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Epithelial ovarian cancer (EOC) is the type of OC with the highest mortality rate. Due to the asymptomatic nature of the disease and few available diagnostic tests, it is mostly diagnosed at the advanced stage. Therefore, the present study aimed to discover predictive and/or early diagnostic novel circulating microRNAs (miRNAs or miRs) for EOC. Firstly, microarray analysis of miRNA expression levels was performed on 32 samples of female individuals: Eight plasma samples from patients with pathologically confirmed EOC (mean age, 45 (30-54) years), eight plasma samples from matched healthy individuals (HIs) (mean age, 44 (30-65) years), eight EOC tissue samples (mean age, 45 (30-54) years) and eight benign ovarian (mean age, 35 (17-70) years) neoplastic tissue samples A total of 31 significantly dysregulated miRNAs in serum and three miRNAs in tissue were identified by microarray. The results were validated using reverse transcription-quantitative PCR on samples from 10 patients with pathologically confirmed EOC (mean age, 47(30-54) years), 10 matched His (mean age, 40(26-65) years], 10 EOC tissue samples (mean age, 47(30-54) years) and 10 benign ovarian neoplastic tissue samples (mean age, 40(17-70) years). The 'Kyoto Encyclopedia of Genes and Genomes' (KEGG) database was used for target gene and pathway analysis. A total of three miRNAs from EOC serum (hsa-miR-1909-5p, hsa-miR-885-5p and hsa-let-7d-3p) and one microRNA from tissue samples (hsa-miR-200c-3p) were validated as significant to distinguish patients with EOC from HIs. KEGG pathway enrichment analysis showed seven significant pathways, which included 'prion diseases', 'proteoglycans in cancer', 'oxytocin signaling pathway', 'hippo signaling pathway', 'adrenergic signaling in cardiomyocytes', 'oocyte meiosis' and 'thyroid hormone signaling pathway', in which the validated miRNAs served a role. This supports the hypothesis that four validated miRNAs, have the potential to be a biomarker of EOC diagnosis and target for treatment.

Introduction: Our knowledge has gaps regarding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replication levels and its association to severity of Coronavirus disease 2019 (COVID-19). The aim of this study was to investigate the association of SARS-CoV-2 viral load with disease severity and serum biomarkers in COVID-19 patients. Methodology: Viral load was determined via cycle threshold (Ct) values of SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in 214 adult patients. Ct values were compared with clinical severity, biochemical and hematological biomarkers. Results: Clinical course of the disease was mild (49.1%), moderate (40.2%), and severe (10.7%). Median Ct value was 28.2 (IQR: 22.2–33.8) during the first week of the disease. Ct values were lower within five days after symptom onset [lowest Ct value on the third day (median: 24, IQR: 20.6–32.3)], but they increased significantly during the second and third weeks. No association was detected between admission Ct values and disease severity. Gender, age, co-morbidity, and mortality did not differ significantly in patients with low (≤ 25) and high (> 25) Ct values. White blood cell, neutrophil, platelet, and especially lymphocyte counts, were significantly lower in patients with low Ct values. Conclusions: No definitive/clear correlation between SARS-CoV-2 viral load and severity and mortality was found in the studied COVID-19 patients. However, neutrophil, platelet, and especially lymphocyte count were significantly lower in patients with a high viral load.

Metabolic syndrome (MetS) and obesity are important public health problems associated with adipose tissue mass. Asprosin, visfatin, and subfatin are new members of which fate in MetS and obesity has not been fully revealed yet. Thus, this study was to investigate the association between asprosin, visfatin, subfatin, and biochemical values, demographic data, and body composition measurement values in MetS patients with and without obesity.Blood samples were taken from a total of 90 people, including 31 MetS patients with obesity, 29 MetS patients without obesity, and 30 healthy (control). Asprosin, visfatin, and subfatin were studied by the ELISA method.There was a negative correlation between asprosin and Body Mass Index (BMI) in the MetS + Obese group. The correlations between asprosin and urea and fasting insulin (FI) levels in the MetS group were positive and statistically significant (p0.05). While there was a statistically significant negative correlation (p0.05) between visfatin and BMI in the MetS + Obese group, the correlation with waist circumference in the MetS + Obese and MetS groups was statistically significant and negative (p0.05). There was a statistically significant negative relationship (p0.05) between aspartate aminotransferase value and visfatin. The results between visfatin values and asprosin and subfatin in all groups were significant (p0.05).There is a direct relationship between circulating amounts of asprosin, visfatin, and subfatin hormones and age, weight, height, diastolic blood pressure, high-density lipoprotein-cholesterol, aspartate aminotransferase, alanine transaminase, and creatinine. Therefore, asprosin, visfatin, and subfatin hormones are the new biomarkers of metabolic turbulence.

