scholarly journals microRNA Heterogeneity, Innate-Immune Defense and the Efficacy of SARS-CoV-2 Infection—A Commentary

2021 ◽  
Vol 7 (2) ◽  
pp. 37
Author(s):  
Walter J. Lukiw
Keyword(s):  
Messenger Rna ◽  
Neurological Complications ◽  
Research Area ◽  
Immune Defense ◽  
Innate Immune ◽  
Viral Genomes ◽  
Naturally Occurring ◽  
Non Coding Rna ◽  
Genetic Individuality ◽  
The Family

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a member of the genus Betacoronavirus in the family Coronaviridae, possesses an unusually large single-stranded viral RNA (ssvRNA) genome of about ~29,811 nucleotides (nt) that causes severe and acute respiratory distress and a highly lethal viral pneumonia known as COVID-19. COVID-19 also presents with multiple ancillary systemic diseases and often involves cardiovascular, inflammatory, and/or neurological complications. Pathological viral genomes consisting of ssvRNA, like cellular messenger RNA (mRNA), are susceptible to attack, destruction, neutralization, and/or modulation by naturally occurring small non-coding RNAs (sncRNAs) within the host cell, some of which are known as microRNAs (miRNAs). This paper proposes that the actions of the 2650 known human miRNAs and other sncRNAs form the basis for an under-recognized and unappreciated innate-immune regulator of ssvRNA viral genome activities and have implications for the efficiency of SARS-CoV-2 invasion, infection, and replication. Recent research indicates that both miRNA and mRNA abundance, speciation, and complexity varies widely amongst human individuals, and this may: (i) In part explain the variability in the innate-immune immunological and pathophysiological response of different human individuals to the initiation and progression of SARS-CoV-2 infection in multiple tissue types; and (ii) further support our understanding of human biochemical and genetic individuality and the variable resistance of individuals to ssvRNA-mediated viral infection and disease. This commentary will briefly address current findings and concepts in this fascinating research area of non-coding RNA and innate-immunity with special reference to natural host miRNAs, SARS-CoV-2, and the current COVID-19 pandemic.

scholarly journals Long non-coding RNAs and enhancer RNAs regulate the lipopolysaccharide-induced inflammatory response in human monocytes

2014 ◽  
Vol 5 (1) ◽  
Author(s):  
Nicholas E. Ilott ◽  
James A. Heward ◽  
Benoit Roux ◽  
Eleni Tsitsiou ◽  
Peter S. Fenwick ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immune Response ◽  
Messenger Rna ◽  
Innate Immune ◽  
Human Monocytes ◽  
Proinflammatory Mediators ◽  
Biological Responses ◽  
Non Coding Rna ◽  
Antisense Lncrnas ◽  
Non Coding Rnas

Abstract Early reports indicate that long non-coding RNAs (lncRNAs) are novel regulators of biological responses. However, their role in the human innate immune response, which provides the initial defence against infection, is largely unexplored. To address this issue, here we characterize the long non-coding RNA transcriptome in primary human monocytes using RNA sequencing. We identify 76 enhancer RNAs (eRNAs), 40 canonical lncRNAs, 65 antisense lncRNAs and 35 regions of bidirectional transcription (RBT) that are differentially expressed in response to bacterial lipopolysaccharide (LPS). Crucially, we demonstrate that knockdown of nuclear-localized, NF-κB-regulated, eRNAs (IL1β-eRNA) and RBT (IL1β-RBT46) surrounding the IL1β locus, attenuates LPS-induced messenger RNA transcription and release of the proinflammatory mediators, IL1β and CXCL8. We predict that lncRNAs can be important regulators of the human innate immune response.

Innate immune responses and type 1 diabetes: A role for a long non-coding RNA?

2014 ◽  
Vol 9 (S 01) ◽  
Author(s):  
MP Ashton ◽  
I Tan ◽  
L Mackin ◽  
C Elso ◽  
E Chu ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Immune Responses ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Non Coding Rna ◽  
Long Non Coding Rna

The roles of grouper TANK in innate immune defense against iridovirus and nodavirus infections

2020 ◽  
Vol 104 ◽  
pp. 506-516
Author(s):  
Jingguang Wei ◽  
Chen Li ◽  
Jisheng Ou ◽  
Xin Zhang ◽  
Zetian Liu ◽  
...  
Keyword(s):  
Immune Defense ◽  
Innate Immune ◽  
Innate Immune Defense

scholarly journals Alpha-1 antitrypsin inhibits TMPRSS2 protease activity and SARS-CoV-2 infection

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lukas Wettstein ◽  
Tatjana Weil ◽  
Carina Conzelmann ◽  
Janis A. Müller ◽  
Rüdiger Groß ◽  
...  
Keyword(s):  
Serine Protease ◽  
Immune Defense ◽  
Innate Immune ◽  
Respiratory Pathogen ◽  
The Novel ◽  
Airway Epithelial ◽  
Protein Library ◽  
Epithelial Cultures ◽  
Alpha 1 Antitrypsin ◽  
Novel Coronavirus

