Non-coding RNAs in Necrotizing Enterocolitis- a New Frontier?

2021 ◽  
Vol 17 ◽  
Author(s):  
Jayasree Nair ◽  
Akhil Maheshwari
Keyword(s):  
Necrotizing Enterocolitis ◽  
Intestinal Inflammation ◽  
Protein A ◽  
Extensive Literature ◽  
Cellular Processes ◽  
Health And Disease ◽  
Bowel Disorders ◽  
Inflammatory Bowel ◽  
Non Coding Rnas ◽  
The Impact

: With the recognition that only 2% of the human genome encodes for a protein, a large part of the “non-coding” portion is now being evaluated for a regulatory role in cellular processes. These non-coding RNAs (ncRNAs) are subdivided based on the size of the nucleotide transcript into microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), but most of our attention has been focused on the role of microRNAs (miRNAs) in human health and disease. Necrotizing enterocolitis (NEC), inflammatory bowel necrosis affecting preterm infants, has a multifactorial, unclear etiopathogenesis, and we have no specific biomarkers for diagnosis or the impact of directed therapies. The information on ncRNAs in NEC, in general, and particularly in NEC, is limited. Increasing information from other inflammatory bowel disorders suggests that these transcripts may play an important role in intestinal inflammation. Here, we review ncRNAs for definitions, classifications, and possible roles in prematurity and NEC using some preliminary information from our studies and from an extensive literature search in multiple databases including PubMed, EMBASE, and Science Direct. miRNAs will be described in another manuscript in this series, hence in this manuscript we mainly focus on lncRNAs.

Enteric Nervous System in Neonatal Necrotizing Enterocolitis

2021 ◽  
Vol 17 ◽  
Author(s):  
Pavithra Chandramowlishwaran ◽  
Shreya Raja ◽  
Akhil Maheshwari ◽  
Shanthi Srinivasan
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
Necrotizing Enterocolitis ◽  
Literature Search ◽  
Extensive Literature ◽  
Research Findings ◽  
Bowel Disorders ◽  
Inflammatory Bowel ◽  
Extensive Literature Search ◽  
Neonatal Necrotizing Enterocolitis

Background: The pathophysiology of necrotizing enterocolitis (NEC) is not clear, but increasing information suggests that the risk and severity of NEC may be influenced by abnormalities in the enteric nervous system (ENS). Objective: The purpose of this review was to scope and examine the research related to ENS-associated abnormalities that have either been identified in NEC or have been noted in other inflammatory bowel disorders (IBDs) with histopathological abnormalities similar to NEC. The aim was to summarize the research findings, identify research gaps in existing literature, and disseminate them to key knowledge end-users to collaborate and address the same in future studies. Methods: Articles that met the objectives of the study were identified through an extensive literature search in the databases PubMed, EMBASE, and Scopus. Results : The sources identified through the literature search revealed that: (1) ENS may be involved in NEC development and post-NEC complications, (2) NEC development is associated with changes in the ENS, and (3) NEC-associated changes could be modulated by the ENS. Conclusions: The findings from this review identify the enteric nervous as a target in the development and progression of NEC. Thus, factors that can protect the ENS can potentially prevent, and treat NEC and post-NEC complications. This review serves to summarize the existing literature and highlights a need for further research on the involvement of ENS in NEC.

scholarly journals Unraveling the Role of ACE2, the Binding Receptor for SARS-CoV-2, in Inflammatory Bowel Disease

2020 ◽  
Vol 26 (12) ◽  
pp. 1787-1795 ◽  
Author(s):  
Mariana Ferreira-Duarte ◽  
Maria Manuela Estevinho ◽  
Margarida Duarte-Araújo ◽  
Fernando Magro ◽  
Manuela Morato
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Current Knowledge ◽  
Renin Angiotensin System ◽  
Biologic Drugs ◽  
Multifunctional Protein ◽  
Expression Activity ◽  
Inflammatory Bowel ◽  
The Impact