The aims of the study were to evaluate the prevalence of sleep-disordered breathing (SDB) by using polysomnography (PSG) in children with MPS IVA and MPS VI who underwent enzyme replacement therapy (ERT) and to analyze the effect on SDB of having upper airway surgery, pulmonary functions, and exercise capacity. A retrospective cross-sectional study was conducted on patients with MPS IVA (n:17) and MPS VI (n:11) aged under 19 years who underwent polysomnography. Descriptive and nonparametric analyses were performed for demographic, PSG, pulmonary function and exercise capacity variables. The frequency of sleep apnea in the study sample was 85.7% (24/28). Four patients (14.3%) had no sleep apnea, 15 (53.6%) had mild, and nine (32.1%) had moderate-to-severe sleep apnea. Two patients (7.1%) had central sleep apnea and 22 had obstructive sleep apnea (OSA) (78.6%). Forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were negatively correlated to apnea-hypopnea index (AHI) (r = -0.594, p = .009; r = -0.636, p = .005, respectively). Despite ERT and previous upper airway surgery, the prevalence of OSA was high in patients with MPS IVA-MPS IV, emphasizing the importance of PSG screening for sleep disorders. Pulmonary function tests may be useful for predicting sleep apnea in patients with MPS IVA and MPS VI.

To investigate the status of thiol-disulphide homeostasis and ischemic-modified albumin and their association with clinicopathological parameters in breast cancer.A cross-sectional descriptive study.Department of Internal Medicine and Department of Medical Oncology, Dicle University, Turkey, from April to September 2021.Forty treatment-naive female patients diagnosed with breast cancer who presented to the Oncology Clinic of the hospital and 33 healthy women with no comorbidities were included. Serum levels of native thiol (NT), disulphide (Ds), total thiol (TT), IMA (ischemic modified albumin) at diagnosis and disulphide/native thiol (Ds/NT), disulphide/total thiol (Ds/TT), and the ratios of native thiol/total thiol (NT/TT) were analysed by the colorimetric method.Median age at diagnosis was 44 (29-70) years. The majority of patients had stage II-III disease (77.5%). Mean serum levels of TT were significantly lower in breast cancer patients (462.45 ± 100.2 μmol/L) compared to healthy controls (507.28 ± 75.72 μmol/L) (p=0.038). Mean serum levels of Ds were significantly lower in breast cancer patients (20.25 ± 5.94 μmol/L) compared to healthy controls (22.99 ± 3.56 μmol/L) (p=0.018). Meanwhile, mean IMA levels were significantly higher in breast cancer patients (0.81 ± 0.05 μmol/L) compared to healthy controls (0.73 ± 0.19 μmol/L) (p=0.016). NT and TT levels showed a moderate correlation with the percentage of fat mass and body mass index (BMI), and a weak correlation with age (p0.05). Univariate and multivariate analyses examining the association between thiol-disulphide levels and patient clinical characteristics demonstrated that NT and TT levels had a statistically significant relationship with body mass index and menopausal status (p0.05), with lower levels of NT and TT in postmenopausal patients and patients with high BMI.Decreased TT and Ds levels and increased IMA levels were determined in patients diagnosed with breast cancer compared to the healthy control group. Thiol-disulphide levels were observed to be associated with clinical characteristics such as menopausal status and BMI.Breast cancer, Thiol, Ischemic modified albumin.

BACKGROUND Non-invasive methods for periodontitis diagnosis would be a clinically important tool. This cross-sectional study aimed to investigate the association between oxidative stress, glycation, and inflammation markers and periodontal clinical parameters in periodontitis and periodontally healthy patients with type 2 diabetes and corresponding systemically healthy controls. METHODS Sixty-seven periodontally healthy (DM-H, n = 32) and periodontitis (DM-P, n = 35) patients with type 2 diabetes, and 54 systemically healthy periodontitis (H-P, n = 26) and periodontally healthy (H-H, n = 28) controls were included. Clinical periodontal parameters, body mass index, fasting glucose, hemoglobin A1c (HbA1c), along with saliva and serum 8-hydroxy-2'-deoxyguanosine (8-OHdG), malondialdehyde (MDA), 4-hydroxy-2-nonenal (4-HNE), advanced glycation end products (AGE), AGE receptor (RAGE) and high sensitivity C-reactive protein (hsCRP) levels were recorded and analyzed. RESULTS Salivary 8-OHdG levels were significantly higher in periodontitis compared to periodontally healthy patients, regardless of systemic status (P

Renalase (RNLS) is synthesized mainly in renal tissues. The function of RNLS in cancerous renal tissues has not been investigated. We investigated the synthesis of RNLS in chromophobe renal cell carcinoma, papillary renal cell carcinoma and clear cell renal cell carcinoma with Fuhrman grades (FG): FG1, nucleoli are absent or inconspicuous and basophilic; FG2, nucleoli are conspicuous and eosinophilic and visible but not prominent; FG3, nucleoli are conspicuous and eosinophilic; FG4, extreme nuclear pleomorphism, multinucleate giant cells, and/or rhabdoid and/or sarcomatoid differentiation. We used 90 tissue samples including 15 healthy controls, 15 chromophobe renal cell carcinoma tissues and 10 papillary renal cell carcinoma renal tissues: 12 FG1, 14 FG 2, 14 FG 3 and 10 FG4. RNLS in the tissue samples was measured using enzyme linked immunosorbent assay and immunostaining of RNLS in these tissues. RNLS was significantly greater in the chromophobe renal cell carcinoma and papillary renal cell carcinoma tissues than the control. The least amount of RNLS was found in the renal tissues of clear cell renal cell carcinoma FG1; the amount of RNLS increased as the FG grades increased. Because RNLS increased significantly in renal tissues due to cancer, except for clear cell renal cell carcinoma FG1, RNLS may be useful biomarker for distinguishing grades of renal cancer. Because RNLS increases cell survival, anti-RNLS preparations may be useful for treating cancer in the future.

