Interferon characterization associates with asthma and is a potential biomarker of predictive diagnosis.
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ABSTRACT:
SUBMITTER: Shu H
PROVIDER: S-EPMC7982770 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe diagnosis of severe asthma (SA) is difficult due to a necessary long-term treatment history currently, while there are few studies on biomarkers in the diagnosis of SA. Long non-coding RNA (lncRNA) growth arrest specific-5 (GAS5) has the potential of playing this role because its binding with glucocorticoid receptor (GR). The purpose of this article is to explore the possibility of lncRNA GAS5 acting as a biomarker for early diagnosis of severe asthma (SA).MethodsPeripheral blood was obtained from healthy volunteers, patients with non-severe asthma (nSA) and SA, and peripheral blood mononuclear cells (PBMCs) were separated. Twenty-four female BALB/c mice (aged 6 weeks) were randomly and averagely divided into 3 groups, i.e., control group, asthma group and dexamethasone group. The mice were sensitized and challenged with ovalbumin (OVA) and lipopolysaccharide (LPS) to establish a murine model of steroid-insensitive asthma. Human bronchial epithelial cells (HBECs) were cultured, transfected with miR-9 mimics, JNK1 inhibitor and treated with interleukin (IL)-2 + IL-4 and dexamethasone. Western blot was used to detect glucocorticoid receptor phosphorylation at serine 226 (GRser226), and quantitative real-time PCR was used to detect GAS5 level.ResultsThe level of GAS5 in PBMCs from nSA group elevated 20-fold higher after dexamethasone treatment in vitro, while it reduced 15-fold lower in SA group (P<0.001). The expression of GRser226 in PBMCs from SA group was significantly higher than that from control group and nSA group after dexamethasone treatment (P<0.001). In the lung tissue of mice, the GAS5 level of dexamethasone group was lower than that of asthma group (P<0.001) and control group (P<0.05). Both treatment with IL-2 + IL-4 and transfection of miR-9 mimics could increase the expression of GRser226 in HBECs (P<0.001). The GAS5 level in HBECs after IL-2 + IL-4 + Dexamethasone treatment was lower than that in HBECs only treated with IL-2 + IL-4 (P<0.001). Similarly, dexamethasone treatment also decreased the level of GAS5 in HBECs transfected with miR-9 mimics (P<0.05). Moreover, transfecting with JNK1 inhibitor could reverse the expression of GAS5 in HBECs transfected with miR-9 mimics and treated with dexamethasone. However, the level of GAS5 in HBECs interfered with IL-2 + IL-4 + Dexamethasone was not affected by JNK1 inhibitor.ConclusionsThe expression of GAS5 is different in PBMCs between nSA and SA, and is affected by glucocorticoids treatment, which is due to GRser226 phosphorylation. GAS5 can be used as a potential biomarker for diagnosis of severe asthma by comparing GAS5 level in PBMCs from patients before and after glucocorticoids treatment in vitro.
