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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.)