scholarly journals 486Serum levels of miRNA-221 and -222 may be predictive biomarkers for cognitive decline

2021 ◽  
Vol 50 (Supplement_1) ◽  
Author(s):  
Yuya Ishihara ◽  
Hiroya Yamada ◽  
Eiji Munetuna ◽  
Chiharu Hagiwara ◽  
Ryosuke Fujii ◽  
...  
Keyword(s):  
Cognitive Decline ◽  
Early Stage ◽  
Predictive Biomarkers ◽  
Serum Levels ◽  
High Serum ◽  
Short Version ◽  
Health Examination ◽  
Potential Candidate ◽  
Odds Ratios ◽  
Serum Mirna

Abstract Background Although dementia is a huge problem in public health, no fundamental biomarker has been established to detect cognitive decline at the early stage. MicroRNAs (miRNAs) regulate gene expression, and are associated with the development of various diseases. Methods The subjects of this prospective study were 162 (75 men, 87 women) residents who attended a health examination in Yakumo town in Hokkaido, in 2012 and re-attended at least once while 2013 to 2015. Serum samples were collected in 2012 and serum miRNA were measured by qRT-PCR. We used a short version of the Mini-Mental State Examination (SMMSE) to screen cognitive function, and calculated the change in SMMSE score per year. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) of serum miRNA levels for cognitive decline (decrease of greater than 0.5 points per year) using the lowest tertile group of miRNAs as the reference by logistic regression analysis. Results The mean age and change in SMMSE score of the subjects was 63.9±9.6 years and -0.03±1.19 points. Odds ratios (ORs) for cognitive decline were significantly higher in the highest tertile of serum miR-221 (OR = 3.24, 95%CI=1.20-8.72) and miR-222 (OR = 4.01, 95%CI=1.36-11.80) even if confounding factors were adjusted. Conclusions High serum levels of miR-221 and -222 were significantly associated with cognitive decline. Key messages High serum levels of miR-221 and -222 may be potential candidate biomarkers for prediction of cognitive decline.

scholarly journals An inflammatory cytokine signature helps predict COVID-19 severity and death

2020 ◽  
Author(s):  
Diane Marie Del Valle ◽  
Seunghee Kim-schulze ◽  
Huang Hsin-hui ◽  
Noam D Beckmann ◽  
Sharon Nirenberg ◽  
...  
Keyword(s):  
New York ◽  
Disease Severity ◽  
Cox Regression ◽  
Predictive Biomarkers ◽  
Clinical Information ◽  
Serum Levels ◽  
The United States ◽  
High Serum ◽  
Laboratory Test Results ◽  
Tnf Α

The COVID-19 pandemic caused by infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to more than 100,000 deaths in the United States. Several studies have revealed that the hyper-inflammatory response induced by SARS-CoV-2 is a major cause of disease severity and death in infected patients. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum IL-6, IL-8, TNF-α, and IL-1β in hospitalized COVID-19 patients upon admission to the Mount Sinai Health System in New York. Patients (n=1484) were followed up to 41 days (median 8 days) and clinical information, laboratory test results and patient outcomes were collected. In 244 patients, cytokine measurements were repeated over time, and effect of drugs could be assessed. Kaplan-Meier methods were used to compare survival by cytokine strata, followed by Cox regression models to evaluate the independent predictive value of baseline cytokines. We found that high serum IL-6, IL-8, and TNF-α levels at the time of hospitalization were strong and independent predictors of patient survival. Importantly, when adjusting for disease severity score, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF-α serum levels remained independent and significant predictors of disease severity and death. We propose that serum IL-6 and TNF-α levels should be considered in the management and treatment of COVID-19 patients to stratify prospective clinical trials, guide resource allocation and inform therapeutic options. We also propose that patients with high IL-6 and TNF-α levels should be assessed for combinatorial blockade of pathogenic inflammation in this disease.

scholarly journals Correlates of Mild Cognitive Impairment of Community-Dwelling Older Adults in Wuhan, China