| S-EPMC7330345 | biostudies-literature
Project description:Purpose: PCa is the second most commonly diagnosed malignancy in men. PCa Diagnosis are based on biopsy sampling that is an invasive, expensive procedure and does not accurately represent multifocal disease. It is desirable to have an easily accessible, minimally invasive way to accurately determine the molecular signature of patient’s tumor that can aid in diagnosis and risk stratification. Methods:we enrolled a total of 70 patients underwent 12-core transrectal ultrasound (TRUS) biopsy of which 48% had cancer in the diagnosis. The mean age at diagnosis was 67.15 (IR 55/75), the mean PSA (ng/ml) at diagnosis was 7.8 (IR 4.1/13.4) and the mean TRUS Volume (ml) was 53.5 (IR 29/86). The cancer biopsy presented 73.1% of positive core. Among all cancer patients, 57% showed a High grade of cancer status (Grade 3). Controls are patients with Benign Prostate Hyperplasia (BPH). MicroRNA-expression profiling (NGS analysis) was performed to identify tumor-related microRNAs (miRs) and determine their association with clinicopathological characteristics. Results: The expression of miRs -4732-3p, let7a, 26b-5p, 98-5p, 30c-5p and 21-5p may identified Prostate Cancer in plasma samples. Higher expression of mir-4732-3p is associated with a high grade tumor Conclusions: miRs signature discriminate Prostate cancer in plasma better to PSA values and is associated with high grade tumor status
2020-11-01 | GSE118038 | GEO
Project description:AbstractRhabdomyosarcoma (RMS) is a common malignant soft tissue sarcoma, which is the third most common soft tissue sarcoma after malignant fibrohistoma and liposarcoma. The discovery of potential postbiomarkers could lead to early and more effective treatment measures to reduce the mortality of RMS. The discovery of biomarker is expected to be the direction of targeted therapy, providing a new direction for the precise treatment of RMS.Gene Expression Omnibus database was used to download the tow gene profiles, GSE28511 and GSE135517. GEO2R was applied to identify differently expressed genes (DEGs) between RMS and normal group. Database for Annotation, Visualization and Integrated Discovery and Metascape can perform the enrichment analysis for the DEGs. Protein-protein interaction network was constructed, and the hub genes was identified by the Cytoscape. Expression and overall survival analysis of hub genes were performed.A total of 15 common DEGs were screened between RMS and normal tissues. The enrichment analysis here showed that the DEGs mainly enriched in the muscle filament sliding, myofibril, protein complex, sarcomere, myosin complex, nuclear chromosome, and tight junction. The 6 hub genes (DNA Topoisomerase II Alpha, Insulin Like Growth Factor 2, HIST1H4C, Cardiomyopathy Associated 5, Myosin Light Chain 2 [MYL2], Myosin Heavy Chain 2) were identified. Compared with the normal tissues, MYL2 were down-regulated in the RMS tissues. RMS patients with low expression level of MYL2 had poorer overall survival times than those with high expression levels (P < .05).In summary, lower expression of MYL2 was 1 prediction for poor prognosis of RMS. MYL2 is hope to be the target of therapy, which leads to more effective treatment and reduces the mortality rate of RMS.
| S-EPMC8483830 | biostudies-literature
Project description:Cardiac-cerebral vascular disease (CCVD), is primarily induced by atherosclerosis, and is a leading cause of mortality. Numerous studies have investigated and attempted to clarify the molecular mechanisms of atherosclerosis; however, its pathogenesis has yet to be completely elucidated. Two expression profiling datasets, GSE43292 and GSE57691, were obtained from the Gene Expression Omnibus (GEO) database. The present study then identified the differentially expressed genes (DEGs), and functional annotation of the DEGs was performed. Finally, an atherosclerosis animal model and neural network prediction model was constructed to verify the relationship between hub gene and atherosclerosis. The results identified a total of 234 DEGs between the normal and atherosclerosis samples. The DEGs were mainly enriched in actin filament, actin binding, smooth muscle cells, and cytokine-cytokine receptor interactions. A total of 13 genes were identified as hub genes. Following verification of animal model, the common DEG, Tropomyosin 2 (TPM2), was found, which were displayed at lower levels in the atherosclerosis models and samples. In summary, DEGs identified in the present study may assist clinicians in understanding the pathogenesis governing the occurrence and development of atherosclerosis, and TPM2 exhibits potential as a promising diagnostic and therapeutic biomarker for atherosclerosis.
| S-EPMC6756910 | biostudies-literature
Project description:An increasing number of studies suggest that subclinical hypothyroidism (SCH) is associated with complications of gestation, including spontaneous abortion (SA). However, the underlying mechanism is not clear. MicroRNA (miRNA) has been demonstrated to be closely related to gynecological reproductive diseases. We determined miRNA expression in patients with SCH, SCH with SA (SCH?+?SA), and in those with SA as well as healthy controls (HCs), and analyzed whether dysregulation in several miRNAs was specific to these cohorts. An Agilent Human miRNA array was used to explore miRNA levels in pooled serum samples as a pilot study, followed by a validation of selected miRNAs by real-time polymerase chain reaction in SCH (N?=?24), SA (N?=?19), SCH?+?SA (N?=?21), and HC cohorts (N?=?18). The relative expression of miR-940 was elevated in the SCH?+?SA group compared with SCH, SA, and HC groups. In addition, miR-486-5p was upregulated in the SCH?+?SA group compared with SA and HC groups, without a difference noted between SCH?+?SA and SCH groups. Further analysis suggested that miR-940 or miR-486-5p may be potential predictive biomarkers for the early diagnosis of SA in patients with SCH.
