Altered Expression of microRNAs in Serum Extracellular Vesicles in Rats with Severe Burns during Shock Stage

2020 ◽  
Vol 20 ◽  
Author(s):  
Mengru Dong ◽  
Yanbin Gao ◽  
Minxiong Li ◽  
Lei Yang

Background: The shock stage of severe burns is a critical determinant of prognosis and the induction of systemic inflammatory response syndrome and multiple organ failure. Extracellular vesicles (EVs) containing abundant miRNAs are known to participate in various biological processes. Due to lack of researches in alternations of miRNAs in severe burns, our study analyzed the miRNA profiles of EVs in severe burns during shock stage. Methods: EVs were extracted from serum of rats with severe burns (30% of total body surface area, III°), and the expression of miRNAs in serum EVs was determined by next generation sequencing. Functional analysis of target genes of miRNAs that were significantly differentially expressed (DE) was performed using GO Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Results: Thirty-four DE miRNAs were identified at the early stage of severe burn shock and 63 at the late stage of severe burn shock. In addition, miRNA-339-5p, miRNA-1, miRNA-382-5p, miRNA134-5p, miRNA-133a-5p, and miRNA-365a5p were DE throughout the entire shock stage, based on P < 0.01 and |log2 (foldchange)| ≥ 1 criteria. GO and KEGG analysis revealed that the target genes of DE miRNAs mainly enriched metabolic process, immune system processes, and signal pathways. Conclusion: To our best knowledge, this is the first study demonstrating the miRNA expression profiles of EVs isolated from serum with severe burns during shock stage. There are significant differences in downregulation and upregulation. Thus, miRNAs have potential for novel biomarkers for the complication of severe burns.

2019 ◽  
Vol 121 (09) ◽  
pp. 974-981 ◽  
Author(s):  
Fengmei Guo ◽  
Hua Zhou ◽  
Jian Wu ◽  
Yingzi Huang ◽  
Guozhong Lv ◽  
...  

AbstractNutrition therapy is considered an important treatment of burn patients. The aim of the study was to delineate the nutritional support in severe burn patients and to investigate association between nutritional practice and clinical outcomes. Severe burn patients were enrolled (n 100). In 90 % of the cases, the burn injury covered above 70 % of the total body surface area. Mean interval from injury to nutrition start was 2·4 (sd 1·1) d. Sixty-seven patients were initiated with enteral nutrition (EN) with a median time of 1 d from injury to first feed. Twenty-two patients began with parenteral nutrition (PN). During the study, thirty-two patients developed EN intolerance. Patients received an average of about 70 % of prescribed energy and protein. Patients with EN providing &lt;30 % energy had significantly higher 28- d and in-hospital mortality than patients with EN providing more than 30 % of energy. Mortality at 28 d was 11 % and in-hospital mortality was 45 %. Multiple regression analysis demonstrated that EN providing &lt;30 % energy and septic shock were independent risk factors for 28- d prognosis. EN could be initiated early in severe burn patients. Majority patients needed PN supplementation for energy requirement and EN feeding intolerance. Post-pyloric feeding is more efficient than gastric feeding in EN tolerance and energy supplement. It is difficult for severe burn patients to obtain enough feeding, especially in the early stage of the disease. More than 2 weeks of underfeeding is harmful to recovery.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1488-1488
Author(s):  
Xiaomei Chen ◽  
Wei Xiong ◽  
Xiangjun Chen ◽  
Cong Lu ◽  
Fang Liu ◽  
...  