2018 ◽  
Vol 15 (12) ◽  
pp. 2705 ◽  
Author(s):  
Xiaojun Liu ◽  
Xiao Yin ◽  
Anran Tan ◽  
Meikun He ◽  
Dongdong Jiang ◽  
...  
Keyword(s):  
Older Adults ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Cognitive Decline ◽  
Chronic Diseases ◽  
Vulnerable Populations ◽  
Early Stage ◽  
Community Dwelling ◽  
Odds Ratios ◽  
Increased Risk

Mild cognitive impairment (MCI) is an early stage of Alzheimer’s disease or other forms of dementia that occurs mainly in older adults. The MCI phase could be considered as an observational period for the secondary prevention of dementia. This study aims to assess potential differences in the risk of MCI among different elderly groups in Wuhan, China, and to further identify the most vulnerable populations using logistic regression models. A total of 622 older adults participated in this study, and the prevalence of MCI was 34.1%. We found that individuals aged 80–84 (odds ratio, OR = 1.908, 95% confidence interval, 95% CI 1.026 to 3.549) or above (OR = 2.529, 95% CI 1.249 to 5.122), and those with two chronic diseases (OR = 1.982, 95% CI 1.153 to 3.407) or more (OR = 2.466, 95% CI 1.419 to 4.286) were more likely to be diagnosed with MCI. Those with high school degrees (OR = 0.451, 95% CI 0.230 to 0.883) or above (OR = 0.318, 95% CI 0.129 to 0.783) and those with a family per-capita monthly income of 3001–4500 yuan (OR = 0.320, 95% CI 0.137 to 0.750) or above (OR = 0.335, 95% CI 0.135 to 0.830) were less likely to experience MCI. The results also showed that those aged 80 or above were more likely to present with cognitive decline and/or reduced activities of daily living (ADL) function, with the odds ratios being 1.874 and 3.782, respectively. Individuals with two, or three or more chronic diseases were more likely to experience cognitive decline and/or reduced ADL function, with odds ratios of 2.423 and 2.631, respectively. Increased risk of suffering from either MCI and/or decline in ADL functioning is strongly positively associated with older age, lower educational levels, poorer family economic status, and multiple chronic diseases. Our findings highlight that the local, regional, and even national specific MCI-related health promotion measures and interventions must target these vulnerable populations.

scholarly journals Changes in Expression of miRNA-320a and miRNA-497-5p in Early Stage of Breast Cancer

2021 ◽  
Keyword(s):  
Breast Cancer ◽  
Healthy Volunteers ◽  
Early Stage ◽  
Quantitative Polymerase Chain Reaction ◽  
Serum Levels ◽  
Healthy Controls ◽  
Medical Sciences ◽  
Serum Samples ◽  
Ribonucleic Acids ◽  
Serum Mirna

Background: Micro-ribonucleic acids (miRNAs) are noncoding small RNA species considered a varying class with a single-stranded structure whose expression is often dysregulated in cancer. The expression of miRNAs has been used as a promising new biomarker for the detection of breast cancer (BC). Objectives: The purpose of the present case-control study was to investigate the expression levels of miRNA-320a and miRNA-497-5p and their potential role in BC patients in comparison to those of the healthy controls in the Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran, in 2019. Methods: The concentrations of miR-320a and miR-497-5p were analyzed in 80 serum samples of 40 patients with a confirmed diagnosis of early-stage BC in comparison to those of 40 age-matched healthy volunteers. Real-time quantitative polymerase chain reaction was carried out for the detection of the expression level of these miRNAs. Results: The results of the current study showed that the serum levels of miR-320a and miR-497-5p were down-regulated in the BC patients, compared to those reported for the healthy controls (P=0.651 and P=0.044, respectively). However, the levels of miR-320a in the early-stage BC samples were not statistically different from those of the healthy volunteers. There was a reduction in the serum miRNA-320a of the premenopausal subjects under 48 years of age. Serum miRNA-497-5p also decreased among the cases under 48 years of age. Conclusions: The identification and effectiveness of these miRNAs were demonstrated in the early-stage BC screening. It seems that miRNAs have the potential to be used as biomarkers for the screening and diagnosis of BC.

