scholarly journals β-Defensin 2, an Antimicrobial Peptide, as a Novel Biomarker for Ulcerative Interstitial Cystitis; Can β-Defensin 2 Suspect the Dysbiosis of Urine Microbiota?

Diagnostics ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 2082
Author(s):  
Sang Wook Lee ◽  
Si Hyun Kim ◽  
Kwang Woo Lee ◽  
Woong Bin Kim ◽  
Hae Woong Choi ◽  
...  

As urine is not sterile, inflammatory reactions caused by dysbiosis of the urinary microbiota may induce interstitial cystitis. A study was conducted to determine whether β-defensin 2 (BD-2), a specific antimicrobial peptide in the bladder, could be used as a novel diagnostic marker for ulcerative interstitial cystitis (IC). Urine samples from three female groups were examined: healthy controls (n = 34, Control group), non-Hunner type IC (n = 40, NHIC group), and Hunner type IC (n = 68, HIC group). Urine samples were collected via a transurethral catheter and assayed for BD-2 levels using enzyme linked immunosorbent assay. Under general or regional anesthesia, cystoscopy with diagnostic and therapeutic hydrodistension was performed in NHIC and HIC groups patients. These patients underwent a biopsy of the bladders. Based on the urinary specimens from 142 patients, BD-2 expression was found to be 18-fold higher in patients with Hunner type IC than in patients with non-Hunner type IC. The enhanced secretion of BD-2 exhibited a strong correlation with increased mast cell counts associated with bladder IC pathology. Enhanced urinary secretion of the antimicrobial peptide BD-2 from Hunner type IC patients associated with clinical phenotypes and demonstrated relatively robust levels to be used as a potential biomarker. Moreover, the increased urinary level of BD-2 may suggest a new possibility of biomarkers caused by dysbiosis of the urinary microbiota in ulcerative IC.

2010 ◽  
Vol 2 ◽  
pp. BIC.S6040 ◽  
Author(s):  
Yulia A. Savitskaya ◽  
Genaro Rico ◽  
Luis Linares ◽  
Roberto González ◽  
René Téllez ◽  
...  

Background Tumor immunology research has led to the identification of a number of tumor-associated self antigens, suggesting that most tumors trigger an immunogenic response, as is the case in osteosarcoma, where the detection of natural serum IgM antibodies might achieve the diagnosis of osteosarcoma. Natural IgM antibodies to tumor-associated proteins may expand the number of available tumor biomarkers for osteosarcoma and may be used together in a serum profile to enhance test sensitivity and specificity. Natural IgM antibodies can be consistently detected in the peripheral blood sera months to years before the tumor is diagnosed clinically. The study of the level of a potential biomarker many months (or years) prior to diagnosis is fundamentally important. Integrated circulating and imaging markers in clinical practice treating osteosarcoma have potential applications for controlling tumor angiogenesis. Objectives To study the expression of natural IgM antibodies to the tumor antigens of angiogenesis in the peripheral blood sera of osteosarcoma patients and healthy individuals, and to develop serum-based predictive biomarkers. Methods Peripheral venous blood samples were collected from 117 osteosarcoma patients and 117 patients with other tumors. All diagnosis was histologically confirmed. Staging of patients was performed according to the Enneking Surgical Staging System. The control group consisted of 117 age- and sex- matched healthy individuals. In this study, novel immunoconjugates were designed, synthesized and then used to develop a rapid, specific and sensitive enzyme-linked immunosorbent assay (ELISA) method to detect angiogenin (ANG)–IgM directly in the peripheral blood sera of humans. Results Serum ANG–IgM levels are significantly higher in osteosarcoma patients than in healthy individuals ( P < 0.005). Serum ANG–IgM levels varied widely, but were highly dependent on the concentration of IgM (r = 0.85; P < 0.0005). We found ANG–IgM in the sera of 85% of newly diagnosed osteosarcoma patients and ANG–IgM levels were significantly higher in osteosarcoma patients compared to any other tumors ( P < 0.001). Conclusions These results demonstrated that the combined biomarker ANG–IgM has greater sensitivity and specificity in early diagnosis of osteosarcoma patients than the traditional biomarkers (ANG and vascular endothelial growth factor). Circulating ANG–IgM immune complexes can potentially serve as a biomarker for increased risk of osteosarcoma, because relatively high serum levels were also detected in otherwise healthy individuals with a first degree family history of osteosarcoma and in patients with a diagnosis of benign conditions. Immunological aspects of angiogenesis for managing osteosarcoma will have a practical value in early diagnosis, prognosis and monitoring response to antiangiogenic therapy.


2018 ◽  
Vol 2018 ◽  
pp. 1-5 ◽  
Author(s):  
Valéria C. Sandrim ◽  
Mayara Caldeira-Dias ◽  
Heloisa Bettiol ◽  
Marco Antonio Barbieri ◽  
Viviane Cunha Cardoso ◽  
...  

