Gastrointestinal Microenvironment and the Gut-Lung Axis in the Immune Responses of Severe COVID-19

The global pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an unprecedented threat to the human health. A close association of the digestive tract is implied by the high frequency of gastrointestinal syndromes among COVID-19 patients. A better understanding of the role of intestinal microenvironment in COVID-19 immunopathology will be helpful to improve the control of COVID-19 associated morbidity and mortality. This review summarizes the immune responses associated with the severity of COVID-19, the current evidence of SARS-CoV-2 intestinal tropism, and the potential involvement of gut microenvironment in COVID-19 severity. Additionally, we discuss the therapeutic potential of probiotics as an alternative medicine to prevent or alleviate severe COVID-19 outcome.

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Role of Gut Microbiome in COVID-19: An Insight Into Pathogenesis and Therapeutic Potential

Frontiers in Immunology ◽

10.3389/fimmu.2021.765965 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ikram Hussain ◽

Gabriel Liu Yuan Cher ◽

Muhammad Abbas Abid ◽

Muhammad Bilal Abid

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Immune Responses ◽

Respiratory Tract ◽

Gut Microbiome ◽

Therapeutic Potential ◽

Circulatory System ◽

Respiratory Illness ◽

Leaky Gut ◽

Insight Into

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in an unprecedented global crisis. Although primarily a respiratory illness, dysregulated immune responses may lead to multi-organ dysfunction. Prior data showed that the resident microbial communities of gastrointestinal and respiratory tracts act as modulators of local and systemic inflammatory activity (the gut–lung axis). Evolving evidence now signals an alteration in the gut microbiome, brought upon either by cytokines from the infected respiratory tract or from direct infection of the gut, or both. Dysbiosis leads to a “leaky gut”. The intestinal permeability then allows access to bacterial products and toxins into the circulatory system and further exacerbates the systemic inflammatory response. In this review, we discuss the available data related to the role of the gut microbiome in the development and progression of COVID-19. We provide mechanistic insights into early data with a focus on immunological crosstalk and the microbiome’s potential as a biomarker and therapeutic target.

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COVID-19 and nutritional deficiency: a review of existing knowledge

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2020-0074 ◽

2021 ◽

Vol 42 (1) ◽

pp. 77-85

Author(s):

Meghana Muthuvattur Pallath ◽

Ashok Kumar Ahirwar ◽

Satyendra Chandra Tripathi ◽

Priyanka Asia ◽

Apurva Sakarde ◽

...

Keyword(s):

Immune Responses ◽

Viral Infection ◽

Close Contact ◽

Omega 3 Fatty Acids ◽

Omega 3 ◽

Antibody Affinity ◽

Global Pandemic ◽

Underlying Diseases ◽

Pro Inflammatory Cytokines

Abstract COVID-19 has resulted in an ongoing global pandemic, which spread largely among people who have had close contact with the infected person. The immunopathology of the SARS-CoV-2 virus includes the production of an excess amount of pro-inflammatory cytokines “a cytokine-storm”. The respiratory system (main), cardiovascular system and the gastrointestinal tract are the most affected body systems during viral infection. It has been found that most of the patients who require admission to hospital are elderly or have chronic underlying diseases. Higher cases of malnutrition and co-morbidities like diabetes mellitus and cardiovascular diseases are reported in elderly patients due to which, the immune system weakens and hence, the response to the virus is diminished in magnitude. A deficiency of micronutrients results in impaired immune responses leading to improper secretion of cytokines, alterations in secretory antibody response and antibody affinity which increases susceptibility to viral infection. The deficiency of various micronutrients in COVID-19 patient can be treated by appropriate nutritional supplements, prescribed after evaluating the patients’ nutritional status. Here we aim to highlight the role of a few particular nutrients namely Vitamin D, Vitamin C, Omega-3 fatty acids, Zinc and Magnesium along with the synergistic roles they play in enhancing immunity and thus, maintaining homeostasis.

