Serum Biomarkers Research Articles

005. The Role of Interleukin-8 in Assisting the Diagnosis of Necrotizing Enterocolitis (NEC) Bell’s Stage I and II in Premature Infants: Literature Review

Background: Necrotizing enterocolitis (NEC) is one of the leading causes of morbidity and mortality in infants, commonly associated with extremely low birth weight (ELBW), low birth weight (LBW), and prematurity. The clinical symptoms are nonspecific and various. This poses a challenge in the early diagnosis. The incidence worldwide ranges from 0.3 to 2.4 per 1,000 live births, with mortality rates reaching 50%. This study aims to assess the role of biomarker IL-8 in diagnosing NEC Bell's stage I and II. Methods: This study is a literature review, conducted electronically in databases including Cochrane Library, PubMed, ScienceDirect, and EBSCO using the keywords: ("Interleukin-8" OR "IL-8") AND ("Necrotizing enterocolitis" OR "NEC" OR “Early NEC” OR “Stage I-II NEC”). Inclusion criteria are study in human, English fulltext within 5 years. Exclusion criteria is comparing NEC any stage with control patients, Results: Based on a review of 23 literatures, there were 6 studies met the inclusion criteria for analysis. IL-8 shows varying sensitivity and specificity as a serum biomarker for diagnosing NEC. Statistical evaluations in previous studies emphasized that significantly elevated levels of biomarker IL-8 were predominantly found in the serum of premature infants with NEC, indicating it could be a potential biomarker for diagnosis with NEC Bell's stage I and II. Conclusion: The measurement of biomarker IL-8 in blood has not yet been established as a reliable diagnostic modality for NEC Bell's stage I and II, indicating the need for further investigation.

Towards the Identification of New Biomarkers in Saliva and Serum for Treatment Monitoring of Equine Gastric Ulcer Syndrome: A Liquid Proteomic Approach

Equine gastric ulcer syndrome (EGUS) is a common condition in horses. This study explores the use of liquid proteomics to identify new biomarkers in saliva and serum to monitor EGUS treatment. The proteomes of horses with EGUS before and after a successful treatment with omeprazole were analysed. In saliva, 503 proteins were identified, with 7 upregulated and 6 downregulated post-treatment. Among the proteins that changed, there was an increase in vimentin, linked to wound healing, and a decrease in podocalyxin, associated with tissue damage. In serum, 206 proteins were found, with significant changes in 5. Keratin type I increased, supporting epithelial integrity, whereas immunoglobulin lambda decreased, indicating a reduced immune response. Gene ontology analysis revealed a decrease in immune-related pathways after successful treatment. Overall, 13 proteins in saliva and 5 in serum showed significant changes after treatment, highlighting the differential responses of saliva and serum in EGUS. This report creates new avenues for discovering potential biomarkers to monitor EGUS treatment, which is of high importance for the management of this prevalent disease.

Adverse Myocardial and vascular side effects of Immune Checkpoint Inhibitors: a prospective multimodal cardiovascular assessment (AMICI study)

Abstract Background Immune checkpoint inhibitors (ICIs) are transformative treatments in oncology, yet they are also associated with a range of cardiovascular (CV) events. Purpose To identify the incidence of CV events (including subclinical) in patients receiving ICIs for solid cancer, either alone or in association with other cancer therapies (e.g., chemotherapies, target therapies). Objectives and methods The Adverse Myocardial and vascular side effects of Immune Checkpoint Inhibitors(AMICI) study prospectively assessed the incidence of CV changes by means of a thorough multimodal assessment. This included repeated CV imaging (transthoracic echocardiograms (TTE), cardiac magnetic resonance imaging (CMR)), serum biomarkers (troponin, brain natriuretic peptides in a single laboratory), and ambulatory ECG monitoring, before and during (at 6 weeks and at 6 months) ICI therapy (Figure). Cardiovascular events included myocarditis, pericarditis, acute coronary syndrome, heart failure (HF), high degree conduction abnormalities (defined as new grade 2 or 3 atrioventricular block) or sustained ventricular arrhythmias (defined as 3 or more ventricular beats at a rate ≥ 120/min), CV death as a composite endpoint, validated by an independent expert panel Results Out of 130 solid cancer patients considered for ICI therapy, 49 patients (38 (77.6%) male; mean age 64.3 (­SD 11.0) years old) were included (June 2020 -December 2021). 22 (55.1%) suffered from kidney or bladder cancer; 7 (14.3%) had CV disease prior to cancer diagnosis; 4 (8.2%) received PD1 and CTLA4 inhibitors. Early CV events were observed in 9 (18.4%) patients at mean 40.1 (SD 5.9) days, with heart failure (HF) in 5 (10.2%), ventricular arrhythmias or new conduction disorders in 4 (8.2%) patients. History of AF (HR 4.49 (CI 1.11-18.14), P=0.035) predicted early CV events at 6 weeks (Table). At 6 months follow-up, 18 CV events were observed in 15/49 (31%) patients, with 6 (12.2%) HF events, 5 (10.2%) significant ventricular arrhythmias or conduction disorders and 4 (8.2%) AF. There was a significant decline in LVEF (P<0.001) in patients even in the absence of CV event (P=0.003) or HF (P=0.003). Higher creatinine at inclusion (HR 0.99 [0.98-1.00], P=0.006) predicted HF. Conclusions Cardiovascular complications arising during cancer treatment with ICIs are primarily due to the exacerbation of pre-existing HF or the onset of non-inflammatory heart rhythm disorders. The majority of these CV changes manifest shortly after starting ICIs and do not need hospital admission. Our results suggest that more close follow-up may be needed in patients with underlying CV conditions when starting ICI therapy, by means of CMR and ambulatory ECG holter monitoring.