Abstract Abstract 1488 Microvesicles (MVs) released by leukemia cells constitute an important part of the leukemia microenvironment. As a cell-to-cell communication tool, MVs transfer microRNA(miRNA) between cells. MVs miRNAs may be valuable not only as a diagnostic tool but may also provide an insight in the role of miRNAs playing in the underlying of pathophysiologic processes of various leukemia. It is worth evaluating whether MVs possess some unique miRNA content depending on their corresponding leukemia origin that could be applicable in diagnosis. Hence, we determined the miRNA expression profiles of ALL-derived MVs using Agilent miRNA microarray analysis. The five miRNAs obtained by microarray profiling were validated using real-time PCR. The putative target genes were predicted by bioformation software. Here, we provided MVs miRNA patterns derived from the healthy controls, B-ALL cell line Nalm 6 cells and T-ALL cell line Jurkat cells. We identified 182 dysregulated miRNAs in MVs derived from Nalm 6 cells as compared with MVs from normal controls (P<0.05); both up regulated(123/182) and down regulated(59/182) expressions were observed. Likewise 166 miRNAs were significantly differentially expressed in MVs derived from Jurkat cells versus MVs from normal peripheral blood (P<0.05), 114 miRNAs of which (114/166) were up expression and 52 miRNAs (52/166) were down expression. We also fould that 44 miRNAs were only detected in B-ALL-derived MVs. MiR-1290, miR-1246, miR-1268, miR-1226, and miR-424 were top 5 expressed in Nalm 6 derived MVs, suggesting that those miRNAs may play an important role in B-ALL. We observed that 16 miRNAs detected only in T cell derived MVs. MiR-96 is up regulated in MVs from T-ALL cells but not expressed in B-ALL. Specific and functional target sites for miR-96, exist in the 3'-UTR of the miRNA that encodes the putative tumor suppressor transcription factor FOXO1. The expression signatures of miR-96 could discriminate B-ALL from T-ALL. In contrast, the MVs from B-ALL cell line, shared 100 miRNAs with MVs from T-ALL cell line, suggestting that those miRNAs play roles in both B-and T-ALL. Of 100 miRNAs, 99 miRNAs were high expression, indicating that miRNAs were active in ALL. This obsearvation suggusted that miRNA differential expression in MVs were partially significantly related to subtypes of acute lymphoblastic leukemia. Intriguing is that miR1290 is top higher expression both in MVs derived from Nalm6 cells and from Jurkat cells; miR-1290 is 475-fold higher expressed in Nalm 6 derived MVs versus MVs from normal cells, whereas this miRNA is 245-fold higher expressed in Jurkat cells. Five of these miRNAs were selected to be further assayed and validated by PCR. The qRT-PCR results correlated well with the microarray data. In addition, we found seven miRNAs(miR-148b, miR-484, miR-let-7f, let-7a, miR-223, miR16 and miR-27b) were located near the 11q23 chromosomal region. With bioinformatic tools (TargetScan), we predicted potential target genes for those miRNAs that exhibited altered expression in MVs from B-ALL and T-ALL. The p85 subunit of phosphatidylinositol 3-kinase (PI3-K) was found to be a potential target of miR-320. Of particular interest, we found that protein tyrosine phosphatase-like member b (PTPLB) may be a potential target of miR-1290. The 474-fold increase in miR-1290 in MVs from Nalm 6 cells, indicating that miR-1290 may participate in the modulation of leukemia by targeting PTPLB, a specific, negative regulator of p210 bcr-abl signal. In conclusion, we identified miRNAs and found that miRNA expression profiles were ALL subtype-specific. Altered miRNA expression levels may lead to an inappropriate expression of target oncoproteins or target tumor suppressors, thereby facilitating the development of leukemia. These findings expanded the potential diagnostic markers of leukemia and provided useful information to ALL pathogenesis. Disclosures: No relevant conflicts of interest to declare.


2020 ◽  
Author(s):  
Xige He ◽  
Rihan Wu ◽  
Yueying Yun ◽  
Xia Qin ◽  
Lu Chen ◽  
...  

Abstract Background: Sunite sheep are a fat-tailed sheep species with a low percentage of intramuscular fat and good quality lean meat, and their tail fat can be used as a source of dietary fat by humans. To understand the potential regulatory mechanism of different growth stages of tail fat in Sunite sheep, we performed high-throughput RNA sequencing to characterize the long noncoding RNA (lncRNA) and messenger RNA (mRNA) expression profiles of the sheep tail fat at the age of 6 months, 18 months, and 30 months.Results: A total of 223 differentially expressed genes (DEGs) and 148 differentially expressed lncRNAs were found in the tail fat of 6-, 18-, and 30-month-old sheep (false discovery rate < 0.05, |Fold Change| ≥ 2). Based on the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, we found that fat-related DEGs were mainly expressed at 6 months of age, and gradually decreased at 18 and 30 months of age. The target gene prediction analysis shows that most of the lncRNAs target more than 20 mRNAs as their trans-regulators (53 mRNAs at most). Further, we obtained several fat-related differentially-expressed target genes; these target genes interact with different differentially expressed lncRNAs at various ages and play an important role in the development of tail fat. Based on the DEGs and differentially expressed lncRNAs, we established three co-expression networks for each comparison group. Conclusions: Finally, we conclude that the development of the sheep tail fat is more active during the early stage of growth and gradually decreases with the increase in age. The mutual regulation of lncRNAs and mRNAs may play a key role in this complex biological process, and our findings will provide some basic theoretical data for future studies on tail fat development of fat-tailed sheep.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kevin DeSpain ◽  
Charles R. Rosenfeld ◽  
Ryan Huebinger ◽  
Xiaofu Wang ◽  
Jayson W. Jay ◽  
...  

