Validation of serum apolipoprotein A1 in rabies virus-infected mice as a biomarker for the preclinical diagnosis of rabies.
Ontology highlight
ABSTRACT:
SUBMITTER: Yamada K
PROVIDER: S-EPMC9292310 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:As a major protein constituent of high density lipoprotein, Apolipoprotein A1 (ApoA-1) might be associated with cancer progression. Our study investigated the serum ApoA-1 level for the prognosis of 443 patients with hepatocellular carcinoma (HCC) and its effects on tumor cells. We found that the serum ApoA-1 level was significantly lower in HCC patients with tumor recurrence, and was an independent indicator of tumor-free survival and overall survival. Low serum ApoA-1 levels were significantly associated with multiple tumors and high Barcelona Clinic Liver Cancer stage. The circulating tumor cell (CTC) levels were significantly higher in patients with low serum ApoA-1 compared with those with high serum ApoA-1 levels (4.03 ± 0.98 vs. 1.48 ± 0.22; p=0.001). In patients with detectable CTCs, those with low ApoA-1 levels had higher recurrence rates and shorter survival times. In vitro experiments showed that ApoA-1 can inhibit tumor cell proliferation through cell cycle arrest and promote apoptosis through down regulating mitogen-activated protein kinase (MAPK) pathway. In addition, ApoA-1 might impair extracellular matrix degradation properties of tumor cells. Taken together, our findings indicate that decreased serum ApoA-1 levels are a novel prognostic factor for HCC, and the role of ApoA-1 in inhibition of proliferation and promotion of apoptosis for tumor cells during their hematogenous dissemination are presumably responsible for the poor prognosis of patients with low ApoA-1 levels. Furthermore, AopA-1 might be a promising therapeutic target to reduce recurrence and metastasis for HCC patients after resection.
| S-EPMC5342581 | biostudies-literature
Project description:To identify plasma-based biomarkers for Parkinson disease (PD) risk.In a discovery cohort of 152 PD patients, plasma levels of 96 proteins were measured by multiplex immunoassay; proteins associated with age at PD onset were identified by linear regression. Findings from discovery screening were then assessed in a second cohort of 187 PD patients, using a different technique. Finally, in a third cohort of at-risk, asymptomatic individuals enrolled in the Parkinson's Associated Risk Study (PARS, n = 134), plasma levels of the top candidate biomarker were measured, and dopamine transporter (DAT) imaging was performed, to evaluate the association of plasma protein levels with dopaminergic system integrity.One of the best candidate protein biomarkers to emerge from discovery screening was apolipoprotein A1 (ApoA1; p = 0.001). Low levels of ApoA1 correlated with earlier PD onset, with a 26% decrease in risk of developing PD associated with each tertile increase in ApoA1 (Cox proportional hazards, p < 0.001, hazard ratio = 0.742). The association between plasma ApoA1 levels and age at PD onset was replicated in an independent cohort of PD patients (p < 0.001). Finally, in the PARS cohort of high-risk, asymptomatic subjects, lower plasma levels of ApoA1 were associated with greater putaminal DAT deficit (p = 0.037).Lower ApoA1 levels correlate with dopaminergic system vulnerability in symptomatic PD patients and in asymptomatic individuals with physiological reductions in dopamine transporter density consistent with prodromal PD. Plasma ApoA1 may be a new biomarker for PD risk.
