scholarly journals A Novel Diagnostic Predictive Model for Idiopathic Short Stature in Children

2021 ◽  
Vol 12 ◽  
Author(s):  
Jinghong Yuan ◽  
Zhi Du ◽  
Zhiwen Wu ◽  
Yanqin Yang ◽  
Xigao Cheng ◽  
...  

ObjectiveIdiopathic short stature (ISS), an endocrine-related disease, is difficult to diagnose. Previous studies have shown that many children with some inflammation-related diseases often have short stature, but whether inflammation is the underlying mechanism of ISS has not been studied. Here, we attempt to explore the role of inflammation in the occurrence and development of ISS and to demonstrate an available clinical diagnostic model of ISS.MethodsFrozen serum samples were collected from ISS patients (n = 4) and control individuals (n = 4). Isobaric tags for relative and absolute quantitation (iTRAQ) combined with LC-MS/MS analysis were applied to quantitative proteomics analysis. To assess clusters of potentially interacting proteins, functional enrichment (GO and KEGG) and protein-protein interaction network analyses were performed, and the crucial proteins were detected by Molecular Complex Detection (MCODE). Furthermore, serum levels of two selected proteins were measured by ELISA between ISS patients (n = 80) and controls (n = 80). In addition, experiments in vitro were used to further explore the effects of crucial proteins on endochondral ossification.ResultsA total of 437 proteins were quantified, and 84 DEPs (60 upregulated and 24 downregulated) were identified between patients with ISS and controls. Functional enrichment analysis showed that the DEPs were primarily enriched in blood microparticle, acute inflammatory response, protein activation cascade, collagen-containing extracellular matrix, platelet degranulation, etc. According to the results of top 10 fold change DEPs and MCODE analysis, C1QA and C1QB were selected to further experiment. The expression levels of C1QA and C1QB were validated in serum samples. Based on the logistic regression analysis and ROC curve analysis, we constructed a novel diagnostic model by serum levels of C1QA and C1QB with a specificity of 91.2% and a sensitivity of 75% (AUC = 0.900, p <0.001). Finally, the western blotting analysis confirmed the expression levels of OCN, OPN, RUNX2, and Collagen X were downregulated in chondrocytes, and the outcome of Collagen II was upregulated.ConclusionOur study is the first to demonstrate the significant role of inflammation in the development of ISS. In addition, we identify C1QA and C1QB as novel serum biomarkers for the diagnosis of ISS.

Author(s):  
Vinod Kumar ◽  
Bhupen Songra ◽  
Richa Jain ◽  
Deeksha Mehta

Background: the present study was under taken to determine the role of CA-125 in the diagnosis of acute appendicitis (AA), to prevent its complications and also in preventing negative appendicectomies in tertiary care hospital. Methods: The study was conducted at a tertiary care and research center between 01/03/2018 to 30/06/2019. Patients admitted to the surgery department with diagnosis of AA were considered for the study. After informed consent, a, standardized history was obtained as a case Performa. Serum samples from all the cases with clinical diagnosis of AA were obtained and stored. Only the cases with histopathologically approved AA were included in the study. Cases operated for clinical diagnosis of AA, but not histopathologically proven AA was not included in the study. CA125 levels in cases with definitive diagnosis of AA were measured. Results: In present study, ROC curve analysis revealed the sensitivity of 87.27 % and specificity of 90.91 % when the CA 125 cut-off value of > 16.8 was taken to diagnose acute appendicitis. AUC was 0.911 with a standard error of 0.0292. Conclusion: In this study we have observed that CA125 showed a positive correlation with acute appendicitis, that was statistically not significant (P>0.05). We didn’t evaluate the correlation with the disease severity. We consider that CA125 can be used as a marker in acute appendicitis cases although further research is still needed. Keywords: CA125, Acute Appendicitis, Surgery.


2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Shaohui Zong ◽  
Gaofeng Zeng ◽  
Ye Fang ◽  
Jinzhen Peng ◽  
Yong Tao ◽  
...  

Study Design.In this study, we investigated the role of IL-17 via activation of STAT3 in the pathophysiology of SCI.Objective.The purpose of the experiments is to study the expression of IL-17 and related cytokines via STAT3 signaling pathways, which is caused by the acute inflammatory response following SCI in different periods via establishing an acute SCI model in rat.Methods.Basso, Beattie, and Bresnahan hind limb locomotor rating scale was used to assess the rat hind limb motor function. Immunohistochemistry was used to determine the expression levels of IL-17 and p-STAT3 in spinal cord tissues. Western blotting analysis was used to determine the protein expression of p-STAT3 in spinal cord tissue. RT-PCR was used to analyze the mRNA expression of IL-17 and IL-23p19 in the spleen tissue. ELISA was used to determine the peripheral blood serum levels of IL-6, IL-21, and IL-23.Results.Compared to the sham-operated group, the expression levels of IL-17, p-STAT3, IL-6, IL-21, and IL-23 were significantly increased and peaked at 24 h after SCI. The increased levels of cytokines were correlated with the SCI disease stages.Conclusion.IL-17 may play an important role in promoting spinal cord neuroinflammation after SCI via activation of STAT3.


