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To explore the relationship between serum levels of midkine and omentin-1 and the severity of sepsis in patients, and their prognostic value. A retrospective analysis was conducted on the clinical data of 180 sepsis patients. According to the severity of the patient's condition, they were separated into sepsis group ( n  = 76), severe sepsis group ( n  = 59), and sepsis shock group ( n  = 45). Based on the survival within 28 days of admission, they were grouped into survivors group ( n  = 128) and nonsurvivors group ( n  = 52). The serum Midkine level and APACHE II score in the sepsis shock group were higher than those in the severe sepsis group and sepsis group, while the Omentin-1 level was lower than that in the severe sepsis group and sepsis group ( p  < 0.05). The serum Midkine level and APACHE II score in the severe sepsis group were higher than those in the sepsis group, while the Omentin-1 level was lower than that in the sepsis group ( p  < 0.05). The Midkine and APACHE II score in the nonsurvivors group was higher than those in the survivors group, while the Omentin-1 score was lower than that in the survivors group ( p  < 0.05). Midkine and APACHE II score were independent risk factors for the prognosis of sepsis patients, while Omentin-1 was a protective factor for the prognosis of sepsis patients ( p  < 0.05). The AUC of the combined prediction of serum Midkine and Ommentin-1 for the prognosis of sepsis patients was 0.880, with a sensitivity of 90.38% and a specificity of 72.66%. The combined prediction of serum Midkine and Ommentin-1 was better than that of individual prediction of Midkine and Ommentin-1. Serum Midkine is highly expressed and Omentin-1 is lowly expressed in sepsis patients, and the combination of the two has a high predictive power for the prognosis of sepsis patients.

Background: Metabolic syndrome is a prevalent and common health problem and numerous studies have revealed the role of diet and lifestyle change in prevention of metabolic syndrome. However, the novel dietary index, cardioprotective index (CPI) and its association with metabolic syndrome is not investigated yet. In the current study, we evaluated the association between metabolic syndrome and its components, CPI, Nesfatin-1 and Omentin-1in a cross-sectional study., Methods: Three hundred forty eight overweight and obese individuals with metabolic syndrome were recruited. Subjects underwent anthropometric and laboratory assays including metabolic markers, Nesfatin-1 and Omentin-1 with commercial kits., Results: Those at the first tertile of CPI had lower high density lipoprotein concentrations (HDL) and higher low density lipoprotein concentrations (LDL), triglyceride (TG), systolic and diastolic blood pressures (SBP, DBP) levels compared with those at the highest tertiles (P < 0.05). After adjustment for the confounding effects of age, sex, body mass index, physical activity and total calorie intake, LDL lost its significance across CPI tertiles. Moreover, serum total cholesterol, insulin and insulin resistance were not significant across CPI tertiles neither in crude nor in adjusted models (P > 0.05). Additionally, being at the third tertile of CPI was accompanied with significantly higher Nesfatin-1 and Omentin-1 levels compared with lowest tertiels (P < 0.05) in crude and confounder - adjusted models., Conclusions: To our findings, CPI was in positive relationship with metabolic parameters, blood pressure, Nesfatin-1 and Omentin-1 levels in metabolic syndrome. Further future studies will help to elaborate the causality., Clinical Trial Number: Not applicable., Competing Interests: Declarations. Ethics approval and consent to participate: Written consent was obtained from all of the participants of the study. The protocol of the study is approved by ethics committee of Alnoor University (143-P912). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Objectives: To investigate the relationship of cerebrospinal fluid and serum levels of soluble interleukin-2 receptor (SIL-2R), endothelial nitric oxide synthase (eNOS), and cluster of differentiation 93 (CD93) with the progression and prognosis of viral encephalitis (VE) in children., Methods: Prospectively, 102 children with VE admitted from January 2021 to January 2024 were selected as the VE group. The patients were divided into a mild subgroup (64 patients) and a severe subgroup (38 patients) according to disease progression. The patients were also divided into a good prognosis subgroup (29 patients) and a poor prognosis subgroup (73 patients) according to prognosis. A control group of 102 children with central nervous system diseases who were examined and found not to have VE during the same period was selected. The factors contributing to the poor prognosis of children with VE and the predictive value of SIL-2R, eNOS, and CD93 in cerebrospinal fluid and serum for the poor prognosis of children with VE were evaluated., Results: Cerebrospinal fluid and serum SIL-2R, eNOS, and CD93 levels were significantly increased in the VE group, severe subgroup, and poor prognosis subgroup ( P <0.05). Multivariate logistic regression analysis showed that high SIL-2R, eNOS, and CD93 levels in cerebrospinal fluid and serum were risk factors for poor prognosis in children with VE ( P <0.05). Receiver operating characteristic curve analysis showed that the combination of cerebrospinal fluid SIL-2R, eNOS, and CD93 was superior to these individual indicators in prediction of poor prognosis in children with VE ( P <0.05). Similarly, the combination of serum SIL-2R, eNOS, and CD93 was superior to these individual indicators in prediction of poor prognosis in children with VE ( P <0.05)., Conclusions: The cerebrospinal fluid and serum levels of SIL-2R, eNOS, and CD93 are significantly elevated in children with VE, and they are associated with VE progression and prognosis.

Objectives: The aim of this research was to evaluate changes in body composition, adipokine levels, and dyslipidemia parameters in males with abdominal obesity following two distinct interventions: exercise alone and exercise combined with an ad libitum diet., Methods: This study included 44 males with abdominal obesity (mean age 34.7 ± 5.5 years, waist circumference [WC] 110.3 ± 8.5, BMI 32.0 ± 3.9), who were randomly assigned to three groups: an experimental group engaging in aerobic-resistance exercise (II, n = 16), an experimental group engaging in aerobic-resistance exercise combined with an ad libitum high-protein, low-glycemic index carbohydrate diet (III, n = 16), both interventions lasting 6 weeks, and a control group without interventions (I, n = 12). Body composition metrics (body mass index [BMI], waist circumference [WC], body fat [BF], abdominal fat [ABD]) and fat-free mass [FFM], along with biochemical blood analyses (irisin [IR], omentin [OMEN], glucose [GLU], insulin [INS], LDL- and HDL-cholesterol), were measured at baseline and after the 6-week intervention. The effects of the interventions on the analyzed variables across groups were assessed using mixed ANOVA tests with post-hoc comparisons. Effect size (ES) was also calculated using partial eta squared ( η p 2 )., Results: The intervention in group III resulted in a significant decrease in IR ( p < 0.01, η p 2 = 0.03) by 41% and LDL-C ( p < 0.01, η p 2 = 0.02) by 14%. These effects were associated with a reduction in BF ( p < 0.01, η p 2 = 0.02) by 14%, ABD ( p < 0.01, η p 2 = 0.03) by 31%, and WC ( p < 0.01, η p 2 = 0.01) by 3%. In group II, decreases after 6 weeks of intervention were noted only in WC ( p = 0.02, η p 2 = 0.01) by 1% and in INS ( p < 0.01, η p 2 = 0.04) by 47%. No differences were found between groups. The use of low-glycemic index carbohydrates ( p < 0.01, η p 2 = 0.06) and increased protein intake ( p < 0.01, η p 2 = 0.30) led to changes in the fiber-to-energy value of the diet ratio ( p < 0.01, η p 2 = 0.18) and a reduction in dietary energy value ( p < 0.01, η p 2 = 0.13) by 23%, resulting in a greater energy deficit than in the II group., Conclusions: These findings highlight the effect of combining dietary and exercise interventions to achieve significant changes in body composition and metabolic parameters, even over a short period of intervention.