| S-EPMC3773265 | biostudies-literature
Project description:The association of single nucleotide polymorphisms (SNPs) in the apolipoprotein (Apo) A1/C3/A4/A5 gene cluster and serum lipid profiles is inconsistent. The present study was undertaken to detect the association between the ApoA1/C3/A5 gene polymorphisms and their haplotypes with serum lipid levels in the general Chinese population.A total of 1030 unrelated subjects (492 males and 538 females) aged 15-89 were randomly selected from our previous stratified randomized cluster samples. Genotyping of the ApoA1 -75 bp G>A, ApoC3 3238C>G, ApoA5 -1131T>C, ApoA5 c.553G>T and ApoA5 c.457G>A was performed by polymerse chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Pair-wise linkage disequilibria and haplotype analysis among the five SNPs were estimated.The levels of high-density lipoprotein cholesterol (HDL-C) and ApoA1 were lower in males than in femailes (P < 0.05 for each). The allelic and genotypic frequencies of the SNPs were no significant difference between males and females except ApoC3 3238C>G. There were 11 haplotypes with a frequency >1% identified in the cluster in our population. At the global level, the haplotypes comprised of all five SNPs were significantly associated with all seven lipid traits. In particular, haplotype G-G-C-C-A (6%; in the order of ApoA5 c.553G>T, ApoA5 c.457G>A, ApoA5 -1131T>C, ApoC3 3238C>G, and ApoA1 -75bp G>A) and G-A-T-C-G (4%) showed consistent association with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), ApoA1, ApoB, and the ApoA1/ApoB ratio. In addition, carriers of haplotype G-G-T-C-G (26%) had increased serum concentration of HDL-C and ApoA1, whereas carriers of G-G-C-G-G (15%) had high concentrations of TC, triglyceride (TG) and ApoB. We also found that haplotypes with five SNPs explain much more serum lipid variation than any single SNP alone, especially for TG (4.4% for haplotype vs. 2.4% for -1131T>C max based on R-square) and HDL-C (5.1% for haplotype vs. 0.9% for c.553G>T based on R-square). Serum lipid parameters were also correlated with genotypes and several environment factors.Several common SNPs and their haplotypes in the ApoA1/C3/A5 gene cluster are closely associated with modifications of serum lipid parameters in the general Chinese population.
| S-EPMC3170230 | biostudies-literature
Project description:BackgroundSince 1920, a decrease in serum cholesterol has been identified as a marker of severe pneumonia. We have assessed the performance of serum apolipoprotein-A1, the main transporter of HDL-cholesterol, to identify the early spread of coronavirus disease 2019 (Covid-19) in the general population and its diagnostic performance for the Covid-19.MethodsWe compared the daily mean serum apolipoprotein-A1 during the first 34 weeks of 2020 in a population that is routinely followed for a risk of liver fibrosis risk in the USA (212,297 serum) and in France (20,652 serum) in relation to a local increase in confirmed cases, and in comparison to the same period in 2019 (266,976 and 28,452 serum, respectively). We prospectively assessed the sensitivity of this marker in an observational study of 136 consecutive hospitalized cases and retrospectively evaluated its specificity in 7,481 controls representing the general population.ResultsThe mean serum apolipoprotein-A1 levels in the survey populations began decreasing in January 2020, compared to the same period in 2019. This decrease was highly correlated with the daily increase in confirmed Covid-19 cases in the following 34 weeks, both in France and USA, including the June and mid-July recovery periods in France. Apolipoprotein-A1 at the 1.25 g/L cutoff had a sensitivity of 90.6% (95%CI84.2-95.1) and a specificity of 96.1% (95.7-96.6%) for the diagnosis of Covid-19. The area under the characteristics curve was 0.978 (0.957-0.988), and outperformed haptoglobin and liver function tests. The adjusted risk ratio of apolipoprotein-A1 for survival without transfer to intensive care unit was 5.61 (95%CI 1.02-31.0; P = 0.04).ConclusionApolipoprotein-A1 could be a sentinel of the pandemic in existing routine surveillance of the general population. NCT01927133, CER-2020-14.
| S-EPMC7679025 | biostudies-literature
Project description:Clinically-informative biomarkers of ischemic stroke are needed for rapid diagnosis and timely treatment. In the present study, APOA1 unique peptide (APOA1-UP), a novel peptide biomarker, was identified and quantified by multiple reaction monitoring (MRM) using labeled reference peptide (LRP). Serum samples of 94 patients in the ischemic stroke group and 37 patients in the non-stroke group were analyzed for the levels of total APOA1-UP, low density lipoprotein cholesterol (LDL-C), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and total cholesterol (TC). Median ratio of total APOA1-UP/LRP was 2.14 (interquartile range, 0.40) in the non-stroke group and 1.32 (0.44) in the ischemic stroke group (p < 0.0001). The serum level of total APOA1-UP was independently correlated with the presence of ischemic stroke by multivariate logistic regression analysis (p < 0.0001). From the receiver operating characteristic (ROC) curve, the area under the curve (AUC) was 0.9750 and the optimal cutoff value of the serum APOA1-UP level was 1.80, which yielded a sensitivity of 90.63% and a specificity of 97.14%. The diagnostic efficiency of HDL-C was lower, with an AUC of 0.7488. Therefore, the serum level of APOA1-UP is a diagnostic biomarker candidate for ischemic stroke in the early stage.