To identify maternal second and third trimester urine metabolomic biomarkers for the detection of fetal congenital heart defects (CHDs). This was a prospective study. Metabolomic analysis of randomly collected maternal urine was performed, comparing pregnancies with isolated, non-syndromic CHDs versus unaffected controls. Mass spectrometry (liquid chromatography and direct injection and tandem mass spectrometry, LC–MS–MS) as well as nuclear magnetic resonance spectrometry, 1H NMR, were used to perform the analyses between 14 0/7 and 37 0/7 weeks gestation. A total of 36 CHD cases and 41 controls were compared. Predictive algorithms using urine markers alone or combined with, clinical and ultrasound (US) (four-chamber view) predictors were developed and compared. A total of 222 metabolites were identified, of which 16 were overlapping between the two platforms. Twenty-three metabolite concentrations were found in significantly altered in CHD gestations on univariate analysis. The concentration of methionine was most significantly altered. A predictive algorithm combining metabolites (histamine, choline, glucose, formate, methionine, and carnitine) plus US four-chamber view achieved an AUC = 0.894; 95% CI, 0814–0.973 with a sensitivity of 83.8% and specificity of 87.8%. Enrichment pathway analysis identified several lipid related pathways that are dysregulated in CHD, including phospholipid biosynthesis, phosphatidylcholine biosynthesis, phosphatidylethanolamine biosynthesis, and fatty acid metabolism. This could be consistent with the increased risk of CHD in diabetic pregnancies. We report a novel, noninvasive approach, based on the analysis of maternal urine for isolated CHD detection. Further, the dysregulation of lipid- and folate metabolism appears to support prior data on the mechanism of CHD.

To determine expression levels of miRNA-582-5p and miRNA-363 in serum of patients with Glioblastoma Multiforme and assess their biomarker potential.The study population consisted of 71 subjects including 35 patients and 36 healthy controls. Realtime polymerase chain reaction was used to determine serum expression levels of miRNA-582-5p and miRNA-363 in patients and control individuals. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic potential of miRNA-582-5p and miRNA-363. Serum caspase-9 level was measured using enzyme-linked immunosorbent assay.Normalized expression levels of miRNA-582-5p and miRNA-363 were calculated using the 2-ΔΔCt method. We found that miRNA-582-5p and miRNA-363 were significantly upregulated in patients compared with healthy controls. High levels of miRNA- 582-5p (Fold change 2.86, p0.0001) and miRNA-363 (Fold change 3.51, p0.0001) were significantly associated with Glioblastoma Multiforme. Additionally, ROC analyses demonstrated that levels of miRNA-582-5p [area under the curve (AUC)=0.938, p=0.0001] and miRNA-363 [AUC=0.951, p=0.0001] were significantly different between the groups. In contrast, there was no correlation between levels of serum caspase-9 and those of miRNA-582-5p (p=0.144) or miRNA-363 (p=0.050).High serum levels of miRNA-582-5p and miRNA-363 are associated with Glioblastoma Multiforme, and are potential biomarkers.

Aim To evaluate the relationship between respiratory problems and oxidative stress markers in exhaled breath condensate (EBC) of patients with esophageal atresia (EA). Methods EA cases with respiratory problems were evaluated retrospectively for age, gender, the type of atresia, surgical treatment, outcome and respiratory symptoms. The results of gastroesophageal reflux (GER) treatment including the use of proton pump inhibitor (PPI) and fundoplication were also documented. EBC samples of 500–1000 μl were obtained by Ecoscreen machine in all cases. The levels of Glutathione (Glut), 8-isoprostane (8-iso), cysteinyl-leukotriene (Cys-LT) were measured with ELISA. Results were compared with healthy control subjects (CG, n = 26) and the relationship between oxidative stress markers and respiratory symptoms was evaluated. The results of GER treatment and oxidative stress markers in EBC were also correlated. Results Twenty-nine patients with a mean age of 8.8 years (3–14 years) were included. The male/female ratio was 16:13. The EA presented with distal fistula in 27 cases. While no fistula was observed in 1 case, both proximal and distal fistulae were present in another single case. Associated anomalies, most of which were cardiovascular anomalies, were observed in 65.5% (n = 19) of cases. The median Glut level was 1.03 mM/ml (0.93–1.15), iso-8 was 38.8 pg/mL (32.03–76.2) and Cys-LT was 0.44 pg/mL (20.17–61.3) in patients with EA. The median levels of oxidative markers in CG were 1.23 mM/mL (1.13–1.36), 66.3 pg/mL (33.5–106.7), and 56.9 pg/mL (27.4–80.1), respectively. Glut levels were significantly lower in EA cases compared to CG (p = 0.01). There was no significant difference between the groups regarding 8-iso and CYS-LT levels (p = 0.9, p = 1.0). Cys-LT levels were significantly lower in patients with PPI treatment [21.7 pg/mL (18.6–48.1)], when compared to patients without PPI treatment [41.1 pg/mL (22.5–83.1)] (p = 0.04) and healthy subjects [56.9 pg/mL (27.4–80.1)] (p = 0.017). The 8-iso levels were significantly decreased in cases with fundoplication compared to the patients without fundoplication (p = 0.02). Conclusion Glut – an antioxidant agent – levels were significantly lower in EBC of EA cases. The decrease in Cys-LT levels in cases with PPI treatment and in 8-iso levels in patients with fundoplication suggests that the oxidative damage in EBC of EA cases may be correlated with GER and its management. Type of study Case control study Level of evidence Level III