Benign ovarian fibroma with ascites and high serum levels of CA125: a case report

2007 ◽  
Vol 67 (05) ◽  
Author(s):  
N Shabani ◽  
T Puchner ◽  
H Schütze ◽  
U Jeschke ◽  
I Mylonas ◽  
...  
Keyword(s):  
Case Report ◽  
Serum Levels ◽  
High Serum ◽  
Ovarian Fibroma

High serum miRNA 550a-5p levels are risk factors for incident fractures in older postmenopausal women with type 2 diabetes

2016 ◽  
Author(s):  
Ursula Heilmeier ◽  
Matthias Hackl ◽  
Susanna Skalicky ◽  
Sylvia Weilner ◽  
Fabian Schroeder ◽  
...  
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Postmenopausal Women ◽  
High Serum ◽  
Serum Mirna

scholarly journals POS0329 GASTROINTESTINAL INVOLVEMENT IN SYSTEMIC SCLEROSIS: PATHOGENETIC ROLE OF GUT MICROBIOME, CYTOKINES AND ADIPOKINES

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 392.1-392
Author(s):  
E. Pigatto ◽  
M. Schiesaro ◽  
M. Caputo ◽  
M. Beggio ◽  
P. Galozzi ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Gut Microbiome ◽  
Serum Levels ◽  
High Serum ◽  
Healthy Population ◽  
Gastrointestinal Involvement ◽  
Degrading Bacteria ◽  
Gi Symptoms ◽  
Low Levels ◽  
The Impact

Background:Gastrointestinal (GI) involvement is very common in patients with Systemic Sclerosis (SSc). The pathophysiology of GI manifestations has not yet been defined. Cell-mediated immunological reactions appear to lead to endothelial damage resulting in fibrosis. The risk of developing malnutrition reinforces the need to better understand GI pathophysiology in these patients.Objectives:The study aimed to evaluate GI symptoms (GIT 2.0) and malnutrition status (MUST) and to determine specific bacterial changes in gut microbiome by investigating the possible presence of positive hot spots in bacterial species in SSc patients and their potential role in the disease progression. We also evaluated serum levels of adipokines and cytokines involved in the pathogenesis of SSc and their role, in addition to gut microbiome, in predicting the onset of GI involvement and malnutrition in SSc patients.Methods:We enrolled 25 scleroderma patients (EULAR/ACR 2013 criteria). UCLA-SCTC GIT 2.0 questionnaire to evaluate GI symptoms and MUST to investigate the risk of malnutrition were used. Gut microbiome was analyzed and the samples were subjected to extraction for the 16S rRNA gene (Earth Microbiome Project and the NIH-Human Microbiome Project). The microbiome was investigated at phenotypic and genotypic level. Serum levels of cytokines and adipokines (adiponectin and leptin) were evaluated by ELISA.Results:79.9% of patients had GERD and 63.5% abdominal distension at GIT 2.0 questionnaires. 48% of patients had moderate risk of malnutrition (MUST=2) and 12% had high risk (MUST=3). Gut microbioma: 19 patients (76%) had low similarity and 11 (44%) low diversity compared to the healthy population. The prevailing enterotypes of gut microbiome was Bacteroides (80%) and Prevotella (20%). The genotypic evaluation showed a reduced concentration of: gluten-digesting (Lactobacillus); lactose-digesting (Faecalibacterium); vitamin K-producing (Enterococcus, Desulfovibrio and Veillonella); acetaldehyde-degrading bacteria. 24 patients (96%) showed a reduction in bacteria devoted to maintaining weight control (Bifidobacterium and Ruminococcus). The patients had an altered intestinal permeability with less mucolytic bacteria (Bacteroides) and reduced production of LPS (Enterobacter and Escherichia). Low levels of butyrate (Eubacterium and Clostridium), acetate and propionate were found for SCFA-producing bacteria. Potentially pathogenic bacteria were also investigated: Salmonella was found in 14 (56%), Klebsiella in 9 (36%) and Enterococcus Faecalis in 3 (12%) patients. 11 (44%) patients had elevated serum levels of IL10 and IL12; 4 (16%) had high value of leptin. Correlation was found in patients who had a reduced concentration of gluten-digesting bacteria and MUST. Elevated MUST was correlated with serological increase in IL17A and IFN-α. Serum levels of IL12 and IL10 were found to correlate with specific bacteria alterations: high concentration of acetaldehyde-producing bacteria and low levels of acetaldehyde-degrade bacteria (also correlated with high serum levels of IL6), mucolytic bacteria and producers of hydrogen sulphide, acetate and propionate. Finally, reduced levels of mucolytic bacteria and acetate producing bacteria correlated with high serum leptin levels.Conclusion:The relationship between the gut microbiome and SSc seems to be multifactorial. In our study genotypic changes of gut microbioma might play a role in damaging the permeability of the mucosa and increasing risk of malnutrition. The evaluation of gut microbiome and cytokine profile is probably going to be of value in the follow-up of SSc. However, further studies are needed to clarify the impact of GI dysbiosis on the immune system in SSc.References:[1]Patrone V. et al. Gut microbiota profile in systemic sclerosis patients with and without clinical evidence of gastrointestinal involvement, Sci Rep. 2017; 7: 14874Disclosure of Interests:None declared

