scholarly journals Calgranulin C (S100A12) Is Differentially Expressed in Subtypes of Chronic Rhinosinusitis

2018 ◽  
Vol 32 (5) ◽  
pp. 380-387 ◽  
Author(s):  
Abigail Pulsipher ◽  
Brock M. Davis ◽  
Kristine A. Smith ◽  
Shaelene Ashby ◽  
Xuan Qin ◽  
...  

Background Calgranulin C (S100A12) is an innate immune peptide at the air–mucosal interface associated with neutrophil involvement, which when overexpressed has been implicated as a biomarker of inflammatory diseases. Decreased epithelial expression of certain innate immune peptides has been reported in chronic rhinosinusitis (CRS). We hypothesized that S100A12 is differentially expressed in the sinonasal mucosa of patients with CRS compared to controls and that S100A12 is a potential biomarker of CRS-specific quality of life (QOL) and disease severity. Methods A prospective observational study was conducted which included 70 patients: 17 controls, 28 having CRS without (CRSsNP), and 25 with (CRSwNP) nasal polyps. The expression of S100A12 and human neutrophil elastase (HNE) was assessed in the anterior ethmoid tissues from all patients using enzyme-linked immunosorbent assay (ELISA) and immunohistochemical (IHC) analyses. Disease-specific QOL (Rhinosinusitis Disability Index) and disease severity (computed tomography [CT] and endoscopy) were evaluated and correlated to the expression levels of S100A12. Results S100A12 and HNE were significantly elevated in patients with CRSsNP compared to normal controls ( P < .05 and P < .001, respectively) and patients with CRSwNP ( P < .05 and P < .001, respectively), as measured by ELISA and IHC analyses. Patients with CRS exhibited worse CRS-specific disease severity compared to normal controls ( P < .05), and the increased protein levels of S100A12 were significantly correlated to disease severity, represented by CT scores ( P < .05). Conclusions S100A12 is differentially expressed in CRS subtypes and is significantly elevated in patients with CRSsNP and associated with CRS-specific disease severity.

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1059
Author(s):  
Yu-Tsai Lin ◽  
Wei-Chih Chen ◽  
Ming-Hsien Tsai ◽  
Jing-Ying Chen ◽  
Chih-Yen Chien ◽  
...  

Janus kinase 2 (JAK2) is a member of the JAK family that transduces cytokine-mediated signals via the JAKs/STATs (signal transducer and activator of transcription proteins) pathway, which plays an important role in many inflammatory diseases. This study investigates the association of p-JAK2 and JAK2-associated cytokines from nasal polyp (NP) tissue with disease severity, and evaluates the p-JAK2-mediated STATs in chronic rhinosinusitis (CRS) with NP. Sixty-one CRSwNP patients with nasal polyps undergoing endoscopic sinus surgery were enrolled, while the turbinate tissues from 26 nasal obstruction patients were examined as the control group. Elevated levels of p-JAK2 were detected in CRSwNP, and significantly correlated with scores of disease severity (LMK-CT, TPS, and SNOT-22). Expressions of the JAK2-associated cytokines, such as IL-5, IL-6, IL-13, G-CSF, and IFN-γ were significantly higher in CRSwNP than in the controls, while the levels of IL-5, IL-6, IL-13, or G-CSF had positive correlation with scores of disease severity. Moreover, markedly increased expression of p-STAT3 in CRSwNP was observed relative to the control. Taken together, these data showed that the JAK2-associated cytokines including IL-6 and G-CSF may stimulate JAK2 phosphorylation to activate p-STAT3, indicating an association with disease severity and supporting its development of JAK2 inhibitor as a potential therapeutic agent for CRS.


2021 ◽  
Author(s):  
Ling-Yu Chu ◽  
Jian-Yuan Zhou ◽  
Yi-Xuan Zhao ◽  
Yan-Ting Ou ◽  
Tian Yang ◽  
...  

Background:Esophagogastric junction tumor (EGJ) is a rare but fatal disease with a rapid rising incidence worldwide in the late 20 years, and it lacks a convenient and safe method for diagnosis. This study aimed to evaluate the potential of serum CYR61 as a biomarker for the diagnosis of EGJ tumor. Methods: Enzyme-linked immunosorbent assay (ELISA) was used to estimate CYR61 levels in sera of 152 EGJ tumor patients and 137 normal controls. Receiver operating characteristics (ROC) was carried out to evaluate the diagnostic accuracy. The Mann–Whitney’s U test was used to compare the difference of serum levels of CYR61 between groups. And chi-square tests were employed to estimate the correlation of the positive rate of serum CYR61 between/among subgroups. Results: Serum CYR61 levels were statistically lower in EGJ tumor and early-stage EGJ tumor patients than those in normal controls (P&lt;0.0001). The sensitivity, specificity, and the area under the curve (AUC) of this biomarker in EGJ tumor were 88.2%, 43.8% and 0.691, respectively, and those for early stage of EGJ tumor were 80.0%, 66.4% and 0.722, respectively. Analyses showed that there was no correlation between the clinical data and the levels of CYR61 (P&gt;0.05). Conclusion: This study showed that CYR61 might be a potential biomarker to assist the diagnosis of EGJ tumor.