Abstract Angiotensin-converting enzyme 2 (ACE2) has been highlighted for its role as a receptor for SARS-CoV-2, responsible for the current COVID-19 pandemic. This review summarizes current knowledge about ACE2 as a multifunctional protein, focusing on its relevance in inflammatory bowel disease (IBD). As an enzyme, ACE2 may be protective in IBD because it favors the counter-regulatory arm of the renin-angiotensin system or deleterious because it metabolizes other anti-inflammatory/repairing elements. Meanwhile, as a receptor for SARS-CoV-2, the impact of ACE2 expression/activity on infection is still under debate because no direct evidence has been reported and, again, both protective and deleterious pathways are possible. Research has shown that ACE2 regulates the expression of the neutral amino acid transporter B0AT1, controlling tryptophan-associated intestinal inflammation and nutritional status. Finally, intact membrane-bound or shed soluble ACE2 can also trigger integrin signaling, modulating the response to anti-integrin biologic drugs used to treat IBD (such as vedolizumab) and fibrosis, a long-term complication of IBD. As such, future studies on ACE2 expression/activity in IBD can improve monitoring of the disease and explore an alternative pharmacological target.

scholarly journals The Impact of miRNAs in Health and Disease of Retinal Pigment Epithelium

2021 ◽  
Vol 8 ◽  
Author(s):  
Daniela Intartaglia ◽  
Giuliana Giamundo ◽  
Ivan Conte
Keyword(s):  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Fine Tuning ◽  
Molecular Networks ◽  
Therapeutic Approaches ◽  
Pathological Conditions ◽  
Health And Disease ◽  
Non Coding Rnas ◽  
The Impact

MicroRNAs (miRNAs), a class of non-coding RNAs, are essential key players in the control of biological processes in both physiological and pathological conditions. miRNAs play important roles in fine tuning the expression of many genes, which often have roles in common molecular networks. miRNA dysregulation thus renders cells vulnerable to aberrant fluctuations in genes, resulting in degenerative diseases. The retinal pigment epithelium (RPE) is a monolayer of polarized pigmented epithelial cells that resides between the light-sensitive photoreceptors (PR) and the choriocapillaris. The demanding physiological functions of RPE cells require precise gene regulation for the maintenance of retinal homeostasis under stress conditions and the preservation of vision. Thus far, our understanding of how miRNAs function in the homeostasis and maintenance of the RPE has been poorly addressed, and advancing our knowledge is central to harnessing their potential as therapeutic agents to counteract visual impairment. This review focuses on the emerging roles of miRNAs in the function and health of the RPE and on the future exploration of miRNA-based therapeutic approaches to counteract blinding diseases.

scholarly journals Going Beyond Bacteria: Uncovering the Role of Archaeome and Mycobiome in Inflammatory Bowel Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Yashar Houshyar ◽  
Luca Massimino ◽  
Luigi Antonio Lamparelli ◽  
Silvio Danese ◽  
Federica Ungaro
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
The Body ◽  
Inflammatory Conditions ◽  
Relapsing Remitting ◽  
Health And Disease ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

Inflammatory Bowel Disease (IBD) is a multifaceted class of relapsing-remitting chronic inflammatory conditions where microbiota dysbiosis plays a key role during its onset and progression. The human microbiota is a rich community of bacteria, viruses, fungi, protists, and archaea, and is an integral part of the body influencing its overall homeostasis. Emerging evidence highlights dysbiosis of the archaeome and mycobiome to influence the overall intestinal microbiota composition in health and disease, including IBD, although they remain some of the least understood components of the gut microbiota. Nonetheless, their ability to directly impact the other commensals, or the host, reasonably makes them important contributors to either the maintenance of the mucosal tissue physiology or to chronic intestinal inflammation development. Therefore, the full understanding of the archaeome and mycobiome dysbiosis during IBD pathogenesis may pave the way to the discovery of novel mechanisms, finally providing innovative therapeutic targets that can soon implement the currently available treatments for IBD patients.

scholarly journals Intestinal Inflammation and the Gut Microflora

1999 ◽  
Vol 13 (6) ◽  
pp. 509-516 ◽  
Author(s):  
Derek M McKay
Keyword(s):  
Scientific Literature ◽  
Intestinal Inflammation ◽  
Enteric Bacteria ◽  
Model Systems ◽  
Laboratory Model ◽  
Functional Bowel Disorders ◽  
Gut Inflammation ◽  
Clinical Investigations ◽  
Bowel Disorders ◽  
Inflammatory Bowel