Insulin-like growth factor binding protein 2 predicts course of concomitant right-ventricular dilation and tricuspid regurgitation after transcatheter edge-to-edge mitral valve repair

Abstract Aims Right ventricular (RV) dilation and secondary tricuspid regurgitation (TR) are highly prevalent comorbidities in patients with mitral regurgitation and are associated with a worse prognosis. TR improvement after successful transcatheter edge-to-edge mitral valve repair (M-TEER) is reported regularly, however specific factors contributing to the recovery of RV function and TR after M-TEER are poorly understood. Particularly the role of serum biomarkers in this context is unclear. We aimed to identify specific biomarkers associated with the course of concomitant RV dilation and TR after M-TEER. Methods and Results We prospectively included 242 patients undergoing M-TEER at our center and obtained pre-procedural blood samples for biomarker analysis. A commercial multiplex protein assay (Cardiovascular III, Olink, Uppsala, Sweden) was used to quantify expression levels of 92 defined biomarkers. We then analyzed differences in biomarker expression between patients with and without right ventricular reverse remodeling (RVRR) as defined by improvement of concomitant TR by at least one grade and/or downsizing of the basal RV diameter of at least 10%. 242 patients were included in this analysis, 94 had no/mild concomitant TR at baseline, 148 had moderate/severe TR. RV diameters correlated with TR severity and were significantly larger in patients with moderate/severe TR. At baseline, expression of numerous cardiometabolic biomarkers was significantly higher in patients with moderate/severe TR. These included NT-proBNP (1.9-fold, p < 0.001), matrix metalloproteinase 2 (1.4-fold, p < 0.001) as well as insulin-like growth factor binding proteins 1 (1.7-fold, p < 0.001), -2 (1.3-fold, p = 0.001) and -7 (1.4-fold, p < 0.001). Follow-up analysis was performed in patients with initial moderate/severe TR. The course of TR and RV dimensions three months after M-TEER could be assessed in 99 patients (56 with moderate TR, 43 with severe TR). RVRR had occurred in 50 patients (50.5%). Patients without RVRR had a higher prevalence of chronic pulmonary disease (24.5 vs. 2.2%, p < 0.001). No further differences in clinical characteristics were found. Specifically, RV diameter, systolic pulmonary artery pressure (sPAP) and right-ventricular systolic function did not differ substantially between both groups. Strikingly however, the expression of insulin-like growth factor binding protein 2 (IGFBP-2) was significantly higher in patients, who did not develop RVRR (fold change 1.3 compared to patients with RVRR, p = 0.022). After adjustment for covariates IGFBP-2 was independently associated with absence of RVRR (Odds Ratio 2.078, 95% Confidence interval 1.108 – 3.897, p = 0.023). Conclusions In patients undergoing M-TEER with concomitant moderate or severe TR, numerous cardiometabolic biomarkers including IGFBP-2 are upregulated. Higher levels of IGFBP-2 at baseline are independently associated with persistent TR and/or RV dilation after M-TEER.

