scholarly journals Integrated miRNA/cytokine/chemokine profiling reveals immunopathological step changes associated with COVID-19 severity

Author(s):  
Julie C. WIlson ◽  
David Kealy ◽  
Sally R. James ◽  
Katherine Newling ◽  
Christopher Jagger ◽  
...  

Circulating microRNAs (miRNAs) are exceptional mechanism-based correlates of disease, yet their potential remains largely untapped in COVID-19. Here, we determined circulating miRNA and cytokine and chemokine (CC) profiles in 171 blood plasma samples from 58 hospitalised COVID-19 patients. Thirty-two miRNAs were differentially expressed in severe cases when compared to moderate and mild cases. These miRNAs and their predicted targets reflected key COVID-19 features including cell death and hypoxia. Compared to mild cases, moderate and severe cases were characterised by a global decrease in circulating miRNA levels. Partial least squares regression using miRNA and CC measurements allowed for discrimination of severe cases with greater accuracy (87%) than using miRNA or CC levels alone. Correlation analysis revealed severity group-specific associations between CC and miRNA levels. Importantly, the miRNAs that correlated with IL6 and CXCL10, two cardinal COVID-19-associated cytokines, were distinct between severity groups, providing a novel qualitative way to stratify patients with similar levels of proinflammatory cytokines but different disease severity. Integration of miRNA and CC levels with clinical parameters revealed severity-specific signatures associated with clinical hallmarks of COVID-19. Our study highlights the existence of severity-specific circulating CC/miRNA networks, providing insight into COVID-19 pathogenesis and a novel approach for monitoring COVID-19 progression.

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Julie Weidner ◽  
Linda Ekerljung ◽  
Carina Malmhäll ◽  
Nicolae Miron ◽  
Madeleine Rådinger

Abstract Background Asthma is a chronic airway disease affecting millions of people. Better methods to define asthma subgroups using clinical parameters and molecular biomarkers are crucial in the development of personalized medicine. Objective The aim of this study was to determine if circulating microRNAs (miRNAs) may be used to distinguish well–defined asthma groups. Methods Blood serum from 116 well-defined subjects, including healthy controls and individuals with allergic or non-allergic asthma, from the West Sweden Asthma Study were included. Serum was analyzed for circulating miRNA expression of miR-126, − 145, −146a, − 155, − 223, and -374a and eosinophil cationic protein (ECP). Correlations between clinical characteristics and circulating miRNA expression as well as potential miRNA gene targets were investigated. Results A subset of miRNAs were differentially expressed between allergic and non-allergic asthmatic individuals. Alterations in expression of miR-155, −146a, −374a and − 145 were observed in allergic asthmatics in response to inhaled corticosteroid usage. Additionally, miR-223 and miR-374a expression varied in non-allergic asthmatics based on blood eosinophil numbers. Numerous clinical parameters, including lung function measurements, correlated with subsets of miRNAs. Finally, pathway analysis revealed a potential role for inhaled corticosteroid induced miRNAs in leukocyte regulation, IL-6 signaling and glucocorticoid response. Conclusion Circulating miRNA expression was altered in subjects with allergic and non-allergic asthma and correlated to clinical parameters including lung function and potential gene targets involved in immune processes. This combination of clinical and molecular data may be a basis for the further, more precise classification of asthma subgroups. Taken together, these findings would further asthma research and benefit future patients through the discovery of molecular mechanisms as well as identifying asthma subgroups contributing to the development of personalized medicine.


2021 ◽  
Vol 21 ◽  
Author(s):  
Ashish Ranjan Sharma ◽  
Garima Sharma ◽  
Manojit Bhattacharya ◽  
Sang-Soo Lee ◽  
Chiranjib Chakraborty

: Atherosclerosis, which is a vascular disease, is characterized by narrowing the arteries and forming plaque inside arteries. There is a record 17.5 million associated deaths recorded annually, representing 31% of global death. It has been noted that there is an association between vascular fibrosis and atherosclerosis. The thickening of the arterial wall and reduction of the lumen diameter may cause unwarranted deposition of extracellular matrix (ECM), and these conditions help in the progression of many clinical diseases and pathological conditions such as atherosclerosis. Here, we reviewed the involvement of various circulating microRNAs (miRNAs) in the very early diagnosis of atherosclerosis. We have also tried to provide an insight into the advantages and validation of circulating miRNAs through different techniques. We have discussed different circulating miRNAs, such as miR-17, miR-17-5p, miR-29b, miR-30, miR-92a, miR-126, miR-143, miR-145, miR-146a, miR-212, miR-218, miR-221, miR-222, miR-361-5p, as a biomarker for clinical diagnosis of atherosclerosis. The insightful demonstration in this review will offer a better opportunity for the researchers and technology developers in understanding the current scenario of circulating miRNA, which could facilitate them in improving the current diagnostic technologies of atherosclerosis in clinics.


Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3680
Author(s):  
Spyros Tastsoglou ◽  
Marios Miliotis ◽  
Ioannis Kavakiotis ◽  
Athanasios Alexiou ◽  
Eleni C. Gkotsi ◽  
...  

Only recently, microRNAs (miRNAs) were found to exist in traceable and distinctive amounts in the human circulatory system, bringing forth the intriguing possibility of using them as minimally invasive biomarkers. miRNAs are short non-coding RNAs that act as potent post-transcriptional regulators of gene expression. Extensive studies in cancer and other disease landscapes investigate the protective/pathogenic functions of dysregulated miRNAs, as well as their biomarker potential. A specialized resource amassing experimentally verified, circulating miRNA biomarkers does not exist. We queried the existing literature to identify articles assessing diagnostic/prognostic roles of miRNAs in blood, serum, or plasma samples. Articles were scrutinized in order to exclude instances lacking sufficient experimental documentation or employing no biomarker assessment methods. We incorporated information from more than 200 biomedical articles, annotating crucial meta-information including cohort sizes, inclusion-exclusion criteria, disease/healthy confirmation methods and quantification details. miRNAs and diseases were systematically characterized using reference resources. Our circulating miRNA biomarker collection is provided as an online database, plasmiR. It consists of 1021 entries regarding 251 miRNAs and 112 diseases. More than half of plasmiR’s entries refer to cancerous and neoplastic conditions, 183 of them (32%) describing prognostic associations. plasmiR facilitates smart queries, emphasizing visualization and exploratory modes for all researchers.


2015 ◽  
Vol 27 (1) ◽  
pp. 144
Author(s):  
J. Ioannidis ◽  
C. Ashworth ◽  
R. Raue ◽  
X. Donadeu

Early diagnosis of pregnancy can shorten calving intervals, improve annual milk production and increase overall profits from modern dairy herds. At present, accurate diagnosis is only possible after the third week of pregnancy. Circulating microRNAs (miRNAs) have been proposed as diagnostic biomarkers for numerous human conditions such as cancer and diabetes. Moreover, distinct circulating miRNA profiles have been associated with different stages of human pregnancy. The objective of this study was to determine whether differential miRNA profiles occur in circulation during early pregnancy (Day 24 or earlier) in cattle that could be used for diagnostic purposes. Holstein-cross heifers were oestrous-synchronised and artificially inseminated (AI, n = 11) or sham-inseminated (control, n = 8) at first detected oestrus. Plasma samples were collected on Days 0, 8, 16 and 24 after insemination. Circulating miRNA levels were independently determined in pooled plasma samples (n = 3 pools for each of pregnant Day 24 and nonpregnant Days 0, 8, and 16) using Qiagen qPCR arrays (Qiagen, Valencia, CA, USA) and in individual samples (n = 11 samples for each pregnant Days 16 and 24, and 8 samples for each of nonpregnant Days 0, 8, and 16, respectively) using Illumina miRNA sequencing. The qPCR array data were analysed using the ΔΔCq method. The miRNA sequencing data were normalised using EdgeR. Differential expression between pregnant and nonpregnant groups was determined using 2-sample t-tests with false discovery rate (FDR) adjustment. Differences in miRNA expression were validated by RT-qPCR. Out of a total of 191 miRNAs analysed in pooled samples using qPCR arrays, 8 were differentially expressed (<3-fold, FDR <0.1) in Day 24 pregnant heifers relative to nonpregnant heifers (Days 0, 8, and 16 combined). No miRNAs were differentially expressed (FDR >0.1) between nonpregnant time-points. Changes in levels of 11 miRNAs were validated by RT-qPCR in individual plasma samples; although expression trends for these miRNAs were the same as in pooled samples, none of the changes in individual samples were significant after FDR adjustment (P > 0.1). Deep sequencing (96 million miRNA reads) identified 231 miRNAs in bovine plasma. There were no significant differences (FDR >0.1) in the expression of any miRNAs between pregnant heifers (Days 16 or 24) and nonpregnant (Days 0, 8, and 16 individually or combined). In addition, no significant differences were identified among nonpregnant time-points. In summary, we successfully performed miRNA profiling of bovine plasma using both deep sequencing and qPCR; however, we did not detect differences in miRNA expression between early pregnant (Day 16 or 24) and nonpregnant heifers. Changes in circulating miRNA levels may involve low abundance miRNAs that cannot be accurately quantified using current technology. Alternatively, changes in circulating miRNA levels may only occur later during pregnancy in cattle.