AbstractSevere burns result in cardiovascular dysfunction, but responses in the peripheral vasculature are unclear. We hypothesize that severe burns disturb arterial contractility through acute changes in adrenergic and cholinergic receptor function. To address this, we investigated the changes in carotid artery contractility and relaxation following a severe burn. Thirty-four adult Sprague–Dawley male rats received a 40% total body surface area (TBSA) scald burn and fluid resuscitation using the Parkland formula. Control animals received sham burn procedure. Animals were serially euthanized between 6 h and 14 days after burn and endothelium-intact common carotid arteries were used for ex vivo force/relaxation measurements. At 6 h after burn, carotid arteries from burned animals demonstrated a > 50% decrease in cumulative dose-responses to norepinephrine (p < 0.05) and to 10−7 M angiotensin II (p < 0.05). Notably, pre-constricted carotid arteries also demonstrated reduced relaxation responses to acetylcholine (p < 0.05) 6 h after burn, but not to sodium nitroprusside. Histologic examination of cross-sectional planes revealed significant increases in carotid artery wall thickness in burned rats at 6 h versus 3 days, with increased collagen expression in tunica media at 3 days (p < 0.05). Carotid artery dysfunction occurs within 6 h after severe burn, demonstrating decreased sensitivity to adrenergic- and angiotensin II-induced vasoconstriction and acetylcholine-induced relaxation.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 64-64
Author(s):  
Joanne Margaret Ramsey ◽  
Glenda Joanne Dickson ◽  
Janetta Jacoba Bijl ◽  
Ken I. Mills ◽  
Terence R.J. Lappin ◽  
...  

Abstract Abstract 64 Altered expression of the HOX-MEIS axis is associated with leukemia, particularly AML, where it plays a role in increased proliferation and impaired differentiation. Particular focus has been placed on the role of HOX-MEIS in leukemia with MLL gene rearrangements and MLL-fusion induced models that represent this poor prognostic subgroup. However more recently, we and others have identified altered expression of HOX-MEIS in AML with normal karyotype (AML-NK) that accounts for the vast majority of patients with this disease. The prognostic outcome of this large subgroup of patients is varied and may depend on other molecular aberrations such as NPM-1 mutation, FLT3-ITD or CEBPB status. A murine model of leukemia using co-overexpression of HOXA9-MEIS1 was developed to investigate their role in an AML-NK setting. Expression levels of the collaborating oncogenes was limited by combination of a bicistronic ires targeting vector, low titre retroviral infection and limiting dilution assay (LDA). HOXA9 and MEIS1 expression was measured using quantitiative PCR (qPCR) and levels obtained in the mouse were similar to those observed for AML-NK patients. The resultant leukemia was transplantable leading to premature death in non-irradiated recipient mice within 30 days (104 cells transplanted). Observed pathology included circulating blasts in the periphery, splenomegaly, tissue infiltration of blast cells (kidney, lung, liver) and enlarged lymph nodes, indicative of leukemia. Blast cells were identified as Kit+, Gr-1+, Mac-1+, CD150lo consistent with a myeloid progenitor phenotype. To evaluate downstream events associated with the leukaemic phenotype TaqMan-based Low Density Arrays (TLDAs) and Open Arrays (Biotrove) were used to obtain gene and microRNA (mIR) expression profiles. The majority of genes assayed 699/821 were either not expressed or showed no appreciable change in expression (ΔΔCT < 2) between the leukaemic and normal bone marrow control samples. Of those genes that showed a measurable change in expression, 111/122 assessed in the pluripotent stem cell, transcription factor and immune arrays were downregulated in the HOXA9-MEIS1 induced leukemia samples compared to control mice (n=4 per group). Individual assays were designed for a subset of candidate genes and validated against the TLDA results. Several genes identified as consistently downregulated in the leukaemic cells, including Smad1 and E2f7, were associated with negative regulation of cell proliferation using DAVID Bioinformatics Resources 6.7. Consistent increased expression of HOXA9 and MEIS1 was confirmed by individual assays as was elevated Elf5, Cd34 and Cd28 levels. mIRs regulate the expression of protein-coding genes in part through cleavage of targeted transcripts by partial or complete base pairing. A growing number of mIRs are differentially regulated in normal and malignant hematopoiesis, where increased mIR levels are associated with downregulation of target gene subsets. mIR expression profiles were compared between leukemic and control mice to investigate their association with the global downregulation of gene expression observed in the leukaemic model. Approximately 16% (48/303) of the mIRs showed measurable changes in expression levels (ΔΔCT >2) between the two models, with >70% (34/48) demonstrating increased expression, up to 360-fold, in the leukemia samples. Candidate mIRs were further examined using the mirDB and/or miRecords target prediction databases. Several of the leukaemia-associated upreglated mIRs putatively target members of the validated subset of downregulated genes e.g. mIR-466c and mIR-181c are predicted to target Smad1 and E2F7 respectively. This study suggests that HOXA9-MEIS1 leukemogenesis occurs in part due to increased expression of a subset of mIRs that are predicted to target genes associated with inhibition of proliferation in an AML-NK model. Disclosures: No relevant conflicts of interest to declare.