AbstractSARS-CoV-2 is a respiratory pathogen and primarily infects the airway epithelium. As our knowledge about innate immune factors of the respiratory tract against SARS-CoV-2 is limited, we generated and screened a peptide/protein library derived from bronchoalveolar lavage for inhibitors of SARS-CoV-2 spike-driven entry. Analysis of antiviral fractions revealed the presence of α1-antitrypsin (α1AT), a highly abundant circulating serine protease inhibitor. Here, we report that α1AT inhibits SARS-CoV-2 entry at physiological concentrations and suppresses viral replication in cell lines and primary cells including human airway epithelial cultures. We further demonstrate that α1AT binds and inactivates the serine protease TMPRSS2, which enzymatically primes the SARS-CoV-2 spike protein for membrane fusion. Thus, the acute phase protein α1AT is an inhibitor of TMPRSS2 and SARS-CoV-2 entry, and may play an important role in the innate immune defense against the novel coronavirus. Our findings suggest that repurposing of α1AT-containing drugs has prospects for the therapy of COVID-19.

scholarly journals Bordetella pertussisAdenylate Cyclase Toxin Disrupts Functional Integrity of Bronchial Epithelial Layers

2017 ◽  
Vol 86 (3) ◽  
Author(s):  
Shakir Hasan ◽  
Nikhil Nitin Kulkarni ◽  
Arni Asbjarnarson ◽  
Irena Linhartova ◽  
Radim Osicka ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Airway Epithelium ◽  
Immune Defense ◽  
Innate Immune ◽  
Camp Signaling ◽  
Apical Surface ◽  
Bronchial Epithelial ◽  
Content Type ◽  
Functional Integrity ◽  
Cell Layers

ABSTRACTThe airway epithelium restricts the penetration of inhaled pathogens into the underlying tissue and plays a crucial role in the innate immune defense against respiratory infections. The whooping cough agent,Bordetella pertussis, adheres to ciliated cells of the human airway epithelium and subverts its defense functions through the action of secreted toxins and other virulence factors. We examined the impact ofB. pertussisinfection and of adenylate cyclase toxin-hemolysin (CyaA) action on the functional integrity of human bronchial epithelial cells cultured at the air-liquid interface (ALI).B. pertussisadhesion to the apical surface of polarized pseudostratified VA10 cell layers provoked a disruption of tight junctions and caused a drop in transepithelial electrical resistance (TEER). The reduction of TEER depended on the capacity of the secreted CyaA toxin to elicit cAMP signaling in epithelial cells through its adenylyl cyclase enzyme activity. Both purified CyaA and cAMP-signaling drugs triggered a decrease in the TEER of VA10 cell layers. Toxin-produced cAMP signaling caused actin cytoskeleton rearrangement and induced mucin 5AC production and interleukin-6 (IL-6) secretion, while it inhibited the IL-17A-induced secretion of the IL-8 chemokine and of the antimicrobial peptide beta-defensin 2. These results indicate that CyaA toxin activity compromises the barrier and innate immune functions ofBordetella-infected airway epithelia.

Unveiling contemporary dimensions in the internationalisation of family firms through bibliometric analysis and thematic analysis

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Sonal Thukral ◽  
Apoorva Jain
Keyword(s):  
Bibliometric Analysis ◽  
Thematic Analysis ◽  
Family Firms ◽  
Research Area ◽  
Research Articles ◽  
Future Research ◽  
Content Type ◽  
Holistic Understanding ◽  
The Family ◽  
Research Stream

Purpose For sustaining a competitive advantage in the integrated world economy, it has become imperative for family firms to internationalise their operations in overseas markets. However, despite the growing set of literature, results are still inconclusive with respect to family firms’ internationalisation. Thus, this study aims to address this gap by systematically reviewing 142 articles (1991–2019) to help researchers in identifying and unfolding the unexplored themes in the underlying area. Design/methodology/approach For systematically reviewing articles, the study uses a three-step methodology following PRISMA guidelines, bibliometric analysis and thematic analysis. Descriptive statistics of 142 research articles are obtained through bibliometric analysis while thematic analysis is carried out to create themes or clusters of various factors relating to family firms’ internationalisation. Findings The current review uncovers the evolving trends in the research streams, most productive authors, top journals and articles, co-citation analysis, as well as the major themes surrounding the family firms’ internationalisation literature. Results from bibliometric analysis indicate that family firms’ internationalisation is an upcoming research area. Also, the review indicates an opportunity for scholars from developing nations to make significant contributions in the underlying research stream. Research limitations/implications Results from bibliometric and thematic analysis will help academicians and researchers in accumulating a holistic understanding relating to family firms’ internationalisation and understanding the upcoming trends in family firms’ research, thereby guiding the future research scope. Also, it will assist the family firms’ leaders and managers in understanding the important dynamics in overseas markets and various factors to be considered while planning their internationalisation. Originality/value Undertaking a systematic literature review presents readers with a state-of-the-art understanding of the underlying research topic. To the best of the knowledge, to date, the study is the first to conduct the review of literature through bibliometric analysis with the help of R Studio software in the field of family firms’ internationalisation. Also, the study is the first to review more than 100 research articles in the underlying area. Finally, the study proposes a comprehensive framework integrating the major themes and facets relating to family firms’ internationalisation.