Residual post-infarct myocardial inflammation detected by 68Ga-DOTATATE PET/MRI predicts long-term adverse cardiac remodelling

Abstract Background Maladaptive inflammatory responses are associated with adverse cardiac remodelling after myocardial infarction (MI), but clinical methods for detecting residual myocardial inflammation post-MI are lacking. Purpose To investigate somatostatin receptor subtype 2 (SST2) positron emission tomography (PET)/magnetic resonance imaging (MRI) using 68Ga-DOTATATE after MI. Methods In a prospective observational cohort study, infarct-related myocardial inflammation detected by 68Ga-DOTATATE PET at 2wk and 3mo post-MI was compared with MRI characteristics including left ventricular (LV) volumetric changes at 1yr, as well circulating immune cell phenotyping and serum proteomic markers. Patients with a prior history of MI or heart failure were excluded. Histological SST2 expression was assessed in myocardial biopsies. Results 38 participants (mean age 60 [SD 9] years; 84% male) with recent MI were enrolled, of whom 58% had an ST-segment elevation MI. Mean peak Troponin I was 16,665 (range 408 to >25,000) ng/L and mean post-infarct LV ejection fraction was 51 (SD 9) %. 68Ga-DOTATATE maximum standardized uptake values (SUVmax) at 10 (SD 4) days accurately localised infarcted myocardial segments defined by late-gadolinium enhancement MRI (LGE; Fig. 1); were 14.2% higher in akinetic/hypokinetic vs. normo-kinetic segments (p<0.0001); and were correlated both with peak segmental strain (r=0.47, p=0.003) and segmental T1 values (r=0.51, p=0.02). Mean infarct SUVmax was 19.7% lower on repeat PET/MRI after a mean 102 (SD 22) days (p<0.0001), and this change was in keeping with parallel reductions in T2-weighted oedema signal on MRI and serum biomarkers of cardiac injury and systemic inflammation. Residual inflammation assessed by mean infarct SUVmax at 3mo was correlated with ΔLV indexed end-diastolic volume at 369 (SD 14) days, after adjustment for baseline infarct size and other clinical variables (p=0.038). The 3mo:2wk ratio of mean infarct SUVmax was an even stronger predictor of adverse myocardial remodelling (p=0.0025). Circulating SST2+ classical monocytes were correlated with infarct 68Ga-DOTATATE signal (r=0.47, p=0.02), and SST2 was co-expressed with CD68+ macrophages in inflamed myocardial specimens of patients with recent MI and ischaemic heart failure. After statistical feature selection and multiple comparisons adjustments, among the blood markers associated with 3mo:2wk infarct SUVmax was CCL25, a chemokine involved in macrophage recruitment which has been implicated in adverse cardiac remodelling. Conclusions Here, in the first prospective clinical study of serial SST2 PET/MRI after MI, we show that 68Ga-DOTATATE can identify and track resolving infarct-related myocardial inflammation. Moreover, residual inflammation detected by 68Ga-DOTATATE is associated with long-term adverse myocardial remodelling and could provide a potential future imaging biomarker to help stratify high-risk patients for emerging immunomodulatory therapies.Figure 1.68Ga-DOTATATE PET-MRI after MI

The impact of maternal serum biomarkers on maternal and neonatal outcomes in twin pregnancies: a retrospective cohort study conducted at a tertiary hospital.

Prior prediction models used for screening preeclampsia (PE) in twin pregnancies were found to be inadequate. In singleton pregnancies, various maternal biomarkers have been shown to be correlated with negative pregnancy outcomes. However, the impact of these biomarkers in twin pregnancies remained uncertain. A retrospective cohort study was carried out on 736 twin pregnancies at a tertiary hospital in Hangzhou, China. Multivariable logistic models were employed to examine the association between levels of serological markers and the likelihood of adverse pregnancy outcomes. The final logistic model was formulated as a user-friendly nomogram. The primary outcome assessed was the occurrence of PE. Results were presented as odds ratios (ORs) with corresponding 95% confidence intervals (CIs). The prevalence of PE in the study was 10.3%. When comparing women diagnosed with PE to those without, it was evident that the former group experienced a significantly higher risk of unfavorable maternal and neonatal outcomes. A multivariable logistic regression analysis revealed notable associations between various factors including maternal age, parity, gestational weight gain, a family history of hypertension, as well as levels of cholesterol, albumin, and creatinine and the risk of developing PE, with a significance level of P < 0.05. The concordance index for the constructed nomogram was determined to be 0.792 (95% CI: [0.739-0.844]). Furthermore, an increment of 1 * 1012/L in red blood cell (RBC) count was associated with more than a two-fold increase in the odds of experiencing adverse maternal outcomes (OR 2.247, 95% CI: [1.229-4.107]). However, no significant correlations were identified between any of the examined variables and neonatal outcomes. In this study, we developed a user-friendly predictive model that achieves notable detection rates by incorporating maternal serum biomarker levels alongside maternal characteristics and medical history. Our findings indicate that the probability of adverse maternal outcomes increases with elevated levels of RBCs. Obstetricians should consider intensifying surveillance for these women in clinical practice.