Examining the impact of Sanjie Zhentong capsules on hormone levels and serum expression of folate receptor 1 (FOLR1) and Mesothelin (MSLN) in endometriosis patients. A cohort of 150 endometriosis patients admitted between June 2019 and June 2023 was divided into 2 groups based on Sanjie Zhentong intake, comprising 75 cases each. Comparative analyses encompassed uterine artery hemodynamic parameters, ultrasound (B-mode) findings, Visual Analog Scale scores, traditional Chinese medicine symptom scores, Endometriosis Health Profile-30 scores, and serum levels of FOLR1, MSLN, and sex hormones before and after treatment. Post-treatment, both groups exhibited increased peak systolic velocity compared to pretreatment, with the Sanjie Zhentong group showing a significantly higher increase (P < .05). Moreover, resistance index decreased in both groups post-treatment, with the Sanjie Zhentong group displaying a greater reduction (P < .05). Adnexal mass diameters, endometrial thickness, and uterine volume decreased post-treatment in both groups, with the Sanjie Zhentong group experiencing a more pronounced decrease (P < .05). Serum FOLR1, MSLN, and sex hormone levels also decreased post-treatment in both groups, with the Sanjie Zhentong group exhibiting a more significant decrease (P < .05). Additionally, pain scores, traditional Chinese medicine symptoms, and Endometriosis Health Profile-30 scores decreased post-treatment in both groups, with the Sanjie Zhentong group demonstrating a greater reduction (P < .05). Sanjie Zhentong capsules demonstrate efficacy in regulating sex hormones, reducing serum FOLR1 and MSLN expression, alleviating pain, shrinking adnexal masses, decreasing uterine size, and improving uterine artery blood flow in endometriosis patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Interstitial lung disease (ILD) may complicate the course of systemic autoimmune rheumatic disease (SARD) and diagnostic biomarkers are needed. Krebs von den Lungen-6 (KL-6), ferritin (FER) and interleukin 6 (IL-6) have been involved in the ILD development. Our study aimed to compare KL-6, FER, IL-6 and soluble mesothelin-related peptide (SMRP) concentrations in a cohort of idiopathic and SARD-ILD., Methods: 3169 patients were enrolled in the "UK Biomarkers in Interstitial Lung Disease (UK-BILD) Study". We selected patients affected by SARD-ILD and idiopathic ILD (usual interstitial pneumonia-idiopathic pulmonary fibrosis and fibrotic non-specific interstitial pneumonia). Serum marker concentrations were measured through chemiluminescent assays (Fujirebio Europe, Ghent, Belgium)., Results: 1013 patients were selected for the study: 520 (51.3%) had idiopathic ILD and 493 (48.7%) SARD-ILD. Idiopathic ILD patients displayed higher KL-6 values than SARD-ILD (p = 0.0002). FER and SMRP, though within normal ranges, were significantly higher in idiopathic ILD (p<0.0001). Logistic regression showed good sensitivity (69.4%) and specificity (80.4%) selecting the variables FER and KL-6 concentrations, age and gender-male correlated with a diagnosis of idiopathic ILD., Conclusion: Our study showed the excellent diagnostic value of KL-6 for detecting ILD, which irrespective of the final diagnosis and extent of disease, is always elevated and is a reliable biomarker of lung fibrosis in various diseases, ranging from idiopathic to autoimmune forms. Our study proposed an ILD differentiation model including clinical background. In this context, combination of serum markers and clinical data, as seen in our cohort, may lead to a further improvement in diagnostic accuracy for ILD., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 d’Alessandro et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Coronary heart disease (CHD) and stroke have become the leading cause of premature mortality and morbidity worldwide. Therefore, sensitive and accurate biomarkers for early detection of CHD and stroke are urgently needed for effective prevention and treatment. We aim to investigate the association between blood-based HYAL2 methylation and the risk of CHD and stroke in Chinese population., Methods: In a prospective nested case-control study comprising 171 CHD cases, 139 stroke cases, who developed the diseases after recruitment and 356 controls who remained healthy during the 2.5 years of follow-up time, the methylation level of HYAL2 in the peripheral blood was quantified using mass spectrometry, and the association was calculated by logistic regression adjusted for covariant., Results: Significant association between HYAL2 methylation in the peripheral blood and increased risk of preclinical CHD and stroke were identified [odds ratios (ORs) per - 10% methylation: 1.35-1.64, p ≤ 0.045 for HYAL2&#95;CpG&#95;1, HYAL2&#95;CpG&#95;2 and HYAL2&#95;CpG&#95;3 in CHD; ORs per - 10% methylation: 0.76-1.64, p ≤ 0.033 for HYAL2&#95;CpG&#95;2 and HYAL2&#95;CpG&#95;4 in stroke]. The association in CHD was further enhanced by female gender, younger age (< 70 years old), without the history of hypertension and cancer. The combination of four HYAL2 methylation sites showed an effective discrimination of CHD and stroke cases without hypertension from controls [area under curve (AUC) = 0.78 and 0.75, respectively]., Conclusions: This study presents a strong association of altered HYAL2 methylation in peripheral blood with preclinical CHD and stroke, providing a novel biomarker for risk assessment and early detection of cardiovascular diseases., (© 2024. The Author(s).)

Introduction: Diabetic foot disease is an advanced complication of diabetes mellitus, which is associated with severe invalidization and high mortality rate among affected people. Many factors are involved in its pathogenesis but not all of them are fully elucidated. Objectives: Adipose tissue and its hormones - adipokines, are related to diabetic complications and metabolic disorders. Until now, there are limited data on their role in diabetic foot. The aim of this cross-sectional study is to determine the levels of the adipokine omentin-1 in people with and without diabetic foot disease and to look for its potential involvement in this complication. Methods: Eighty patients with type 2 diabetes and mean age of 60.8±10.5 years were included in this study. They were divided into two groups: with (n=36) and without (n=44) diabetic foot disease. Standard antrometric, clinical and laboratory tests were made. Body composition was analyzed by bioelectrical impedance based device. Serum omentin-1 was measured using ELISA method. Results: Levels of omentin-1 were significantly higher among people with diabetic foot disease (700.2±345.1 ng/ml), compared to the other group (560.2±176.7 ng/ml). This difference remained significant even after adjusting for potential confounders. In a regression model omentin-1 proved its predictive value for development of diabetic foot. Conclusion: Adipokines, and particularly omentin-1, might be included in the pathogenesis of diabetic foot disease., Competing Interests: Declaration of Conflicting InterestsThe Authors declare that there is no conflict of interest.

The hemojuvelin-hepcidin regulatory axis may play a key role in the iron metabolism both systemically and locally. There is a pressing need to evaluate this tightly regulated network of iron parameters and their potential impact on the development of ischemic stroke (IS). We aimed to assess iron metabolism biomarkers in patients after IS, evaluating changes over time and considering their clinical features. We studied 45 patients diagnosed with IS. We assessed major iron metabolism parameters, such as hepcidin, soluble hemojuvelin (sHJV), soluble transferrin receptor (sTfR), and ferritin, using immunoenzymathic methods at two time points: on admission and on the 7th day post IS. We found increased ferritin levels on the 7th day post IS compared to admission, and this was observed in the entire study group ( p = 0.03) and in the subgroup treated with thrombolysis ( p = 0.02). The hepcidin levels, on the other hand, showed a significant decrease on the 7th day, though this difference was only evident in the entire study group ( p = 0.04). We also discovered significantly elevated sHJV levels in patients with PACI stroke compared to other stroke locations, both on admission and on the 7th day post IS ( p < 0.05). Significantly higher sHJV levels were observed in patients treated with thrombolysis compared to those receiving conventional treatment, regardless of the time point ( p < 0.0001 and p = 0.0002, respectively). Our study revealed changes in the iron metabolism parameters during stroke. The patients with anterior cerebral infarction and those treated with thrombolysis presented significantly elevated sHJV levels.

Breast cancer (BC) is the most frequently diagnosed cancer and a leading cause of cancer-related mortality among women globally. Resistin, omentin and ghrelin, adipokines involved in inflammation and metabolic regulation, have been implicated in cancer development, yet their associations with BC remain unclear. This systematic review and meta-analysis aimed to elucidate the relationships between resistin, omentin, and ghrelin concentrations and BC, while exploring potential moderators such as body mass index (BMI) and menopausal status. A comprehensive search of electronic databases up to 13 May 2024 identified studies comparing resistin and omentin, but not ghrelin, concentrations in BC patients and healthy controls. Standardized mean differences (SMDs) were calculated using random-effects models, and meta-regression and subgroup analyses were performed to investigate sources of heterogeneity. Analysis of 11 studies showed that BC patients exhibited significantly higher resistin concentrations compared to controls, with a pooled SMD of 2.05 (95 % CI 1.24 to 2.86, p < 0.001). Meta-regression indicated that BMI significantly moderated the resistin-BC association (p = 0.003). In contrast, omentin concentrations presented a complex picture, with a pooled SMD of -0.27 (95 % CI -1.39 to 0.84, I^ 2  = 96.2 %, p < 0.001), indicating substantial heterogeneity and inconclusive results, whereas only one study investigated ghrelin. Our findings support a significant association between elevated resistin concentrations and BC, suggesting a potential role of resistin in BC pathophysiology. The data on omentin and ghrelin remain inconclusive, warranting further investigation. Future research should focus on large, longitudinal studies with standardized methodologies to validate these findings and clarify the role of adipokines in BC., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Immune dysfunction is one of the risk factors which plays an important role in the development of non-Hodgkin lymphoma (NHL), and inflammation may be involved in its etiology. Minimal data is available on the effect of cytokine levels on neurobehavioral function in lymphoma before the initiation of chemotherapy. Therefore, we aimed to explore the risk of NHL by assessment of cytokine and adipokine levels and their correlation with neurobehavioral changes., Methods: This case-control study enrolled 62 subjects (age-sex matched: 31 cases and 31 controls). Neurobehavioral assessment was done using Montreal Cognitive Assessment questionnaire (MoCA) and Patient Health Questionnaire (PHQ-9). EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) was used to assess quality of life. Questionnaire assessment and sample collection were done after the patient enrolment and before first cycle of chemotherapy., Results: Mean age of NHL patients and healthy controls was 51.9 ± 11.8 and 50 ± 10.9 years, respectively. NHL patients showed significantly higher levels of IL-6 (0.77 ± 0.11) and TNF- α (1.47 ± 1.31) than controls (0.55 ± 0.4 and 0.66 ± 0.89, respectively) with p-value<0.005. Also, NHL patients showed significantly lower levels of adiponectin (0.31 ± 0.24) and omentin (0.46 ± 0.1) than controls (0.42 ± 0.13 and 0.53 ± 0.11, respectively) with p-value<0.005. Lower MoCA and EORTC QLQ C-30 scores and higher PHQ-9 scores were observed in NHL patients in comparison to healthy control., Conclusion: Our results showed that adiponectin, omentin IL-6 and TNF-α may be used as pre-diagnostic markers of NHL risk. Neurobehavioral changes observed in NHL patients may alter the quality of life., Competing Interests: Declaration of competing interest The authors declare no competing interests, (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Natural killer (NK) cells are traditionally identified by flow cytometry using a combination of markers (CD16/CD56/CD3), because a specific NK-cell marker is still missing. Here we investigated the utility of CD314, CD335 and NKp80, compared to CD16/CD56/CD3, for more robust identification of NK-cells in human blood, for diagnostic purposes., Methods: A total of 156 peripheral blood (PB) samples collected from healthy donors (HD) and patients with diseases frequently associated with loss/downregulation of classical NK-cell markers were immunophenotyped following EuroFlow protocols, aimed at comparing the staining profile of total blood NK-cells for CD314, CD335 and NKp80, and the performance of distinct marker combinations for their accurate identification., Results: NKp80 showed a superior performance (vs. CD314 and CD335) for the identification of NK-cells in HD blood. Besides, NKp80 improved the conventional CD16/CD56/CD3-based strategy to identify PB NK-cells in HD and reactive processes, particularly when combined with CD16 for further accurate NK-cell-subsetting. Although NKp80+CD16 improved the identification of clonal/tumor NK-cells, particularly among CD56 - cases (53%), aberrant downregulation of NKp80 was observed in 25% of patients, in whom CD56 was useful as a complementary NK-cell marker. As NKp80 is also expressed on T-cells, we noted increased numbers of NKp80 + cytotoxic T-cells at the more advanced maturation stages, mostly in adults., Conclusion: Here we propose a new robust approach for the identification of PB NK-cells, based on the combination of NKp80 plus CD16. However, in chronic lymphoproliferative disorders of NK-cells, addition of CD56 is recommended to identify clonal NK-cells, due to their frequent aberrant NKp80 - phenotype., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Morán-Plata, Muñoz-García, González-González, Pozo, Carretero-Domínguez, Mateos, Barrena, Belhassen-García, Lau, Teixeira, Santos, Yeguas, Balanzategui, García-Sancho, Orfao and Almeida.)

