Plasma Metabolomics Signature of Gout and Asymptomatic Hyperuricemia

Abstract Background: Gout is a metabolic disease and is the most common form of inflammatory arthritis affecting men. However, the pathogenesis of gout is still uncertain, and novel biomarkers are needed for early prediction and diagnosis of gout. To reveal the metabolic alterations in plasma of gout patients and hyperuricemia patients and discover novel molecular biomarkers for early diagnosis. Metabonomics was employed to screen and identify novel biomarkers of gout based on human plasma. High performance liquid chromatography-diode array detector (HPLC-DAD) and orthogonal signal correction partial least squares discriminate analysis (OPLS-DA) were also used for metabonomics study.Results: 80 and 62 features were selected as remarkable significant variables in the two modes between gout and control group, 90 and 50 features between hyperuricemia (HUA) and control group, 63 and 60 features between gout and HUA group, respectively. 25 potential metabolic biomarkers which at least in two comparison groups were remained. Among 25 metabolites, 34% presented high area under the curve (AUC) values (AUC >0.75). Four metabolites including Lys-Ser, L-Pipecolic acid, glycine, arecoline were screened out. They were used to distinguish gout from hyperuricemia with AUC>0.75, which was greater than the AUC of uric acid.Conclusion: The differential metabolites of gout screened out were involved in amino acid metabolism, including glycine, serine and threonine metabolism, arginine biosynthesis, glutathione metabolism. Lys-Ser, L-pipecolic acid, glycine, arecoline were down-regulated in gout patients compared with hyperuricemia patients. The metabolomics signatures could serve as an efficient tool for early diagnosis and provide novel insights into the pathogenesis of gout.

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Mean Platelet Volume: Is It a Predictive Parameter in Diagnosis of Acute Mesenteric Ischemia?

International Surgery ◽

10.9738/intsurg-d-14-00268.1 ◽

2015 ◽

Vol 100 (5) ◽

pp. 962-965 ◽

Cited By ~ 3

Author(s):

Ahmet Türkoğlu ◽

Mesut Gül ◽

Abdullah Oğuz ◽

Zübeyir Bozdağ ◽

Burak Veli Ülger ◽

...

Keyword(s):

Early Diagnosis ◽

Mean Platelet Volume ◽

Mesenteric Ischemia ◽

Area Under The Curve ◽

Acute Mesenteric Ischemia ◽

The Elderly ◽

Control Group ◽

Characteristic Analysis ◽

Platelet Volume ◽

Cell Counts

Our objective for this study was to discuss the usability of mean platelet volume, which is associated with numerous vascular pathologies, in the early diagnosis of acute mesenteric ischemia. Acute mesenteric ischemia is an uncommon, life-threatening clinical condition mostly seen in the elderly. Early diagnosis of acute mesenteric ischemia and correction of blood circulation before necrosis occurs are important factors affecting prognosis. A total of 95 patients who underwent emergency surgery for acute mesenteric ischemia and 90 healthy volunteers as control group were included in this study. Age, gender, hemoglobin values, white blood cell counts, mean platelet volume, and platelet counts are recorded for evaluation. The mean platelet volume values were significantly higher in patients with acute mesenteric ischemia than in the controls (9.4 ± 1.1 fL and 7.4 ± 1.4 fL, respectively; P < 0.001). Receiver-operating characteristic analysis demonstrated a cutoff value of mean platelet volume as 8.1 fL (area under the curve, 0.862), a sensitivity of 83.2%, and a specificity of 80%. As a result, in the patients who are admitted to the hospital with acute nonspecific abdominal pain and suspected of having acute mesenteric ischemia, high mean platelet volume values in routine hemograms support the diagnosis of acute mesenteric ischemia.

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Predictive value of the neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-neutrophil ratio, and neutrophil-to-monocyte ratio in lupus nephritis

Lupus ◽

10.1177/0961203320929753 ◽

2020 ◽

Vol 29 (9) ◽

pp. 1031-1039

Author(s):

Peng Liu ◽

Peiyuan Li ◽

Zhong Peng ◽

Yazhou Xiang ◽

Chenqi Xia ◽

...