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N-Acetylcysteine (NAC): Impacts on Human Health

Antioxidants ◽

10.3390/antiox10060967 ◽

2021 ◽

Vol 10 (6) ◽

pp. 967

Author(s):

Micaely Cristina dos Santos Tenório ◽

Nayara Gomes Graciliano ◽

Fabiana Andréa Moura ◽

Alane Cabral Menezes de Oliveira ◽

Marília Oliveira Fonseca Goulart

Keyword(s):

Human Health ◽

Therapeutic Potential ◽

Experimental Studies ◽

Primary Role ◽

Necrosis Factor Alpha ◽

Biochemical Basis ◽

Tnf Α ◽

Factor Alpha ◽

Anti Inflammatory

N-acetylcysteine (NAC) is a medicine widely used to treat paracetamol overdose and as a mucolytic compound. It has a well-established safety profile, and its toxicity is uncommon and dependent on the route of administration and high dosages. Its remarkable antioxidant and anti-inflammatory capacity is the biochemical basis used to treat several diseases related to oxidative stress and inflammation. The primary role of NAC as an antioxidant stems from its ability to increase the intracellular concentration of glutathione (GSH), which is the most crucial biothiol responsible for cellular redox imbalance. As an anti-inflammatory compound, NAC can reduce levels of tumor necrosis factor-alpha (TNF-α) and interleukins (IL-6 and IL-1β) by suppressing the activity of nuclear factor kappa B (NF-κB). Despite NAC’s relevant therapeutic potential, in several experimental studies, its effectiveness in clinical trials, addressing different pathological conditions, is still limited. Thus, the purpose of this chapter is to provide an overview of the medicinal effects and applications of NAC to human health based on current therapeutic evidence.

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The complex functions of microRNA-150 in allergy, autoimmunity and immune tolerance

AIMS Allergy and Immunology ◽

10.3934/allergy.2021016 ◽

2021 ◽

Vol 5 (4) ◽

pp. 195-221

Author(s):

Katarzyna Nazimek ◽

Keyword(s):

Immune Responses ◽

Immune Tolerance ◽

Therapeutic Potential ◽

Current Knowledge ◽

Signaling Cascades ◽

Cell Functions ◽

Regulatory Circuits ◽

Complex Functions ◽

Genetic Level

<abstract> <p>At present, special efforts are being made to develop the strategies allowing for activation of long-lasting antigen-specific immune tolerance in therapy of allergic and autoimmune diseases. Some of these therapeutic approaches are aimed at modulating cell functions at genetic level by using miRNA-based and miRNA-targeting treatments. Simultaneously, the crucial role of extracellular vesicles as natural miRNA conveyors is highlighted for induction of antigen-specific immune tolerance, especially that they appear to be easily manipulatable for therapeutic applications. Among other immune-related miRNAs, miR-150 is getting special attention as it is differently expressed by immune cells at various stages of their maturation and differentiation. In addition, miR-150 is involved in different signaling cascades orchestrating humoral and cell-mediated mechanisms of both innate and adaptive immune responses. Therefore, miR-150 is considered a master regulator of immunity in mammals. Currently, physiological miR-150-dependent regulatory circuits and causes of their malfunctioning that underlie the pathogenesis of allergic and autoimmune disorders are being unraveled. Thus, present review summarizes the current knowledge of the role of miR-150 in the pathogenesis and complications of these diseases. Furthermore, the involvement of miR-150 in regulation of immune responses to allergens and self-antigens and in induction of antigen-specific immune tolerance is discussed with the special emphasis on the therapeutic potential of this miRNA.</p> </abstract>

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Nitric Oxide and Immune Responses in Cancer: Searching for New Therapeutic Strategies

Current Medicinal Chemistry ◽

10.2174/0929867328666210707194543 ◽

2021 ◽

Vol 28 ◽

Author(s):

Adeleh Sahebnasagh ◽

Fatemeh Saghafi ◽

Sina Negintaji ◽

Tingyan Hu ◽

Mojtaba Shabani-Boroujeni ◽

...