Evaluation of aortic inflammation in marfan syndrome patients with 18-fluorodeoxyglucose positron emission and computed tomography

Abstract Background The role of inflammation in Marfan Syndrome (MS) has been well studied in current research. These studies have investigated the role of serum Interleukin 6 (IL-6), Transforming Growth Factor-b (TGF-b) and Macrophage Colony Stimulating Factor (MCSF) as biomarkers of disease severity and progression. Surgical repair is the recommended treatment of aortic aneurysms when aortic diameter reaches the indication threshold. It has been observed however that dissection may occur even before this threshold is reached. 18-fluorodeoxyglucose (18 F-FDG) positron emission tomography / computed tomography (PET/CT) is the gold standard imaging modality to noninvasively assess vascular inflammation. Purpose Our aim was to investigate whether MS patients have increased aortic wall inflammation as assessed by 18F-FDG PET/CT, and the relationship between aortic wall inflammation with serum levels of IL-6, TGF-b and MCSF. Methods The study population consisted of fifteen MS patients and seventeen sex and age matched controls. In all subjects, serum levels of circulating IL-6, TGF-b and MCSF were measured. In PET/CT, the arterial target-to-background ratio (TBR) was calculated for aortic root (AR), ascending aorta(As), aortic arch (AA) and descending aorta (DA). Also, all patients were assessed with transthoracic echocardiography where the diameters of AR, As, AA, and DA were estimated at baseline and were reexamined at the end of the follow up period. Results TBR for MS vs. controls was 2.17±0.75 vs 2.01±0.36, p=0.75 at AR; 2.15±0.67 vs 1.84±0.35, p=0.040 at As; 2.16±0.64 vs 1.70±0.25, p=0.03 at AA and 1.97±0.52 vs 1.83±0.42, p=0.23 at DA respectively. Additionally, Marfan patients had increased levels of serum biomarkers. However, this difference was statistically significant (SS) only for IL-6 serum levels; 2.17±0.46 vs 1.08±0.12 p=0.011 and IL-6 was SS associated with AR TBR (rho=0.572, p=0.033), As TBR (rho=0.604, p=0.022) and DA TBR (rho=0.714, p=0.004). Two of our patients were operated due to severe dilatation of the aortic root and the surgical specimens showed aortic wall inflammation of moderate severity along with fibrosis. Conclusion MS patients have increased of aortic wall inflammation as assessed by 18F-FDG PET/CT, a finding that highlights the role of inflammation in the pathway of disturbed TGF signaling. Further research is needed to determine its prognostic role and value in identifying patients with an indication for early intervention.

Lipidomics-based deep learning algorithms can enhance prediction of obstructive coronary artery disease

Abstract Background Lipidomics emerge as a promising research field with the potential to help in personalized risk stratification and also improve our understanding on the functional role of individual lipid species in the metabolic perturbations occurring in coronary artery disease (CAD). The existing technological challenges to detect diverse yet structurally similar lipids and their isomers, as well as the need for novel statistical and computational tools to handle the high-dimensional lipidome may be responsible for the reduced clinical translation of the very first lipidomics research outcomes. Methods To that end, this post-hoc analysis of the prospective CorLipid trial aimed to investigate the predictive capability of a lipidomics panel for obstructive CAD risk through an extreme gradient boosting (XGBoost) machine learning (ML) approach. The lipid profiles of 146 individuals with suspected CAD were investigated through liquid chromatography-mass spectrometry. Fasting blood samples were drawn prior to invasive coronary angiography execution. Obstructive CAD was defined as SYNTAX Score (SS) &amp;gt;0 compared to non-obstructive CAD (SS=0). Results Study participants (75.3% male, mean age: 61 ±10.5 years old) were divided into two categories based on the existence of obstructive CAD (54.8% with SS&amp;gt;0 and 45.2% with SS=0). In total, 517 lipid species were identified, from which 290 lipid species were finally quantified in participants’ serum [glycerophospholipids (52.1%), glycerolipids (28.6%) and sphingolipids (19.3%)]. The levels of glycerophospholipid, sphingolipid and glycerolipid classes were significantly different in patients with obstructive CAD. Finally, a ML XGBoost algorithm identified a panel of 17 serum biomarkers (5 sphingolipids, 7 glycerophospholipids, triacylglycerols, galectin-3, glucose, LDL and LDH) as totally sensitive (100% sensitivity, 62.1% specificity and 100% negative predictive value) for the prediction of obstructive CAD. Conclusions These findings provide molecular insights into the role of dysregulated lipid metabolism in the development and progression of CAD while validating the existing body of evidence from similar research studies. Further (ML-based) investigation of lipid metabolism could hold promises for novel therapeutic strategies and improvement of the existing risk stratification schemes.Lipidomics panel importance