2011 ◽  
Vol 3 ◽  
pp. BIC.S7154 ◽  
Author(s):  
Veyis Itik ◽  
Ozgur Kemik ◽  
Ahu Kemik ◽  
A. Cumhur Dulger ◽  
Aziz Sümer ◽  
...  

Aims and background YKL-40 is secreted by several types of tumors. Increased serum YKL-40 levels have been reported in prostate, glioblastoma, breast and colorectal cancers. Determination of YKL-40 levels may serve as a valuable biomarker for the diagnosis and treatment of gastric cancer. The purpose of this study was to determine the serum YKL-40 levels expressed in gastric carcinomas. Methods Between 2009 and 2011, we retrospectively reviewed 100 patients with gastric cancer and compared their serum samples to 75 healthy volunteers. YKL-40 levels were determined by an enzyme-linked immunosorbent assay (ELISA). Results We found significantly higher serum levels of YKL-40 in patients with gastric cancer compared to the healthy population ( P < 0.0001). We also found significant differences in serum YKL-40 levels between female and male patients with gastric cancer ( P < 0.01). Conclusions YKL-40 is over-expressed in gastric cancer, suggesting a more aggressive phenotype. YKL-40 may be a useful serum biomarker for gastric cancer identification, and future studies should focus on the role of YKL-40 in the tumorigenesis of gastric cancer and responsiveness toward treatment.


2018 ◽  
Vol 26 (11) ◽  
pp. 1429-1438 ◽  
Author(s):  
Kai-Lun Hu ◽  
Hongcui Zhao ◽  
Zheying Min ◽  
Yilei He ◽  
Tianjie Li ◽  
...  

Kisspeptins are a family of neuropeptides that are essential for fertility. Recent experimental data suggest a putative role of kisspeptin signaling in the direct control of ovarian function. To explore the expression of KISS1 and KISS1 receptor (KISS1R) in human granulosa lutein cells and the potential role of KISS1/KISS1R system in the pathogenesis of polycystic ovary syndrome (PCOS), we measured the concentration of KISS1 in follicular fluid, the expression of KISS1 and KISS1R in granulosa lutein cells, and the circulating hormones. The expression levels of KISS1 and KISS1R were significantly upregulated in human granulosa lutein cells obtained from women with PCOS. The expression levels of KISS1 in human granulosa lutein cells highly correlated with those of KISS1R in non-PCOS patients, but not in patients with PCOS, most likely due to the divergent expression patterns in women with PCOS. Additionally, the expression levels of KISS1 highly correlated with the serum levels of anti-Müllerian hormone (AMH). The expression levels of KISS1 and KISS1R, as well as the follicular fluid levels of KISS1, were not significantly different between the pregnant and nonpregnant patients in both PCOS and non-PCOS groups. In conclusion, the increased expression of KISS1 and KISS1R in human granulosa lutein cells may contribute to the pathogenesis of PCOS. The expression levels of KISS1 highly correlated with the serum levels of AMH. The KISS1 and KISS1R system in the ovary may not have a remarkable role in predicting the in vitro fertilization (IVF) outcome.


Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2988-2988 ◽  
Author(s):  
Katsushige Inada ◽  
Yasushi Okoshi ◽  
Yukiko Cho ◽  
Hitoaki Saito ◽  
Tatsuo Iijima ◽  
...  

