scholarly journals The effect of BKV reactivation on cytokines behavior in kidney transplanted patients

2022 ◽  
Vol 23 (1) ◽  
Author(s):  
Zahra Rahimi ◽  
Ramin Yaghobi ◽  
Afsoon Afshari ◽  
Jamshid Roozbeh ◽  
Mohammad Javad Mokhtari ◽  
...  

Abstract Background BK virus associated nephropathy (BKVAN) is one of the common causes of graft loss among kidney transplanted recipients (KTRs). The current treatment for BKV nephropathy is decreasing the immunosuppressive regimen in KTRs. Interleukin-27 (IL-27) is a multifunctional cytokine that might be the front-runner of an important pathway in this regard. Therefore, in current study it is tried to evaluate the changes in the expression level of IL-27 and some related molecules, resulting from BKV reactivation in KTR patients. Methods EDTA-treated blood samples were collected from all participants. Patients were divided into two groups, 31 kidney transplant recipients with active and 32 inactive BKV infection, after being monitored by Real time PCR (Taq-Man) in plasma. Total of 30 normal individuals were considered as healthy control group. Real time PCR (SYBR Green) technique is used to determine the expression level of studied genes. Results The results of gene expression comparisons showed that the expression level of IL-27, IFN-γ, TNF-α, TNFR2 and IRF7 genes was significantly higher in inactive group in comparison to active group. The expression level of TLR4 was lower in both active and inactive groups in comparison to control group. ROC curve analysis showed that IL-27 and IRF7 are significantly different amongst other studied genes. Finally, the analyses revealed that the expression level of most of the studied genes (except for TNF-α and TLR4) have significant correlation with viral load. Conclusions Our findings revealed that IL-27, IFN-γ, TNF-α, TNFR2 and IRF7 expression level is higher in inactive group and TLR4 expression level is lower in patients’ groups in comparison to control group. Also, ROC curve analysis showed IL-27 and IRF7 can significantly differentiate studied groups (BKV active vs. inactive). Therefore, these results might help elucidating the pattern in charge of BKV reactivation in kidney transplanted patients.

2021 ◽  
Vol 70 (3) ◽  
Author(s):  
S. Abbes ◽  
H. Sellami ◽  
S. Neji ◽  
H. Trabelsi ◽  
F. Makni ◽  
...  

Introduction. Trichosporon asahii has been recognized as an opportunistic agent having a limited sensitivity to antifungal treatment. Hypothesis/Gap Statement. Molecular mechanisms of azole resistance have been rarely reported for Trichosproron asahii. Similar to other fungi, we hypothesized that both ERG11 gene mutation and efflux pumps genes hyper-expression were implicated. Aim. The current work aimed to study the sensitivity of clinical T. asahii isolates to different antifungal agents and to explore their resistance mechanisms by molecular methods including real-time PCR and gene sequencing. Methods. The sensitivity of T. asahii isolates to fluconazole, amphotericin B and voriconazole was estimated by the Etest method. Real-time PCR was used to measure the relative expression of Pdr11, Mdr and ERG11 genes via the ACT1 housekeeping gene. Three pairs of primers were also chosen to sequence the ERG11 gene. This exploration was followed by statistical study including the receiver operating characteristic (ROC) curve analysis to identify a relationship between gene mean expression and the sensitivity of isolates. Results. In 31 clinical isolates, the resistance frequencies were 87, 16.1 and 3.2 %, respectively, for amphotericin B, fluconazole and voriconazole. Quantitative real-time PCR demonstrated that only Mdr over-expression was significantly associated with FCZ resistance confirmed by univariate statistical study and the ROC curve analysis (P <0.05). The ERG11 sequencing revealed two mutations H380G and S381A in TN325U11 (MIC FCZ=8 µg ml−1) and H437R in TN114U09 (MIC FCZ=256 µg ml−1) in highly conserved regions (close to the haem-binding domain) but their involvement in the resistance mechanism has not yet been assigned. Conclusion. T. asahii FCZ resistance mechanisms are proven to be much more complex and gene alteration sequence and/or expression can be involved. Only Mdr gene over-expression was significantly associated with FCZ resistance and no good correlation was observed between FCZ and VCZ MIC values and relative gene expression. ERG11 sequence alteration seems to play a major role in T. asahii FCZ resistance mechanism but their involvement needs further confirmation.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xin Zhang ◽  
Ming-Feng Hsueh ◽  
Janet L. Huebner ◽  
Virginia B. Kraus