scholarly journals Integrative Analysis of lncRNAs, miRNAs, and mRNA-Associated ceRNA Network in an Atopic Dermatitis Recurrence Model

2018 ◽  
Vol 19 (10) ◽  
pp. 3263 ◽  
Author(s):  
Xiaoyu Wang ◽  
Kaifan Bao ◽  
Peng Wu ◽  
Xi Yu ◽  
Can Wang ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Messenger Rna ◽  
Integrative Analysis ◽  
Ample Evidence ◽  
Cerna Network ◽  
Non Coding Rna ◽  
Recurrence Model ◽  
Non Coding Rnas ◽  
Remission Phase ◽  
Long Non Coding Rna

Atopic dermatitis (AD) is a prevalent inflammatory skin disease characterized by its chronic nature and relapse. Ample evidence suggests that non-coding RNAs play a major role in AD pathogenesis. However, the mechanism remains unknown, particularly in AD recurrence. Dynamic morphological and cytokine changes were measured throughout the whole course of an FITC-induced AD recurrence murine model. Microarray assay and integrative analysis were performed to comprehensively explore long non-coding RNA (lncRNA), messenger RNA (mRNA), and microRNA (miRNA) networks. Our results showed that an AD recurrence model was established. Overall, 5766 lncRNAs, 4025 mRNAs, and 202 miRNAs changed after elicitation, whereas, 419 lncRNAs, 349 mRNAs, and more notably, only 23 miRNAs, were dysregulated in the remission phase. Gene ontology (GO) and KEGG pathway enrichment analyses were used to investigate the potential functions of the dysregulated genes. The altered regulation of seven miRNAs and seven lncRNAs were validated in different stages of the model. The competing endogenous RNA (ceRNA) network inferred that lncRNA humanlincRNA0490+ could compete for miR-155-5p binding, through which it might affect Pkiα expression. Altogether, our findings have provided a novel perspective on the potential roles of non-coding RNAs in AD, and suggest that specific non-coding RNAs could be new therapeutic targets against AD recurrence.

Black carp STING functions importantly in innate immune defense against RNA virus

2017 ◽  
Vol 70 ◽  
pp. 13-24 ◽  
Author(s):  
Liang Lu ◽  
Xu Wang ◽  
Sizhong Wu ◽  
Xuejiao Song ◽  
Ziqi Zou ◽  
...  
Keyword(s):  
Rna Virus ◽  
Immune Defense ◽  
Innate Immune ◽  
Black Carp ◽  
Innate Immune Defense

scholarly journals Quinolizidine-Based Variations and Antifungal Activity of Eight Lupinus Species Grown under Greenhouse Conditions

Molecules ◽  
2022 ◽  
Vol 27 (1) ◽  
pp. 305
Author(s):  
Willy Cely-Veloza ◽  
Diego Quiroga ◽  
Ericsson Coy-Barrera
Keyword(s):  
Antifungal Activity ◽  
Biological Activities ◽  
Structural Diversity ◽  
Economic Losses ◽  
Quinolizidine Alkaloids ◽  
Mycelium Growth ◽  
Reference Information ◽  
Naturally Occurring ◽  
The Family ◽  
External Standard

Fusarium oxysporum is an aggressive phytopathogen that affects various plant species, resulting in extensive local and global economic losses. Therefore, the search for competent alternatives is a constant pursuit. Quinolizidine alkaloids (QA) are naturally occurring compounds with diverse biological activities. The structural diversity of quinolizidines is mainly contributed by species of the family Fabaceae, particularly the genus Lupinus. This quinolizidine-based chemo diversity can be explored to find antifungals and even mixtures to address concomitant effects on F. oxysporum. Thus, the antifungal activity of quinolizidine-rich extracts (QREs) from the leaves of eight greenhouse-propagated Lupinus species was evaluated to outline promising QA mixtures against F. oxysporum. Thirteen main compounds were identified and quantified using an external standard. Quantitative analysis revealed different contents per quinolizidine depending on the Lupinus plant, ranging from 0.003 to 32.8 mg/g fresh leaves. Bioautography showed that all extracts were active at the maximum concentration (5 µg/µL). They also exhibited >50% mycelium growth inhibition. All QREs were fungistatic except for the fungicidal QRE of L. polyphyllus Lindl. Angustifoline, matrine, 13α-hydroxylupanine, and 17-oxolupanine were ranked to act jointly against the phytopathogen. Our findings constitute reference information to better understand the antifungal activity of naturally afforded QA mixtures from these globally important plants.

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