The idea that the enteric microflora play a role in the pathogenesis or pathophysiology of inflammatory bowel disease (IBD) is not new. Indeed, identification of an infective cause for chronic IBD, and particularly for Crohn’s disease, has been the focus of extensive research efforts. During the 1990s, there has been a noticeable re-emergence of interest in the link between bacteria and functional bowel disorders, and the value of antibiotic therapy to treat gut inflammatory disorders. A variety of experimental evidence from both laboratory model systems and clinical investigations is reviewed with respect to a pivotal role for enteric bacteria in gut inflammation. The voluminous scientific literature on this subject precludes any comprehensive synopsis of the area; instead, pertinent studies are cited to illustrate the ability of bacteria and their products to evoke or exacerbate gut inflammation.

scholarly journals Muscling in on mitochondrial sexual dimorphism; role of mitochondrial dimorphism in skeletal muscle health and disease

2017 ◽  
Vol 131 (15) ◽  
pp. 1919-1922 ◽  
Author(s):  
Gareth A. Nye ◽  
Giorgos K. Sakellariou ◽  
Hans Degens ◽  
Adam P. Lightfoot
Keyword(s):  
Skeletal Muscle ◽  
Sexual Dimorphism ◽  
Mitochondrial Function ◽  
Recent Article ◽  
Cellular Processes ◽  
Wide Range ◽  
Health And Disease ◽  
Muscle Health ◽  
The Impact

Mitochondria are no longer solely regarded as the cellular powerhouse; instead, they are now implicated in mediating a wide-range of cellular processes, in the context of health and disease. A recent article in Clinical Science, Ventura-Clapier et al. highlights the role of sexual dimorphism in mitochondrial function in health and disease. However, we feel the authors have overlooked arguably one of the most mitochondria-rich organs in skeletal muscle. Many studies have demonstrated that mitochondria have a central role in mediating the pathogenesis of myopathologies. However, the impact of sexual dimorphism in this context is less clear, with several studies reporting conflicting observations. For instance in ageing studies, a rodent model reported female muscles have higher antioxidant capacity compared with males; in contrast, human studies demonstrate no sex difference in mitochondrial bioenergetics and oxidative damage. These divergent observations highlight the importance of considering models and methods used to examine mitochondrial function, when interpreting these data. The use of either isolated or intact mitochondrial preparations in many studies appears likely to be a source of discord, when comparing many studies. Overall, it is now clear that more research is needed to determine if sexual dimorphism is a contributing factor in the development of myopathologies.

scholarly journals IL-23–responsive innate lymphoid cells are increased in inflammatory bowel disease

2011 ◽  
Vol 208 (6) ◽  
pp. 1127-1133 ◽  
Author(s):  
Alessandra Geremia ◽  
Carolina V. Arancibia-Cárcamo ◽  
Myles P.P. Fleming ◽  
Nigel Rust ◽  
Baljit Singh ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Inflammation ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Human Intestine ◽  
Health And Disease ◽  
Inflammatory Bowel ◽  
Selective Increase

Results of experimental and genetic studies have highlighted the role of the IL-23/IL-17 axis in the pathogenesis of inflammatory bowel disease (IBD). IL-23–driven inflammation has been primarily linked to Th17 cells; however, we have recently identified a novel population of innate lymphoid cells (ILCs) in mice that produces IL-17, IL-22, and IFN-γ in response to IL-23 and mediates innate colitis. The relevance of ILC populations in human health and disease is currently poorly understood. In this study, we have analyzed the role of IL-23–responsive ILCs in the human intestine in control and IBD patients. Our results show increased expression of the Th17-associated cytokine genes IL17A and IL17F among intestinal CD3− cells in IBD. IL17A and IL17F expression is restricted to CD56− ILCs, whereas IL-23 induces IL22 and IL26 in the CD56+ ILC compartment. Furthermore, we observed a significant and selective increase in CD127+CD56− ILCs in the inflamed intestine in Crohn’s disease (CD) patients but not in ulcerative colitis patients. These results indicate that IL-23–responsive ILCs are present in the human intestine and that intestinal inflammation in CD is associated with the selective accumulation of a phenotypically distinct ILC population characterized by inflammatory cytokine expression. ILCs may contribute to intestinal inflammation through cytokine production, lymphocyte recruitment, and organization of the inflammatory tissue and may represent a novel tissue-specific target for subtypes of IBD.