Abstract Introduction: MicroRNA (miRNA) is a class of non-coding small RNA (~22 nucleotides), which regulates post-transcriptional gene expression through binding to complementary sites of target messenger RNA. Recent studies have revealed that miRNA plays important roles in oncogenesis mainly by regulating oncogenes or tumor suppressor genes. As miRNA exists not only within cells but also in peripheral blood, circulating miRNA can be an easily obtainable cancer biomarker. Furthermore, circulating miRNA, which exists within exosomes or as a complex with particular proteins such as argonaute2, is a suitable and convenient sample for handling because of its stability. Based on these findings, this study planned to pursue the possibility that circulating miRNA could be used for the early diagnosis of diffuse large B-cell lymphoma (DLBCL). Materials and Methods: This study was performed with the permission of our IRB. Expression levels of mature miRNA (both the 5p and 3p strands) were evaluated using different types of materials, namely serum, exosome-enriched serum, and formalin-fixed paraffin-embedded (FFPE) tissue. Serum samples were obtained from patients with newly diagnosed DLBCL (n=33) or healthy volunteers (n=22) at our institution between 2012 and 2014. The exosome-enriched samples were obtained from serum using a total exosome isolation reagent (Invitrogen, CA). The FFPE biopsy samples were obtained from DLBCL lesions, mainly from lymph nodes (n=22), or from reactive hyperplastic lymph nodes (n=6). Based on the results of previous reports, ten miRNAs (the 5p and 3p strands of miR-15a, miR-21, miR-155, miR-181a, and miR-210) were selected as candidate biomarkers. Expression levels of miRNA were analyzed by the quantitative Real-Time PCR method, and were normalized to hsa-miR-24-3p. Diagnostic accuracy was evaluated using receiver operating characteristics (ROC) curve analysis. Results and Discussion: In serum samples, the expression levels of hsa-miR-15a-3p, hsa-miR-21-5p, hsa-miR-181a-5p, and hsa-miR-210-5p were significantly different between DLBCL patients and healthy volunteers (p<0.05). ROC curve analysis revealed that hsa-miR-15a-3p and hsa-miR-21-5p were valuable biomarkers for differentiating patients with DLBCL from healthy volunteers with an area under the ROC curve (AUC) of 0.676 (p=0.029) and 0.711 (p=0.009), respectively. However, substantial percentages of false-positive and false-negative samples were also observed. To improve diagnostic accuracy, we next analyzed the expression levels of miRNAs in exosome-enriched serum samples. Among the candidate miRNAs, expression levels of hsa-miR-15a-3p, hsa-miR-21-5p, and hsa-miR-181a-5p were significantly different between DLBCL and healthy volunteer in exosome-enriched serum samples (p<0.05). ROC curve analysis revealed that hsa-miR-15a-3p, hsa-miR-21-5p, and hsa-miR-181a-5p were valuable biomarkers with AUCs of 0.714 (p=0.033), 0.779 (p=0.001), and 0.672 (p=0.047), respectively. Contrary to these results, expression levels of these miRNAs in FFPE were not significantly different between DLBCL and reactive lymph nodes. We thus consider that some miRNAs in serum or exosome-enriched serum might be useful in the differential diagnosis of DLBCL. These miRNAs seem to be produced outside of the lymphoma tissue. To use miRNAs as an accurate and sensitive diagnostic biomarker, it is necessary to first identify lymphoma cell-derived miRNA in blood. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Maria Abreu ◽  
Marta Miranda ◽  
Mafalda Castro ◽  
Iolanda Fernandes ◽  
Renata Cabral ◽  
...  

The itch associated with cutaneous T-cell lymphoma (CTCL), including Mycosis Fungoides (MF) and Sézary syndrome (SS), is often severe and poorly responsive to treatment with antihistamines. Recent studies have highlighted the possible role of interleukins in nonhistaminergic itch. We investigated the role of IL-31 and IL-8 in CTCL, concerning disease severity and associated itch. Serum samples of 27 patients with CTCL (17 MF and 10 SS) and 29 controls (blood donors) were analyzed for interleukin- (IL-) 31 and IL-8; correlations with disease and itch severity were evaluated. IL-31 serum levels were higher in CTCL patients than in controls and higher in SS than in MF. Also, serum IL-31 levels were higher in patients with advanced disease compared to those with early disease, and they correlated positively with lactate dehydrogenase and beta 2-microglobulin levels, as well as with the Sézary cell count. Itch affected 67% of CTCL patients (MF: 47%; SS: 100%). Serum IL-31 levels were higher in itching patients than in controls and in patients without itching. There was no association between serum IL-8 and disease severity, nor with itching. Serum IL-8 levels correlated positively with peripheral blood leukocyte and neutrophil counts in CTCL patients. Our study suggests a role for IL-31 in CTCL-associated itch, especially in advanced disease and SS, offering a rational target for new therapeutic approaches. Increased serum IL-8 observed in some patients may be related to concomitant infections, and its role in exacerbating itch by recruiting neutrophils and promoting the release of neutrophil proteases deserves further investigation.


2020 ◽  
Vol 9 (12) ◽  
pp. 3968
Author(s):  
Jung-Sun Lee ◽  
Eun-Ju Lee ◽  
Jae-Hyun Lee ◽  
Seok-Chan Hong ◽  
Chang-Keun Lee ◽  
...  