FAS system diagnostic and prognostic value in patients with chronic heart failure

The authors conducted the descriptive literature synthesis to present the structure and mechanism of the FAS family action, the purpose of determining the concentration of biomarkers in blood serum, the relationship of various FAS ligands levels with the patient’s clinical condition - the HF functional class (FC), as well as the sFASL using possibility to predict the HF course. The review analyzed 22 studies on the FAS system biomarkers participation in the HF pathogenesis and the relationship of their serum concentrations with the HF severity. A threshold sFASL value of 0.0999 ng/ml is associated with this pathology unfavorable course, while the increase in sFASL degree directly correlates with an increase in the FC of HF, the progression and death risks.

Clinical profiles of leucine-rich alpha-2 glycoprotein for indicating mucosal healing in ulcerative colitis patients under administration of molecular targeted drug.

Leucine-rich alpha-2 glycoprotein (LRG) is a useful serum biomarker for monitoring disease activity during remission in ulcerative colitis (UC). Because LRG levels differ among patients, it is necessary to assess them after profiling patients, especially in patients with refractory UC undergoing treatment with molecular targeted drugs. This study aimed to analyze LRG levels that indicate mucosal healing according to clinical characteristics and molecular targeted drugs. Among 214 patients with UC treated with biologics or Janus kinase (JAK) inhibitors, this study evaluated 111 patients (174 measurements) who achieved mucosal healing based on colonoscopy performed within 2 months before and after LRG measurement and experienced no changes in disease status or treatment during the same period. We analyzed the relationship of LRG with clinical characteristics (including sex, age, body mass index, and disease type and duration) and molecular targeted drugs. Compared with men, women had significantly higher LRG levels (9.5 μg/mL vs. 11.3 μg/mL, P&lt;0.001). In addition, LRG levels were significantly higher in older patients (12.0 μg/mL vs. 9.8 μg/mL, P&lt;0.01). LRG levels were the highest in patients treated with vedolizumab and lower in patients treated with JAK inhibitors (vedolizumab: 12.7 μg/mL; tofacitinib: 8.9 μg/mL; upadacitinib: 8.5 μg/mL; and filgotinib: 9.1 μg/mL; P&lt;0.0001). Among the patients who achieved mucosal healing, LRG levels were significantly higher in women and older patients. LRG levels differed according to the molecular targeted drug used, and were higher with vedolizumab and lower with JAK inhibitors.

Dose Adjustments in Renal Failure: Does the Dettli Formula Need an Update Moving Away from Linearity?

Chronical Kidney Disease (CKD) causes deterioration of renal function with reduction of glomerular filtration (GFR). Drugs which are mainly excreted through the kidney have reduced renal elimination (Clrenal) in CKD. For decades dosage adjustments for these drugs have been computed based on GFR and clearance measurement of biomarker serum creatinine (Clcr), respectively, and according to the rule of Dettli [1-3] where the appropriate dose D compared to the normal dose (Dnorm) may be assessed through the individual elimination fraction Q:

Significance of neurodegeneration and neuroplasticity serum biomarkers in Parkinson’s disease patients treated with subthalamic stimulation

The ability of serum biomarkers to predict the prognosis and response to deep-brain stimulation (DBS) therapy in Parkinson’s disease (PD) patients is promising. Here, we showed that NfL differed between healthy individuals and PD patients and that changes in NfL, GFAP, and BDNF occurred only transiently after DBS surgery. Therefore, subthalamic stimulation does not promote neurodegeneration, and these biomarkers do not serve as clinical improvement endpoints in PD DBS patients.