scholarly journals H89 Treatment Reduces Intestinal Inflammation and Candida albicans Overgrowth in Mice

2020 ◽  
Vol 8 (12) ◽  
pp. 2039
Author(s):  
Corentin Dumortier ◽  
Rogatien Charlet ◽  
Ali Bettaieb ◽  
Samir Jawhara
Keyword(s):  
Candida Albicans ◽  
Gut Microbiota ◽  
Intestinal Inflammation ◽  
Innate Immune ◽  
Intestinal Epithelial ◽  
Opportunistic Pathogens ◽  
Inflammatory Bowel ◽  
The Impact ◽  
Migration Of Macrophages ◽  
Pro Inflammatory Cytokines

Deregulation of the dynamic crosstalk between the gut microbiota, intestinal epithelial cells, and immune cells is critically involved in the development of inflammatory bowel disease and the overgrowth of opportunistic pathogens, including the human opportunistic fungus Candida albicans. In the present study, we assessed the effect of N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H89), a protein kinase A inhibitor, on the migration of macrophages to C. albicans through dextran sulphate sodium (DSS)-challenged Caco-2 cells. We also investigated the impact of H89 on intestinal inflammation and C. albicans clearance from the gut, and determined the diversity of the gut microbiota in a murine model of DSS-induced colitis. H89 reduced the migration of macrophages to C. albicans through DSS-challenged Caco-2 cells. In addition, H89 decreased C. albicans viability and diminished the expression of pro-inflammatory cytokines and innate immune receptors in macrophages and colonic epithelial Caco-2 cells. In mice with DSS-induced colitis, H89 attenuated the clinical and histological scores of inflammation and promoted the elimination of C. albicans from the gut. H89 administration to mice decreased the overgrowth of Escherichia coli and Enterococcus faecalis populations while Lactobacillus johnsonii populations increased significantly. Overall, H89 reduced intestinal inflammation and promoted the elimination of C. albicans from the gut.

scholarly journals The Impact of Farnesoid X Receptor Activation on Intestinal Permeability in Inflammatory Bowel Disease

2012 ◽  
Vol 26 (9) ◽  
pp. 631-637 ◽  
Author(s):  
Maja Stojancevic ◽  
Karmen Stankov ◽  
Momir Mikov
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Intestinal Tract ◽  
Intestinal Inflammation ◽  
Strong Support ◽  
Receptor Activation ◽  
Farnesoid X Receptor ◽  
Necrosis Factor Alpha ◽  
Inflammatory Bowel ◽  
The Impact

The most important function of the intestinal mucosa is to form a barrier that separates luminal contents from the intestine. Defects in the intestinal epithelial barrier have been observed in several intestinal disorders such as inflammatory bowel disease (IBD). Recent studies have identified a number of factors that contribute to development of IBD including environmental triggers, genetic factors, immunoregulatory defects and microbial exposure. The current review focuses on the influence of the farnesoid X receptor (FXR) on the inhibition of intestinal inflammation in patients with IBD. The development and investigation of FXR agonists provide strong support for the regulatory role of FXR in mucosal innate immunity. Activation of FXR in the intestinal tract decreases the production of proinflammatory cytokines such as interleukin (IL) 1-beta, IL-2, IL-6, tumour necrosis factor-alpha and interferon-gamma, thus contributing to a reduction in inflammation and epithelial permeability. In addition, intestinal FXR activation induces the transcription of multiple genes involved in enteroprotection and the prevention of bacterial translocation in the intestinal tract. These data suggest that FXR agonists are potential candidates for exploration as a novel therapeutic strategy for IBD in humans.

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