ObjectivesTo identify plasma extracellular vesicles (EVs) associated with radiographic knee osteoarthritis (OA) progression.MethodsEVs of small (SEV), medium (MEV) and large (LEV) sizes from plasma of OA participants (n=30) and healthy controls (HCs, n=22) were profiled for surface markers and cytokine cargo by high-resolution flow cytometry. The concentrations of cytokines within (endo-) and outside (exo-) EVs were quantified by multiplex ELISA. EV associations with knee radiographic OA (rOA) progression were assessed by multivariable linear regression (adjusted for baseline clinical variables of age, gender, BMI and OA severity) and receiver operating characteristic (ROC) curve analysis.ResultsBased on integrated mean fluorescence intensity (iMFI), baseline plasma MEVs carrying CD56 (corresponding to natural killer cells) predicted rOA progression with highest area under the ROC curve (AUC) 0.714 among surface markers. Baseline iMFI of TNF-α in LEVs, MEVs and SEVs, and the total endo-EV TNF-α concentration, predicted rOA progression with AUCs 0.688, 0.821, 0.821, 0.665, respectively. In contrast, baseline plasma exo-EV TNF-α (the concentration in the same unit of plasma after EV depletion) did not predict rOA progression (AUC 0.478). Baseline endo-EV IFN-γ and exo-EV IL-6 concentrations were also associated with rOA progression, but had low discriminant capacity (AUCs 0.558 and 0.518, respectively).ConclusionsPlasma EVs carry pro-inflammatory cargo that predict risk of knee rOA progression. These findings suggest that EV-associated TNF-α may be pathogenic in OA. The sequestration of pathogenic TNF-α within EVs may provide an explanation for the lack of success of systemic TNF-α inhibitors in OA trials to date.


2019 ◽  
Vol 26 (5) ◽  
pp. 341-350
Author(s):  
Zhao-Juan Er ◽  
Chun-Fang Yin ◽  
Wen-Jing Wang ◽  
Xue-Jun Chen

This study aimed to examine whether stromal cell-derived factor-1 (SDF-1) or C-X-C chemokine ligand 12 (CXCL12) participates in the development of lumbar disc degeneration, as implicated earlier by the level of CXCL12 correlating with this disease. It enrolled 145 patients with symptomatic lumbar intervertebral disc degeneration (IDD) and 130 asymptomatic healthy controls with no indication of IDD. Radiological assessment of the IDD patients was targeted at the lumbar vertebra region, based on Pfirrmann grade. Degeneration of the multifidus and psoas major muscles was evaluated using Goutallier classification. Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI) scores were obtained for assessing the severity of manifestation. The levels of serum CXCL12, IL-6 and TNF-α were determined by ROC curve analysis, resulting in their prognostic value for Pfirrmann grading. Higher levels of serum CXCL12 were found in patients with IDD than in asymptomatic individuals, and were positively related to the Pfirrmann grade as well as multifidus muscle degeneration. Furthermore, serum CXCL12 concentration showed a significant correlation with the VAS and ODI scores. In addition, elevated serum CXCL12 levels were related to serum levels of TNF-α and IL-6. The ROC curve analysis implicated that CXCL12 could function as a biomarker of the early-mediate phase of IDD development. In summary, the serum CXCL12/SDF-1 level is positively related with lumbar IDD and its clinical severity.


2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Huandi Zhou ◽  
Le Jiang ◽  
Guohui Wang ◽  
Linlin Su ◽  
Liubing Hou ◽  
...  