Serum proteomic analysis identified ITIH4 as a potential novel biomarker for feline infectious peritonitis

Feline infectious peritonitis (FIP) is a fatal feline disease. At present, the reference standard for FIP diagnosis is immunohistochemistry (IHC) of organs, but this method involves high time-related costs, invasive sampling procedures and professional requirements. Serological detection is a common auxiliary method for diagnosing diseases. As a result, we assessed the changes in the serum proteome of FIP patients with the aim of identifying novel specific serum biomarkers that could aid in the clinical diagnosis of FIP. Pre- and postinfection groups were compared and 92 differentially expressed proteins (DEPs) were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEPs revealed that the enriched GO terms and KEGG pathways among the DEPs were immune activation, peptidase regulator activity and the complement and coagulation cascade pathways. The level of peptidase regulator interalpha-trypsin inhibitor heavy chain 4 (ITIH4) in cat serum was significantly correlated with FIP. The areas under the ROC curve (AUCs) of full-length ITIH4 (f-ITIH4) and cleaved ITIH4 (c-ITIH4) expression were 0.922 and 1.000, respectively, which allowed the discrimination of FIP cats from healthy cats. These results suggest that ITIH4 may be a potential serum biomarker for detecting early FIP. SignificanceFIP causes fatal disease in cats of almost all ages, and there is currently no effective vaccine or treatment for FIP. Therefore, early diagnosis is extremely important for disease prevention and control. The results of the model and clinical samples revealed that ITIH4 was significantly increased in the serum of FIP cats. This study is the first to propose ITIH4 as a diagnostic biomarker in cats with FIP and our results suggest that serum ITIH4 levels might identify cats with FIP during the early stage.

Unhealthy plant-based diet is associated with a higher cardiovascular disease risk in patients with prediabetes and diabetes: a large-scale population-based study

BackgroundThe role of plant-based dietary patterns in preventing cardiovascular disease (CVD) among individuals with prediabetes and diabetes remains unclear. We aimed to evaluate the associations of plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI) with cardiovascular disease (CVD) risk and explore potential contributing factors among people with prediabetes and diabetes.MethodsA total of 17,926 participants with prediabetes and 7798 with diabetes were enrolled from the UK Biobank between 2006 and 2010 and followed until the end of 2020. We calculated the PDI, hPDI, and uPDI based on 18 major food groups including plant-based foods and animal-based foods and applied Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD risk related to PDI, hPDI, and uPDI. Decomposition analysis was performed to assess the role of dietary components, and mediation analysis was performed to assess the potential mediating role of serum biomarkers underlying these associations.ResultsA total of 2324 CVD events were documented among individuals with prediabetes, while 1461 events occurred among patients with diabetes. An inverse association was found between hPDI and CVD risk among individuals with prediabetes (HR T3 vs. T1 = 0.88, 95% CI = 0.79–0.98, Ptrend = 0.025) but not those with diabetes. A positive association was found between uPDI and CVD risk among individuals with prediabetes (HR T3 vs. T1 = 1.17, 95% CI = 1.05–1.30, Ptrend = 0.005) and those with diabetes (HR T3 vs. T1 = 1.14, 95% CI = 1.00–1.29, Ptrend = 0.043). High-sugar-sweetened beverages (SSB) intake accounted for 35% of the hPDI-CVD association and 15% of the uPDI-CVD association among individuals with prediabetes, whereas low intake of whole grain accounted for 36% of the association among patients with diabetes. Elevated cystatin C levels explained the largest proportion of the association between uPDI and CVD risk among individuals with prediabetes (15%, 95% CI = 7–30%) and diabetes (44%, 95% CI = 9–86%).ConclusionsAdherence to an unhealthy plant-based diet is associated with a higher CVD risk in people with prediabetes or diabetes, which may be partially attributed to low consumption of whole grains, high intake of SSB, and high blood cystatin C levels.

Use of Biomarkers in Nutrition Intervention Studies of Children: A Scoping Review

Obesity in youth is an increasingly prevalent public health concern worldwide. Lifestyle interventions aim to help participants establish healthy habits and reduce obesity-related disease risk by targeting physical activity and dietary habits. Most studies assess weight loss, but biomarkers may enable more rapid and comprehensive assessment of intervention success. This scoping review aims to synthesize the published literature on which biomarkers are assessed during interventions for pediatric obesity to inform future use. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature search of five databases conducted in February 2022 returned 1579 unique and relevant articles published between 2006 and 2021. After screening titles, abstracts, and full text, four reviewers determined that 43 studies met eligibility requirements. Quality screening was conducted, and 97.7% of papers were of fair or good quality. Of the 43 studies, 47% reported measures of adipose-related signaling molecules inclusive of adipokines, 74% included insulin-related biomarkers, 63% reported lipid-related biomarkers, 40% reported proinflammatory cytokine biomarkers, 12% reported measures of skin and/or plasma carotenoids, 40% measured blood pressure, and 21% included liver enzymes. Sixty-seven percent of studies measured biomarkers in whole blood, 40% measured biomarkers in plasma, 56% measured biomarkers in serum, and 2% measured biomarkers in urine. This work summarizes the current use of biomarkers in lifestyle intervention studies enrolling children. These biomarkers could be clinically relevant for pediatric weight management interventions.