2020 ◽  
Vol 21 (20) ◽  
pp. 7691
Author(s):  
Erik Kudela ◽  
Marek Samec ◽  
Lenka Koklesova ◽  
Alena Liskova ◽  
Peter Kubatka ◽  
...  

Breast cancer, which is the most common malignancy in women, does not form a uniform nosological unit but represents a group of malignant diseases with specific clinical, histopathological, and molecular characteristics. The increasing knowledge of the complex pathophysiological web of processes connected with breast cancercarcinogenesis allows the development of predictive and prognostic gene expressionand molecular classification systems with improved risk assessment, which could be used for individualized treatment. In our review article, we present the up-to-date knowledge about the role of miRNAs and their prognostic and predictive value in luminal A breast cancer. Indeed, an altered expression profile of miRNAs can distinguish not only between cancer and healthy samples, but they can classify specific molecular subtypes of breast cancer including HER2, Luminal A, Luminal B, and TNBC. Early identification and classification of breast cancer subtypes using miRNA expression profilescharacterize a promising approach in the field of personalized medicine. A detection of sensitive and specific biomarkers to distinguish between healthy and early breast cancer patients can be achieved by an evaluation of the different expression of several miRNAs. Consequently, miRNAs represent a potential as good diagnostic, prognostic, predictive, and therapeutic biomarkers for patients with luminal A in the early stage of BC.


Author(s):  
Noe E. Crespo ◽  
Alexandra Torres-Bracero ◽  
Jessicca Y. Renta ◽  
Robert J. Desnick ◽  
Carmen L. Cadilla

Background: Setleis syndrome (SS) is a focal facial dermal dysplasia presenting with bilateral temporal skin lesions, eyelash abnormalities and absent meibomian glands. SS is a rare autosomal recessive disorder caused by mutations in the TWIST2 gene, which codes for a transcription factor of the bHLH family known to be involved in skin and facial development. Methods: We obtained gene expression profiles by microarray analyses from control and SS patient primary skin fibroblast and lymphoblastoid cell lines. Results: Out of 983 differentially regulated genes in fibroblasts (fold change ≥ 2.0), 479 were down-regulated and 509 were up-regulated, while in lymphoblasts, 1248 genes were down-regulated and 73 up-regulated. RT-PCR reactions confirmed altered expression of selected genes. Conclusions: TWIST2 is described as a repressor, but expression profiling suggests an important role in gene activation as well, as evidenced by the number of genes that are down-regulated, with a much higher proportion of down-regulated genes found in lymphoblastoid cells from an SS patient. As expected, both types of cell types showed dysregulation of cytokine genes. These results identify potential TWIST2 target genes in two important cell types relevant to rare disorders caused by mutations in this bHLH gene.


Reproduction ◽  
2019 ◽  
Vol 157 (6) ◽  
pp. 525-534 ◽  
Author(s):  
Hang Qi ◽  
Guiling Liang ◽  
Jin Yu ◽  
Xiaofeng Wang ◽  
Yan Liang ◽  
...  