Object. Hepatocellular carcinoma is one of the most common malignant tumors worldwide owing to its complicated molecular and cellular heterogeneity and its high incidence rate every year. It is an urgent need to search for new efficient molecular markers of HCC to reduce mortality and improve HCC prognosis. In this article, MCM4, a member of a family of proteins closely related to DNA replication and cell proliferation, was selected as a potential biomarker of HCC prognosis. Methods. MCM4 expression difference in HCC were analyzed from TCGA and GEO data and verified by real-time PCR and western blot. ROC curve was used to analyze the diagnostic value of MCM4 and AFP. Additionally, the relationship between MCM4 and stage or nodal metastasis status or grade or age in TCGA cohort with HCC was observed from the UALCAN website. The univariate and multivariate Cox and functional analyses were done to explore the prognostic value of MCM4 in TCGA cohort. Results. It was found that MCM4 was significantly highly expressed in HCC tissues from TCGA, GEO, and experimental data. Furthermore, ROC curve analysis showed that MCM4 was superior to be a diagnostic biomarker than AFP from TCGA ( AU C MCM 4 = 0.9461 , AU C AFP = 0.7056 ) and GEO (GSE19665: AU C MCM 4 = 0.8800 , AU C AFP = 0.5100 ; GSE64041 AU C MCM 4 = 0.8038 , AU C AFP = 0.6304 ). AUC of MCM4 from real-time PCR result in 60 pairs of HCC and adjacent tissues was 0.7172, demonstrating the prediction value of MCM4. Besides, different expression tendencies of MCM4 among different stages or nodal metastasis status or grade or age were observed from the UALCAN website. In addition, multiROC analysis showed the advantage of MCM4 as a survival prediction at 1, 3, and 5 years with the higher AUC at 0.69 of 1 year, 0.65 of 3 years, and 0.61 of 5 years. It was shown that MCM4 was independently associated with OS in univariate and multivariate Cox analysis. And GSEA displayed that MCM4 was highly enriched in KEGG_CELL_CYCLE signaling pathway following higher correlation positively with CDC6, PLK1, CRC1, and BUB1B in HCC. Conclusion. MCM4 might be a potential biomarker in guiding the prognostic status of HCC patients.


2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 214-214
Author(s):  
Motoyasu Kan ◽  
Shuichi Mitsunaga ◽  
Masafumi Ikeda ◽  
Izumi Ohno ◽  
Hironobu Tsubouchi ◽  
...  

214 Background: Non PDAC tissue-originated proteins are cleaved by proteases derived from PDAC, which can result in abnormal cleavage patterns in the urine of PDAC patients. Urinary proteomic analysis for quantifying the ratios of the abnormal protein fragments to the non-fragmented protein levels in the urine may be useful to distinguish early PDAC from healthy controls. This proof-of-concept study was planned to determine the usefulness of measuring the protein fragments from non PDAC tissue-originated proteins in the urine using the multiple-reaction-monitoring technique (MRM) for discriminating resectable PDAC from healthy controls. Methods: Urinary proteins were digested with trypsin, and resultant peptides were measured by MRM analysis and the ratio of the level of each fragment to the non-fragmented protein level (fragmentation ratio) was calculated. Fragments for which the fragmentation ratios were higher in the PDAC group than those in the healthy group were defined as abnormal protein fragments. The diagnostic capability of each abnormal protein fragment for discriminating cases of PDAC from healthy controls was evaluated by receiver operating characteristic (ROC) curve analysis. Results: A total of 21 patients with resectable PDAC and 30 healthy control subjects were enrolled in this study. All the PDAC patients were treated by pancreatic resection. Urine samples for this study were collected prior to the surgery from the PDAC patients. The non PDAC tissue-originated protein was determined as a liver-originated protein. The fragmentation ratios for six fragments were found to be higher in the PDAC group as compared to those in the healthy control group, and these fragments were determined as abnormal protein fragments. ROC curve analysis was performed for each of the abnormal fragments to determine the areas under the curve (AUCs) for discriminating cases of PDAC from healthy controls. The best AUC was 0.81 (95% CI, 0.68-0.91). Conclusions: The urinary fragmentation ratios showed the ability to discriminate cases of resectable PDAC from a healthy control group; abnormal fragmentation ratios may be promising, noninvasively measurable biomarkers of early PDAC.


2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Zheng Zhong ◽  
Yukai Huang ◽  
Yuqi Liu ◽  
Junming Chen ◽  
Meng Liu ◽  
...  

