurov ◽  
Abigail Lauterbach ◽  
Erica Budina ◽  
Aaron T. Alpar ◽  
Jeffrey A. Hubbell ◽  
...  
Keyword(s):  
Side Effects ◽  
Protein Engineering ◽  
Autoimmune Diseases ◽  
Inflammatory Cytokines ◽  
Therapeutic Efficacy ◽  
Cytokine Therapy ◽  
Toxicity Profile ◽  
Wild Type ◽  
Systemic Side Effects ◽  
Secondary Lymphoid Organs

Since the discovery of cytokines, much effort has been put forth to achieve therapeutic translation for treatment of various diseases, including cancer and autoimmune diseases. Despite these efforts, very few cytokines have cleared regulatory approval, and those that were approved are not commonly used due to their challenging toxicity profile and/or limited therapeutic efficacy. The main limitation in translation has been that wild-type cytokines have unfavorable pharmacokinetic and pharmacodynamic profiles, either eliciting unwanted systemic side effects or insufficient residence in secondary lymphoid organs. In this review, we address protein engineering approaches that have been applied to both pro- and anti-inflammatory cytokines to enhance their therapeutic indices, and we highlight diseases in which administration of engineered cytokines is especially relevant.

scholarly journals Recent advances in understanding NRF2 as a druggable target: development of pro-electrophilic and non-covalent NRF2 activators to overcome systemic side effects of electrophilic drugs like dimethyl fumarate

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 2138 ◽  
Author(s):  
Takumi Satoh ◽  
Stuart Lipton
Keyword(s):  
Side Effects ◽  
Specific Interaction ◽  
Dimethyl Fumarate ◽  
Carnosic Acid ◽  
European Medicines Agency ◽  
Related Factor ◽  
Inflammatory Phase ◽  
First Case ◽  
Systemic Side Effects ◽  
Transcriptional Pathway

Dimethyl fumarate (DMF) is an electrophilic compound previously called BG-12 and marketed under the name Tecfidera®. It was approved in 2013 by the US Food and Drug Administration and the European Medicines Agency for the treatment of relapsing multiple sclerosis. One mechanism of action of DMF is stimulation of the nuclear factor erythroid 2-related factor 2 (NRF2) transcriptional pathway that induces anti-oxidant and anti-inflammatory phase II enzymes to prevent chronic neurodegeneration. However, electrophiles such as DMF also produce severe systemic side effects, in part due to non-specific S-alkylation of cysteine thiols and resulting depletion of glutathione. This mini-review presents the present status and future strategy for NRF2 activators designed to avoid these side effects. Two modes of chemical reaction leading to NRF2 activation are considered here. The first mode is S-alkylation (covalent reaction) of thiols in Kelch-like ECH-associated protein 1 (KEAP1), which interacts with NRF2. The second mechanism involves non-covalent pharmacological inhibition of protein-protein interactions, in particular domain-specific interaction between NRF2 and KEAP1 or other repressor proteins involved in this transcriptional pathway. There have been significant advances in drug development using both of these mechanisms that can potentially avoid the systemic side effects of electrophilic compounds. In the first case concerning covalent reaction with KEAP1, monomethyl fumarate and monoethyl fumarate appear to represent safer derivatives of DMF. In a second approach, pro-electrophilic drugs, such as carnosic acid from the herb Rosmarinus officinalis, can be used as a safe pro-drug of an electrophilic compound. Concerning non-covalent activation of NRF2, drugs are being developed that interfere with the direct interaction of KEAP1-NRF2 or inhibit BTB domain and CNC homolog 1 (BACH1), which is a transcriptional repressor of the promoter where NRF2 binds.

scholarly journals Anti-phospholipid syndrome and COVID-19 thrombosis: connecting the dots

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Moon Ley Tung ◽  
Bryce Tan ◽  
Robin Cherian ◽  
Bharatendu Chandra
Keyword(s):  
Endothelial Dysfunction ◽  
Severe Acute Respiratory Syndrome ◽  
Potential Role ◽  
Molecular Mimicry ◽  
Thromboembolic Events ◽  
The Past ◽  
High Prevalence ◽  
Connecting The Dots ◽  
Anti Phospholipid Syndrome

Abstract As the coronavirus disease 2019 (COVID-19) pandemic, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly worldwide, it has emerged as a leading cause of mortality, resulting in >1 million deaths over the past 10 months. The pathophysiology of COVID-19 remains unclear, posing a great challenge to the medical management of patients. Recent studies have reported an unusually high prevalence of thromboembolic events in COVID-19 patients, although the mechanism remains elusive. Several studies have reported the presence of aPLs in COVID-19 patients. We have noticed similarities between COVID-19 and APS, which is an autoimmune prothrombotic disease that is often associated with an infective aetiology. Molecular mimicry and endothelial dysfunction could plausibly explain the mechanism of thrombogenesis in acquired APS. In this review, we discuss the clinicopathological similarities between COVID-19 and APS, and the potential role of therapeutic targets based on the anti-phospholipid model for COVID-19 disease.