Background: Patients with ankylosing spondylitis (AS) have increased levels of protein phosphatase magnesium-dependent 1A (PPM1A) and autoantibodies. We evaluated the usefulness of serum anti-PPM1A antibodies as a biomarker for AS. Methods: Serum samples from 58 AS patients were obtained from a multicenter registry prior to the initiation of anti-TNF agents. The serum levels of anti-PPM1A antibodies were measured using ELISA. Spinal radiographic progression was defined as an increase in the modified stoke ankylosing spondylitis spinal score (mSASSS) by ≥2 units or a newly developed syndesmophyte. The role of exogenous PPM1A on bone mineralization was evaluated using primary osteoprogenitors acquired from patients with AS and non-inflammatory controls. Results: The baseline levels of anti-PPM1A antibodies and mSASSS were higher in the radiographic progression group than in the non-progression group. In logistic regression analysis, baseline mSASSS and serum anti-PPM1A antibodies were associated with a higher risk of progression. The level of anti-PPM1A antibodies for predicting progression had an AUC of 0.716 (cut-off value: 43.77 ng/mL). PPM1A stimulation increased matrix mineralization in AS-osteoprogenitors but not in controls. Conclusion: Along with mSASSS, the serum levels of anti-PPM1A antibodies might be useful as a predictor of radiographic progression after treatment with anti-TNF agents.


2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 497-497 ◽  
Author(s):  
Michela Del Prete ◽  
Mario Scartozzi ◽  
Tiziana Prochilo ◽  
Luca Faloppi ◽  
Riccardo Giampieri ◽  
...  

497 Background: Although a demonstrated clinical efficacy, a non negligible proportion of colorectal cancer patients does not seem to benefit from regorafenib and are consequently exposed to unnecessary toxicity. LDH serum levels represent an indirect marker of tumour hypoxia, neo-angiogenesis and worse prognosis in many tumour types. In colorectal cancer LDH showed a correlation with treatment outcome for patients receiving antiangiogenetic treatment, thus suggesting a possible interaction with the activity profile of these drugs. We analyzed the role of LDH serum levels in predicting clinical outcome for pre-treated metastatic colorectal cancer patients receiving regorafenib. The final aim was to individuate a potentially reliable and easy to use marker for patients stratification. Methods: 118 colorectal cancer patients treated with regorafenib were available for our analysis. For all patients, LDH values were collected within one month before the procedure and after treatment end. LDH cutoff value was determined by ROC curve analysis, patients were then divided into two groups (A and B, below and above cut-off level respectively). Patients were also classified according to the variation in LDH serum levels pre- and post-treatment (increased patients vs. decreased patients). Results: Patients in group A and B proved homogeneous for all clinical characteristics analyzed. In group A patients median progression free survival (PFS) was 3.18 months, whereas it was 1.87 months in group B patients (p = 0.0018). Median overall survival (OS) was 6.23 months and 3.28 months in group A and B respectively (p = 0.048). Significant differences were not noted among the 2 groups for response rate. All the other clinical variables analyzed failed to show any correlation with patients outcome. Conclusions: Our observations seem to suggest a role of LDH as a marker of clinical outcome in colorectal cancer patients receiving regorafenib. We can then speculate that high LDH patients may not be optimal candidates for regorafenib. After further confirmation in larger trial, these findings may be relevant for a better patients stratification and selection.


2020 ◽  
Author(s):  
Lun Wu(Former Corresponding Author) ◽  
Wen-Bo Zhou ◽  
Jiao Zhou ◽  
Ying Wei ◽  
Hong-Mei Wang ◽  
...  

Abstract Background Circulating exosomal microRNAs are reflective of the characteristics of the tumor, are valuable biomarkers in different types of tumors, and play important roles in tumor progression and metastasis. The purpose of this study was to investigate the circulating exosomal microRNAs miRNA-21 and miRNA-210 as novel biomarkers for patients with pancreatic cancer (PC).Methods Serum exosomal microRNAs were extracted from the serum of PC and chronic pancreatitis (CP) patients using an RNA Isolation kit. To identify the exosomes in the serum, we used transmission electron micrographs for the crystalline structure, western blotting, and NanoSight for exosomal markers and nanoparticle characterization. The relative expression levels of exosomal microRNAs were quantified using quantitative PCR and compared between PC and CP patients.Results A total of 40 serum samples (30 PC and 10 CP) were collected. The expression levels of both exosomal miRNA-21 and miRNA-210 were obviously higher in PC patients compared with those in CP patients (both P<0.001). However, no significant difference in the relative serum levels of free miR-21 and miR-210 was observed between these two groups (both P>0.05). Exosomal miRNA-21 and miRNA-210 were related to tumor stage, as well as other factors. The diagnostic of exosomal miRNA-21 and miRNA-210 levels was 83% and 85%, respectively. Furthermore, when combining the expression of exosomal miRNA with serum CA19-9, the accuracy increased to 90%.Conclusions We herein identified that the serum exosomal miRNAs miRNA-21 and miRNA-210 may be of value as potential biomarkers and therapeutic targets for the diagnosis and treatment of PC.


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