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Increased Expression of microRNA-141-3p Improves Necrotizing Enterocolitis of Neonates Through Targeting MNX1.

ABSTRACT: Objective: MicroRNA-141-3p (miR-141-3p) has been investigated in various kinds of cancers. This research delves into the functions and regulatory mechanisms of miR-141-3p in necrotizing enterocolitis (NEC) of neonates. Methods: NEC tissues were obtained from neonatal mice, and subsequently, expression of miR-141-3p and motor neuron and pancreas homeobox 1 (MNX1) was assayed via RT-qPCR. Moreover, the intestinal histopathological changes and histiocytic apoptosis were observed via hematoxylin and eosin (H&E) and TUNEL staining. The correlative inflammatory factors and oxidative stress markers were evaluated to uncover the influence of miR-141-3p in NEC tissue damage. Further, the relation between MNX1 and miR-141-3p was predicated, and the functions of MNX1 in inflammatory response and cell growth of IEC-6 cells were investigated. Results: Downregulated miR-141-3p and upregulated MNX1 were discovered in NEC tissues. Moreover, miR-141-3p clearly alleviated inflammation response and oxidative stress damage in NEC, which was achieved through regulating inflammatory cytokines (IL-1?, IL-6, and TNF-?) and oxidative stress markers (MPO, MDA, and SOD) expression. MNX1 was forecasted as a target gene of miR-141-3p; meanwhile, MNX1 overexpression overturned the influence of miR-141-3p in the inflammatory response and cell growth process of IEC-6 cells. Conclusion: These explorations reveal that increased expression of miR-141-3p could improve the damage to intestinal tissues in NEC through targeting MNX1. The research might exhibit a neoteric therapeutic strategy for NEC.

SUBMITTER: Chen H

PROVIDER: S-EPMC7399201 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Increased Expression of microRNA-141-3p Improves Necrotizing Enterocolitis of Neonates Through Targeting MNX1.

Chen Hui H Zeng Lichun L Zheng Wei W Li Xiaoli X Lin Baixing B

Frontiers in pediatrics 20200728

<b>Objective:</b> MicroRNA-141-3p (miR-141-3p) has been investigated in various kinds of cancers. This research delves into the functions and regulatory mechanisms of miR-141-3p in necrotizing enterocolitis (NEC) of neonates. <b>Methods:</b> NEC tissues were obtained from neonatal mice, and subsequently, expression of miR-141-3p and motor neuron and pancreas homeobox 1 (MNX1) was assayed via RT-qPCR. Moreover, the intestinal histopathological changes and histiocytic apoptosis were observed via h ...[more]

PMID: 32850524

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Project description:ObjectiveNecrotizing enterocolitis (NEC) is an inflammatory disease of the gastrointestinal tract characterized by ischemic necrosis of the intestinal mucosa, mostly affecting premature neonates. Management of NEC includes medical care and surgical approaches, with supportive care and empirical antibiotic therapy recommended to avoid any disease progression. However, there is still no clear evidence-based consensus on empiric antibiotic strategies or surgical timing. This study was aimed to review the available evidence on the effectiveness and safety of different antibiotic regimens for NEC.Study designMEDLINE, EMBASE, Cochrane CENTRAL, and CINAHL databases were systematically searched through May 31, 2020. Randomized controlled trials (RCTs) and nonrandomized interventions reporting data on predefined outcomes related to NEC treatments were included. Clinical trials were assessed using the criteria and standard methods of the Cochrane risk of bias tool for randomized trials, while the risk of bias in nonrandomized studies of interventions was evaluated using the ROBINS-I tool. The certainty in evidence of each outcome's effects was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach.ResultsFive studies were included in this review, two RCTs and three observational studies, for a total amount of 3,161 patients. One RCT compared the outcomes of parenteral (ampicillin plus gentamicin) and oral (gentamicin) treatment with parenteral only. Three studies (one RCT and two observational) evaluated adding anaerobic coverage to different parenteral regimens. The last observational study compared two different parenteral antibiotic combinations (ampicillin and gentamicin vs. cefotaxime and vancomycin).ConclusionNo antimicrobial regimen has been shown to be superior to ampicillin and gentamicin in decreasing mortality and preventing clinical deterioration in NEC. The use of additional antibiotics providing anaerobic coverage, typically metronidazole, or use of other broad-spectrum regimens as first-line empiric therapy is not supported by the very limited current evidence. Well-conducted, appropriately sized comparative trials are needed to make evidence-based recommendations.Key points· Ampicillin and gentamicin are effective in decreasing mortality and preventing clinical deterioration in NEC.. · Metronidazole could be added in patients with surgical NEC.. · No study with high-quality evidence was found..

Project description:BackgroundNecrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in newborn neonates. Bacteria are believed to be important in the pathogenesis of NEC but bacterial characterization has only been done on human faecal samples and experimental animal studies. The aim of this study was to investigate the microbial composition and the relative number of bacteria in inflamed intestinal tissue surgically removed from neonates diagnosed with NEC (n=24). The bacterial populations in the specimens were characterized by laser capture microdissection and subsequent sequencing combined with fluorescent in situ hybridization (FISH), using bacterial rRNA-targeting oligonucleotide probes.ResultsBacteria were detected in 22 of the 24 specimens, 71% had moderate to high densities of bacteria. The phyla detected by 16S rRNA gene sequencing were: Proteobacteria (49.0%), Firmicutes (30.4%), Actinobacteria (17.1%) and Bacteroidetes (3.6%). A major detected class of the phylum Proteobacteria belonged to δ-proteobacteria. Surprisingly, Clostridium species were only detected in 4 of the specimens by FISH, but two of these specimens exhibited histological pneumatosis intestinalis and both specimens had a moderate to a high density of C. butyricum and C. parputrificum detected by using species specific FISH probes. A 16S rRNA gene sequence tag similar to Ralstonia species was detected in most of the neonatal tissues and members of this genus have been reported to be opportunistic pathogens but their role in NEC has still to be clarified.ConclusionIn this study, in situ identification and community analysis of bacteria found in tissue specimens from neonates with NEC, were analysed for the first time. Although a large variability of bacteria was found in most of the analyzed specimens, no single or combination of known potential pathogenic bacteria species was dominating the samples suggestive NEC as non-infectious syndrome. However there was a significant correlation between the presence of C. butyricum & C. parputrificum and histological pneumatosis intestinalis. Finally this study emphasizes the possibility to examine the microbial composition directly on excised human tissues to avoid biases from faecal samples or culturing.

Dataset Information

Increased Expression of microRNA-141-3p Improves Necrotizing Enterocolitis of Neonates Through Targeting MNX1.

Publications

Increased Expression of microRNA-141-3p Improves Necrotizing Enterocolitis of Neonates Through Targeting MNX1.

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