Preeclampsia is the major cause of maternal and fetal deaths worldwide. Circulating biomarker concentrations to predict preeclampsia must be determined. Therefore, the objective was to evaluate heme oxygenase-1 (HO-1) concentration in both plasma and urine samples from pregnant women before the development of preeclampsia and to identify a potential biomarker for preeclampsia development. We performed a case-control study nested in a prospective study cohort at University Hospital of the Ribeirao Preto Medical School, University of São Paulo (HCFMRP-USP), Ribeirao Preto, Brazil. Of 1400 pregnant women evaluated at 20–25 weeks of gestation, 460 delivered in hospitals outside our institution. Of 940 pregnant women who completed the protocol, 30 developed preeclampsia (cases, 14 cases of severe preeclampsia and 16 cases of mild preeclampsia). Healthy pregnant women (controls, n=90) were randomly selected from the remaining 910 participants. HO-1 concentration was evaluated in plasma/urine samples by using a commercial enzyme-linked immunosorbent assay kit. We found similar HO-1 levels in the plasma and urine for case and control groups. In the subgrouped preeclampsia, lower plasma HO-1 levels were found in mild compared with severe preeclampsia. We conclude that plasma HO-1 levels were not altered at 20–25 weeks of gestation before the manifestation of preeclampsia symptoms. Pregnant women who subsequently develop severe preeclampsia show higher expression of HO-1. This may be indicative of important underlying pathophysiologic mechanisms that differentiate between mild and severe preeclampsia and may possibly be related to a higher prooxidative status even before the development of clinical symptoms.


2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Zhaoqiang Jiang ◽  
Shibo Ying ◽  
Wei Shen ◽  
Xianglei He ◽  
Junqiang Chen ◽  
...  

Fibulin-3 has been reported as a potential biomarker for mesothelioma. However, little is known about the diagnostic efficacies of fibulin-3 for asbestos-related diseases (ARDs) in China. This study was to investigate the utility of fibulin-3 for asbestos exposure and ARDs. A total of 430 subjects were recruited from Southeast China, including healthy individuals, asbestos-exposed (AE) individuals, and patients with pleural plaques (PP), asbestosis, and malignant pleural mesothelioma (MPM). Plasma fibulin-3 was measured using the enzyme-linked immunosorbent assay. Linear regression analyses were applied to explore the influencing factors of fibulin-3. Receiver operating characteristic curves were used to determine the cutoff values. The median fibulin-3 level of subjects in the mesothelioma group was higher than that in other groups. Subjects in the asbestosis group had higher median fibulin-3 level than those in the control group. A higher fibulin-3 level was found in the group with ≥10 years of asbestos exposure as compared with control groups. The AUCs of fibulin-3 for distinguishing MPM subjects from control, AE, PP, and asbestosis subjects were 0.92, 0.88, 0.90, and 0.81, respectively. Our study provided evidence that fibulin-3 could be a potential biomarker for the early screening of MPM, but not of other nonmalignant ARDs in Chinese populations.


2020 ◽  
Author(s):  
Bárbara Santana ◽  
Maria Alice Queiroz ◽  
Rodrigo Cerveira ◽  
Claudia Rodrigues ◽  
Ednelza Amoras ◽  
...  

Abstract Background: Human 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.Methods: This 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). Results: ANXA1 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=1,000). Conclusions: Our 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.


2021 ◽  
Vol 24 (4) ◽  
pp. E611-E618
Author(s):  
Xiong Zhang ◽  
Ya-Wang Shao ◽  
Ya-Lan Zhang ◽  
Yi Liu

Background: Kawasaki disease (KD) is an inflammatory disease associated with coronary vasculitis in children. In this study, we explored the correlation between Lipoprotein associated phospholipase A2 (Lp-PLA2) and coronary artery lesions (CAL) in children with KD. Methods: Ninety-three children with KD were divided into a normal coronary artery (NCA, 54 cases) group and coronary artery lesions (CAL, 39 cases) group, according to the results of echocardiography. Another 42 healthy children were selected as the control group. The serumal levels of Lp-PLA2, Interferon-γ(IFN-γ) and Interleukin-6 (IL-6) were determined by using an enzyme-linked immunosorbent assay. In addition, erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) level were analyzed. The left main coronary artery (LMCA), diameters of left anterior descending coronary artery (LADC), right proximal coronary artery (PRCA), and carotid intima-media thickness (IMT) were obtained by color Doppler ultrasound. The correlation between the above indexes and KD was analyzed. Results: The levels of white blood cell counts (WBC), ESR, CRP, IFN-γ, IL-6 and Lp-PLA2 as well as IMT were significantly increased in KD children (P < 0.05), and the levels of CRP, IFN-γ, IL-6 and Lp-PLA2 as well as IMT in the CAL group increased more significantly (P < 0.05). An increasing trend also has been described in the diameters of LMCA, LADC and PRCA for KD children with CAL compared with with NCA. The results of logistic regression analysis showed that the elevated levels of CRP, IFN-γ, IL-6 and Lp-PLA2 were independent risk factors for KD with CAL. Correlation analysis showed that Lp-PLA2 level was positively correlated with the levels of IFN-γ, IL-6 and CRP in CAL group and NCA group (respectively, all P < 0.01). In addition, a similar correlation was also described between Lp-PLA2 level and the diameters of LMCA, LADC and PRCA in CAL group (respectively, all P < 0.01). Conclusion: Lp-PLA2 may participate in the pathological mechanism of KD. Detection of the serum Lp-PLA2 level can be used in the diagnosis of KD disease and the assessment of coronary artery lesions in KD children.