Objectives Pulmonary neuroendocrine cells (NEC) increase with the age due to pulmonary maturity. The aim of this study was to determine whether open lung biopsies from patients with interstitial lung diseases have increased pulmonary NEC compared with NEHI. Our second aim was to assess pulmonary NECs in the lung autopsy of children without lung disease who died from different causes. Methods Lung tissue of 5 infants with neuroendocrine cell hyperplasia of infancy (NEHI); 21 patients with pediatric interstitial lung disease (chILD); 17 lung autopsies of infants at varying age without lung disease were included. The percentage of the airways containing neuroendocrine cells, the average percentage of NECs per airway and the number of neuroendocrine bodies (NEBs) in each case were analyzed. Results The mean percentage of the airways containing neuroendocrine cells were 95% in NEHI group, 30% in chILD group, 89% under intrauterine 37 weeks, 70% between intrauterine 37-40 weeks, 52% at postnatal 4 days-6 months of autopsy ages. In NEHI group, diffuse NE cell distribution and large NEBs were noticed in the lung biopsy. In chILD group, neuroendocrine cells were dispersed, did not form clusters and NE cells showed solitary distribution. In lung autopsy group, linear NE cells were detected at younger aged fetuses and solitary distribution of NE cells was detected with the older increasing age. Conclusions Our findings confirm that NECs are seen in many other childhood ILDs; NE cell hyperplasia may be a marker of decreased pulmonary development and NE cells decrease with the increasing age of the fetus during intrauterine life. This article is protected by copyright. All rights reserved.

Background: Apoptosis inhibitor of macrophage (AIM) and monocyte chemotactic protein-1 (MCP-1) are molecules that cause migration of M1 macrophages to visceral adipocytes, which is the first step i...

Aydoğdu, Uğur (Balikesir Author), The aim of this study was to evaluate the biomarkers of cardiac damage such as heart-type fatty acid-binding protein (H-FABP), pentraxin-3 (PTX-3), and thrombomodulin (TM) for the detection and prognosis of bovine traumatic pericarditis (TP). Spontaneous TP was diagnosed on the basis of history, clinical signs, complete blood count, glutaraldehyde test, ultrasonography, and pericardiocentesis findings. H-FABP, PTX-3 and TM levels in serum were compared between 25 Holstein cows diagnosed with spontaneous TP and 10 healthy control cows using bovine-specific ELISA kits. Serum H-FABP in cattle with TP was significantly (P < 0.05) higher than in the control group and positively correlated with cardiac troponin-I (cTnI), creatine kinase myocardial band (CK-MB), PTX-3 and TM (r = 0.683, 0.342, 0.448 and 0.424, respectively; P < 0.05). The serum levels of PTX-3 (P < 0.05) and TM (P < 0.05) in cattle with TP were significantly higher than in the control group. Cardiac damage biomarkers H-FABP, PTX-3 and TM may be useful in the diagnosis of bovine TP.

Alzheimer's disease (AD) is one of the most severe neurodegenerative diseases observed in the elderly population. Although the hallmarks of AD have been identified, the methods for its definitive diagnosis and treatment are still lacking. Extracellular vesicles (EVs) have become a promising source for biomarkers since the identification of their content. EVs are released from multiple cell types and, when released from neurons, they pass from the brain to the blood with their cargo molecules. Hence, neuron-specific EV-resident microRNAs (miRNAs) are promising biomarkers for diagnosis of AD. This study aimed to identify altered miRNA content in small neuron-derived extracellular vesicles (sNDEVs) isolated from AD patients and healthy individuals. Furthermore, we examined the role of sNDEV-resident miRNAs in neuron-glia cellular interaction to understand their role in AD propagation. We identified 10 differentially expressed miRNAs in the sNDEVs of patients via next-generation sequencing and validated the most dysregulated miRNA, let-7e, with qRT-PCR. Let-7e was significantly increased in the sNDEVs of AD patients compared with those of healthy controls in a larger cohort. First, we evaluated the diagnostic utility of let-7e via ROC curve analysis, which revealed an AUC value of 0.9214. We found that IL-6 gene expression was increased in human microglia after treatment with sNDEVs of AD patients with a high amount of let-7e. Our study suggests that sNDEV-resident let-7e is a potential biomarker for AD diagnosis, and that AD patient-derived sNDEVs induce a neuroinflammatory response in microglia.