| S-EPMC4848914 | biostudies-literature
Project description:Early identification of severe acute pancreatitis (SAP) is critical for clinical decision-making. The apolipoprotein B-to-apolipoprotein A1 ratio (ApoB/A1 ratio) reflects the balance between pro-inflammation and anti-inflammation in vivo. This study investigated the association between serum ApoB/A1 ratio at admission and acute pancreatitis (AP) severity. A total of 375 patients with first attack of AP were retrospectively recruited from January 2014 to December 2017. The severity of AP was assessed at admission based on the 2012 revised Atlanta Classification. Serum lipids levels were tested on the first 24 h of hospitalization, of which the correlations with clinical features or scoring systems were also measured. The ApoB/A1 ratio markedly increased across disease severity of AP. The ApoB/A1 ratio, expressed as both quartile and continuous variables, was significantly associated with a high risk of SAP, even after adjustment for other conventional SAP risk factors. The ApoB/A1 ratio positively correlated with the revised 2012 Atlanta Classification, Ranson score, Bedside Index for Severity in AP score, Modified Computed Tomography Severity Index score, and Acute Physiology and Chronic Health Evaluation II score for AP severity. The optimal cut-off value of ApoB/A1 ratio for detecting SAP was 0.88, with a sensitivity of 83.08% and a specificity of 69.03%. Serum ApoB/A1 ratio at admission is closely correlated with disease severity in patients with AP and can serve as a reliable indicator for SAP in clinical setting.
| S-EPMC6533319 | biostudies-literature
Project description:BackgroundHuman T-lymphotropic virus 1 (HTLV-1) is etiologically associated with the chronic inflammatory neurodegenerative disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) Annexin A1 (AnxA1) is an anti-inflammatory protein with proposed neuroprotective and anti-neuroinflammatory functions. We hypothesized that ANXA1 gene expression may be dysregulated in HTLV-1-infected HAM/TSP patients.MethodsThis study involved 37 individuals infected with HTLV-1, including 21 asymptomatic (AS) carriers and 16 with HAM/TSP, and a control group of 30 individuals negative for HTLV-1 and HTLV-2. For AS HTLV-1-positive and HAM/TSP patients, ANXA1 and formyl peptide receptor (FPR1, FPR2 and FPR3) expression and HTLV-1 proviral load (PVL) in peripheral blood cells were evaluated by real-time quantitative PCR (qPCR), and plasma AnxA1 levels were determined by enzyme-linked immunosorbent assay (ELISA).ResultsANXA1 gene expression was increased in the AS group compared with the HAM/TSP and control groups, but the differences were not statistically significant. FPR1 gene expression was higher in patients with HTLV-1 than in controls (AS, p = 0.0032; HAM/TSP, p < 0.0001). Plasma AnxA1 levels were higher in the AS group than in the HAM/TSP group (p = 0.0045), and PVL was higher in patients with HAM/TSP than in AS individuals (p = 0.0162). The use of a combined ROC curve using Annexin 1 levels and proviral load significantly increased the sensitivity and specificity to predict progression to HAM/TSP (AUC = 0.851 and AUC = 0.937, respectively, to AUC = 1000).ConclusionsOur results suggest that AnxA1 may be dysregulated in HAM/TSP patients. Serological detection of AnxA1 in association with proviral load may provide a prognostic biomarker for HTLV-1-associated neurodegenerative disease.
| S-EPMC7908672 | biostudies-literature
Project description:The discovery of novel plasma-based biomarkers could lead to new approaches in the treatment of Parkinson's disease (PD). Here, we explore the role of plasma apolipoprotein A1 (ApoA1) as a risk marker for PD and evaluate the influence of APOA1 promoter variation on plasma ApoA1 levels. Plasma ApoA1 and the single-nucleotide polymorphism, rs670, were assayed in a discovery cohort (cohort 1) of 301 PD patients, 80 normal controls (NCs), and 165 subjects with other neurodegenerative diseases, as well as a cohort (cohort 2) of 158 PD patients from a second clinical site. Additionally, rs670 was genotyped in a third cohort of 1,494 PD and 925 NC subjects from both clinical sites. Compared to both normal and disease controls, PD patients have lower plasma ApoA1 (P < 0.001 for both comparisons). Moreover, in PD patients, plasma ApoA1 levels are correlated with genotype at the APOA1 promoter polymorphism, rs670. Specifically, lower plasma ApoA1 levels were found in rs670 major allele (G) homozygotes in both cohort 1 (P = 0.009) and in a replication cohort (cohort 2; n = 158 PD patients; P = 0.024). Finally, evaluating rs670 genotype frequencies in 1,930 PD cases versus 997 NCs, the rs670 GG genotype shows a trend toward association (odds ratio: 1.1; P = 0.10) with PD. Our results are compatible with a model whereby circulating ApoA1 levels may be useful in risk-stratifying subjects for the development of PD, with higher ApoA1 levels suggesting relative protection. Future studies evaluating modulation of ApoA1 as a novel therapeutic strategy in PD are warranted. © 2014 International Parkinson and Movement Disorder Society.