Coronavirus disease 2019 (COVID-19) has been a major public health burden. We hypothesised that circulating extracellular vesicles (cEVs), key players in health and disease, could trace the cell changes during COVID-19 infection and recovery. Therefore, we studied the temporal trend of cEV and inflammatory marker levels in plasma samples of COVID-19 patients that were collected within 24 h of patient admission (baseline, n = 80) and after hospital discharge at day-90 post-admission (n = 59). Inflammatory markers were measured by standard biochemical methods. cEVs were quantitatively and phenotypically characterized by high-sensitivity nano flow cytometry. In patients recovered from COVID-19 lower levels of inflammatory markers were detected. cEVs from vascular (endothelial cells) and blood (platelets, distinct immune subsets) cells were significantly reduced at day-90 compared to admission levels, a pattern also observed for cEVs from progenitor, perivascular and epithelial cells. The best discriminatory power for COVID-19 severity was found for inflammatory markers lactate dehydrogenase and neutrophil-to-lymphocyte ratio and for granulocyte/macrophage-released CD66b + /CD68 + -cEVs. Albeit inflammatory markers were good indicators of systemic inflammatory response and discriminators of COVID-19 remission, they do not completely reveal cell stress and organ damage states. cEVs reaching baseline pre-infection levels at 90 days post-infection in recovered patients discriminate parental cells affected by disease., (© 2024 The Author(s). Journal of Extracellular Vesicles published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)

Background: Arterial calcification due to deficiency of CD73 (ACDC; OMIM 211800) is a rare genetic disease resulting in calcium deposits in arteries and small joints causing claudication, resting pain, severe joint pain, and deformities. Currently, there are no standard treatments for ACDC. Our previous work identified etidronate as a potential targeted ACDC treatment, using in vitro and in vivo disease models with patient-derived cells. In this study, we test the safety and effectiveness of etidronate in attenuating the progression of lower-extremity arterial calcification and vascular blood flow based on the computed tomography (CT) calcium score and ankle-brachial index (ABI)., Methods: Seven adult patients with a confirmed genetic diagnosis of ACDC were enrolled in an open-label, nonrandomized, single-arm pilot study for etidronate treatment. They took etidronate daily for 14 days every 3 months and were examined at the NIH Clinical Center bi-annually for 3 years. They received a baseline evaluation as well as yearly follow up after treatment. Study visits included imaging studies, exercise tolerance tests with ABIs, clinical blood and urine testing, and full dental exams., Results: Etidronate treatment appeared to have slowed the progression of further vascular calcification in lower extremities as measured by CT but did not have an effect in reversing vascular and/or periarticular joint calcifications in our small ACDC cohort., Conclusions: Etidronate was found to be safe and well tolerated by our patients and, despite the small sample size, appeared to show an effect in slowing the progression of calcification in our ACDC patient cohort. (ClinicalTrials.gov Identifier NCT01585402) ., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Spinal and bulbar muscular atrophy (SBMA) is a slowly progressing disease with limited sensitive biomarkers that support clinical research. We analyzed plasma and serum samples from patients with SBMA and matched healthy controls in multiple cohorts, identifying 40 highly reproducible SBMA-associated proteins out of nearly 3,000 measured. These proteins were robustly enriched in gene sets of skeletal muscle expression and processes related to mitochondria and calcium signaling. Many proteins outperformed currently used clinical laboratory tests (e.g., creatine kinase [CK]) in distinguishing patients from controls and in their correlations with clinical and functional traits in patients. Two of the 40 proteins, Ectodysplasin A2 receptor (EDA2R) and Repulsive guidance molecule A (RGMA), were found to be associated with decreased survival and body weight in a mouse model of SBMA. In summary, we identified what we believe to be a robust and novel set of fluid protein biomarkers in SBMA that are linked with relevant disease features in patients and in a mouse model of disease. Changes in these SBMA-associated proteins could be used as an early predictor of treatment effects in clinical trials.

Background: Tumor recurrence remains the main barrier to survival after surgery for pleural mesothelioma (PM). Soluble mesothelin-related protein (SMRP) and cancer antigen 125 (CA-125) are established blood-based biomarkers for monitoring PM. We prospectively studied the utility of these biomarkers after pleurectomy decortication (PD)., Methods: Patients who underwent PD and achieved complete macroscopic resection with available preoperative SMRP levels were included. Tumor marker levels were determined within 60 days of three timepoints: (1) preoperation, (2) post-operation, and (3) recurrence., Results: Of 356 evaluable patients, 276 (78%) had recurrence by the end of follow-up interval. Elevated preoperative SMRP levels were associated with epithelioid histology (p < 0.013), advanced TNM (p < 0.001) stage, and clinical stage (p < 0.001). Preoperative CA-125 levels were not significantly associated with clinical covariates. Neither biomarker was associated with survival or disease-free survival. With respect to nonpleural and nonlymphatic recurrences, mean SMRP levels were elevated in patients with pleural (p = 0.021) and lymph node (p = 0.042) recurrences. CA-125 levels were significantly higher in patients with abdominal (p < 0.001) and lymph node (p = 0.004) recurrences. Among patients with all three timepoints available, we observed an average decrease in SMRP levels by 1.93 nmol/L (p < 0.001) postoperatively and again an average increase at recurrence by 0.79 nmol/L (p < 0.001). There were no significant changes in levels of CA-125 across the study timepoints (p = 0.47)., Conclusions: Longitudinal changes in SMRP levels corresponded with a radiographic presence of disease in a subset of patients. SMRP surveillance could aid in detection of local recurrences, whereas CA-125 could be helpful in recognizing abdominal recurrences., (© 2024 The Authors. Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

Objective: The aim of this study was to assess and correlate the serum and GCF levels of omentin with the periodontal status of rheumatoid arthritis (RA) patients with and without periodontitis., Methods: Forty-four patients were divided into four groups: group H: 11 systemically and periodontally healthy subjects; group P: 11 systemically healthy subjects with periodontitis; group RA: 11 periodontally healthy subjects with rheumatoid arthritis and group RA + P: 11 rheumatoid arthritis subjects with periodontitis. Periodontal parameters (plaque index, modified gingival index, probing depth, and clinical attachment level) were recorded and serum and GCF samples were collected for the estimation of omentin using ELISA., Results: The mean value of plaque index, modified gingival index, probing depth, and clinical attachment level were significantly higher whereas serum and GCF omentin levels were found to be decreased in group IV when compared to the other groups. The significant correlation was found between the serum and GCF omentin levels with all the periodontal parameters., Conclusion: The omentin level in serum and GCF was found to be lower in RA patients with periodontitis. It is also inversely correlated with the periodontal parameters. Thus, omentin can serve as a significant diagnostic and therapeutic tool in both periodontal and rheumatoid disease., (© 2023 Wiley Periodicals LLC.)

Purpose: Mucosal inflammation is a key feature of ulcerative colitis (UC), a chronic relapsing and remitting form of inflammatory bowel disease. Omentin-1, a newly discovered adipokine, is reported to have anti-inflammatory effects and has been found to be decreased in patients with inflammatory bowel disease. The aim of our study was to investigate the association between serum omentin-1 levels and mucosal disease activity in patients with UC., Study Design: A total of 126 patients with UC and 77 healthy volunteers were enrolled in the study. Serum omentin-1 expression levels were measured using enzyme-linked immunosorbent assay to evaluate its potential for monitoring disease activity, including clinical and endoscopic activity., Results: Serum omentin-1 levels were significantly lower in patients with UC compared to healthy controls (HC) (UC, 61.7 interquartile range: 51.5-72.6 versus healthy controls, 103.5 interquartile range: 48.3-156.2 ng/ml; P < .001). Furthermore, serum omentin-1 levels were associated with both clinical and endoscopic activity in patients with UC. Notably, omentin-1 levels were significantly lower in patients who achieved mucosal healing. Receiver operating characteristic curves indicated that serum omentin-1 levels could potentially serve as an activity index for evaluating UC., Conclusions: These findings provide further insight into the association between omentin-1 and UC, suggesting that omentin-1 may be a useful biomarker for monitoring mucosal disease activity in patients with UC., (© The Author(s) 2024. Published by Oxford University Press on behalf of Fellowship of Postgraduate Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Changes in blood transcript abundance levels have been associated with pathogenesis in a wide range of diseases. While next generation sequencing technology can measure transcript abundance on a genome-wide scale, downstream clinical applications often require small sets of genes to be selected for inclusion in targeted panels. Here we set out to gather information from the literature and transcriptome datasets that would help researchers determine whether to include the gene CEACAM6 in such panels., Methods: We employed a workflow to systematically retrieve, structure, and aggregate information derived from both the literature and public transcriptome datasets. It consisted of profiling the CEACAM6 literature to identify major diseases associated with this candidate gene and establish its relevance as a biomarker. Accessing blood transcriptome datasets identified additional instances where CEACAM6 transcript levels differ in cases vs controls. Finally, the information retrieved throughout this process was captured in a structured format and aggregated in interactive circle packing plots., Results: Although it is not routinely used clinically, the relevance of CEACAM6 as a biomarker has already been well established in the cancer field, where it has invariably been found to be associated with poor prognosis. Focusing on the blood transcriptome literature, we found studies reporting elevated levels of CEACAM6 abundance across a wide range of pathologies, especially diseases where inflammation plays a dominant role, such as asthma, psoriasis, or Parkinson's disease. The screening of public blood transcriptome datasets completed this picture, showing higher abundance levels in patients with infectious diseases caused by viral and bacterial pathogens., Conclusions: Targeted assays measuring CEACAM6 transcript abundance in blood may be of potential utility for the management of patients with diseases presenting with systemic inflammation and for the management of patients with cancer, where the assay could potentially be run both on blood and tumor tissues., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Rinchai D and Chaussabel D.)