Serum Level of Cadherin-P (CDH3) Is a Novel Predictor of Cardiovascular Events Related to Atherosclerosis in a 3-Year Follow-Up Study

Background: Placental cadherin (CDH3) is an adhesion molecule expressed in many malignant tumors. The role of serum CDH3 in atherosclerosis is unclear. Methods: This 3-year follow-up study measured atherosclerosis and serum CDH3 in 218 angiography inpatients. Coronary stenosis was assessed as the Gensini score. The brachiocephalic and femoral plaques were quantified by ultrasound. Microarray serum profiling was conducted in selected samples. CDH3 in the serum was measured using an indirect ELISA. The odds ratio (OR), ROC analysis, and logistic regressions were used to evaluate the associations between CDH3 content, atherosclerotic lesions, and various serum biomarkers. Results: Serum CDH3 was associated with the severity of atherosclerosis and diastolic blood pressure. The levels of CDH3 were able to discriminate patients with total subclinical and hemodynamically significant atherosclerotic lesions in all circulation pools (coronary, brachiocephalic, and femoral). Elevated serum CDH3 appeared to be a risk factor for cardiovascular outcomes after 3-year follow up with OR = 1.81 (95% CI: 1.07–3.72; p = 0.022). Endothelin-1 and NOx were associated with the content of CDH3 in the serum, suggesting the involvement of certain signal transduction pathways that may participate in plaque formation. Conclusions: CDH3 was associated with cardiovascular outcomes adjusted for coronary plaque presence, indicating a role of CDH3 in plaque biology.

Residential fungal β-(1,3)-D-glucan exposure is associated with decreased pulmonary function in fibrotic pulmonary sarcoidosis.

Background: Sarcoidosis is a multi-system disease frequently affecting the lungs. It is thought to be mediated by gene-environment interaction; for example, epidemiological data show organic aerosol exposure increases risk of pulmonary sarcoidosis. Research Question: Does exposure to bioaerosol associate with worse lung disease in patients with pulmonary sarcoidosis? Study Design and Methods: Using an observational, cohort study design, we measured residential exposure to fungal and bacterial cell wall material, β-(1,3)-D-glucan (BDG) and endotoxin, respectively, in healthy control subjects and those with pulmonary sarcoidosis. In the case cohort, we compared bioaerosol concentrations to pulmonary disease severity, assessed by pulmonary function testing, qualitative chest computed tomography (CT), and serum biomarkers. Log-transformed bioaerosol concentrations were compared to lung function and significance and correlation determined by Pearson correlation. Results: Homes of subjects with sarcoidosis had higher BDG and endotoxin concentrations than control subjects. Patients with significant pulmonary fibrosis had greater disease severity (Wasfi severity score, visual analogue scale) and reduced pulmonary function compared to those without fibrosis (all P <0.01). Residential fungal BDG correlated with declining FVC, only in patients with fibrosis on CT imaging ( P =0.02). Survey data revealed higher BDG concentrations were found in homes of cat-owners, and the number of houseplants owned correlated with declines in FVC and FEV 1 ( P =0.05 and 0.02, respectively). In patients without fibrosis, eight inflammatory markers correlated with BDG (6CKine/CCL21, IL-9, IL-17F, IL-21, IL-28A, I-309, MIP-1β, TARC), while in those with pulmonary fibrosis, BDG correlated with two inflammatory markers (Eotaxin-3, M-CSF), suggesting immune anergy to inhaled antigens in patients with fibrosis. Interpretation: In patients with pulmonary fibrosis, disease severity was correlated with residential exposure to fungal cell wall material, but not gram-negative bacterial cell wall material. These patients may experience immune anergy to inhaled antigens.

Dietary glycerides of valerate ameliorate diarrhea and impact intestinal physiology and serum biomarkers in weaned piglets infected with enterotoxigenic Escherichia coli F18.