Keyword(s):

Lupus Nephritis ◽

Healthy Subjects ◽

Area Under The Curve ◽

Neutrophil To Lymphocyte Ratio ◽

Control Group ◽

Receiver Operating Characteristic Curves ◽

Lymphocyte Ratio ◽

And Control ◽

First Time

Objective To evaluate the role of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-neutrophil ratio (PNR), platelet-to-monocyte ratio (PMR), and neutrophil-to-monocyte ratio (NMR) as predictors for lupus nephritis (LN) patients without infection or as biomarkers for distinguishing between infection or flare with LN patients. Methods LN patients were divided into three groups: LN without infection, LN with infection, and LN with flare. A total of 57 healthy subjects were enrolled as controls. The differentiation was analyzed between LN without infection and control group, and LN with infection and LN with flare. Correlations among variables were assessed in the LN group without infection. Receiver operating characteristic curves were constructed in two comparable groups. Results NLR, PLR, and MLR were increased significantly in the LN group without infection as compared with those in healthy controls. NLR (area under the curve (AUC): 0.75) and MLR (AUC: 0.79) were useful for distinguishing between LN patients without infection and healthy subjects. In differentiating LN patients without infection from the controls, optimal cutoffs of NLR and MLR were 3.43 (sensitivity: 45.6%, specificity: 96.5%, and overall accuracy: 68.8%) and 0.24 (sensitivity: 75.0%, specificity: 73.7%, and overall accuracy: 73.6%), respectively. In addition, NLR ( r = 0.322, p = 0.011) and PLR ( r = 0.283, p = 0.026) were positively correlated with CRP. Importantly, NLR and NMR were increased while PNR was decreased in the LN group with infection in comparison with those in the LN group with flare. NLR (AUC: 0.80), NMR (AUC: 0.78), and PNR (AUC: 0.74) were useful in differentiating LN patients with infection and flare, and their optimal cutoffs were 4.02 (sensitivity: 82.6%, specificity: 69.6%, and overall accuracy: 75.5%), 12.19 (sensitivity: 80.4%, specificity: 73.9%, and overall accuracy: 77.5%), and 28.26 (sensitivity: 65.2%, specificity: 76.8%, and overall accuracy: 71.6%), respectively. Conclusions We demonstrated, for the first time, that MLR or NMR had the best accuracy in differentiating LN patients without infection from healthy subjects, or differentiating infection from flare in LN patients, respectively. Our results implied that NLR, MLR, PNR, and NMR may be useful biomarkers in predicting LN.

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Razvoj SPE-HPLC-DAD metode za određivanje florfenikola i florfenikol amina u cerebrospinalnoj tekućini svinja

Veterinarska stanica ◽

10.46419/vs.51.2.3 ◽

2020 ◽

Vol 51 (2) ◽

pp. 129-138

Author(s):

Ksenija Šandor ◽

Svjetlana Terzić ◽

Anja Vujnović ◽

Eleonora Perak Junaković ◽

Irena Žarković ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

High Performance ◽

Solid Phase ◽

Biological Fluids ◽

Experimental Period ◽

Intramuscular Administration ◽

Array Detector ◽

Control Group ◽

Pharmacokinetic Studies ◽

Experimental Conditions

A study of florfenicol (FF) and its metabo- lite florfenicol amine (FFA) in pig cerebrospinal fluid was conducted following repeated intramuscular administration of the original (reference) and a generic veterinary medicinal product (VMP) under the same experimental conditions (20 mg FF/kg body weight, 48-hour interval). Both VMPs are solutions for injection containing FF as an active substance in the concentration of 300 mg/mL and have been authorized in Croatia for use in cattle and pigs. In this study, clinically healthy pigs were randomly divided into three groups. The first group was treated with the reference VMP, the second with the generic VMP, while the third served as the control group. Animals were sacrificed at 216, 288 and 384 hours after the first drug administration. Cerebrospinal fluid samples were analysed by the optimized and validated high-performance liquid chromatography-diode array detector method (HPLC-DAD). The solid-phase extraction (SPE) technique was chosen for sample preparation. The HPLC-DAD method provides good linearity over the concentration range of 0.05 to 5.00 μg/mL for FF and FFA. Limits of detection were 0.0023 μg/mL for FF and 0.0100 μg/mL for FFA. Extraction recoveries of FF were from 86.6% to 111.8%, and of FFA from 91.7% to 98.8%. The SPE-HPLC-DAD method has been demonstrated to be a selective, sensitive and suitable analytical method for the determination of FF and FFA in cerebrospinal fluid. The present study was based on a preliminary study that quantified FF in pig plasma at 216 hours after the first application of reference or generic VMP. However, FF and FFA were not detected in any of the cerebrospinal fluid samples during the experimental period. According to the nature of biological fluids, the SPE-HPLC-DAD method can be suitable for further pharmacokinetic studies of FF in pig plasma and serum after intramuscular administration of VMPs.