MicroRNA (miRNA) expression profiles in tubal endometriosis (EM) are still poorly understood. In this study, we analyzed the differential expression of miRNAs and the related gene networks and signaling pathways in tubal EM. Four tubal epithelium samples from tubal EM patients and five normal tubal epithelium samples from uterine leiomyoma patients were collected for miRNA microarray. Bioinformatics analyses, including Ingenuity Pathway Analysis (IPA), Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were performed. Quantitative real-time polymerase chain reaction (qRT-PCR) validation of five miRNAs was performed in six tubal epithelium samples from tubal EM and six from control. A total of 17 significantly differentially expressed miRNAs and 4343 potential miRNA-target genes involved in tubal EM were identified (fold change >1.5 and FDR-adjustedPvalue <0.05). IPA indicated connections between miRNAs, target genes and other gynecological diseases like endometrial carcinoma. GO and KEGG analysis revealed that most of the identified genes were involved in the mTOR signaling pathway, SNARE interactions in vesicular transport and endocytosis. We constructed an miRNA-gene-disease network using target gene prediction. Functional analysis showed that the mTOR pathway was connected closely to tubal EM. Our results demonstrate for the first time the differentially expressed miRNAs and the related signal pathways involved in the pathogenesis of tubal EM which contribute to elucidating the pathogenic mechanism of tubal EM-related infertility.


2020 ◽  
Vol 10 (10) ◽  
pp. 2316-2323
Author(s):  
Danqi Liu ◽  
Fang Lian ◽  
Shan Xiang ◽  
Ying Guo ◽  
Haicui Wu ◽  
...  

Objective: The objective of this study was to investigate the micro-RNA differences between women of advanced age with a diminished ovarian reserve (DOR) and young women with a normal ovarian reserve (NOR), and the causes leading to the decline of ovarian reserve function and oocyte function in women, which may be related to aging. Methods: The prospective cohort investigation method was used in this study. We used microRNA sequencing to detect the microRNA expression profiles for women of advanced age with DOR function and young women with NOR function. Then, the differentially expressed microRNAs were compared and the agerelated mechanism was predicted by the target genes. Results: The microRNA sequencing results revealed that 70 microRNA expressions were different, including 45 downregulated expressions and 25 upregulated expressions. Specifically, miR-221-3p, miR-146b-5p, miR-378a-3p, miR-143-5p, miR-222-5p, and miR-221-5p were significantly downregulated; miR-6881-3p, miR-4787-3p, miR-4745-5p, miR-6513-3p, and miR-3179 were upregulated. The primary pathways are PI3K-Akt, MAPK, Phospholipase D, and Chemokine. Conclusions: Differences were observed between the expression profiles of microRNAs in the granulosa cells of the ovaries of patients with DOR and NOR. These differences may be age-related.


2022 ◽  
Vol 13 ◽  
Author(s):  
Natalia Ogonowski ◽  
Stefanny Salcidua ◽  
Tomas Leon ◽  
Nayaret Chamorro-Veloso ◽  
Cristian Valls ◽  
...  

The rate of progression from Mild Cognitive Impairment (MCI) to Alzheimer's disease (AD) is estimated at &gt;10% per year, reaching up to 80–90% after 6 years. MCI is considered an indicator of early-stage AD. In this context, the diagnostic screening of MCI is crucial for detecting individuals at high risk of AD before they progress and manifest further severe symptoms. Typically, MCI has been determined using neuropsychological assessment tools such as the Montreal Cognitive Assessment (MoCA) or Mini-Mental Status Examination (MMSE). Unfortunately, other diagnostic methods are not available or are unable to identify MCI in its early stages. Therefore, identifying new biomarkers for MCI diagnosis and prognosis is a significant challenge. In this framework, miRNAs in serum, plasma, and other body fluids have emerged as a promising source of biomarkers for MCI and AD-related cognitive impairments. Interestingly, miRNAs can regulate several signaling pathways via multiple and diverse targets in response to pathophysiological stimuli. This systematic review aims to describe the current state of the art regarding AD-related target genes modulated by differentially expressed miRNAs in peripheral fluids samples in MCI subjects to identify potential miRNA biomarkers in the early stages of AD. We found 30 articles that described five miRNA expression profiles from peripheral fluid in MCI subjects, showing possible candidates for miRNA biomarkers that may be followed up as fluid biomarkers or therapeutic targets of early-stage AD. However, additional research is needed to validate these miRNAs and characterize the precise neuropathological mechanisms.


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