Author(s):  
Soo Kyoung Park ◽  
Rui-Ning Han ◽  
Jun Xu ◽  
Sun Hee Yeon ◽  
Sung Bok Lee ◽  
...  

Background and Objectives The nucleotide-binding oligomerization domain-like receptor (NLRP) 3 is known as a member of the NLR family, and it has been confirmed that the NLRP3 inflammasome is associated with various diseases such as asthma, inflammatory bowel disease, metabolic disorders and multiple sclerosis, as well as other auto-immune and auto-inflammatory diseases. However, the role of NLRP3 in chronic rhinosinusitis with nasal polyps (CRSwNP) has not yet been explored.Subjects and Method Forty-four specimens of nasal polyps and 25 specimens of uncinate processes were collected from patients with chronic rhinosinusitis with nasal polyps, and 25 specimens of uncinate tissues were collected from patients who underwent other rhino-surgeries. The western blot assay was employed to analyze the expression of NLRP3; interleukin (IL)-1β and IL-17A were detected using immunohistochemistry and real-time polymerase chain reaction. The production of lipopolysaccharide (LPS) induced IL-1β and IL-17A with or without the NLRP3 inflammasome inhibitor (MCC950) was measured using an enzyme linked immunosorbent assay in cultured dispersed nasal polyp cells.Results NLRP3 showed a high level of expression in nasal polyps than in the control group (<i>p</i><0.01). The expression of IL-1β and IL-17A was significantly higher in nasal polyps in the CRSwNP group than in the control group (<i>p</i><0.05). LPS-induced production of IL-1β was significantly suppressed by treatment with the NLRP3 inflammasome inhibitor (<i>p</i><0.05).Conclusion The NLRP3 inflammasome plays an essential role in the pathogenesis of CRSwNP, and thus MCC950 can be considered a prospective therapeutic for NLRP3 inflammasome-mediated inflammation in nasal polyps. Our data provide new evidence that IL-17A is involved in inflammasome-associated inflammation in nasal polyps.


2020 ◽  
Vol 7 ◽  
Author(s):  
Jun Liao ◽  
Qian Fu ◽  
Wenfang Chen ◽  
Jun Li ◽  
Wenhui Zhang ◽  
...  

Previous studies have implicated the role of CD146 and its soluble form (sCD146) in the pathogenesis of inflammatory diseases. However, the association between CD146 and acute rejection in kidney transplant patients remains unexplored. In this study, fifty-six patients with biopsy-proved rejection or non-rejection and 11 stable allograft function patients were retrospectively analyzed. Soluble CD146 in plasma was detected in peripheral blood by enzyme linked immunosorbent assay (ELISA), and local CD146 expression in graft biopsy was detected by immunohistochemistry. We found that plasma soluble CD146 in acute rejection recipients was significantly higher than in stable patients without rejection, and the biopsy CD146 staining in the rejection group was higher than that of the non-rejection group. Multivariate analysis demonstrated soluble CD146 as an independent risk factor of acute rejection. The area under the receiver operating characteristic curve (AUC) of sCD146 for AR diagnosis was 0.895, and the optimal cut-off value was 75.64 ng/ml, with a sensitivity of 87.8% and a specificity of 80.8%, which was better than eGFR alone (P = 0.02496). Immunohistochemistry showed CD146 expression in glomeruli was positively correlated with the Banff-g score, and its expression in tubules also had a positive relationship with the Banff-t score. Therefore, soluble CD146 may be a potential biomarker of acute rejection. Increased CD146 expression in the endothelial or tubular epithelial cells may imply that endothelial/epithelial dysfunction is involved in the pathogenesis of immune injury.


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.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hawra Abdulwahab ◽  
Muna Aljishi ◽  
Ameera Sultan ◽  
Ghada Al-Kafaji ◽  
Kannan Sridharan ◽  
...  