In the commercial swine farm setting, the post-weaning period is a critical window during which piglets are highly susceptible to infection and enterotoxigenic E. coli (ETEC)-associated diarrhea. Short chain fatty acids and their glycerides are compounds which may influence intestinal health; however, valerate is one that has not been well-characterized for its role as a dietary supplement. Therefore, the major objective of this experiment was to investigate two forms of valerate glycerides on diarrhea, intestinal physiology, and systemic immunity of weaned pigs experimentally infected with ETEC F18. Dietary treatments included a control diet and three additional diets supplemented with 0.075% monovalerin, 0.1% monovalerin, or 0.1% trivalerin, respectively. Piglets were weaned (21-24 d of age), individually housed, and experimental diets were fed throught the 28-day trial period. After a seven-day period, all piglets were inoculated on three consecutive days with 1010 CFU ETEC F18/3mL. Growth performance was monitored throughout the trial and daily diarrhea scores were recorded. Rectal swabs were collected for bacterial culture to confirm the presence or absence of β-hemolytic coliforms throughout the trial. Serum samples were collected and analyzed for inflammatory biomarkers on d 0, 3, 6, and 21 post-inoculation (PI) and untargeted metabolomics on d 6 PI. Intestinal mucosa and tissue sections were harvested from pigs sacrificed on d 7 PI for gene expression and histology analysis. All data, except for frequency of diarrhea and metabolomics, were analyzed by ANOVA using the PROC MIXED of SAS. Dietary trivalerin reduced (P < 0.05) the frequency of severe diarrhea over the entire trial period and the frequency of β-hemolytic coliforms on d 7 PI compared with control. The intestinal villus height on d 7 PI in jejunum tissue was increased (P < 0.05) in pigs fed trivalerin. The mRNA expression of TNF-α was decreased (P < 0.05) in the trivalerin group, while that of ZO1 was increased (P < 0.05) compared with control. Throughout the trial, serum TNF-α was reduced in pigs fed trivalerin compared with control. Serum metabolites, adenosine, inosine, and shikimic acid were reduced (P < 0.05) on d 6 PI in all treatment groups compared with control. In conclusion, the present results indicate supplementing dietary valerate glycerides exhibited beneficial impacts on diarrhea, inflammation, and intestinal gene expression of piglets during the post-weaning period.

Establishment and research progress of early diagnosis system for pleural mesothelioma

Pleural mesothelioma (PMe) was associated with asbestos exposure.The Diagnosis of PMe is difficult due to the lack of specificity of clinical signs and symptoms, although there are many tools available for early diagnosis of mesothelioma. Most PMe patients are diagnosed at an advanced stage. This article reviews advances in strategies for early diagnosis of mesothelioma, focusing on breath analysis, early diagnosis of pleural effusion cytology in patients with mesothelioma, serum biomarkers and miRNA.

Exploring diagnostic biomarkers of type 2 cardio-renal syndrome based on secreted proteins and bioinformatics analysis

Chronic heart failure (CHF) can induce chronic kidney disease (CKD), called type 2 cardio-renal syndrome (CRS2). The mechanism is not completely clear, and there is a lack of early warning biomarkers of CKD in the context of CHF. Two CKD, one CHF-PBMC and four CHF-cardiac tissue expression profile datasets were obtained from GEO database. Differential expression analysis and WGCNA were used to detect CKD key genes and CHF-related secreted proteins. Protein–protein interaction (PPI), functional enrichment, and cMAP analysis reveal potential mechanisms and drugs of CHF-related CKD. Five machine learning algorithms were used to screen candidate biomarkers, construct a diagnostic nomogram for CKD and validate it in two external cohorts. Clinical serum samples were collected in our hospital to evaluate the correlation and diagnostic value of biomarkers and CKD. 225 CKD key genes and 316 CHF-related secreted proteins were identified. Four key subgroups, including 204 genes, were identified as CRS2-related pathogenic genes by PPI analysis. Enrichment analysis revealed that the identified subgroups exhibited significant enrichment in cytokine action, immune responses, and inflammatory processes. The cMAP analysis highlighted metiradone as a drug with greater potential for therapeutic intervention for CRS2. Utilizing five machine learning algorithms, three hub genes (CD48, COL3A1, LOXL1) were pinpointed as potential biomarkers for CKD, and a nomogram model was constructed. Receiver operating characteristic analysis demonstrated that the nomogram’s area under the curve (AUC) exceeded 0.80 in both the CKD combined dataset and two external cohorts. In addition, the three biomarkers were significantly correlated with the glomerular filtration rate, and the AUC of the model predicting disease progression was 0.944. Furthermore, analysis of immune cell infiltration indicated a correlation between the three biomarkers and the infiltration fraction of macrophages, neutrophils, and other immune cells in CKD. Our clinical cohort validated the expression patterns of three biomarkers in serum, and the diagnostic model achieved an AUC of 0.876. CHF has the potential to facilitate the progression of CKD via the release of cardiac and PBMC secreted proteins. Furthermore, CD48, COL3A1, and LOXL1 have been identified as potential biomarkers for the detection of CKD.