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disorder with a high rate of recurrence. This study aimed to explore biomarkers for identifying patients with recurrent CRSwNP (rCRSwNP)., Methods: We recruited two independent cohorts. In the discovery cohort, rCRSwNP patients and non-recurrent CRSwNP (non-rCRSwNP) patients were recruited, and the serum proteomic profile was characterized. The top 5 upregulated and downregulated proteins were confirmed in the validation cohort by ELISA, WB, and qRT-PCR, and their predictive values for postoperative recurrence were assessed. In vitro, human nasal epithelial cells (HNEpCs) were employed to assess the ability of candidate proteins to induce epithelial-mesenchymal transition (EMT)., Results: Serum proteomics identified 53 different proteins, including 30 increased and 23 decreased, between the rCRSwNP and non-rCRSwNP groups. ELISA results revealed that serum levels of CD163 and TGF-β1 were elevated, CD109 and PRDX2 were decreased in the rCRSwNP group compared to the non-rCRSwNP group, and serum CD163, TGF-β1, and CD109 levels were proved to be associated with the risk of postoperative recurrence. In addition, qRT-PCR and WB revealed that tissue CD163, TGF-β1, and CD109 expressions in rCRSwNP patients were enhanced compared to those non-rCRSwNP patients. Kaplan-Meier analysis showed that increased CD163 and TGF-β1 expression and decreased CD109 expression are associated with the risk of recurrence in CRSwNP patients. Receiver operating characteristic curves showed that TGF-β1 and CD109 had superior diagnostic performances for rCRSwNP. In vitro experiments showed that TGF-β1 promoted EMT in HNEpCs, and overexpression of CD109 reversed this effect. Functional recovery experiments confirmed that CD109 could attenuate EMT in HNEpCs by inhibiting the TGF-β1/Smad signaling pathway, attenuating EMT in epithelial cells., Conclusion: Our data suggested that TGF-β1 and CD109 might serve as promising predictors of rCRSwNP. The TGF-β1/Smad pathway was implicated in fostering EMT in epithelial cells, particularly those exhibiting low expression of CD109. Consequently, the absence of CD109 expression in epithelial cells could be a potential mechanism underlying rCRSwNP., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Circulating omentin levels have been positively associated with insulin sensitivity. Although a role for adiponectin in this relationship has been suggested, underlying mechanisms remain elusive. In order to reveal the relationship between omentin and systemic metabolism, this study aimed to investigate associations of serum concentrations of omentin and metabolites., Research Design and Methods: This study is based on 1124 participants aged 61-82 years from the population-based KORA (Cooperative Health Research in the Region of Augsburg) F4 Study, for whom both serum omentin levels and metabolite concentration profiles were available. Associations were assessed with five multivariable regression models, which were stepwise adjusted for multiple potential confounders, including age, sex, body mass index, waist-to-hip ratio, lifestyle markers (physical activity, smoking behavior and alcohol consumption), serum adiponectin levels, high-density lipoprotein cholesterol, use of lipid-lowering or anti-inflammatory medication, history of myocardial infarction and stroke, homeostasis model assessment 2 of insulin resistance, diabetes status, and use of oral glucose-lowering medication and insulin., Results: Omentin levels significantly associated with multiple metabolites including amino acids, acylcarnitines, and lipids (eg, sphingomyelins and phosphatidylcholines (PCs)). Positive associations for several PCs, such as diacyl (PC aa C32:1) and alkyl-alkyl (PC ae C32:2), were significant in models 1-4, whereas those with hydroxytetradecenoylcarnitine (C14:1-OH) were significant in all five models. Omentin concentrations were negatively associated with several metabolite ratios, such as the valine-to-PC ae C32:2 and the serine-to-PC ae C32:2 ratios in most models., Conclusions: Our results suggest that omentin may influence insulin sensitivity and diabetes risk by changing systemic lipid metabolism, but further mechanistic studies investigating effects of omentin on metabolism of insulin-sensitive tissues are needed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: Repulsive guidance molecule A (RGMa) is upregulated in neurodegenerative diseases. To assess RGMa levels in human serum and cerebrospinal fluid (CSF), a quantification method was developed and validated according to ICH M10 guideline. Methods & results: Sample preparation consisted of immunoprecipitation (IP, only for serum), digestion and purification followed by MS. Conclusion: An UPLC-MS/MS method was established and used to assess normal range of soluble RGMa levels in serum and CSF of healthy controls, and patients with mild cognitive impairment or Alzheimer's disease. The normal range was between 13.0-44.8 ng/ml (CSF) and 9.9-20.9 ng/ml (serum) in healthy controls. In the CSF of patients with mild cognitive impairment and Alzheimer's disease, total soluble RGMa was twofold lower while unchanged in serum.

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver condition worldwide. NAFLD is often associated with features of Metabolic Syndrome such as obesity and insulin resistance., Methods: The current comprehensive meta-analysis was performed to evaluate the association between circulating Omentin levels and NAFLD. A systematic search in Scopus, Web of Science, PubMed, and Google Scholar databases was conducted to identify relevant studies up until 5th May 2022. The standard mean difference (SMD) values and 95% confidence intervals (CIs) were computed for the association of Omentin levels with NAFLD risk in a random effect model., Results: The meta-analysis involved 6 case-control studies with a total of 371 cases and 269 controls. Pooled SMD showed no significant difference in serum Omentin between NAFLD and healthy groups (SMD= -0.047 and 95% CI -0.957&#95;0.862 P=0.91). Subgroup analysis based on sample size showed that the average Omentin levels were significantly higher in NAFLD patients in studies with sample size ≥70 (SMD=0.356 CI 0.056&#95;0.655 P=0.02)., Conclusion: Additional well-designed studies with more sample sizes are essential to clarify the potential role of Omentin as a risk marker of NAFLD., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The anti-inflammatory adipokine intelectin-1, which is encoded by the ITLN1 gene, is hypothesized to be linked to the pathogenesis of type 2 diabetes (T2DM) and obesity. The purpose of this study was to examine the effect of the ITLN1 gene polymorphism rs2274907 on obesity and T2DM in Turkish adults. The impact of genotype on lipid profiles and serum intelectin levels in the obese and diabetes groups was also investigated. Randomly selected 2266 adults (mean age, 55.0 ± 11.7 years; 51.2% women) participating in the population-based Turkish adult risk factor study were cross-sectionally analyzed. The genotyping of rs2274907 A > T polymorphism was performed by using the hybridization probe based LightSNiP assay in real-time PCR. T2DM were defined using the criteria of the American Diabetes Association. Obesity was described as Body mass index ≥ 30 kg/m 2 . Statistical analyses were used to investigate the association of genotypes with clinical and biochemical measurements. According to findings, there was no vital connection between the rs2274907 polymorphism and obesity, T2DM, or serum intelectin-1 level. The TA+AA carriers had significantly higher triglyceride levels (p = 0.007) compared with the TT carriers in both obese and T2DM women when adjusted for relevant covariates. ITLN1 rs2274907 polymorphism is not correlated with the risk of obesity and T2DM and not affect serum ITLN1 levels in Turkish adults. However, this polymorphism appears to be important in regulating triglyceride levels in obese and diabetic women., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The role of sortilin and omentin-1 in the pathogenesis of atherosclerosis and vascular disease is an emerging topic in recent years. These molecules can be found circulating in the blood. Recent studies have shown how these biomarkers appear to correlate with the severity of PAD. The levels of these molecules appear to be inversely proportional to each other. Their relationship may provide further insight into the management of the very old diabetic patients with PAD. This study aimed to assess the possible role of sortilin/omentin-1 ratio as easy-to-measure marker in peripheral artery disease (PAD) in type-2 diabetic patients., Methods: This study analyzed the association between sortilin and omentin-1 serum levels and the presence of clinically significant lower limb PAD in diabetic individuals. We enrolled 295 diabetic patients, including 179 with PAD. Serum levels were collected and correlated with clinical characteristics of the patients., Results: Sortilin concentration was significantly higher in the latter group compared to the former and there was a trend toward increased sortilin levels as disease severity increased. Omentin-1 serum levels were significantly lower in diabetic patients with PAD than in diabetic controls and the levels gradually decreased in proportion to disease severity. The ratio of sortilin to omentin-1 was significantly higher in patients with PAD compared to the other group., Conclusion: The sortilin to omentin-1 ratio appears to be a predictive factor for PAD in patients with type-2 diabetes and it may be a promising marker for clinically significant atherosclerosis of the lower limbs. Further studies are needed to confirm this finding and to evaluate its clinical usefulness., (Copyright © 2022 Elsevier B.V. All rights reserved.)