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Nesfatin-1 and Vaspin as Potential Novel Biomarkers for the Prediction and Early Diagnosis of Gestational Diabetes Mellitus

International Journal of Molecular Sciences ◽

10.3390/ijms20010159 ◽

2019 ◽

Vol 20 (1) ◽

pp. 159 ◽

Cited By ~ 11

Author(s):

Radzisław Mierzyński ◽

Elżbieta Poniedziałek-Czajkowska ◽

Dominik Dłuski ◽

Jolanta Patro-Małysza ◽

Żaneta Kimber-Trojnar ◽

...

Keyword(s):

Diabetes Mellitus ◽

Early Diagnosis ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Medical Complication ◽

Uncomplicated Pregnancy ◽

Novel Biomarkers

Gestational diabetes mellitus (GDM) is considered to be one of the most frequent medical complication observed among pregnant women. The role of adipokines in the pathogenesis of GDM remains strictly unknown. Different adipokines have been studied throughout gestation, and they have been proposed as biomarkers of GDM and other pregnancy-related complications; however, there is no biomarker reported for GDM screening at present. The aim of this study was to evaluate serum nesfatin-1 and vaspin levels in GDM and non-GDM women, to characterize the correlation between these adipokines, and to assess the potential role of circulating adipokines in the prediction of risk of gestational diabetes mellitus. Serum concentrations of nesfatin-1 and vaspin were measured in 153 women with GDM, and in 84 patients with uncomplicated pregnancy by enzyme-linked immunosorbent assay (ELISA) kits, according to the manufacturer’s instructions. Circulating levels of nesfatin-1 and vaspin were significantly lower in the GDM group than in the control group. Nesfatin-1 levels were negatively correlated with vaspin levels. The results of this study point out the possible role of nesfatin-1 and vaspin as potential novel biomarkers for the prediction and early diagnosis of GDM. Further studies are necessary to evaluate the influence of nesfatin-1 and vaspin on glucose metabolism in the early stages of GDM.

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Circulating miRNAs as Biomarkers for Prostate Cancer Diagnosis in Subjects with Benign Prostatic Hyperplasia

Journal of Immunology Research ◽

10.1155/2020/5873056 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Wei Jin ◽

Xiang Fei ◽

Xia Wang ◽

Fangjie Chen ◽

Yan Song

Keyword(s):

Prostate Cancer ◽

Benign Prostatic Hyperplasia ◽

Statistical Tests ◽

Specific Antigen ◽

Area Under The Curve ◽

Prostatic Hyperplasia ◽

Control Group ◽

Circulating Mirnas ◽

Noninvasive Biomarker ◽

Novel Biomarkers

Body fluids often contain freely circulating nucleic acids, many of which can be exploited as noninvasive tools for the diagnosis of cancer as well as for clinical prognostication. Identifying microRNAs (miRNAs) in subjects’ blood with various malignancies means that they can serve as novel biomarkers for prostate cancer (PCa) diagnosis. This study analyzed serum-circulating miRNAs as a noninvasive biomarker in subjects with PCa and subjects with benign prostatic hyperplasia (BPH). In total, 31 PCa subjects and 31 BPH subjects were included, with the BPH group serving as the control group. RT-qPCR was used to quantify the levels of 10 miRNAs, which included miR-18a, miR-34a, miR-106b, miR-183, miR-200a, miR-301a, miR-141, miR-182, miR-200b, and miR-375 in serum. Statistical tests were used to assess the relationship between the levels of miRNAs and the clinicopathological data. A significant increase was observed in the relative expression ratios of miR-141, miR-182, miR-200b, and miR-375 (1.89-, 2.09-, 2.41-, and 2.27-folds, respectively) in the PCa group when compared to the BPH group. Based on the receiver operating characteristic (ROC) analysis, the largest area under the curve (AUC), 0.923, was associated with the miR-200b group, indicating effective diagnostic properties for this biomarker. A correlation was observed between total prostate-specific antigen (TPSA) and the relative levels of miR-141, miR-182, miR-200b, and miR-375. The Gleason score and the miR-200b expression level were also correlated. These results are consistent with previous studies regarding the possibility of differentiating between PCa subjects and healthy controls based on the detection of miRNA. The findings attest to a distinctive expression profile of miRNA that is detectable in the blood of PCa subjects, thereby confirming the role of miRNAs as diagnostic biomarkers for PCa.

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Evaluation of The 10 Warning Signs In Immunodeficient Patients: Additional Suggestions

10.21203/rs.3.rs-1189503/v1 ◽

2021 ◽

Author(s):

Fadime Ceyda Eldeniz ◽

Yahya Gül ◽

Alaattin Yorulmaz ◽

Şükrü Nail Güner ◽

Sevgi Keles ◽

...