scholarly journals Thrombomodulin is upregulated in the kidneys of women with pre-eclampsia

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Cleo C. L. van Aanhold ◽  
Manon Bos ◽  
Katrina M. Mirabito Colafella ◽  
Marie-Louise P. van der Hoorn ◽  
Ron Wolterbeek ◽  
...  
Keyword(s):  
Glomerular Filtration ◽  
Early Stage ◽  
Vascular Inflammation ◽  
Angiogenesis Inhibitor ◽  
Serum Levels ◽  
Dependent Manner ◽  
Glomerular Filtration Barrier ◽  
Soluble Thrombomodulin ◽  
Filtration Barrier ◽  
Glomerular Endothelium

AbstractThe endothelial glycoprotein thrombomodulin regulates coagulation, vascular inflammation and apoptosis. In the kidney, thrombomodulin protects the glomerular filtration barrier by eliciting crosstalk between the glomerular endothelium and podocytes. Several glomerular pathologies are characterized by a loss of glomerular thrombomodulin. In women with pre-eclampsia, serum levels of soluble thrombomodulin are increased, possibly reflecting a loss from the glomerular endothelium. We set out to investigate whether thrombomodulin expression is decreased in the kidneys of women with pre-eclampsia and rats exposed to an angiogenesis inhibitor. Thrombomodulin expression was examined using immunohistochemistry and qPCR in renal autopsy tissues collected from 11 pre-eclamptic women, 22 pregnant controls and 11 hypertensive non-pregnant women. Further, kidneys from rats treated with increasing doses of sunitinib or sunitinib in combination with endothelin receptor antagonists were studied. Glomerular thrombomodulin protein levels were increased in the kidneys of women with pre-eclampsia. In parallel, in rats exposed to sunitinib, glomerular thrombomodulin was upregulated in a dose-dependent manner, and the upregulation of glomerular thrombomodulin preceded the onset of histopathological changes. Selective ETAR blockade, but not dual ETA/BR blockade, normalised the sunitinib-induced increase in thrombomodulin expression and albuminuria. We propose that glomerular thrombomodulin expression increases at an early stage of renal damage induced by antiangiogenic conditions. The upregulation of this nephroprotective protein in glomerular endothelial cells might serve as a mechanism to protect the glomerular filtration barrier in pre-eclampsia.

scholarly journals Serum surfactant protein D in COVID-19 is elevated and correlated with disease severity

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ming Tong ◽  
Ying Xiong ◽  
Chen Zhu ◽  
Hong Xu ◽  
Qing Zheng ◽  
...  
Keyword(s):  
Acute Phase ◽  
Early Stage ◽  
Recovery Period ◽  
Serum Levels ◽  
Surfactant Protein ◽  
Mean Value ◽  
Multivariate Logistic Regression Model ◽  
Surfactant Protein D ◽  
Multivariate Logistic Regression ◽  
Roc Curve Analysis