We investigated the effects of 12 weeks of high-intensity interval training (HIIT) on selected circulating adipokines and other cardiovascular diseases risks factors in men with obesity. Thirty men with obesity (age: 24.96±3.11 year, BMI: 30.92±1.04 kg/m 2 ) were randomly assigned to HIIT and control groups. The HIIT group participated in a 12-week HIIT program (5×2 min interval bout at an intensity of 85-95% HRmax interspersed by 1 min passive recovery, three times per week), while the control group maintained their usual lifestyles. Blood lipids, insulin resistance, and select serum adipokines were assessed before and after 12 weeks of the intervention period. HIIT improved body composition and lipid profiles (p<0.05) and also decreased fasting insulin levels (p=0.001) and HOMA-IR (p=0.002) levels. Furthermore, HIIT increased levels of lipocalin-2 (p=0.002) while decreasing omentin-1 levels (p=0.001) in men with obesity. Changes in lcn2 and omentin-1 concentrations correlated with the changes in risk factors in the HIIT group (p<0.05). The results indicate that 12 weeks of supervised HIIT significantly improves both circulating concentrations of lcn2 and omentin-1, two recently described adipokines, and risk markers of cardiovascular diseases in men with obesity. Further research is necessary to understand the molecular mechanisms involved with these changes., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

In India, diabetic nephropathy (DN) is the most common cause of chronic kidney disease. Timely detection of microalbuminuria and appropriate intervention can reverse or arrest the progress of nephropathy. The pathogenesis of diabetic nephropathy has revealed that during the early onset of kidney involvement in diabetics, inflammation and fibrosis progress from tubular to glomerular damage. This study was designed to elucidate the association of chemokines, Omentin 1, and interleukin 6 (IL-6) with microalbuminuria., Material: Settings and Design: This cross-sectional observational study was conducted as a collaborated study in the Departments of General Medicine and Biochemistry, All India Institute of Medical Sciences, Bhubaneswar, India, during 2019-2020., Methods and Material: Our study group comprised 116 diabetes mellitus patients. They were grouped into two, each of 58 on the basis of their urine albumin levels; Group 1 (controls) had UACR &lt; 30 μg/mg, eGFR&gt; 90ml/ min and Group 2 (cases) had UACR ≥ 30 μg/mg and &lt; 300 μg/mg, eGFR&gt;60ml/min and &lt; 90ml/min. Serum omentin 1 and IL-6, creatinine, glycated haemoglobin (HbA1c), fasting (FBS) and postprandial blood sugar (PPBS), lipid profile, total protein, albumin, and fasting insulin, HOMA-IR were studied., Observation: Our study showed that Omentin 1 levels were decreased, and IL-6 levels were increased in the DN group compared to the T2DM without DN. The risk estimates calculated revealed that diabetes mellitus patients having an IL-6: omentin ratio ≥ 0.26 had Odds of 3.97 of developing DN, which was statistically significant (CI 2.36-6.68). Therefore, a ratio of ≤ 0.26 was found to be kidney protective among diabetes mellitus patients., Conclusion: From the results of this present study, we recommend that estimation of serum IL-6: omentin 1 ratio of T2DM will aid in identifying early stages of DN before the onset of microalbuminuria., (© Journal of the Association of Physicians of India 2011.)

Background: The effects of weight loss therapies on omentin-1 levels have been unclear, showing both elevations and decreases in circulating levels. The role of dietary fat might have an important role. The aim of our investigation was to evaluate the influence of weight decrease on omentin-1 levels after two different high-fat hypocaloric diets., Methods: 319 Caucasian obese subjects were randomly allocated during 12 weeks (Diet M (high monounsaturated fat diet) vs. Diet P (high polyunsaturated fat diet)). The mean age was 47.2 ± 5.0 years (range: 26-64), and the mean body mass index (BMI) was 37.9 ± 4.1 kg/m 2 (range: 30.6-39.8). Sex distribution was 237 females (74.7%) and 72 males (25.3%). Anthropometric and biochemical parameters were evaluated at basal and after both diets. SPSS 23.0 has been used to realize univariant and multivariant statistical analysis., Results: After both diets, BMI, weight, fat mass, waist circumference, systolic blood, LDL-cholesterol, insulin levels, and HOMA-IR decreased in a statistical way from basal values. These improvements were similar in both diets. After Diet P, omentin-1 levels increase (21.2 ± 9.1 ng/ml: P = 0.02), and after Diet M, this adipokine increases (47.1 ± 11.2 ng/ml: P = 0.02), too. The increase of omentin-1 with Diet M was statistically significantly higher than that after Diet P ( P = 0.01). A multiple regression analyses adjusted by age and sex reported a statistical relation between BMI (kg/m 2 ) and insulin (UI/L) with omentin-1 levels., Conclusions: Our study demonstrated a significant improvement on serum omentin-1 levels after weight loss secondary to both diets; in contrast, omentin-1 improvement was higher with Diet M than with Diet P., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Daniel de Luis et al.)

Objectives: This study sought to explore the expression patterns of repulsive guidance molecules a (RGMa) in neuromyelitis optica spectrum disorders (NMOSD) and to explore the correlation between RGMa and the clinical features of NMOSD., Methods: A total of 83 NMOSD patients and 22 age-matched healthy controls (HCs) were enrolled in the study from October 2017 to November 2021. Clinical parameters, including Expanded Disability Status Scale (EDSS) score, degree of MRI enhancement, and AQP4 titer were collected. The expression of serum RGMa was measured by enzyme-linked immunosorbent assay (ELISA) and compared across the four patient groups. The correlation between serum RGMa levels and different clinical parameters was also assessed., Results: The average serum expression of RGMa in the NMOSD group was significantly higher than that in the HC group ( p < 0.001). Among the patient groups, the acute phase group exhibited significantly higher serum RGMa levels than did the remission group ( p < 0.001 ). A multivariate analysis revealed a significant positive correlation between RGMa expression and EDSS score at admission, degree of MRI enhancement, and segmental length of spinal cord lesions. There was a significant negative correlation between the expression of RGMa in NMOSD and the time from attack to sampling or delta EDSS., Conclusions: The current study suggests that RGMa may be considered a potential biomarker predicting the severity, disability, and clinical features of NMOSD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tang, Zeng, Yang, Zhang, Li, Chen, Tang, Luo, Qin and Feng.)

Background: Coronary artery disease (CAD) is the primary cause of death worldwide. It is mainly caused by atherosclerosis that initiates from a genetic-environmental interaction. Studies highlighted the association of numerous gene polymorphisms with CAD. Omentin-1 is secreted from visceral adipose tissues, intestine, and others; it has anti-inflammatory and insulin sensitivity improving roles., Aim: To explore the association of the omentin-1 gene polymorphisms (rs2274907 and rs2274908) with serum lipid concentrations and CAD in a sample of the Iraqi population., Methods: A case-control study was followed, in which CAD patients were analyzed versus a group of healthy persons. Serum lipid concentrations were measured by enzymatic methods. Genotyping of the omentin-1 gene for rs2274907 SNP was achieved by ARMS-PCR, while for rs2274908 SNP by allele-specific PCR (AS-PCR) techniques., Results: Atherogenic serum lipid concentrations increased significantly in CAD patients relative to the control group. Genotyping of the omentin-1 gene for rs2274907 SNP revealed a significant (OR = 4.11, P = 0.035) elevation of the AT genotype carriers in CAD versus the control groups. The genotype analysis of the rs2274908 SNP failed to exhibit a significant variation. The two analyzed SNPs were indicated to be in linkage disequilibrium (r = 0.772, P < 0.0001). The global haplotype association of the 2 SNPs was demonstrated to be significant (P = 0.006). Serum lipid concentrations were found to be independent of the genotype distribution of the rs2274907 SNP., Conclusion: Carriers of the AT genotype of rs2274907 SNP in the omentin-1gene may have a four-fold risk of developing CAD compared to those of the wild genotype. Alterations of serum lipid concentrations may do not depend on the genotypes of this SNP., (Copyright © 2021 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the association of omentin-1 and inflammatory factors in serum and visceral adipose tissue (VAT) of women with gestational diabetes mellitus (GDM) compared to normal pregnant (NP) subjects. Furthermore, to examine their correlation with maternal clinical characteristics., Methods: We compared 116 GDM women to 115 NP women, at the time of cesarean section. Circulating omentin-1 and pro-inflammatory (IL-1β, IL-6, TNF-α), and anti-inflammatory cytokines (IL-1RA, IL-10) were examined. Moreover, their mRNA expression in VAT, along with inflammatory factors involved in the NF-κB pathway (TLR2, TLR4, NF-κB, IKκB), were examined., Results: Circulating omentin-1 (p = 0.022) was lower and circulating IL-1-β, IL-1RA, as well as IL-10 (p = 0.005, p = 0.007, and p = 0.015, respectively), were higher in GDM compared to NP women. Omentin-1 correlated negatively with pre-pregnancy and gestational BMI, and HOMA-IR in all women, but was not associated with cytokines. TLR2, TLR4, IL-1β, IL-1RA, IL-6, IL-10 mRNA expression in VAT was lower in GDM compared with controls (p < 0.05 all). In multivariate analysis, BMI at delivery was significantly correlated to omentin-1 concentrations in all and NP subjects. In addition, omentin-1 expression was correlated to inflammatory gene expression in all, GDM and NP, women (p < 0.05 all)., Conclusion: Serum levels and VAT gene expression of omentin-1 are not independently linked to GDM; notwithstanding, GDM women have a VAT-altered inflammatory status. In addition, no systemic association between omentin-1 and inflammatory factors was found, whereas associations between their expression in all women were observed, indicating that expression of these adipokines is linked between them regardless of GDM., (© 2021. Italian Society of Endocrinology (SIE).)