scholarly journals Polyglandular Autoimmune Syndrome Triggered after CTLA-4 and PD-1L Immunotherapy Treatment

Reports ◽  
2021 ◽  
Vol 4 (1) ◽  
pp. 1
Author(s):  
Juan Luis Fernández-Morera ◽  
Alfredo Renilla González ◽  
Carmen Elena Calvo Rodríguez ◽  
Judit Romano-García
Keyword(s):  
Immune Response ◽  
Side Effects ◽  
Autoimmune Diseases ◽  
Autoimmune Diabetes ◽  
Hashimoto Thyroiditis ◽  
Polyglandular Autoimmune Syndrome ◽  
Autoimmune Syndrome ◽  
Previous Diagnosis ◽  
Optimal Approach

Background: CTLA-4 and PD-1L are novel immune checkpoint targets for cancer treatment with specific side effects such as autoimmune diseases. Less frequently, the presence of several autoimmune diseases in the same patient has been described. In this communication, we illustrate the case of a 45-year-old patient with a previous diagnosis of advanced cancer that, after starting treatment with this immunotherapy, developed in the following months autoimmune diabetes, lymphocytic hypophysitis, and a Hashimoto thyroiditis in an abrupt and intense manner that would correspond to an autoimmune polyglandular disease. Discussion: The activation of autoimmunity and associated diseases is increasing in parallel with augmented indication of these immunotherapeutic treatments in cancer patients. A closer follow-up of these patients could be necessary for an optimal approach to this type of pathology. Conclusions: Different autoimmune diseases can converge in the same patient when immunotherapy for cancer is indicated to boost immune response against tumor, caused by altering immune tolerance.

scholarly journals A Narrative Review of Early Oral Stepdown Therapy for the Treatment of Uncomplicated Staphylococcus aureus Bacteremia: Yay or Nay?

2020 ◽  
Vol 7 (6) ◽  
Author(s):  
Michael Dagher ◽  
Vance G Fowler ◽  
Patty W Wright ◽  
Milner B Staub
Keyword(s):  
Staphylococcus Aureus ◽  
Hospital Readmission ◽  
Potential Role ◽  
Review Article ◽  
Narrative Review ◽  
Oral Antibiotics ◽  
Staphylococcus Aureus Bacteremia ◽  
Complete Treatment

Abstract Historically, intravenous (IV) antibiotics have been the cornerstone of treatment for uncomplicated Staphylococcus aureus bacteremia (SAB). However, IV antibiotics are expensive, increase the rates of hospital readmission, and can be associated with catheter-related complications. As a result, the potential role of oral antibiotics in the treatment of uncomplicated SAB has become a subject of interest. This narrative review article aims to summarize key arguments for and against the use of oral antibiotics to complete treatment of uncomplicated SAB and evaluates the available evidence for specific oral regimens. We conclude that evidence suggests that oral step-down therapy can be an alternative for select patients who meet the criteria for uncomplicated SAB and will comply with medical treatment and outpatient follow-up. Of the currently studied regimens discussed in this article, linezolid has the most support, followed by fluoroquinolone plus rifampin.

Efficacy of ultra-low-dose (0.1 mg) ranibizumab intravitreal injection for treatment of prethreshold type 1 retinopathy of prematurity: A case series

2018 ◽  
Vol 30 (1) ◽  
pp. 40-47 ◽  
Author(s):  
Islam SH Ahmed ◽  
Ahmed MA Hadi ◽  
Hassan H Hassan
Keyword(s):  
Side Effects ◽  
Intravitreal Injection ◽  
Retinopathy Of Prematurity ◽  
Large Scale ◽  
Low Dose ◽  
Case Series ◽  
Results Of Treatment ◽  
Case Series Study ◽  
Systemic Side Effects

Aim: To report the results of treatment of type 1 prethreshold retinopathy of prematurity using intravitreal injection of ultra-low dose of ranibizumab (0.1 mg in 0.01 mL). Design: A retrospective observational case series study. Methods: Review of files of eligible infants who received this form of treatment to determine the outcome of treatment and any associated ocular or systemic side effects. Results: The study included 24 eyes of 12 preterm infants with mean gestational age of 29.75 ± 1.54 weeks and mean birth weight of 1074.58 ± 320.59 g. A total of 22 eyes (91.67%) had zone II disease while 2 eyes of one infant (8.33%) had zone I disease. All cases showed regression of the signs of the active retinopathy of prematurity with complete retinal vascularization. None of the cases required retreatment. Three eyes developed ocular complications. Apart from mild feeding intolerance that lasted for 24 h after injection in one infant, none of the cases developed systemic side effects. Conclusion: Intravitreal injection of ultra-low-dose ranibizumab showed promising efficacy and good ocular safety. However, further large-scale studies are required to give stronger evidence about the efficacy and safety of ultra-low-dose ranibizumab.

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