Abstract Background The serum surfactant protein D (SP-D) level is suggested to be a useful biomarker for acute lung injuries and acute respiratory distress syndrome. Whether the serum SP-D level could identify the severity of coronavirus disease 2019 (COVID-19) in the early stage has not been elucidated. Methods We performed an observational study on 39 laboratory-confirmed COVID-19 patients from The Fourth People’s Hospital of Yiyang, Hunan, China. Receiver operating characteristic (ROC) curve analysis, correlation analysis, and multivariate logistic regression model analysis were performed. Results In the acute phase, the serum levels of SP-D were elevated significantly in severe COVID-19 patients than in mild cases (mean value ± standard deviation (SD), 449.7 ± 125.8 vs 245.9 ± 90.0 ng/mL, P<0.001), while the serum levels of SP-D in the recovery period were decreased dramatically than that in the acute phase (mean value ± SD, 129.5 ± 51.7 vs 292.9 ± 130.7 ng/ml, P<0.001), and so were for the stratified patients. The chest CT imaging scores were considerably higher in the severe group compared with those in the mild group (median value, 10.0 vs 9.0, P = 0.011), while markedly lower in the recovery period than those in the acute phase (median value, 2.0 vs 9.0, P<0.001), and so were for the stratified patients. ROC curve analysis revealed that areas under the curve of lymphocyte counts (LYM), C-reaction protein (CRP), erythrocyte sedimentation rate (ESR), interleukin-6 (IL-6), and SP-D for severe COVID-19 were 0.719, 0.833, 0.817, 0.837, and 0.922, respectively. Correlation analysis showed that the SP-D levels were negatively correlated with LYM (r = − 0.320, P = 0.047), while positively correlated with CRP (r = 0.658, P<0.001), IL-6 (r = 0.471, P = 0.002), the duration of nucleic acid of throat swab turning negative (r = 0.668, P<0.001), chest CT imaging score on admission (r = 0.695, P<0.001) and length of stay (r = 0.420, P = 0.008). Multivariate logistic regression model analysis showed that age (P = 0.041, OR = 1.093) and SP-D (P = 0.008, OR = 1.018) were risk factors for severe COVID-19. Conclusions Elevated serum SP-D level was a potential biomarker for the severity of COVID-19; this may be useful in identifying patients whose condition worsens at an early stage.

scholarly journals Integration of early disease-resistance phenotyping, histological characterization, and transcriptome sequencing reveals insights into downy mildew resistance in impatiens

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Ze Peng ◽  
Yanhong He ◽  
Saroj Parajuli ◽  
Qian You ◽  
Weining Wang ◽  
...  
Keyword(s):  
Disease Resistance ◽  
Downy Mildew ◽  
Transcriptome Sequencing ◽  
Early Stage ◽  
Economic Losses ◽  
Potential Candidate ◽  
Early Disease ◽  
True Leaf ◽  
Cotyledon Stage ◽  
Wide Range

AbstractDowny mildew (DM), caused by obligate parasitic oomycetes, is a destructive disease for a wide range of crops worldwide. Recent outbreaks of impatiens downy mildew (IDM) in many countries have caused huge economic losses. A system to reveal plant–pathogen interactions in the early stage of infection and quickly assess resistance/susceptibility of plants to DM is desired. In this study, we established an early and rapid system to achieve these goals using impatiens as a model. Thirty-two cultivars of Impatiens walleriana and I. hawkeri were evaluated for their responses to IDM at cotyledon, first/second pair of true leaf, and mature plant stages. All I. walleriana cultivars were highly susceptible to IDM. While all I. hawkeri cultivars were resistant to IDM starting at the first true leaf stage, many (14/16) were susceptible to IDM at the cotyledon stage. Two cultivars showed resistance even at the cotyledon stage. Histological characterization showed that the resistance mechanism of the I. hawkeri cultivars resembles that in grapevine and type II resistance in sunflower. By integrating full-length transcriptome sequencing (Iso-Seq) and RNA-Seq, we constructed the first reference transcriptome for Impatiens comprised of 48,758 sequences with an N50 length of 2060 bp. Comparative transcriptome and qRT-PCR analyses revealed strong candidate genes for IDM resistance, including three resistance genes orthologous to the sunflower gene RGC203, a potential candidate associated with DM resistance. Our approach of integrating early disease-resistance phenotyping, histological characterization, and transcriptome analysis lay a solid foundation to improve DM resistance in impatiens and may provide a model for other crops.

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