Keyword(s):

Nitric Oxide ◽

Immune Responses ◽

Therapeutic Potential ◽

Relevant Literature ◽

Cochrane Library ◽

Signaling Molecule ◽

No Donors ◽

The Cochrane Library ◽

Oxide Synthase

: In recent years, there has been an increasing interest in understanding the mysterious functions of nitric oxide (NO) and how this pleiotropic signaling molecule contributes to tumorigenesis. This review attempts to expose and discuss the information available on the immunomodulatory role of NO in cancer and recent approaches to the role of NO donors in the area of immunotherapy. To address the goal, the following databases were searched to identify relevant literature concerning empirical evidence: The Cochrane Library, Pubmed, Medline, EMBASE from 1980 through March 2020. Valuable attempts have been made to develop distinctive NO-based cancer therapy. Although the data do not allow generalization, the evidence seems to indicate that low / moderate levels may favor tumorigenesis while higher levels would exert anti-tumor effects. In this sense, the use of NO donors could have an important therapeutic potential within immunotherapy, although there are still no clinical trials. The emerging understanding of NO-regulated immune responses in cancer may help unravel the recent features of this “double-edged sword” in cancer physiological and pathologic processes and its potential use as a therapeutic agent for cancer treatment. In short, in this review, we discuss the complex cellular mechanism in which NO, as a pleiotropic signaling molecule, participates in cancer pathophysiology. We also debate the dual role of NO in cancer and tumor progression, and clinical approaches for inducible nitric oxide synthase (iNOS) based therapy against cancer.

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Azilsartan: Current Evidence and Perspectives in Management of Hypertension

International Journal of Hypertension ◽

10.1155/2019/1824621 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8

Author(s):

Akshyaya Pradhan ◽

Ashish Tiwari ◽

Rishi Sethi

Keyword(s):

Antihypertensive Drugs ◽

Angiotensin Receptor Blockers ◽

Financial Burden ◽

Daily Practice ◽

Current Evidence ◽

Hypertension Management ◽

Angiotensin Receptor ◽

Global Pandemic ◽

Receptor Blockers

Hypertension continues to be global pandemic with huge mortality, morbidity, and financial burden on the health system. Unfortunately, most patients with hypertension would eventually require two or more drugs in combination to achieve their target blood pressure (BP). To this end, emergence of more potent antihypertensive drugs is a welcome sign. Angiotensin receptor blockers (ARBs) are cornerstones of hypertension management in daily practice. Among all ARBs, azilsartan is proven to be more potent in most of the head-to-head trials till date. Azilsartan is the latest ARB approved for hypertension with greater potency and minimal side effects. This review highlights the role of azilsartan in management of hypertension in the current era.

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NFKB1 and Cancer: Friend or Foe?

Cells ◽

10.3390/cells7090133 ◽

2018 ◽

Vol 7 (9) ◽

pp. 133 ◽

Cited By ~ 17

Author(s):

Julia Concetti ◽

Caroline L Wilson

Keyword(s):

Immune Responses ◽

Cancer Progression ◽

Multiple Roles ◽

Current Evidence ◽

Cellular Processes ◽

Specific Manner ◽

Organ Specific ◽

A Cell ◽

Potential Cancer

Current evidence strongly suggests that aberrant activation of the NF-κB signalling pathway is associated with carcinogenesis. A number of key cellular processes are governed by the effectors of this pathway, including immune responses and apoptosis, both crucial in the development of cancer. Therefore, it is not surprising that dysregulated and chronic NF-κB signalling can have a profound impact on cellular homeostasis. Here we discuss NFKB1 (p105/p50), one of the five subunits of NF-κB, widely implicated in carcinogenesis, in some cases driving cancer progression and in others acting as a tumour-suppressor. The complexity of the role of this subunit lies in the multiple dimeric combination possibilities as well as the different interacting co-factors, which dictate whether gene transcription is activated or repressed, in a cell and organ-specific manner. This review highlights the multiple roles of NFKB1 in the development and progression of different cancers, and the considerations to make when attempting to manipulate NF-κB as a potential cancer therapy.