Background. The C-reactive protein (CRP) to albumin (ALB) ratio (CAR) has emerged as a novel inflammatory biomarker. This study was designed to investigate the role of CAR in the disease activity of axial spondyloarthritis (axSpA). Methods. A total of 241 patients and 61 healthy controls were retrospectively enrolled in this study. AxSpA patients were further divided into the inactive group ( n = 176 ) and active group ( n = 65 ) according to Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) cutoff value of 4. Laboratory data and clinical assessment indices were recorded. Spearman’s correlation analysis, receiver operation characteristic (ROC) curve analysis, and binary logistic regression analysis were performed. Results. In axSpA patients, CAR was significantly higher than the healthy group ( P < 0.001 ). Similarly, axSpA patients in the active group had higher CAR than the inactive group ( P < 0.001 ). Besides, CAR was positively correlated with erythrocyte sedimentation rate (ESR) ( r = 0.704 , P < 0.001 ), CRP ( r = 0.996 , P < 0.001 ), BASDAI ( r = 0.329 , P < 0.001 ), and Bath Ankylosing Spondylitis Functional Index (BASFI) ( r = 0.330 , P < 0.001 ). ROC curve analysis suggested that the area under the curve (AUC) of CAR for axSpA of the active group was 0.701, which was higher than that of CRP and ESR. The optimal cutoff point of CAR for axSpA of the active group was 0.3644, with a sensitivity and specificity of 58.5% and 79.0%. Binary logistic analysis results revealed that CAR was an independent predictive factor for axSpA disease activity ( odds   ratio = 4.673 , 95% CI: 1.423-15.348, P = 0.011 ). Conclusions. CAR was increased in axSpA and axSpA of the active group. CAR may be a novel and reliable indicator for axSpA disease activity.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Beata Smok ◽  
Krzysztof Domagalski ◽  
Małgorzata Pawłowska

Purpose. The aim of this study was to evaluate the diagnostic and prognostic value of IL-6 and sTREM-1 in the course of SIRS and sepsis in children with reference to routinely used CRP and PCT. Methods. A prospective study included 180 patients at the ages from 2 months to 18 years hospitalized due to fever from November 2015 to January 2017. Forty-nine children without fever hospitalized due to noninfectious causes formed the control group. IL-6 and sTREM-1 serum concentrations were assessed with the enzyme-linked immunosorbent assay method. Results. The mean serum concentrations of all the analyzed biomarkers were statistically significantly higher in the study group compared to the control group. Mean IL-6, sTREM-1, and PCT serum concentrations were statistically significantly higher in the group of patients with SIRS/sepsis compared to the group of feverish patients without diagnosed SIRS (N-SIRS). Based on the ROC curve analysis, it was shown that of all the biomarkers tested, only two—IL-6 and procalcitonin—had potential usefulness in the diagnosis of SIRS/sepsis in children with fever. Conclusion. Elevated levels of IL-6 and PCT are important risk factors for the development of SIRS/sepsis in children with fever. It seems that elevated IL-6 baseline serum level may predict a more severe course of febrile illness in children, because based on the ROC curve analysis, it was found that IL-6 is a statistically significant prognostic marker of prolonged fever≥3 days and prolonged hospitalization>10 days. The assessment of the usefulness of sTREM-1 in the diagnosis of SIRS/sepsis in feverish children requires further research.


2017 ◽  
Vol 41 (4) ◽  
pp. 1596-1604 ◽  
Author(s):  
Xiaoming Peng ◽  
Xiongzhi Shi ◽  
Jinmin Zhao ◽  
Jichen He ◽  
Keke Li ◽  
...  

Background/Aims: This study focused on investigating the regulatory mechanism of miR-136-5p in mouse astrocytes stimulated with interleukin-17(IL-17). Methods: C57BL/6 mouse astrocytes were stimulated with IL-17 (100ng/ml) for various periods of time (0-48 hours) and at various doses (0-200 ng), and the expression levels of inflammatory cytokine and chemokine genes (IL-6, TNF-α, MCP-1, MCP-5 and MIP-2) were then detected by real-time PCR. The expression of the A20 gene was measured with real-time PCR in cells that were stimulated with IL-17 (50 ng/ml) for various periods of time (0-48 hours). C57BL/6 mouse astrocytes were transfected with Ctrl-anti-miR-136-5p or LNA -anti-miR-136-5p for 48 h. Thereafter, the cells were stimulated with or without IL-17 (50ng/ml) for 6 h. The level of A20 protein (TNFα-induced protein 3, TNFAIP3) was detected by Western blot analysis. Results: (1) Compared with the DMEM control group, within six hours, IL-17 stimulation significantly increased the expression levels of inflammatory cytokine and chemokine genes and clearly decreased the expression level of the A20 protein. (2) Without IL-17 stimulation, the expression level of the miR-136-5p gene was significantly decreased, whereas in the miR-136-5p-inhibition group, the A20 protein expression was elevated. IL-17 stimulation slightly decreased the expression of the A20 protein in the miR-136-5p-inhibition group, but it was still slightly higher than in the control group. Conclusion: This study demonstrated that miR-136-5p affected the expression of A20 in IL-17-stimulated astrocytes.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ying Luo ◽  
Ying Xue ◽  
Guoxing Tang ◽  
Qun Lin ◽  
Huijuan Song ◽  
...  