Keyword(s):

Family History ◽

Early Diagnosis ◽

Chronic Diarrhea ◽

Warning Signs ◽

Control Group ◽

Healthy Children ◽

Physician Awareness ◽

History Of ◽

And Control ◽

Immunological Evaluation

Abstract Objective: Ten warning signs of primary immunodeficiency (PID) were suggested by the Jeffrey Modell Foundation (JMF), to increase physician awareness of PID. These warning signs have not yet been evaluated for patients with secondary immunodeficiency (SID). This study investigated whether the 10 warning signs used for the diagnosis of PID are sufficient for the diagnosis of SID, and explored the possibility of additional signs.Methods: This prospective study was conducted between June and December 2020. The mothers of 162 patients with PID and SID, and mothers of 200 healthy children, were asked to complete a questionnaire about family and personal history in addition to the warning signs of PID developed by the JMF. A JMF score was created by giving one point for each “Yes” answer for the 10 warning signs of PID. Medical records of the patients were evaluated for possible additional warning signs for PID and SID. Results: The JMF scores of the PID (3.36 ± 1.65) and SID (3.72 ± 1.12) groups were significantly higher than the scores of the control group (0.34 ± 0.61) (p < 0.05). A sign for immunological evaluation in two patients without warning signs in the PID group was found to be chronic diarrhea. In addition to the 10 JMF warning signs, we found that consanguinity and a family history of tuberculosis were statistically significant in our PID group, compared with the SID and control groups. Conclusions: The JMF warning signs are important for early diagnosis of PID. Our study showed that these signs may also be used for the early diagnosis of SID in patients and, according to our results, in addition to the 10 JMF signs for PID, parental consanguinity, chronic diarrhea, and a family history of tuberculosis may also be considered warning signs for the early diagnosis of PID.

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L-Carnitine and Acetyl-L-Carnitine: Potential Novel Biomarkers for Major Depressive Disorder

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.671151 ◽

2021 ◽

Vol 12 ◽

Author(s):

Li-Juan Nie ◽

Jun Liang ◽

Feng Shan ◽

Bao-Shi Wang ◽

Yuan-Yuan Mu ◽

...

Keyword(s):

Major Depressive Disorder ◽

Treatment Group ◽

Depressive Disorder ◽

Neural Plasticity ◽

High Performance ◽

Pearson Correlation ◽

Area Under The Curve ◽

Healthy Controls ◽

Major Depressive ◽

Novel Biomarkers

The lack of biomarkers greatly limits the diagnosis and treatment of major depressive disorder (MDD). Endogenous L-carnitine (LC) and its derivative acetyl-L-carnitine (ALC) play antidepressant roles by improving brain energy metabolism, regulating neurotransmitters and neural plasticity. The levels of ALC in people and rodents with depression are significantly reduced. It is necessary to determine whether serum LC and ALC might be used as novel biomarkers for the diagnosis of MDD. Here, ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to determine the concentration of LC and ALC in the serum of healthy controls and patients with MDD; among the latter, in patients who were responsive (effective group) and non-responsive (ineffective group) after 2 weeks of treatment. The diagnostic value of serum LC and ALC for MDD was assessed. Compared with healthy controls, the serum LC and ALC concentrations in patients with MDD were significantly decreased (P < 0.001). Pearson correlation analysis shows that the HDRS-24 score was negatively associated with serum ALC (r = −0.325, P = 0.007). Receiver operating characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.801 with 83.1% sensitivity and 66.3% specificity for LC, and an AUC of 0.898 with 88.8% sensitivity and 76.4% specificity for ALC, differentiating patients with MDD from healthy controls. Furthermore, the concentration of LC and ALC in patients with depression was significantly increased in the effective treatment group, and no significant change was observed in the ineffective treatment group. These results suggest that serum LC and ALC may be novel biomarkers for the diagnosis of MDD.

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Identification of Dyes in Coptic Textiles from the Museum of Faculty of Archaeology, Cairo University

Heritage ◽

10.3390/heritage4040176 ◽

2021 ◽

Vol 4 (4) ◽

pp. 3147-3156

Author(s):

Ioannis Karapanagiotis ◽

Omar Abdel-Kareem ◽

Paraskevi Kamaterou ◽

Dimitrios Mantzouris

Keyword(s):