| S-EPMC5897420 | biostudies-literature
Project description:Cholangiocarcinoma (CCA) is the second most common-primary liver cancer. The difficulties in diagnosis limit successful treatment of CCA. At present, histological investigation is the standard diagnosis for CCA. However, there are some poor-defined tumor tissues which cannot be definitively diagnosed by general histopathology. As molecular signatures can define molecular phenotypes related to diagnosis, prognosis, or treatment outcome, and CCA is the second most common cancer found after hepatocellularcarcinoma (HCC), the aim of this study was to develop a predictive model which differentiates CCA from HCC and normal liver tissues. An in-house PCR array containing 176 putative CCA marker genes was tested with the training set tissues of 20 CCA and 10 HCC cases. The molecular signature of CCA revealed the prominent expression of genes involved in cell adhesion and cell movement, whereas HCC showed elevated expression of genes related to cell proliferation/differentiation and metabolisms. A total of 69 genes differentially expressed in CCA and HCC were optimized statistically to formulate a diagnostic equation which distinguished CCA cases from HCC cases. Finally, a four-gene diagnostic equation (CLDN4, HOXB7, TMSB4 and TTR) was formulated and then successfully validated using real-time PCR in an independent testing set of 68 CCA samples and 77 non-CCA controls. Discrimination analysis showed that a combination of these genes could be used as a diagnostic marker for CCA with better diagnostic parameters with high sensitivity and specificity than using a single gene marker or the usual serum markers (CA19-9 and CEA). This new combination marker may help physicians to identify CCA in liver tissues when the histopathology is uncertain.
| S-EPMC3938437 | biostudies-literature
Project description:In the absence of a gold standard for the diagnosis of latent tuberculosis (TB) infection (LTBI), the current tests available for the diagnosis of LTBI are limited by their inability to differentiate between LTBI and active TB disease. We investigated IP-10 as a potential biomarker for LTBI among household contacts exposed to sputum positive active TB cases.Active TB cases and contacts were recruited into a cohort with six months' follow-up. Contacts were tested for LTBI using QuantiFERON®-TB Gold In-Tube (QFN) assay and the tuberculin skin test (TST). Baseline supernatants from the QFN assay of 237 contacts and 102 active TB cases were analysed for Mycobacterium tuberculosis (MTB) specific and mitogen specific IP-10 responses.Contacts with LTBI (QFN+TST+) had the highest MTB specific IP-10 responses at baseline, compared to uninfected contacts (QFN-TST-) p<0.0001; and active cases, p = 0.01. Using a cut-off of 8,239 pg/ml, MTB specific IP-10 was able to diagnose LTBI with a sensitivity of 87.1% (95% CI, 76.2-94.3) and specificity of 90.9% (95% CI, 81.3-96.6). MTB specific to mitogen specific IP-10 ratio was higher in HIV negative active TB cases, compared to HIV negative latently infected contacts, p = 0.0004. Concentrations of MTB specific IP-10 were higher in contacts with TST conversion (negative at baseline, positive at 6-months) than in those that were persistently TST negative, p = 0.001.IP-10 performed well in differentiating contacts with either latent or active TB from those who were uninfected but was not able to differentiate LTBI from active disease except when MTB specific to mitogen specific ratios were used in HIV negative adults. In addition, IP-10 had the potential to diagnose 'recent TB infection' in persons classified as having LTBI using the TST. Such individuals with strong IP-10 responses would likely benefit from chemoprophylaxis.