Background: The dynamic monitoring of perioperative carcinoembryonic antigen (CEA) is recommended by current colorectal cancer (CRC) guidelines, while the benefits of additional measurements of carbohydrate antigen 19-9 (CA19-9) and carbohydrate antigen 125 (CA125) have remained controversial., Methods: This retrospective longitudinal cohort included 3539 CRC patients who underwent curative resection. Distinct trajectory groups were identified by the latent class growth mixed model. Patients were grouped into subgroups jointly by CEA, CA19-9, and CA125 according to preoperative levels and longitudinal trajectories, respectively. The end points were overall survival (OS) and recurrence-free survival (RFS)., Findings: Three distinct trajectory groups were characterized for serum CEA, CA19-9, and CA125: low-stable, early-rising, and later-rising. Jointly, patients were grouped into six preoperative (trajectory) joint groups. Compared with the three-low group, the adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) associated with death were 1.87 (1.29-2.70), 3.82 (2.37-6.17), 1.87 (0.97-3.61), 2.81 (1.93-4.11), and 4.99 (2.80-8.86) for the CEA-high, CA19-9-high, CA125-high, two-high, and three-high group, respectively. And compared with the three-stable trajectory group, the corresponding HRs (95% CIs) were 1.59 (1.10-2.30), 1.55 (0.77-3.10), 6.25 (4.02-9.70), 4.05 (2.73-6.02), and 12.40 (5.77-26.70) for the five rising trajectory groups, respectively. Similar associations between joint groups and RFS were observed. Notably, the trajectory joint group still had prognostic significance after adjusting for preoperative levels. The CA19-9-high group (HR: 3.82, 95% CI: 2.37-6.17) was associated with higher risk of death than the two-high group (HR: 2.81, 95% CI: 1.93-4.11). Likewise, for the CA125-rising trajectory group and two-rising trajectory group, the HRs (95% CIs) were 6.13 (3.75-10.00) and 3.99 (2.63-6.05) for death, and 3.08 (2.07-4.58) and 2.10 (1.52-2.90) for recurrence., Interpretation: In addition to CEA, the dynamic measurements of CA19-9 and CA125 are recommended to monitor the prognosis of CRC patients., Funding: National Natural Science Foundation of China [81973147, 82001986, 81960592, 82073569, 81660545]., Competing Interests: Declaration of Competing Interest All authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Acute Coronary Syndromes (ACS) with plaque erosion display dysregulated hyaluronan metabolism, with increased hyaluronidase-2 (HYAL2) expression. However, the expression and the role of this enzyme on platelets has never been explored. We evaluated the platelet's HYAL2 ( plt HYAL2) levels on I) stable angina (SA) and II) ACS patients, furtherly sub-grouped in Intact-Fibrous-Cap (IFC) and Ruptured-Fibrous-Cap (RFC), according to Optical Coherence Tomography. We assessed the HYAL2 role through an in vitro model setting of co-cultured monocytes and platelets, before and after treatment with low-molecular-weight hyaluronic acid (HA) as pro-inflammatory stimulus and with or without HYAL2-antibody to inhibit HYAL2 activity. ACS patients exhibit higher plt HYAL2 levels comparing to SA, with the higher expression for IFC group. The addition of HYAL2-antibody significantly reduced the percentage of monocyte-platelet binding, suggesting that plt HYAL2 enrichment at the site of the culprit lesion is a key mediator in the systemic thrombo-inflammatory status of ACS presenting with plaque erosion.

Coronavirus disease 2019 (COVID-19) is associated with systemic inflammation. A wide range of adipokines activities suggests they influence pathogenesis and infection course. The aim was to assess concentrations of chemerin, omentin, and vaspin among COVID-19 patients with an emphasis on adipokines relationship with COVID-19 severity, concomitant metabolic abnormalities and liver dysfunction. Serum chemerin, omentin and vaspin concentrations were measured in serum collected from 70 COVID-19 patients at the moment of admission to hospital, before any treatment was applied and 20 healthy controls. Serum chemerin and omentin concentrations were significantly decreased in COVID-19 patients compared to healthy volunteers (271.0 vs. 373.0 ng/ml; p < 0.001 and 482.1 vs. 814.3 ng/ml; p = 0.01, respectively). There were no correlations of analyzed adipokines with COVID-19 severity based on the presence of pneumonia, dyspnea, or necessity of Intensive Care Unit hospitalization (ICU). Liver test abnormalities did not influence adipokines levels. Elevated GGT activity was associated with ICU admission, presence of pneumonia and elevated concentrations of CRP, ferritin and interleukin 6. Chemerin and omentin depletion in COVID-19 patients suggests that this adipokines deficiency play influential role in disease pathogenesis. However, there was no relationship between lower adipokines level and frequency of COVID-19 symptoms as well as disease severity. The only predictive factor which could predispose to a more severe COVID-19 course, including the presence of pneumonia and ICU hospitalization, was GGT activity., (© 2021. The Author(s).)

Alzheimer's disease (AD) is classified pathologically as a progressive neurological disorder associated with memory decline. The study was designed to assess the underlying molecular signaling involved in the neuroprotective effect of the 2-(hydroxyl-(2-nitrophenyl)methyl)cyclopentanone (2NCP) as a novel therapeutic agent for AD. In this connection, in vitro cholinesterases inhibitory and antioxidant activities were investigated. In vivo studies were carried out on a well-known 5xFAD mice model in different behavioural models such as light/dark box,balance beam, rotarod, elevated plus maze (EPM),novel object recognition (NOR), paddling Y-maze, and Morris water maze (MWM) tests. Hippocampus (HC) and frontal cortex (FC) homogenates were examined for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) activities, 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radicals, glutathione S-transferase (GST), glutathione (GSH), and catalase. Further, we examined the expression of inflammatory cytokines and Nrf2 in the HC and FC through RT-PCR. Computational studies were conducted to predict the binding mode of the 2NCP with target sites of nuclear factor-κB (NF-κB) and cholinesterases. The findings of in vitro assays revealed that the IC 50 values of the 2NCP against AChE and BChE were 17 and 23 µg/ml respectively. DPPH antioxidant assay displayed an IC 50 value for the 2NCP was 62 µg/ml. Whereas, theex vivo study depicted that the activities of AChE and BChEwere significantly reduced. Moreover, free radicals load, GSH level, catalase and GST activities were significantly declined. Furthermore, in vivostudies showed that the 2NCP treated animals exhibited gradual memory improvement and improved motor functions. RT-PCR study revealed that mRNA levels of the inflammatory mediators (IL-1β, IL-6, TNF-α) were significantly reduced, while the expression of antioxidant Nrf2 was significantly increased.The molecular docking studies further confirmed that the 2NCP showed excellent binding affinities for NF-κB and cholinesterases. Taken together, the 2NCP improves spatial memory and learning, short- and long-term memory,markedly inhibits cholinesterases, reduced neuroinflammation, and mitigated oxidative stress in the 5xFAD mice; hence the 2NCP may be a potential candidate for the management of AD., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aims: Data about the influence of short-term lifestyle intervention in children with obesity on long-term follow-up body weight, adipokines and cardiometabolic risk parameters is scarce., Methods: In a subgroup of the LOGIC-trial (Long-term Effects of Lifestyle Intervention in Obesity and Genetic Influence in Children), we assessed anthropometry (BMI, BMI-SDS (Standard Deviation Score), adipokines (omentin-1, chemerin, leptin, adiponectin) and cardiometabolic risk parameters, (e.g. hsCRP) in children with overweight/obesity after 4 weeks of lifestyle intervention (n = 156, 14.0 ± 1.8 yrs) and after one year follow-up (n = 50). Data were compared to normal weight children (JuvenTUM school cohort; n = 152, 13.3 ± 0.7 yrs)., Results: Short-term lifestyle intervention was associated with a significant reduction in BMI and BMI-SDS (p < 0.001), with significant reductions in hsCRP, leptin, and chemerin levels, and an increase in adiponectin and omentin-1 levels (p < 0.001 for all). After one year follow-up a significant reduction in BMI and BMI-SDS was observed in children from the LOGIC-trial (p < 0.001). Improvements in adiponectin (p = 0.025) and chemerin levels (p = 0.027) were seen in children with clear weight loss success (BMI-SDS reduction ≥ 0.2), whereas children with no or only mild weight loss success showed an increase in leptin levels (p < 0.001). An increase in omentin-1 levels was observed after 1 year independent of weight change (p < 0.001)., Conclusion: Effects of short-term weight reduction on mean BMI and BMI-SDS persist over one year. Improvements in omentin-1 levels were independent of short-term or long-term weight loss., Trial Registration: ClinicalTrials.gov: LOGIC-trial: NCT01067157, JuvenTUM-trial: NCT00988754., Competing Interests: Conflict of interest The authors declare no conflicts of interest., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Aberrant circulating omentin-1, which is an anti-inflammatory and pro-apoptotic adipokine, has been reported in various solid tumors. Therefore, we investigated whether or not circulating omentin-1 could be associated with postmenopausal BC (PBC) and could be used as a potential diagnostic and clinical tool taking into consideration clinicopathologic features, tumor markers, as well as anthropometric, metabolic, and inflammatory parameters. Serum omentin-1, tumor markers (CA15-3 and CEA); metabolic (insulin, glucose, HOMA index, and serum lipids), anthropometric (BMI, waist circumference, and fat mass), and inflammatory (TNF-α, IL-6, hsCRP) parameters; classic adipokines (leptin and adiponectin); the Mediterranean diet (MedDiet) score; and cardiovascular (CVD) risk were determined in 103 postmenopausal women with pathologically confirmed incident invasive BC, 103 controls matched on age, 51 patients with benign breast lesions (BBL), and 50 obese postmenopausal women of similar age. The mean serum omentin-1 was significantly lower in cases than in controls and patients with BBL ( p < 0.001). In the patients, omentin-1 was inversely associated with tumor, metabolic and inflammatory biomarkers, cancer stage, and the number of infiltrated lymph nodes ( p < 0.05). In all study participants, omentin-1 was negatively correlated with CVD risk and positively correlated with MedDiet score. Lower circulating omentin-1 was independently associated with PBC occurrence above and beyond known risk factors. According to the ROC curve analysis, the overall diagnostic performance of omentin-1 (0.84, 95% CI 0.79-0.89) is similar to CA15-3. Circulating omentin-1 may be a biomarker at the intersection of PBC and cardiometabolic risk in postmenopausal women, and could be modulated by the adoption of a MedDiet. Further mechanistic and large multicentric prospective and longitudinal studies are required to elucidate the ontological role of omentin-1 in BC and CVD risks, as well as its diagnostic and prognostic ability and its therapeutic potential.