2020 ◽  
Vol 2020 ◽  
pp. 1-5
Author(s):  
Yuanzhen Chen ◽  
Liangke Liang ◽  
Shengnan Cao ◽  
Guangjian Hou ◽  
Qian Zhang ◽  
...  

Objective. Cognitive impairment is considered to be an important complication of spinal cord injury (SCI), but its underlying mechanism remains unclear. The purpose of this study is to explore whether serum CCL21 can be used as a potential biomarker of cognitive impairment in SCI. Methods. In Neck-Shoulder and Lumbocrural Pain Hospital, Shandong First Medical University & Shandong Academy of Medical Sciences, hospitalized or treated acute SCI patients were included in the study as the SCI group (SCI). At the same time, a normal control group (NC) matching the age and sex of the SCI group was recruited in the outpatient clinic. Once the two groups were enrolled, their demographics and clinical characteristics were collected immediately. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum CCL21 levels within 24 hours of admission. Three months later, the Montreal Cognitive Assessment (MoCA) was used to test the cognitive function of the population. Results. A total of 84 SCI patients and 49 NC populations were eligible for inclusion in the study. There was no significant statistical difference in the demographics and clinical characteristics (age, gender, BMI, TG, LDL-C, FBG, SBP, and DBP) between the two groups ( p > 0.05 ). Compared with the NC group, the SCI group had a higher serum CCL21 level ( p < 0.001 ) and a lower MoCA score ( p < 0.001 ). Serum CCL21 level in SCI was negatively correlated with MoCA score ( p = 0.023 ). Multivariable analyses showed that serum CCL21 level is an independent prognostic factor of cognitive impairment in SCI. Conclusions. MoCA score has a linear relationship with serum CCL21 quartile, and SCI cognitive function has a negative correlation with serum CCL21. Serum CCL21 is an independent risk factor for cognitive impairment after SCI.


2018 ◽  
Vol 46 (6) ◽  
pp. 2576-2586 ◽  
Author(s):  
Min Jiang ◽  
Gendie E. Lash ◽  
Xueqing Zhao ◽  
Yan Long ◽  
Caijiao Guo ◽  
...  

Background/Aims: Circular RNAs (circRNAs) are transcribed prevalently in the genome; however, their potential roles in multiple cardiovascular diseases, particularly preeclampsia (PE), are not yet well understood. This study investigated the expression profiles of circRNAs and explored circRNA-mediated pregnancy-associated plasma protein A (PAPP-A) expression as a potential biomarker for PE before 20 weeks of pregnancy. Methods: A nested case-control two-phase screening/validation study was performed in pregnant women before 20 weeks of gestation (before clinical diagnosis) at Guangzhou Women and Children’s Medical Center from 2012 to 2015. In the screening phase, circRNA expression profiles of blood cells were assessed using a human circRNA microarray, which was designed to detect simultaneously 5396 circRNAs, in 5 patients with PE and 5 age- and gestational week-matched controls. In the validation phase, 18 circRNAs in blood cells predicted by bioinformatics tools were validated by quantitative reverse transcription PCR in a cohort of 60 patients (PE and age-, gestational week-, and sample storage time-matched controls). Then, we examined the involvement of circRNAs in PE-related pathways via interactions with miRNAs by multiple bioinformatics approaches. Bioinformatics analysis predicted that hsa_circ_0004904 and hsa_circ_0001855 miRNA sponges directly target PAPP-A. PAPP-A was verified in the serum of the same cohort of patients using an enzyme-linked immunosorbent assay. Finally, we combined PAPP-A with circRNAs to create a novel preclinical diagnostic model for PE with logistic regression and evaluated the efficiency of this model with receiver operating curve analysis. Results: Volcano plot analysis using various parameters showed that circRNAs were differentially expressed among both groups (P < 0.01, fold change > 2). In the screening phase, we found that 2178 circRNAs were differentially expressed between the control and PE groups, in which 884 circRNAs were downregulated and 1294 circRNAs were upregulated in the PE group compared with the control group. In the validation phase, two circRNAs, hsa_circ_0004904 and hsa_circ_0001855, were significantly upregulated in PE patients compared with healthy pregnant women (P < 0.05). PAPP-A expression levels, related to the two circRNAs based on bioinformatics prediction, were increased in the PE group compared with the control group. The area under the curve of the combined model was 0.94 in the predicted PE subjects. Conclusions: This is the first study to report circRNA profiling in patients with PE prior to the onset of symptoms. Our data suggested that hsa_circ_0004904 and hsa_circ_0001855 combined with PAPP-A might be promising biomarkers for the detection of PE. Moreover, circRNAs may provide new insights into the potential mechanisms underlying the pathophysiology of PE.