Background and ObjectivesTo evaluate the predictive value of serum neurofilament light chain (sNfL) and CSF NfL (cNfL) in patients with radiologically isolated syndrome (RIS) for evidence of disease activity (EDA) and clinical conversion (CC).MethodssNfL and cNfL were measured at RIS diagnosis by single-molecule array (Simoa). The risk of EDA and CC according to sNfL and cNfL was evaluated using the Kaplan-Meier analysis and multivariate Cox regression models including age, spinal cord (SC) or infratentorial lesions, oligoclonal bands, CSF chitinase 3–like protein 1, and CSF white blood cells.ResultsSixty-one patients with RIS were included. At diagnosis, sNfL and cNfL were correlated (Spearman r = 0.78,p< 0.001). During follow-up, 47 patients with RIS showed EDA and 36 patients showed CC (median time 12.6 months, 1–86). When compared with low levels, medium and high cNfL (>260 pg/mL) and sNfL (>5.0 pg/mL) levels were predictive of EDA (log rank,p< 0.01 andp= 0.02, respectively). Medium-high cNfL levels were predictive of CC (log rank,p< 0.01). In Cox regression models, cNfL and sNfL were independent factors of EDA, while SC lesions, cNfL, and sNfL were independent factors of CC.DiscussioncNfL >260 pg/mL and sNfL >5.0 pg/mL at diagnosis are independent predictive factors of EDA and CC in RIS. Although cNfL predicts disease activity better, sNfL is more accessible than cNfL and can be considered when a lumbar puncture is not performed.Classification of EvidenceThis study provides Class II evidence that in people with radiologic isolated syndrome (RIS), initial serum and CSF NfL levels are associated with subsequent evidence of disease activity or clinical conversion.

Transforming growth factor‐β (TGF‐β) becomes rapidly activated in the infarcted heart. Hence, TGF‐β‐mediated persistent activation of cardiac fibroblasts (CFs) and exaggerated fibrotic responses may result in adverse cardiac remodelling and heart failure. Additionally, peptidylarginine deiminase 4 (PAD4) was described to be implicated in organ fibrosis. Here, we investigated the impact of PAD4 on CF function and myofibroblast transdifferentiation in vitro. The expression of fibrosis‐related genes was largely similar in cultured WT and PAD4‐/‐ CFs of passage 3, although collagen III was reduced in PAD4‐/‐ CFs. Exposure to TGF‐β inhibited proliferation and increased contractile activity and migration of WT CFs, but not of PAD4‐/‐ CFs. However, under baseline conditions, PAD4−/− CFs showed comparable functional characteristics as TGF‐β‐stimulated WT CFs. Although the SMAD‐dependent TGF‐β pathway was not disturbed in PAD4‐/‐ CFs, TGF‐β failed to activate protein kinase B (Akt) and signal transducer and activator of transcription 3 (STAT3) in these cells. Similar results were obtained in WT CFs treated with the PAD4 inhibitor Cl‐amidine. Abrogated Akt activation was associated with diminished levels of phosphorylated, inactive glycogen synthase kinase‐3β (GSK‐3β). Consequently, PAD4‐/‐ CFs did not upregulate collagen I and α‐smooth muscle actin (α‐SMA) expression after TGF‐β treatment. Thus, PAD4 is substantially involved in the regulation of non‐canonical TGF‐β signalling and may represent a therapeutic target for the treatment of adverse cardiac remodelling.

Aim: We sought to determine the relationship between presence of atrial fibrillation (AF) and serum biomarkers, including native thiol (antioxidant), disulphide/native thiol ratio, Hs-CRP and high-sensitivity Troponin-I (Hs-TnI) in hypertrophic cardiomyopathy (HCM). Materials & methods: We enrolled consecutive 121 HCM outpatients without AF and 40 HCM outpatients with AF. A 12-lead electrocardiogram, transthoracic echocardiography and 24/48-h ambulatory rhythm monitoring were performed for all patients. Fasting venous blood samples were taken from all study patients to measure serum thiol-disulphide homeostasis, Hs-CRP and Hs-TnI. Results: Serum-native thiol was lower and disulphide/native thiol ratio was more oxidized in HCM patients with AF (p

The molecules human interleukin (IL-18), the soluble cluster of differentiation (sCD40), platelet factor 4 variant 1 (PF4V1), and neutrophil gelatinase-associated lipocalin (NGAL) are all markers of inflammation in biological systems and are linked to prognosis in several inflammatory diseases as well. Since there is no study in which the above-mentioned molecules are studied together in ocular Behçet's disease (OBD), the aim of this study is to reveal whether these molecules are activity markers in active (OABD) and inactive (OIBD) disease.30 OABD and 30 OIBD and 30 healthy individuals were included in the study. IL-18, sCD40, PF4V1, and NGAL molecules were studied in blood samples by the ELISA method.When OABD and OIBD were compared to healthy individuals, the levels of IL-18, sCD40, PF4V1, and NGAL molecules were found to be statistically significant. These values were even more significantly higher in patients with OABD.When ROC values of IL-18, sCD40, PF4V1, and NGAL are evaluated, it is clear that these four molecules can be used as biomarkers to aid activity and diagnosis in OBD.