High Performance ◽

Array Detector ◽

Rubia Tinctorum ◽

Ancient Egyptian ◽

Relative Composition ◽

Hplc Peak ◽

Peak Areas ◽

Quantitative Results ◽

And Control ◽

Very High

High Performance Liquid Chromatography coupled to a Diode-Array-Detector (HPLC-DAD) is used to investigate samples which were extracted from ancient Egyptian textiles (4th–5th c. AD) of the Museum of Faculty of Archaeology, Cairo University. Madder is identified in several samples. According to semi-quantitative results, which are obtained from HPLC peak areas measured at 254 nm, madder that is rich in purpurin and poor in alizarin is identified in samples which were treated (i) only with madder and (ii) with madder and either indigo/woad (Indigofera species and other/Isatis tinctoria L.) or weld (Reseda luteola L.). The madder dye used in these samples could have been originated from Rubia peregrina L. However, the possible use of Rubia tinctorum L. (or other plants of the Rubiaceae family) by the Egyptian dyers cannot be ruled out, particularly if methods were developed by the ancient dyers to affect and control the relative composition of madder dye. The HPLC peak area ratio of alizarin versus purpurin is very high (>2.2) for samples which were treated with madder (probably originated from R. tinctorum) and a tannin source. Finally, in some samples, only indigoid dyes (indigo/woad) are identified.

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An exploratory study of neopterin and kynurenine pathway in pterygium

Pteridines ◽

10.1515/pteridines-2019-0019 ◽

2019 ◽

Vol 30 (1) ◽

pp. 153-157

Author(s):

Bilge Kilicarslan ◽

Aziz Cardak ◽

Gozde Girgin ◽

Ozlem Evren Kemer ◽

Terken Baydar

Keyword(s):

High Performance ◽

Degradation Process ◽

Serum Levels ◽

Kynurenine Pathway ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Cell Immunity ◽

Degenerative Disorder ◽

And Control ◽

Clinical Potential

Abstract Pterygium is an inflammatory, vascular and degenerative disorder with unknown aetiology. The aim of this study was to evaluate the changes in neopterin levels, reflecting T-cell immunity, and the kynurenine pathway, the main degradation process of tryptophan, in pterygium. For this purpose, neopterin concentrations were measured in serum and tear samples by enzyme-linked immunosorbent assay (ELISA) in pterygium patients (n=31) and control group (n=32). Kynurenine (KYN) and tryptophan (TRP) serum levels were simultaneously determined by high-performance liquid chromatography (HPLC) for evaluation of the kynurenine pathway. Serum neopterin concentrations and kynurenine to tryptophan ratio (KYN/TRP) as an index of tryptophan breakdown were found increased in pterygium compared to controls (p<0.05). Although there was a 3-fold difference observed between serum and tear neopterin levels, no significant relationship was found. It can be concluded that neopterin may be used as a nonspecific biomarker that reflects immunological activity in pterygium and has clinical potential for evaluation of pterygium pathogenesis. These immune- or inflammatory-mediated changes were also supported by an increased KYN/TRP ratio in pterygium patients.

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Role of MicroRNAs (224 and 96) as Novel Biomarkers for Hepatocellular Carcinoma

Current Cancer Therapy Reviews ◽

10.2174/1573394716999201103225735 ◽

2020 ◽

Vol 16 ◽

Author(s):

Amal A. Mohamed ◽

Mokhtar M. El-Zawahry ◽

Omnia I. Tantawi ◽

Amyan Aalkhalegy ◽

Lamiaa Abdelfattah Fathalla ◽

...

Keyword(s):

Liver Cirrhosis ◽

Statistical Significance ◽

Control Group ◽

P Value ◽

Significance Level ◽

Real Time Quantitative Pcr ◽

Novel Biomarkers ◽

Laboratory Investigations ◽

And Control

Background:: In the early stages of HCC, it is unsatisfactory to depend on alpha-fetoprotein for diagnosis. Objective:: The current study evaluated the possibility of the two miRNAs which are miRNA-96 and miRNA-224 to act as biomarkers for HCC diagnosis. Methods:: This study included 50 patients with HCV-induced HCC and 50 patients with HCV-induced liver cirrhosis for comparison as well as 67 healthy volunteers as controls. All participants were subjected to history taking, clinical examination, and laboratory investigations as well as quantification of serum miRNA-96 and miRNA-224 by real-time quantitative PCR. Results:: MicroRNA 224 level was significantly higher in HCC than the other two groups and was significantly higher in liver cirrhosis than the control group. MicroRNA 96 level was higher in HCC than the control group and was higher in cirrhotic group than both HCC and control groups. However, it doesn’t reach the statistical significance level. The best cut-off value of microRNA 96 for detecting HCC was 3.414 with a sensitivity of 67% and a specificity of 67%, (p-value <0.001). The best cut-off value of microRNA 224 for detecting HCC was 16.75 with a sensitivity of 88% and a specificity of 85% (p-value<0.001). Conclusion:: miRNA-224 could serve as a biomarker for the HCC diagnosis.

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