BackgroundNovel approaches for tuberculosis (TB) diagnosis, especially for distinguishing active TB (ATB) from latent TB infection (LTBI), are urgently warranted. The present study aims to determine whether the combination of HLA-DR on Mycobacterium tuberculosis (MTB)-specific cells and TB antigen/phytohemagglutinin (TBAg/PHA) ratio could facilitate MTB infection status discrimination.MethodsBetween June 2020 and June 2021, participants with ATB and LTBI were recruited from Tongji Hospital (Qiaokou cohort) and Sino-French New City Hospital (Caidian cohort), respectively. The detection of HLA-DR on MTB-specific cells upon TB antigen stimulation and T-SPOT assay were simultaneously performed on all subjects.ResultsA total of 116 (54 ATB and 62 LTBI) and another 84 (43 ATB and 41 LTBI) cases were respectively enrolled from Qiaokou cohort and Caidian cohort. Both HLA-DR on IFN-γ+TNF-α+ cells and TBAg/PHA ratio showed discriminatory value in distinguishing between ATB and LTBI. Receiver operator characteristic (ROC) curve analysis showed that HLA-DR on IFN-γ+TNF-α+ cells produced an area under the ROC curve (AUC) of 0.886. Besides, TBAg/PHA ratio yield an AUC of 0.736. Furthermore, the combination of these two indicators resulted in the accurate discrimination with an AUC of 0.937. When the threshold was set as 0.36, the diagnostic model could differentiate ATB from LTBI with a sensitivity of 92.00% and a specificity of 81.82%. The performance obtained in Qiaokou cohort was further validated in Caidian cohort.ConclusionsThe combination of HLA-DR on MTB-specific cells and TBAg/PHA ratio could serve as a robust tool to determine TB disease states.


2021 ◽  
Vol 19 (8) ◽  
pp. 13-19
Author(s):  
Amjed H. Abbas ◽  
Muna Abdulridha Rasheed ◽  
Hayder Abdul-Amir Al-Hindy ◽  
Mazin J. Mousa ◽  
Hadeel Abd Ameir Al-Shalah

Background: Asthma is a chronic airway disorder, in which cytokines are probably contributing in the inflammation and in the pathophysiology of the disease. This study aimed to determine the benefit of measurement of FENO and IL-1β in the diagnosis of asthma. Method: The study was conducted in Merjan Medical City and Spiro private clinic in Babylon province in the period from March to June 2019, 127 asthmatic patients were compared with 60 healthy subjects as control group. The age ranged from 10 to 60 years old, fractional exhaled nitric oxide (FENO) test was performed to assess asthma by using (Medisoft® company, Belgium). Body mass index (BMI) was subtracted as weight (kg)/height (m2). Waist circumference/cm (WC) was calculated between the inferior margin of thoracic ribs and midline of the iliac-crest. Hip circumference/cm (HC) was calculated from the broadest hip eminent before the waist/hip ratio (W/H) computed. The FENO measures had classified into low (<25 ppb) or intermediate-high (⩾25 ppb) according to the ‘’American Thoracic Society recommendations’’. Iterleukine-1 beta (IL-1β) was measured in the sera by ELISA technique using Human IL-1β (Interleukin 1-Beta) ELISA Kit from Elabscience®. Results: there was no significant correlation between the levels of FENO and IL-1β with body weight as measured by the way of BMI and waist/hip ratio. There was no correlation between duration of asthma with the levels of FENO and IL-1β. ROC curve analysis of FENO test in BA patients showed significant (p-0.001) high sensitivity (92%) and specificity (90%). However, ROC curve analysis of IL-1β in BA patients revealed non-significant (p-0.53), lower accuracy (56.4%), sensitivity 962%) and specificity (57%) to distinguish BA patients). Conclusion: No relation between obesity and eosinophilic airways inflammation. The measurement of FENO level is more important in assessment of asthma inflammation than IL-1β.


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