TRACP-5b can be used to monitor the response of treatments in osteoporosis. We investigated the effect of feeding on levels of TRACP-5b and how these markers perform in a clinical setting. After feeding, there was no effect on levels TRACP-5b. It has similar diagnostic accuracy to CTX and PINP.Bone turnover markers (BTMs) can be used to monitor response to osteoporosis treatment. However, some are affected by food intake and are not suitable to measure in a clinical setting. An assay is available which is capable of detecting the active isoform 5b of tartrate resistance acid phosphatase (TRACP-5b) and it may have minimal biological variation. Our aims were to investigate the effect of feeding on levels of TRACP-5b and compare this to CTX and PINP and then to compare the diagnostic accuracy of TRACP-5b to CTX and PINP in patients with osteoporosis given commonly used treatments.Eighteen patients were recruited to investigate the effect of feeding on BTMs. Ninety-seven patients (74 females and 23 males) receiving 5 mg annual intra-venous zoledronate (mean age 70) and 97 patients receiving no treatment were recruited as group-matched controls. Sixteen patients receiving 60 mg subcutaneous denosumab every 6 months, (mean age 76) and 16 matched controls were recruited. Seventy-six patients were receiving oral bisphosphonates: 70 mg alendronate weekly, 35 mg risedronate and 150 mg monthly ibandronate (4%). Thirty of these patients had BMD measured at the total hip and lumbar spine. An estimate of compliance was not determined. Eighty patients receiving no treatment were recruited as group-matched controls. TRACP-5b (ELISA, Nittobo) and CTX and PINP were measured in serum in the non-fasting state between 0800 and 1700.After feeding, there was no effect on levels TRACP-5b and significant reductions in CTX and PINP, 29% and 10%, respectively (p 0.001). In the zoledronate and denosumab groups, there were no differences in the areas under the curves (AUCs) between TRACP-5b, PINP and CTX. In the oral bisphosphonates group, the AUCs between TRACP-5b and PINP and TRACP-5b and CTX were significantly different, p 0.01 and p = 0.001, respectively. TRACP-5b was negatively correlated with BMD.TRACP-5b is not affected by food intake, unlike CTX and PINP. All three BTMs correlate with change in BMD at the lumbar spine and total hip. TRACP-5b has similar diagnostic accuracy to CTX and PINP with commonly used treatments for osteoporosis with the exception of oral bisphosphonate therapy.

(Leukaemia derived) dendritic cells (DC, DC

TAK-653 is a novel α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-positive allosteric modulator being developed as a potential therapeutic for major depressive disorder (MDD). Currently, there are no translational biomarkers that evaluate physiological responses to the activation of glutamatergic brain circuits available. Here, we tested whether noninvasive neurostimulation, specifically single-pulse or paired-pulse motor cortex transcranial magnetic stimulation (spTMS and ppTMS, respectively), coupled with measures of evoked motor response captures the pharmacodynamic effects of TAK-653 in rats and healthy humans. In the rat study, five escalating TAK-653 doses (0.1–50 mg/kg) or vehicle were administered to 31 adult male rats, while measures of cortical excitability were obtained by spTMS coupled with mechanomyography. Twenty additional rats were used to measure brain and plasma TAK-653 concentrations. The human study was conducted in 24 healthy volunteers (23 males, 1 female) to assess the impact on cortical excitability of 0.5 and 6 mg TAK-653 compared with placebo, measured by spTMS and ppTMS coupled with electromyography in a double-blind crossover design. Plasma TAK-653 levels were also measured. TAK-653 increased both the mechanomyographic response to spTMS in rats and the amplitude of motor-evoked potentials in humans at doses yielding similar plasma concentrations. TAK-653 did not affect resting motor threshold or paired-pulse responses in humans. This is the first report of a translational functional biomarker for AMPA receptor potentiation and indicates that TMS may be a useful translational platform to assess the pharmacodynamic profile of glutamate receptor modulators.

Objectives: To analyze the prognostic value of serum presepsin value in community-acquired pneumonia focal sepsis using sepsis-3 criteria and its relationship with other biomarkers and clinical severity scores. Methods: For this prospective observational study, 176 patients above 18 years old, diagnosed with community-acquired pneumonia, pneumonia focal sepsis and septic shock were included. It was performed in a tertiary hospital between May 2020 and December 2020. Blood samples were obtained from patients for presepsin levels at the time of diagnosis in the emergency room. The serum presepsin levels of 3 groups were statistically compared with each other. Results: The sepsis group had significantly higher serum presepsin levels than the pneumonia group (p=0.004). The septic shock group had serum presepsin levels than sepsis group; however, the difference was not statistically significant (p=0.25). Non survivor patients had significantly higher serum presepsin levels than survivors (p=0.001). Significant correlation determined between serum presepsin level and procalcitonin, C-reactive protein, lactate, pneumonia severity index, and quick sequential organ failure assessment (qSOFA). Conclusion: Serum presepsin level is a new biomarker that can be used an indicator of sepsis and mortality in community-acquired pneumonia. However, for determining the prognosis of sepsis, there was no superiority detected over other biomarkers and clinical severity scores.