Following therapy, breast cancer survivors (BCS) have an increased risk of infections because of age and cancer dysregulation of inflammation and neutrophil functions. Neutrophil functions may be improved by exercise training, although limited data exist on exercise and neutrophil functions in BCS.Sixteen BCS [mean age: 56 (SD 11) years old] completed 16 weeks of community-based exercise training and a 45-minute acute bout of cycling before (Base) and after (Final) the exercise training program. Exercise training consisted of 3 x 40 - 60 minute mixed mode aerobic exercises, comprising 10 - 30 minutes aerobic and 30 minutes resistance training. At Base and Final, we took BCS blood samples before (PRE), immediately after (POST), and 1 hour after (1Hr) acute exercise to determine neutrophil counts, phenotype, bacterial killing, IL-6, and IL-8 levels. Eleven healthy, age- and physical activity levels-matched women (Control) completed the acute bout of exercise once as a healthy response reference. Resting Responses. BCS and Controls had similar Base PRE absolute neutrophil counts [mean (SD): 3.3 (1.9) v 3.1 (1.2) x 10 9 /L, p=0.801], but BCS had lower bacterial phagocytosis [3991 (1233) v 4881 (417) MFI, p=0.035] and higher oxidative killing [6254 (1434) v 4709 (1220) MFI, p=0.005], lower CD16 [4159 (1785) v 7018 (1240) MFI, p<0.001], lower CXCR2 [4878 (1796) v 6330 (1299) MFI, p=0.032] and higher TLR2 [98 (32) v 72 (17) MFI, p=0.022] expression, while IL-6 [7.4 (5.4) v 4.0 (2.7) pg/mL, p=0.079] levels were marginally higher and IL-8 [6.0 (4.7) v 7.9 (5.0) pg/mL, p=0.316] levels similar. After 16 weeks of training, compared to Controls, BCS Final PRE phagocytosis [4510 (738) v 4881 (417) MFI, p=0.146] and TLR2 expression [114 (92) v 72 (17) MFI, p=0.148] were no longer different. Acute Exercise Responses. As compared to Controls, at Base, BCS phagocytic Pre-Post response was lower [mean difference, % (SD): 12% (26%), p=0.042], CD16 Pre-Post response was lower [12% (21%), p=0.016] while CD16 Pre-1Hr response was higher [13% (25%), p=0.022], TLR2 Pre-Post response was higher [15% (4%) p=0.002], while IL-8 Pre-Post response was higher [99% (48%), p=0.049]. As compared to Controls, following 16 weeks of training BCS phagocytic Pre-Post response [5% (5%), p=0.418], CD16 Pre-1Hr response [7% (7%), p=0.294], TLR2 Pre-Post response [6% (4%), p=0.092], and IL-8 Pre-Post response [1% (9%), p=0.087] were no longer different. Following cancer therapy, BCS may have impaired neutrophil functions in response to an acute bout of exercise that are partially restored by 16 weeks of exercise training. The improved phagocytosis of bacteria in BCS may represent an exercise-induced intrinsic improvement in neutrophil functions consistent with a reduced risk of infectious disease., Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03760536., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bartlett, Hanson, Lee, Wagoner, Harrell, Sullivan, Bates, Alzer, Amatuli, Deal, Jensen, MacDonald, Deal, Muss, Nyrop and Battaglini.)

Background/aim: A member of the adipokine family, omentin-1 is selectively secreted from visceral fat tissue and the omentum. It has been shown that omentin-1 is involved in the pathogenesis of certain diseases and can be used as a prognostic marker. This study first investigated the prognostic significance of omentin-1 in surgical intensive care patients. In addition, the relationship between omentin-1 and laboratory and clinical parameters commonly used in intensive care units (ICUs) was evaluated., Materials and Methods: One hundred and fifty-four patients hospitalized in the surgical ICU were included in the study. Blood samples for omentin-1 were collected from the patients displaying clinical condition changes. Changes in omentin-1 levels were observed during the hospital stay of the patients. A total of 423 blood samples were evaluated. Omentin-1 levels were compared to the laboratory parameters routinely monitored in the ICU and the prognostic significance of omentin-1 for surgical intensive care patients was investigated., Results: The median APACHE II score of all patients was (median-IQR, 8.0–6.0 ng/mL). Omentin-1 levels of the alive patients in the ICU (median-IQR, 339.04–407.68 ng/mL) were significantly higher compared to dead patients (median-IQR, 166.40–363.60 ng/mL). Omentin-1 levels were higher in nonsepsis patients compared to the levels of the patients in sepsis and septic shock (p < 0.001). Omentin-1 values were negatively correlated with the C-reactive protein and procalcitonin levels, body temperature, and the SOFA (sequential organ failure assessment score) scores and they were positively correlated with albumin, prealbumin, and glucose levels., Conclusion: Omentin-1 may play a role in the complex constructs of inflammation and metabolic events in intensive care patients. Reduced omentin-1 levels in surgical intensive care patients were associated with poor prognosis and increased mortality., Competing Interests: The authors declare that there is no conflict of interest., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Adenine nucleotides are important signaling molecules that mediate biological functions in many conditions, including cancer. The enzymes CD39 and CD73 produce adenosine in the extracellular milieu that has a very important role in tumor development. This study aimed to evaluate nucleotide hydrolysis in the plasma blood of breast cancer elderly patients. In this prospective cohort study, we investigated the ectonucleotidases activity in breast cancer elderly patients, at the moment of diagnosis and after treatment. Control group consisted of elderly women without cancer diagnostic. The nucleotide hydrolysis assay was performed by the malachite green method and used ATP, ADP, or AMP as substrates. Paired t test or Wilcoxon rank-sum test was used. Our data showed that breast cancer patients presented high levels of ATP and AMP hydrolyses when compared to control group at the moment of diagnosis. When analyzing the differences between the samples at the time of diagnostic and 6 months after treatment, we observed a significant reduction on CD73 activity after all treatments used: surgery, chemotherapy, radiotherapy, or hormone therapy. The results with APCP, a specific CD73 inhibitor, showed that the AMP hydrolysis was inhibited in all conditions evaluated. We observed a diminished ADPase activity in the patients without metastasis when compared to metastatic breast cancer patients. The results showed that AMP hydrolysis was reduced in the blood plasma of breast cancer elderly patients after different treatments. This study strengthens the potential role of CD73 enzyme as a biomarker for breast cancer treatment response., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The RECK gene, a tumor suppressor gene, inhibits angiogenesis, invasion, and tumor metastasis. Epigenetic regulation of the RECK gene constitutes a potent approach to the molecular basis of liver malignancy. This study aims to evaluate the promoter methylation status of the RECK gene and its serum level in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) and the potential association of RECK gene methylation with clinical criteria of HCC. One hundred and fifty-five subjects were included (healthy control [55], chronic HCV patients [55], HCV-related HCC patients [45]). The methylation status of the RECK gene promoter and serum RECK level were investigated by methylation-specific PCR and enzyme-linked immunosorbent assay techniques, respectively. RECK gene promoter hypermethylation was recorded in 46.7% of HCC patients, and 10.9% of HCV patients, but not in control subjects (0%). It was related to RECK protein level, varices, edema, ascites, lymph node metastasis, vascular invasion, and the largest diameter of focal lesions. Meanwhile, it was not associated with focal lesion number nor distant metastasis of HCC. In conclusion, RECK gene promoter hypermethylation is linked to HCV genotype-4-related HCC. Moreover, different degrees of RECK gene promoter methylation are associated with serum RECK level, lymph node metastasis, and vascular invasion, which could prove its pathogenic role in hepatocarcinogenesis in chronic HCV-infected patients., (© 2021 Wiley Periodicals LLC.)

Objectives: Molecular subtypes are employed as a guide for targeted treatment and important prognostic factors. This study focused on investigating the association of serum levels of CEA, CA15-3, and CA125 with clinicopathological characteristics of breast cancer to find prognostic markers for breast cancer and provide precise targeted therapy., Materials and Methods: In this study, 961 breast cancer patients with preoperative serum levels of CEA, CA15-3, and CA125 and molecular subtypes were analyzed. Cut-off values of 5 ng/ml, 25 U/ml, and 35 U/ml were used for CEA, CA15-3, and CA125, respectively. The χ 2 test and Fisher exact test along with logistic multivariate regression analysis were performed for investigating the correlation of CEA, CA15-3, and CA125 serum levels with molecular subtypes and associated factors., Results: An increase in the serum concentrations of CEA, CA15-3, and CA125 was discovered in 48 (4.99%), 54 (5.62%), and 55 (5.72%) breast cancer patients, respectively. Univariate analysis demonstrated that the levels of CEA ( p < 0.01) and CA15-3 ( p < 0.05) were significantly linked with molecular types of breast cancer. Moreover, patients having larger tumor size ( p < 0.01, p < 0.0001, and p < 0.05, respectively) along with nodal metastasis ( p < 0.05, p = 0.0001, and p < 0.05, respectively) exhibited higher rates of elevated CEA, CA15-3, and CA125 levels. Status of Her-2 positive ( p < 0.01) had a significant connection with elevated CEA levels. Multivariate analysis further indicated that molecular subtypes were independent factors associated with CEA and CA15-3 levels. Also, Her-2 status was significantly and independently related to CEA levels., Conclusion: Preoperative serum levels of CEA and CA15-3 were independently associated with molecular subtypes of breast cancer. CEA and CA15-3 might improve the prognostic prediction for patients with breast cancer and inform the selection of specific therapies. A further biological analysis is needed for investigating the relationship between Her-2 expression and CEA levels., Competing Interests: The authors of this study declare no conflict of interests., (Copyright © 2021 Wenjing Zhao et al.)

Background: Cytokeratin 19 fragment 21-1 (CYFRA21-1) and carcinoembryonic antigen (CEA) are effective prognostic biomarkers for lung cancer. This study investigated the predictive effects of change rates of CYFRA21-1 and CEA before and after the first cycles of chemotherapy on advanced IIIb/IIIc or IV stage non-small-cell lung cancer (NSCLC) patients., Methods: Data of 103 NSCLC patients who received chemotherapy in Zhejiang Provincial People's Hospital from February 2018 to November 2020 were retrospectively analyzed. All patients received platinum doublet chemotherapy for at least 2 cycles. CYFRA21-1 and CEA levels of patients were detected before and after the first chemotherapy cycle, respectively. After the second cycle, the efficacy was evaluated, and patients were divided into the disease control (DC) and progressive disease (PD) groups. The generalized linear model (GLM) and linear trend test assessed the relationship between change rates of CYFRA21-1 and CEA levels and chemotherapeutic efficacy before and after chemotherapy. Moreover, the receiver operating characteristic (ROC) curve determined the predictive value of change rates of CYFRA21-1 and CEA on chemotherapeutic efficacy., Results: After the second chemotherapeutic cycle, there were 92 patients in the DC group and 11 in the PD group. GLM and linear trend test both indicated that change rates of CYFRA21-1 and CEA were inversely correlated with chemotherapeutic efficacy for NSCLC. Change rates of CYFRA21-1 and CEA were used to predict area under the ROC curve of chemotherapeutic efficacy (0.87, 0.71-1.00), which is better than single index prediction of CYFRA21-1 (0.71, 0.49-0.94) or CEA change rate (0.85, 0.69-1.00) ( p < 0.001)., Conclusion: Before and after chemotherapy of the first cycle for advanced NSCLC patients, combining serum CYFRA21-1 and CEA levels could increase sensitivity and specificity to predict the chemotherapeutic efficacy and guide the following therapy of advanced NSCLC patients., Competing Interests: All authors confirm no potential conflicts of interest in this research., (Copyright © 2021 Tongwei Zhao et al.)