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Platelet Function in Viral Immunity and SARS-CoV-2 Infection

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0041-1726033 ◽

2021 ◽

Author(s):

Afaf Allaoui ◽

Akif A. Khawaja ◽

Oussama Badad ◽

Mariam Naciri ◽

Marie Lordkipanidzé ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Infectious Diseases ◽

Immune Responses ◽

Cytokine Storm ◽

Blood Components ◽

Viral Immunity ◽

Cytokines And Chemokines ◽

Activated Platelets ◽

Viral Receptors

AbstractPlatelets, as nonnucleated blood components, are classically recognized for their pivotal role in hemostasis. In recent years, however, accumulating evidence points to a nonhemostatic role for platelets, as active participants in the inflammatory and immune responses to microbial organisms in infectious diseases. This stems from the ability of activated platelets to secrete a plethora of immunomodulatory cytokines and chemokines, as well as directly interplaying with viral receptors. While much attention has been given to the role of the cytokine storm in the severity of the coronavirus disease 2019 (COVID-19), less is known about the contribution of platelets to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we give a brief overview on the platelet contribution to antiviral immunity and response during SARS-CoV-2 infection.

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Neutrophils in cystic fibrosis

Biological Chemistry ◽

10.1515/hsz-2015-0271 ◽

2016 ◽

Vol 397 (6) ◽

pp. 485-496 ◽

Cited By ~ 32

Author(s):

Julie Laval ◽

Anjali Ralhan ◽

Dominik Hartl

Keyword(s):

Cystic Fibrosis ◽

Lung Disease ◽

Structural Damage ◽

Fungal Pathogens ◽

Therapeutic Potential ◽

Inflammatory Cells ◽

Current Evidence ◽

Infection And Inflammation ◽

Shed Light

Abstract Cystic fibrosis (CF) lung disease is characterized by chronic infection and inflammation. Among inflammatory cells, neutrophils represent the major cell population accumulating in the airways of CF patients. While neutrophils provide the first defensive cellular shield against bacterial and fungal pathogens, in chronic disease conditions such as CF these short-lived immune cells release their toxic granule contents that cause tissue remodeling and irreversible structural damage to the host. A variety of human and murine studies have analyzed neutrophils and their products in the context of CF, yet their precise functional role and therapeutic potential remain controversial and incompletely understood. Here, we summarize the current evidence in this field to shed light on the complex and multi-faceted role of neutrophils in CF lung disease.

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Integrated role of microRNA-30e-5p through targeting negative regulators of innate immune pathways during HBV infection and SLE

10.1101/2020.02.29.969014 ◽

2020 ◽

Author(s):

Richa Mishra ◽

Sanjana Bhattacharya ◽

Bhupendra S Rawat ◽

Ashish Kumar ◽

Akhilesh Kumar ◽

...

Keyword(s):

Innate Immunity ◽

Mouse Model ◽

Immune Responses ◽

Therapeutic Potential ◽

Innate Immune ◽

Locked Nucleic Acid ◽

Type I ◽

Innate Immune Responses ◽

Negative Regulators

AbstractPrecise regulation of innate immunity is crucial for the development of appropriate host immunity against microbial infections and the maintenance of immune homeostasis. The microRNAs are small non-coding RNA, post-transcriptional regulator of multiple genes and act as a rheostat for protein expression. Here, we identified microRNA(miR)-30e-5p (miR-30e) induced by the hepatitis B virus (HBV) and other viruses that act as a master regulator for innate immune responses. Moreover, pegylated type I interferons treatment to HBV patients for viral reduction also reduces the miRNA. Additionally, we have also shown the immuno-pathological effects of miR-30e in systemic lupus erythematous (SLE) patients and SLE mouse model. Mechanistically, the miR-30e targets multiple negative regulators namely TRIM38, TANK, ATG5, ATG12, BECN1, SOCS1, SOCS3 of innate immune signaling pathways and enhances innate immune responses. Furthermore, sequestering of endogenous miR-30e in PBMCs of SLE patients and SLE mouse model respectively by the introduction of antagomir and locked nucleic acid based inhibitor significantly reduces type I interferon and pro-inflammatory cytokines. Collectively, our study demonstrates the novel role of miR-30e in innate immunity and its prognostic and therapeutic potential in infectious and autoimmune diseases.

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