Developing a deeper understanding of biological components of sperm is essential to improving cryopreservation techniques and reproductive technologies. To fully ascertain the functional determinants of fertility, lipidomic methods have come to the forefront. Lipidomics is the study of the lipid profile (lipidome) within a cell, tissue, or organism and provides a quantitative analysis of the lipid content in that sample. Sperm cells are composed of various lipids, each with their unique contribution to the overall function of the cell. Lipidomics has already been used to find new and exciting information regarding the fatty acid content of sperm cells from different species. While the applications of lipidomics are rapidly evolving, gaps in the knowledge base remain unresolved. Current limitations of lipidomics studies include the number of available samples to analyze and the total amount of cells within those samples needed to detect changes in the lipid profiles across different subjects. The information obtained through lipidomics research is essential to systems and cellular biology. This review provides a concise analysis of the most recent developments in lipidomic research. This scientific resource is important because these developments can be used to not only combat the reproductive challenges faced when using cryopreserved semen and artificial reproductive technologies in livestock such as cattle, but also other mammals, such as humans or endangered species.

Glioblastoma multiforme (GBM) is the most aggressive brain tumor with poor prognosis to most patients. Immunotherapy of GBM is a potentially beneficial treatment option, whose optimal implementation may depend on familiarity with tumor specific antigens, presented as HLA peptides by the GBM cells. Furthermore, early detection of GBM, such as by a routine blood test, may improve survival, even with the current treatment modalities. This study includes large-scale analyses of the HLA peptidome (immunopeptidome) of the plasma-soluble HLA molecules (sHLA) of 142 plasma samples, and the membranal HLA of GBM tumors of 10 of these patients' tumor samples. Tumor samples were fresh-frozen immediately after surgery and the plasma samples were collected before, and at multiple visits after surgery. In total, this HLA peptidome analysis involved 52 different HLA allotypes and resulted in the identification of more than 35,000 different HLA peptides. Strong correlations were observed in the signal intensities and in the repertoires of identified peptides between the tumors and plasma-soluble HLA peptidomes of the individual patients, whereas low correlations were observed between these HLA peptidomes and the tumors' proteomes. HLA peptides derived from Cancer/Testis Antigens (CTAs) were selected based on their presence among the HLA peptidomes of the patients and absence of expression of their source genes from any healthy and essential human tissues, except from immune-privileged sites. Additionally, peptides were selected as potential biomarkers if their levels in the plasma-sHLA peptidome were significantly reduced after the removal of tumor mass. The CTAs identified among the analyzed HLA peptidomes provide new opportunities for personalized immunotherapy and for early diagnosis of GBM.

Paper-based electrodes modified with molybdenum disulfide (MoS2) in the form of bulk crystals or exfoliated nanosheets were developed and used as a biosensing platform for the impedimetric detection of miRNAs (miRNA-155 and miRNA-21) related to early diagnosis of lung cancer. For this purpose, MoS2 crystals or nanosheets were used for the modification of the working electrode area of paper-based platform for the first time in this study. The proposed assay offers sensitive and selective detection of microRNAs by electrochemical impedance spectroscopy (EIS) technique. The entire assay, both the electrode modification and the miRNA detection being completed in 30 min and a single sample droplet (5 mu L) was enough to cover working electrode area which enabled analysis in low sample volumes. The limits of detection (LOD) for miRNA-21 and miRNA-155 were calculated both in buffer and fetal bovine serum media. It is found that the LOD is varying between 1 and 200 ng/mL. In comparison to nanosheets, a larger electroactive surface area was obtained with bulk MoS2 resulting in lower LOD values on miRNA detection. The paper-based electrodes showed high specificity towards their target sequences. Moreover, they effectively discriminated single base mismatched non-target sequences. The advantages of these MoS2 paper based electrodes include high sensitivity, and low-cost provide great potential for improved monitoring of miRNA biomarkers even in artificial serum media., Newton-Katip Celebi funding program; Turkish Scientific and Technological Research Council TUBITAK [215Z702]; British Council [216182787]; Turkish Academy of Sciences (TUBITAK); Invest Northern Ireland under a Biodevices grant [RD0714186]; TUBITAK [215Z702], This project was supported by the Newton-Katip Celebi funding program, and authors acknowledge financial support from the Turkish Scientific and Technological Research Council TUBITAK Project no. 215Z702) and the British Council (Newton Fund, Institutional Links, Ref: 216182787). A.E. would also like to express her gratitude to the Turkish Academy of Sciences (TUBA) as a principal member for its partial support. E.Y. and E.E., master's students and PhD, respectively, acknowledge a project scholarship (TUBITAK Project no. 215Z702). Authors also acknowledge to helpful discussion of Assoc. Prof. Yildiz Uludag as the project consultant during project (TUBITAK; Project no. 215Z702). P.P. acknowledges support from Invest Northern Ireland under a Biodevices grant, Ref. RD0714186.