Author(s):  
Yumi Watanabe ◽  
Yoshitoshi Hirao ◽  
Kensaku Kasuga ◽  
Takayoshi Tokutake ◽  
Kaori Kitamura ◽  
...  

Introduction: Biomarkers of Alzheimer’s disease (AD) that can easily be measured in routine health checkups are desirable. Urine is a source of biomarkers that can be collected easily and noninvasively. We previously reported on the comprehensive profile of the urinary proteome of AD patients and identified proteins estimated to be significantly increased or decreased in AD patients by a label-free quantification method. The present study aimed to validate urinary levels of proteins that significantly differed between AD and control samples from our proteomics study (i.e., apolipoprotein C3 [ApoC3], insulin-like growth factor-binding protein 3 [Igfbp3], and apolipoprotein D [ApoD]). Methods: Enzyme-linked immunosorbent assays (ELISAs) were performed using urine samples from the same patient and control groups analyzed in the previous proteomics study (18 AD and 18 controls, set 1) and urine samples from an independent group of AD patients and controls (13 AD, 5 mild cognitive impairment [MCI], and 32 controls) from the National Center for Geriatrics and Gerontology Biobank (set 2). Results: In set 1, the crude urinary levels of ApoD, Igfbp3, and creatinine-adjusted ApoD were significantly higher in the AD group relative to the control group (p = 0.003, p = 0.002, and p = 0.019, respectively), consistent with our previous proteomics results. In set 2, however, the crude urinary levels of Igfbp3 were significantly lower in the AD+MCI group than in the control group (p = 0.028), and the levels of ApoD and ApoC3 did not differ significantly compared to the control group. Combined analysis of all samples revealed creatinine-adjusted ApoC3 levels to be significantly higher in the AD+MCI group (p = 0.015) and the AD-only group (p = 0.011) relative to the control group. Conclusion: ApoC3 may be a potential biomarker for AD, as validated by ELISA. Further analysis of ApoC3 as a urinary biomarker for AD is warranted.


2020 ◽  
Vol 14 (02) ◽  
pp. 239-244 ◽  
Author(s):  
Teodora Karteva ◽  
Neshka Manchorova-Veleva

Abstract Objectives Asymptomatic apical periodontitis (AAP) is one of the most widespread chronic inflammatory diseases in the field of dental medicine. Active matrix metalloproteinase (aMMP-8) previously demonstrated diagnostic potential as a biomarker for AAP in gingival crevicular fluid (GCF). The aim of this study was to determine the levels and diagnostic accuracy of aMMP-8 in GCF from teeth with AAP. Materials and Methods In this cross-sectional study, GCF samples were obtained from teeth with AAP (sample group, n = 31) and their contralateral teeth (control group, n = 31). Clinical and cone beam computed tomography (CBCT) parameters were used for the diagnosis and assessment of AAP and the determination of clinically healthy marginal periodontal tissues. One pool GCF sample per tooth was obtained from the whole crevice’s perimeter. aMMP-8 levels were determined by enzyme-linked immunosorbent assay (ELISA). Statistical Analysis Wilcoxon signed ranks test and Spearman rank correlation coefficient (rs) were used as statistical tools. The significance level was set at p < .05. Results The two groups demonstrated biomarker levels corresponding to a healthy marginal periodontal tissue. aMMP-8 levels were statistically and significantly higher in the samples collected from teeth with AAP. Lesions with greater volume showed correspondingly larger diameters. No statistically significant correlation between aMMP-8 levels and lesions’ volume or diameter was discovered. Conclusion GCF composition is modified by AAP only to a minimal extent. Further research is needed to substantiate the utilization of aMMP-8 as a potential biomarker for the diagnosis of the disease as well as to explore its relationship with other biomarkers.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Bárbara Brasil Santana ◽  
Maria Alice Freitas Queiroz ◽  
Rodrigo Arcoverde Cerveira ◽  
Claudia Mendonça Rodrigues ◽  
Ednelza da Silva Graça Amoras ◽  
...  

Abstract Background Human 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. Methods This 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). Results ANXA1 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). Conclusions Our 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.


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