| S-EPMC4362847 | biostudies-literature
Project description:BACKGROUND:Early ante-mortem laboratory confirmation of human rabies is essential to aid patient management and institute public health measures. Few studies have highlighted the diagnostic value of antibody detection in CSF/serum in rabies, and its utility is usually undermined owing to the late seroconversion and short survival in infected patients. This study was undertaken to examine the ante-mortem diagnostic utility and prognostic value of antibody detection by rapid fluorescent focus inhibition test (RFFIT) in cerebrospinal fluid (CSF)/serum samples received from clinically suspected human rabies cases from January 2015 to December 2017. METHODOLOGY/PRINCIPAL FINDINGS:Samples collected ante-mortem and post-mortem from 130 and 6 patients with clinically suspected rabies respectively, were received in the laboratory during the study period. Ante-mortem laboratory confirmation was achieved in 55/130 (42.3%) cases. Real time PCR for detection of viral nucleic acid performed on saliva, nuchal skin, brain tissue and CSF samples could confirm the diagnosis in 15 (27.2%) of the 55 laboratory confirmed cases. Ante-mortem diagnosis could be achieved by RFFIT (in CSF and/or serum) in 45 (34.6%) of the 130 clinically suspected cases, accounting for 81.8% of the total 55 laboratory confirmed cases. The sensitivity of CSF RFFIT increased with the day of sample collection (post-onset of symptoms) and was found to be 100% after 12 days of illness. Patients who had received prior vaccination had an increased probability of a positive RFFIT and negative PCR result. Patients who were positive by RFFIT alone at initial diagnosis had longer survival (albeit with neurological sequelae) than patients who were positive by PCR alone or both RFFIT and PCR. CONCLUSIONS/SIGNIFICANCE:Detection of antibodies in the CSF/serum is a valuable ante-mortem diagnostic tool in human rabies, especially in patients who survive beyond a week. It was also found to have a limited role as a prognostic marker to predict outcomes in patients.
| S-EPMC6368332 | biostudies-literature
Project description:An immunosuppressive microenvironment plays a major role in the occurrence and development of tumors. Low apolipoprotein A1 (ApoA1) is closely related to tumor development, but the underlying mechanisms are unclear. This study investigated the association between the serum ApoA1 level and immune microenvironment in endometrial, ovarian, and lung cancers. The serum ApoA1 level was decreased significantly in patients with endometrial and ovarian cancers compared with healthy controls. In endometrial cancer tissues, the low serum ApoA1 group showed increased CD163+ macrophages and decreased CD8+ T cell infiltration compared with the normal serum ApoA1 group. Compromised tumor-infiltrating CD8+ T cell functions and decreased CD8+ T cell infiltration were also found in tumor-bearing ApoA1-knockout mice. CD8+ T cell depletion experiments confirmed that ApoA1 exerted its antitumor activity in a CD8+ T cell-dependent manner. In vitro experiments showed that ApoA1 mimetic peptide L-4F directly potentiated the antitumor activity of CD8+ T cells via the HIF-1α-mediated glycolysis pathway. Mechanistically, ApoA1 suppressed the ubiquitin-mediated degradation pathway of HIF-1α protein by downregulating HIF-1α subunit α inhibitor, which maintained the stability of HIF-1α protein and HIF-1α signal activation. Tumor-bearing ApoA1 transgenic mice showed an increased response to anti-PD-1 therapy with inhibited tumor growth and increased tumor necrosis. Here, the data demonstrate the critical roles of ApoA1 in enhancing CD8+ T cell immune functions via HIF-1α-mediated glycolysis, which supports clinical investigation of combined ApoA1 supplementation and anti-PD-1 therapy for tumors.
2024-05-08 | GSE252538 | GEO