Paper-based biosensors are considered simple and cost-efficient sensing platforms for analytical tests and diagnostics. Here, a paper-based electrochemical biosensor was developed for the rapid and sensitive detection of microRNAs (miRNA-155 and miRNA-21) related to early diagnosis of lung cancer. Hydrophobic barriers to creating electrode areas were manufactured by wax printing, whereas a three-electrode system was fabricated by a simple stencil approach. A carbon-based working electrode was modified using either reduced graphene oxide or molybdenum disulfide nanosheets modified with gold nanoparticle (AuNPs/RGO, AuNPs/MoS2) hybrid structures. The resulting paper-based biosensors offered sensitive detection of miRNA-155 and miRNA-21 by differential pulse voltammetry (DPV) in only 5.0 mu L sample. The duration in our assay from the point of electrode modification to the final detection of miRNA was completed within only 35 min. The detection limits for miRNA-21 and miRNA-155 were found to be 12.0 and 25.7 nM for AuNPs/RGO and 51.6 and 59.6 nM for AuNPs/MoS2 sensors in the case of perfectly matched probe-target hybrids. These biosensors were found to be selective enough to distinguish the target miRNA in the presence of single-base mismatch miRNA or noncomplementary miRNA sequences., Newton-Katip Celebi funding program; Turkish Scientific and Technological Research Council (TUBITAK) [215Z702]; British Council (Newton Fund) [216182787]; Invest Northern Ireland under a Biodevices grant [RD0714186], This project was supported by the Newton-Katip Celebi funding program, and received a financial support from the Turkish Scientific and Technological Research Council (TUBITAK; Project no. 215Z702), the British Council (Newton Fund, Institutional Links, Ref: 216182787) and Invest Northern Ireland under a Biodevices grant, Ref. RD0714186.

Purpose Decades of quality control efforts have raised the standards of immunohistochemistry (IHC), the principle method used for biomarker testing in breast cancer; however, computational pathology and reverse transcription quantitative PCR (RT-qPCR) may also hold promise for additional substantial improvements. Methods Herein, we investigated discrepancies in the assessment of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and marker of proliferation Ki67 comparing routinely obtained IHC (and FISH) data (ORI) with the results of manual (REV) and semi-automated (DIA) re-evaluation of the original IHC slides and then with RNA expression data from the same tissue block using the MammaTyper® (MT) gene expression assay. Results Correlation for ER and PR was high between ORI IHC and the other three study methods (REV, DIA and RT-qPCR). For HER2, 10 out of 96 discrepant cases can be detected between ORI and REV that involved at least one call in the equivocal category (except for one case). For Ki67, 22 (29.1%) cases were categorized differently by either REV alone (n = 17), DIA alone (n = 15) or both (n = 10) and 28 cases (29.2%) for RT-qPCR. Most of the discrepant Ki67 cases changed from low to high between the original and following assessment and belonged to the intermediate Ki67 expression range (between 9 and 30%). Conclusions Determination of the breast cancer biomarkers ER, PR, HER2 and Ki67 at the mRNA level shows high degree of correlation with IHC and compares well with correlations between original with subsequent independent manual or semi-automated IHC assessments. The use of methods with wider dynamic range and higher reproducibility such as RT-qPCR may offer more precise assessment of endocrine responsiveness, improve Ki67 standardization and help resolve HER2 cases that remain equivocal or ambiguous by IHC/FISH. In summary, our findings seem to configure RT-qPCR as a complementary method to be used in cases of either equivocal results or presenting, at the traditional determination assays, biomarkers expressions close to the cut-off values.

WOS: 000372174600020, PubMed ID: 26864298, Background/Aims: Familial Mediterranean fever (FMF) is an autosomal recessive disorder characterized by attacks of fever and diffuse abdominal pain. The primary concern with this presentation is to distinguish it from acute appendicitis promptly. Thus, we aimed to evaluate the role of neutrophil lymphocyte ratio (NLR) to leverage the differential diagnosis of acute FMF attack with histologically proven appendicitis. Methods: Twenty-three patients with histologically confirmed acute appendicitis and 88 patients with acute attack of FMF were included in the study. NLR, C-reactive protein and other hematologic parameters were compared between the groups. Results: Neutrophil to lymphocyte ratio was significantly higher in patients with acute appendicitis compared to the FMF attack group (8.24 +/- 6.31 vs. 4.16 +/- 2.44, p = 0.007). The performance of NLR in diagnosing acute appendicitis with receiver operating characteristic analysis with a cut-off value of 4.03 were; 78% sensitivity, 62% specificity, and area under the curve 0.760 (95% confidence interval, 0.655 to 0.8655; p < 0.001). Conclusions: This study showed that NLR, the simple and readily available inflammatory marker may have a useful role in distinguishing acute FMF attack from acute appendicitis.