AbstractSickle cell disease, a common genetic blood disorder, results from a point mutation in the β-globin gene affecting the configuration of hemoglobin, predisposing to painful vaso-occlusive crisis (VOC) and multi-organ dysfunctions. There is a huge variation in the phenotypic expressions of SCD and VOC owing to genetic and environmental factors. This study aimed to characterize the whole blood gene expression profile using Microarray technology in Bahraini patients with SCD determining the differentially expressed genes in steady-state (n = 10) and during VOC (n = 10) in comparison to healthy controls (n = 8). Additionally, the study intended to identify potential genetic marker associated with hemolysis. The analysis identified 2073 and 3363 genes that were dysregulated during steady-state and VOC, respectively, compared to healthy controls. Moreover, 1078 genes were differentially expressed during VOC compared to steady state. The PLSCR4 gene was almost 6-fold up-regulated in microarray, 4-fold in polymerase chain reaction, and a mean protein concentration of 0.856 ng/ml was observed in enzyme-linked immunosorbent assay during VOC compared to steady-state (0.238 ng/ml) (p < 0.01). Amongst these genes, PLSCR4 is involved in erythrocyte membrane deformity thus, predisposing to hemolysis, adhesion, and thrombosis. In conclusion, PLSCR4 may serve as a potential biomarker for VOC and future large-scale validation are recommended.


2019 ◽  
Author(s):  
Guanhong Li ◽  
Cai Yue ◽  
Xiaohong Fan ◽  
Yubing Wen ◽  
Gang Chen ◽  
...  

Abstract Background: Circulating levels of aberrantly glycosylated IgA1 and its immune complexes (IgA/IgG-IC) are elevated and correlated with disease severity in IgA nephropathy (IgAN). The pathologic IgA containing immune complexes deposits in the kidney were found to be in dimeric or polymeric forms, suggesting that those deposited IgA immune complexes contain joining chain, which is critical for the multimerization and transportation of IgA. Both the dimeric IgA and polymeric IgA can cause renal damage by inducing the release of cytokines from mesangial cells. We aimed to investigate the urinary J chain containing IgG immune complexes/creatinine ratio (UJGCR) and analyze its relationship with disease severity in IgAN. Methods: The UJGCR were measured by sandwich enzyme linked immunosorbent assay in 26 patients with IgAN, 31 patients with other kidney diseases and 32 healthy volunteers. Results: The levels of UJGCR were higher in patients with IgAN than that in non-IgAN patients ( P =0.006) and healthy volunteers ( P <0.0001). Importantly, receiver operating characteristics curve analysis confirmed that UJGCR had good discrimination between non-IgAN patients and IgAN patients. The levels of UJGCR positively correlated with 24-hour urinary protein excretion (r=0.63, P =0.0006), serum creatinine (r=0.55, P =0.003), and negatively correlated with estimated glomerular filtration rate (r= -0.61, P =0.0008) in IgAN. Furthermore, the levels of UJGCR were higher in IgAN patients with IgA mesangial deposition of (+/++) than patients with (+++/++++). And IgAN patients with tubular atrophy/interstitial fibrosis showed higher levels of UJGCR than that without ( P =0.03). Similarly, the levels of urinary IgA-IgG/creatinine ratio (UAGCR) were also found to be elevated and associated with clinical and pathological parameters as UJGCR in IgAN. Besides, significant correlation between the levels of UJGCR and UAGCR was shown, suggesting UJGCR was mainly composed of J-IgA-IgG. Conclusions: The levels of UJGCR are associated with disease severity in IgAN. UJGCR is a potential biomarker for both glomerular and tubulointerstitial lesions in IgAN.


2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yan Wang ◽  
Zhaohui Zheng ◽  
Yuxian Yang ◽  
Jianan Lang ◽  
Ning Zhang ◽  
...  

Abstract Background Circulating angiopoietin-like 2 (ANGPTL2) protein levels are known to be significantly increased in numerous chronic inflammatory diseases and are associated with the diagnosis and/or prognosis of cardiovascular diseases, diabetes, chronic kidney disease, and various types of cancers. However, no data regarding the relationship between ANGPTL2 and diabetic foot ulcers (DFUs) are available. Here, we explored the potential link between ANGPTL2 and DFUs. Methods A total of 68 participants with type 2 diabetes mellitus (T2DM) were recruited, including 28 patients with DFU and 40 diabetic patients without DFUs. The clinical characteristics of T2DM patients with and without DFUs were compared. Serum concentrations of ANGPTL2 and VEGF were measured using enzyme-linked immunosorbent assay (ELISA) kits. The correlations between ANGPTL2 and clinical variables were analyzed. Multiple linear regression and logistic regression models were constructed to test the associations between ANGPTL2 and the severity and presence of DFUs. Results Serum levels of ANGPTL2 were higher in patients with DFUs than those in diabetic controls. Serum ANGPTL2 levels were higher in the advanced stages of DFUs. Spearman correlation analysis revealed strong positive associations of ANGPTL2 with CRP, VEGF and ESR in all subjects. In addition, serum ANGPTL2 was still positively correlated with DFUs stage after adjusting the risk factors. After adjusting for age, sex, HbA1C and duration of diabetes, ANGPTL2 was found to be independently associated with the presence of DFUs. Conclusions Circulating ANGPTL2 levels are an independent risk factor for DFUs. This suggests that ANGPTL2 may play important roles in the development of DFUs, a possibility that needs to investigated in prospective studies.