| S-EPMC4714877 | biostudies-literature
Project description:Introduction: The nature of nocturnal cough is largely unknown. It might be a valid marker for asthma control but very few studies characterized it as a basis for better defining its role and its use as clinical marker. This study investigated prevalence and characteristics of nocturnal cough in asthmatics over the course of four weeks.Methods: In two centers, 94 adult patients with physician-diagnosed asthma were recruited. Patient-reported outcomes and nocturnal sensor data were collected by a smartphone with a chat-based study app.Results: Patients coughed in 53% of 2212 nights (range: 0-345 coughs/night). Median coughs per hour were 0 (IQR 0-1). Nocturnal cough rates showed considerable inter-individual variance. The highest counts were measured in the first 30 min in bed (4.5-fold higher than rest of night). Eighty-six percent of coughs were part of a cough cluster. Clusters consisted of a median of two coughs (IQR 2-4). Nocturnal cough was persistent within patient.Conclusion: To the best of the authors' knowledge, this study is the first to describe prevalence and characteristics of nocturnal cough in asthma over a period of one month, demonstrating that it was a prevalent symptom with large variance between patients and high persistence within patients. Cough events in asthmatics were 4.5 times more frequent within the first 30 min in bed indicating a potential role of positional change, and not more frequent during the early morning hours. An important next step will investigate the association between nocturnal cough and asthma control.
| S-EPMC7721277 | biostudies-literature
Project description:ObjectiveAnxiety is a prevalent comorbidity in lung cancer (LC) patients associated with a decline in quality of life. Dehydroepiandrosterone (DHEA), a neuroactive steroid, levels rise in response to stress. Prior research on the association between DHEA and anxiety has yielded contradictory results and no study has investigated this association in LC patients.MethodsA total of 213 patients with LC were recruited from a general hospital. Data on demographic and cancer-related variables were collected. Using the Chinese version of the Hospital Anxiety and Depression Scale (HADS), the degree of anxiety was determined. Cortisol, DHEA, and Dehydroepiandrosterone sulfate (DHEA-S) levels in saliva were measured. Adjusting for confounding variables, a multivariate regression analysis was conducted.Results147 men and 66 women comprised our group with an average age of 63.75 years. After accounting for demographic and treatment-related factors, anxiety levels were significantly correlated with, post-traumatic stress symptoms (PTSSs) (β = 0.332, p < 0.001) and fatigue (β = 0.247, p = 0.02). Association between anxiety and three factors, including DHEA, PTSSs, and fatigue, was observed in patients with advanced cancer stages (III and IV) (DHEA β = 0.319, p = 0.004; PTSS β = 0.396, p = 0.001; fatigue β = 0.289, p = 0.027) and those undergoing chemotherapy (DHEA β = 0.346, p = 0.001; PTSS β = 0.407, p = 0.001; fatigue β = 0.326, p = 0.011).ConclusionsThe association between anxiety and DHEA remained positive in advanced cancer stages and chemotherapy patients. Further study is necessary to determine whether DHEA is a potential biomarker of anxiety in LC patients.
| S-EPMC11021003 | biostudies-literature
Project description:BackgroundThe influence of the microbiome on neurological diseases has been studied for years. Recent findings have shown a different composition of gut microbiota detected in patients with multiple sclerosis (MS). The role of this dysbiosis is still unknown.ObjectiveWe analyzed the gut microbiota of 15 patients with active relapsing-remitting multiple sclerosis (RRMS), comparing with diet-matched healthy controls.MethodTo determine the composition of the gut microbiota, we performed high-throughput sequencing of the 16S ribosomal RNA gene. The specific amplified sequences were in the V3 and V4 regions of the 16S ribosomal RNA gene.ResultsThe gut microbiota of RRMS patients differed from healthy controls in the levels of the Lachnospiraceae, Ezakiella, Ruminococcaceae, Hungatella, Roseburia, Clostridium, Shuttleworthia, Poephyromonas, and Bilophila genera. All these genera were included in a logistic regression analysis to determine the sensitivity and the specificity of the test. Finally, the ROC (receiver operating characteristic) and AUC with a 95% CI were calculated and best-matched for Ezakiella (AUC of 75.0 and CI from 60.6 to 89.4) and Bilophila (AUC of 70.2 and CI from 50.1 to 90.4).ConclusionsThere is a dysbiosis in the gut microbiota of RRMS patients. An analysis of the components of the microbiota suggests the role of some genera as a predictive factor of RRMS prognosis and diagnosis.
| S-EPMC9140870 | biostudies-literature