2020 ◽  
Vol 12 (2) ◽  
pp. 287 ◽  
Author(s):  
Yang Zhong ◽  
Aiwen Lin ◽  
Lijie He ◽  
Zhigao Zhou ◽  
Moxi Yuan

It is important to analyze the expansion of an urban area and the factors that drive its expansion. Therefore, this study is based on Defense Meteorological Satellite Program Operational Linescan System (DMSP/OLS) night lighting data, using the landscape index, spatial expansion strength index, compactness index, urban land fractal index, elasticity coefficient, the standard deviation ellipse, spatial correlation analysis, and partial least squares regression to analyze the spatial and temporal evolution of urban land expansion and its driving factors in the Yangtze River Economic Belt (YREB) over a long period of time. The results show the following: Through the calculation of the eight landscape pattern indicators, we found that during the study period, the number of cities and towns and the area of urban built-up areas in the YREB are generally increasing. Furthermore, the variations in these landscape pattern indicators not only show more frequent exchanges and interactions between the cities and towns of the YREB, but also reflect significant instability and irregularity of the urbanization development in the YREB. The spatial expansion intensity indices of 1992–1999, 1999–2006, and 2006–2013 were 0.03, 0.16, and 0.34, respectively. On the whole, the urban compactness of the YREB decreased with time, and the fractal dimension increased slowly with time. Moreover, the long axis and the short axis of the standard deviation ellipse of the YREB underwent a small change during the inspection period. The spatial distribution generally showed the pattern of “southwest-north”. In terms of gravity shift, during the study period, the center of gravity moved from northeast to southwest. In addition, the Moran's I values for the four years of 1992, 1999, 2006, and 2013 were 0.451, 0.495, 0.506, and 0.424, respectively. Furthermore, by using correlation analysis, we find that the correlation coefficients between these four driving indicators and the urban expansion of the YREB were: 0.963, 0.998, 0.990 and 0.994, respectively. Through the use of partial least squares regression, we found that in 1992-2013, the four drivers of urban land expansion in the YREB were ranked as follows: gross domestic product (GDP), total fixed asset investment, urban population, total retail sales of consumer goods.


NIR news ◽  
2017 ◽  
Vol 28 (2) ◽  
pp. 3-6 ◽  
Author(s):  
Raphael Henn ◽  
Christian G. Kirchler ◽  
Christian W. Huck

This article gives an insight into the advances of miniaturized spectrometers on their way to success dealing with the determination of main carbohydrates in syrups. To evaluate the performances of such portable spectrometers, a comparison of the prediction ability, applying Partial Least Squares Regression models, was carried out. Spectra were recorded using a commercially available handheld and a conventional benchtop spectrometer. This work shows that NIR spectroscopy (both benchtop and handheld) can be used for the determination of the main carbohydrates sucrose, glucose and fructose in syrups. Measuring these main constituents in syrups is of great importance in the producing industries. Usually, these sugars are determined via enzymatic hydrolysis with high accuracy, but this method is expensive, time- and resource-consuming. These drawbacks brought up the question of possible alternatives which, if possible, are not restricted to a laboratory environment. NIR spectroscopy fulfills those requirements and was therefore considered to be an attractive alternative for this application.


2006 ◽  
Vol 95 (5) ◽  
pp. 955-962 ◽  
Author(s):  
Hanne C. Bertram ◽  
Knud E. Bach Knudsen ◽  
Anja Serena ◽  
Anders Malmendal ◽  
Niels Chr. Nielsen ◽  
...  

This study presents an NMR-based metabonomic approach to elucidate the overall endogenous biochemical effects of a wholegrain diet. Two diets with similar levels of dietary fibre and macronutrients, but with contrasting levels of wholegrain ingredients, were prepared from wholegrain rye (wholegrain diet (WGD)) and non-wholegrain wheat (non-wholegrain diet (NWD)) and fed to four pigs in a crossover design. Plasma samples were collected after 7 d on each diet, and 1H NMR spectra were acquired on these. Partial least squares regression discriminant analysis (PLSDA) on spectra obtained for plasma samples revealed that the spectral region at 3·25 parts per million dominates the differentiation between the two diets, as the WGD is associated with higher spectral intensity in this region. Spiking experiments and LC–MS analyses of the plasma verified that this spectral difference could be ascribed to a significantly higher content of betaine in WGD plasma samples compared with NWD samples. In an identical study with the same diets, urine samples were collected, and1H NMR spectra were acquired on these. PLS-DA on spectra obtained for urine samples revealed changes in the intensities of spectral regions, which could be ascribed to differences in the content of betaine and creatine/creatinine between the two diets, and LC–MS analyses verified a significantly lower content of creatinine in WGD urine samples compared with NWD urine samples. In conclusion, using an explorative approach, the present studies disclosed biochemical effects of a wholegrain diet on plasma betaine content and excretion of betaine and creatinine.


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