2021 ◽  
Vol 1 ◽  
pp. 97-101
Author(s):  
Faiq Gorial ◽  
Samaa Ezat ◽  
Mahmood Raheem Mahmood

Background: Rheumatoid arthritis is the most common cause of inflammatory polyarthritis. Interleukin‐37 (IL-37) has been found to play an important regulatory role in the development of inflammatory diseases. Objectives: To assess serum IL-37 level in rheumatoid arthritis (RA) patients compared to controls, to evaluate its diagnostic and predictive utility in RA patients and to investigate IL-37 level correlation with demographic and clinical characteristics of RA. Methods: Eighty subjects, 40 RA patients aged between 23-63 years and 40 healthy controls aged between 28-67 years were evaluated. An enzyme-linked immunosorbent assay (ELISA) was used to analyze the serum IL-37 levels. Results: Serum IL-37 was significantly higher in RA patients compared to healthy controls. At optimum cut off value of >58.275 pg/ml, serum IL-37 had 100% accuracy, positive predictive value, negative predictive value, sensitivity, and specificity. Serum IL‐37 level was not significantly related to Disease Activity Score of 28 joints‐erythrocyte sedimentation rate (DAS28‐ESR), also not correlated with C-reactive protein(CRP), rheumatoid factor(RF) and anti-cyclic citrullinated peptide antibody (Anti-CCP). Also there was no correlation between the level of IL-37 and treatment. Conclusions: IL-37 was significantly higher in RA patients compared to healthy controls with a high diagnostic and predictive ability, and may be a potential biomarker for diagnosis and prediction of RA.


2019 ◽  
Author(s):  
Guanhong Li ◽  
Cai Yue ◽  
Xiaohong Fan ◽  
Yubing Wen ◽  
Gang Chen ◽  
...  

Abstract Background: Circulating levels of aberrantly glycosylated IgA1 and its immune complexes (IgA/IgG-IC) are elevated and correlated with disease severity in IgA nephropathy (IgAN). The pathologic IgA containing immune complexes deposits in the kidney were found to be in dimeric or polymeric forms, suggesting that those deposited IgA immune complexes contain joining chain, which is critical for the multimerization and transportation of IgA. Dimeric IgA and polymeric IgA both can cause renal damage by inducing release of cytokines from mesangial cells. We aimed to investigate the urinary J chain containing IgG immune complexes/creatinine ratio (UJGCR) and analyze its relationship with disease severity in IgAN. Methods: The UJGCR were measured by sandwich enzyme linked immunosorbent assay in 26 patients with IgAN, 31 patients with other kidney diseases and 32 healthy volunteers. Results: The levels of UJGCR were higher in patients with IgAN than that in non-IgAN patients ( P =0.006) and healthy volunteers ( P <0.0001). Importantly, receiver operating characteristics curve analysis confirmed that UJGCR had good discrimination between non-IgAN patients and IgAN patients. The levels of UJGCR positively correlated with 24-hour urinary protein excretion (r=0.63, P =0.0006), serum creatinine (r=0.55, P =0.003), and negatively correlated with estimated glomerular filtration rate (r= -0.61, P =0.0008) in IgAN. Furthermore, the levels of UJGCR were higher in IgAN patients with IgA mesangial deposition of (+/++) than patients with (+++/++++). And IgAN patients with tubular atrophy/interstitial fibrosis showed higher levels of UJGCR than that without ( P =0.03). Similarly, the levels of urinary IgA-IgG/creatinine ratio (UAGCR) were also found to be elevated and associated with clinical and pathological parameters as UJGCR in IgAN. Besides, significant correlations between the levels of UJGCR and UAGCR were shown, suggesting UJGCR were mainly composed of J-IgA-IgG. Conclusions: The levels of UJGCR are associated with disease severity in IgAN. UJGCR is a potential biomarker for both glomerular and tubulointerstitial lesions in IgAN.


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