Ataxia-telangiectasia (A-T) is a multisystem disorder caused by biallelic pathogenic variants in the gene encoding A-T mutated (ATM) kinase, a master regulator of the DNA damage response (DDR) pathway. Most A-T patients show cellular and/or humoral immunodeficiency that has been associated with cancer risk and reduced survival, but NK cells have not been thoroughly studied. Here we investigated NK cells of A-T patients with a special focus on the NKG2D receptor that triggers cytotoxicity upon engagement by its ligands (NKG2DLs) commonly induced via the DDR pathway on infected, transformed, and variously stressed cells. Using flow cytometry, we examined the phenotype and function of NK cells in 6 A-T patients as compared with healthy individuals. NKG2D expression was evaluated also by western blotting and RT-qPCR; plasma soluble NKG2DLs (sMICA, sMICB, sULBP1, ULBP2) were measured by ELISA. Results showed that A-T NK cells were skewed towards the CD56 neg anergic phenotype and displayed decreased expression of NKG2D and perforin. NKG2D was reduced at the protein but not at the mRNA level and resulted in impaired NKG2D-mediated cytotoxicity in 4/6 A-T patients. Moreover, in A-T plasma we found 24-fold and 2-fold increase of sMICA and sULBP1, respectively, both inversely correlated with NKG2D expression. Overall, NK cells are disturbed in A-T patients showing reduced NKG2D expression, possibly caused by persistent engagement of its ligands, that may contribute to susceptibility to cancer and infections and represent novel targets for therapeutic interventions., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Lung cancer is one of the most common malignancies, and there is a trend of increasing incidence in young patients. The preoperative diagnosis of pulmonary nodules is mainly based on the combination of imaging and tumor markers. There is no relevant report on the diagnostic value of tumor markers in young pulmonary nodules. Our study was designed to explore the value of five tumor markers in young patients with pulmonary nodules., Methods: We reviewed the medical records of 390 young patients (age ≤45 years) with pulmonary nodules treated at two separate centers from January 1, 2015, to January 1, 2021. Malignant pulmonary nodules were confirmed in 318 patients, and the other 72 patients were diagnosed with benign pulmonary nodules. The gold standard for diagnosis of pulmonary nodules was surgical biopsy. The conventional serum biomarkers included cytokeratin 19 (CYFRA21-1), pro-gastrin-releasing-peptide (ProGRP), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and squamous cell carcinoma-associated antigen (SCCA). The diagnostic values of five tumor markers were analyzed by receiver operating characteristic (ROC) curves., Results: There were no significant differences in the expression of five tumor markers between the groups (p > 0.05). Single tumor marker (CYFRA21-1, ProGRP, CEA, NSE, and SCCA) showed a limited value in the diagnosis of malignant pulmonary nodules, with the AUC of 0.506, 0.503 0.532, 0.548, and 0.562, respectively. The AUC of the combined examination was only 0.502~0.596, which did not improve the diagnostic value., Conclusions: Five conventional tumor markers had a limited diagnostic value in young patients with pulmonary nodules., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Allium hookeri (AH) is a medicinal food that has been used in Southeast Asia for various physiological activities. The objective of this study was to investigate the activation of the cholinergic system and the anti-neuroinflammation effects of AH on scopolamine-induced memory impairment in mice. Scopolamine (1 mg/kg body weight, i.p.) impaired the performance of the mice on the Y-maze test, passive avoidance test, and water maze test. However, the number of error actions was reduced in the AH groups supplemented with leaf and root extracts from AH. AH treatment improved working memory and avoidance times against electronic shock, increased step-through latency, and reduced the time to reach the escape zone in the water maze test. AH significantly improved the cholinergic system by decreasing acetylcholinesterase activity, and increasing acetylcholine concentration. The serum inflammatory cytokines (IL-1β, IL-6, and IFN-γ) increased by scopolamine treatment were regulated by the administration of AH extracts. Overexpression of NF-κB signaling and cytokines in liver tissue due to scopolamine were controlled by administration of AH extracts. AH also significantly decreased Aβ and caspase-3 expression but increased NeuN and ChAT. The results suggest that AH extracts improve cognitive effects, and the root extracts are more effective in relieving the scopolamine-induced memory impairment. They have neuroprotective effects and reduce the development of neuroinflammation.

Background: Some studies have suggested that patients with diabetes and foot complications have worse cardiovascular and cerebrovascular risk profiles, higher degrees of endothelial dysfunction and arterial stiffness and a higher inflammatory background than patients with diabetes without diabetic foot complications. Patients with diabetes mellitus have an alteration in the sympathovagal balance as assessed by means of heart rate variability (HRV) analysis, which is also related to the presence of endothelial dysfunction. Other studies suggest a possible role of inflammation coexisting with the alteration in the sympathovagal balance in favor of the atherosclerotic process in a mixed population of healthy subjects of middle and advanced age., Aims: The aim of this study was to evaluate the degree of alteration of sympathovagal balance, assessed by HRV analysis, in a cohort of patients with diabetes mellitus with diabetic foot and in control subjects without diabetic foot compared with a population of healthy subjects and the possible correlation of HRV parameters with inflammatory markers and endothelial dysfunction indices., Methods: We enrolled all patients with diabetic ulcerative lesions of the lower limb in the Internal Medicine with Stroke Care ward and of the diabetic foot outpatient clinic of P. Giaccone University Hospital of Palermo between September 2019 and July 2020. 4-h ECG Holter was performed. The following time domain HRV measures were analyzed: average heart rate, square root of the mean of successive differences of NN (RMSSD), standard deviation or square root of the variance (SD), and standard deviation of the means of the NN intervals calculated over a five-minute period (SDANN/5 min). The LF/HF ratio was calculated, reactive hyperemia was evaluated by endo-PAT, and serum levels of vaspine and omentin-1 were assessed by blood sample collection., Results: 63 patients with diabetic foot, 30 patients with diabetes and without ulcerative complications and 30 patients without diabetes were enrolled. Patients with diabetic ulcers showed lower mean diastolic blood pressure values than healthy controls, lower MMSE scores corrected for age, lower serum levels of omentin-1, lower RHI values, higher body weight values and comparable body height values, HF% and LF/HF ratio values. We also reported a negative correlation between the RHI value and HRV indices and the expression of increased parasympathetic activity (RMSDD and HF%) in subjects with diabetic foot and a statistically significant positive correlation with the LF/HF ratio and the expression of the sympathovagal balance., Discussion: Patients with diabetic foot show a higher degree of activation of the parasympathetic system, expressed by the increase in HF values, and a lower LF/HF ratio. Our findings may corroborate the issue that a parasympathetic dysfunction may have a possible additive role in the pathogenesis of other vascular complications in subjects with diabetic foot., (© 2021. The Author(s).)

Background: Serum biomarkers have been widely adopted in clinical practice for assisting lung cancer diagnoses, therapeutic monitoring, and prognostication. The function of a well-performing tumor biomarker depends on a reliable reference interval (RI) with consideration of the study subjects' age, gender, and geographical location. This study aimed to establish a RI for each of 6 lung cancer biomarkers for use in the whole country of China on Mindray platform., Methods: The levels of serum 6 lung cancer biomarkers-namely progastrin-releasing peptide (ProGRP), neuron-specific enolase (NSE), squamous cell carcinoma antigen (SCC), carcinoembryonic antigen (CEA), cytokeratin-19 fragment (CYFRA21-1), and human epididymis protein 4 (HE4)-were measured utilizing the chemiluminescence immunoassay on the Mindray CL-6000i platform following the laboratory standard operating procedures in apparently healthy Chinese individuals on large cohort, multicenter, and geographical consideration bases. The CLSI EP28-A3C guideline was followed for the enrollment of study subjects., Results: The age-stratified, gender-specific RIs for ProGRP, NSE, SCC, CEA, CYFRA21-1, and HE4 lung cancer biomarkers in the Chinese population have been established as described in the results and discussion in this work. In addition, various levels of the six lung cancer biomarkers among nine geographical locations in China have been observed., Conclusions: The sample volume of study cohort, age, and geographical location should be considered upon establishing a reliable biomarker RI. A RI for each of six lung cancer biomarkers has been established. The results from this study would be helpful for clinical laboratories in interpreting the analytical results and for clinicians in patient management., (© 2021 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.)

Aim: RBP4, Vaspin and omentin-1 are adipokines, which play an important role in the development of obesity-related complications. The main aim of this study was to investigate the effects of different kinds of fat intake on adipokine levels in obese women., Methods: A total of 272 obese women (BMI ≥ 30) were included in the current cross-sectional study, according to the inclusion and exclusion criteria. Body composition was measured using a body composition analyzer. For the measurement of retinol binding protein 4 (RBP4), vaspin and omentin-1 serum concentrations, an enzyme-linked immunosorbent assay (ELISA) method was used. Dietary intake was assessed using a 3-day 24-h dietary recall., Results: Statistically significant differences were found between polyunsaturated fatty acid (PUFAs) and linoleic acid intake and vaspin and omentin-1 levels. In addition, there were found statistically significant relationships between cholesterol, monounsaturated fatty acid (MUFAs) and total fat intakes with omentin-1 levels. Also, RBP4 and vaspin levels were different significant with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake. Moreover, the results revealed that there were statistically significant differences between RBP4 levels and α-linolenic acid and oleic acid intake., Conclusion: This study revealed that by examining RBP4, vaspin and omentin-1 as adipokines, a novel link between fat intakes and adipokine levels was found., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)