Serum Biomarkers Research Articles

307 Use of defatted black soldier fly larvae meal (BSFLM) as an alternative and functional ingredient in canine nutrition

Abstract Black soldier fly (Hermetia illucens) larvae meal (BSFLM) is an alternative, sustainable, and nutrient-rich ingredient for pet foods. However, limited information is available on optimal inclusion levels and its functional properties. The objective of the study was to evaluate the effects of incremental levels of BSFLM (15% or 30%) as a partial or full substitute for chicken by-product meal (CM) in extruded diets. Three complete and balanced diets were formulated and extruded: Control, 15% BSFLM, and 30% BSFLM. The effects of the diets on nutrient digestibility, fecal metabolites and microbiota, and serum oxidative stress and inflammatory biomarkers in adult dogs were examined. A complete randomized design was used with adult Beagles (n = 10/treatment). The experimental period lasted 70 d, consisting of a 14-d adaptation to the control diet followed by 56-d test period. Data were analyzed using SAS Proc Mixed 9.4 with P ≤ 0.05 significance. All diets were well-accepted by the dogs; food intake and fecal output were not affected (P > 0.05) by treatment. Apparent total tract digestibility (ATTD) of dry matter, crude protein, and fat did not differ among treatments, whereas ATTD of organic matter (81.2%) and total dietary fiber (18.9%) was less (P < 0.05) for dogs fed 30% BSFLM in contrast with the Control group (83.2% and 30.3%, respectively). Fecal concentrations of total short-chain fatty acids and total phenols were less (P < 0.05) for dogs fed 30% BSFLM relative to dogs fed Control. No treatment effect was observed for serum biomarkers of oxidative stress and inflammation. Fecal microbial diversity differed between Control and 30% BSFLM groups. Overall, extruded diets containing 15% or 30% were well-digested by dogs as demonstrated by similar ATTD coefficients compared with Control. Intrinsic presence of chitin in BSFLM, and other insect-derived ingredients, can behave like insoluble dietary fiber in a food matrix, which would explain the decreased ATTD for organic matter and total dietary fiber, as well as less fecal concentration of total short-chain fatty acids. The inclusion of 30% BSFLM may have decreased protein hindgut fermentation due to less fecal concentration of total phenols. Altogether, the inclusion of 15% BSFLM resulted in similar physiological responses in comparison with dogs fed the Control diet. Greater inclusion levels of BSFLM may impact ATTD, however, it also has the potential to modulate fecal metabolites and microbiota, without negatively affecting fecal microbial richness.

An efficient electrochemical biosensor based on double-conductive hydrogel as antifouling interface for ultrasensitive analysis of biomarkers in complex serum medium

Electrochemical biosensors are suitable for trace detection of biomarkers in serum due to their high sensitivity and fast response time. However, the extensive adsorption of non-specific biomolecules may affect detection results and reduce the operating life of sensors. Herein, an efficient electrochemical biosensor based on double-conductive antifouling hydrogel was developed for ultrasensitive detection of carcinoembryonic antigen (CEA) in serum. Specifically, the antifouling hydrogel was designed with MXene as the conductive framework, and its inherent surface hydrophilicity made it have good antifouling ability. Meanwhile, the introduction of conductive poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) further improved the conductivity and stability and of antifouling hydrogel. Furthermore, the prepared MXene nanosheets exhibited large surface area, which could load a large amount of [Ru(NH3)6]3+ as internal standards. Importantly, the encapsulation of [Ru(NH3)6]3+ in hydrogel can not only eliminate the environmental and instrument errors, but also realize the integration of antifouling and internal standards, thus simplifying the construction process and improving the detection accuracy of the biosensor. Based on this, the proposed signal “on-off” electrochemical antifouling biosensor realized trace detection of CEA in a wide linear range (1 pg/mL ∼ 1 μg/mL), with a detection limit as low as 0.41 pg/mL (3δ/k). This study broadens the application of hydrogels in electrochemical antifouling systems, providing a positive reference for sensitive and accurate determination of biomarkers in serum samples.

Exploring the correlation between periodontal disease and serum biomarkers in haemodialysis patients

BackgroundPatients undergoing haemodialysis are more susceptible to infectious diseases, including periodontitis. This study aimed to investigate the Correlation between periodontal disease and serum markers in Yemeni haemodialysis patients.MethodsA cross-sectional study was conducted on a sample of 70 haemodialysis patients. Patient interviews, clinical examinations, and laboratory tests were performed to collect data. Serum levels of albumin, calcium, phosphorus, haemoglobin, ferritin, and creatinine were measured, with separate measurements for cystatin C The association between categorical variables was assessed using the chi-square test and Pearson’s correlation coefficient, considering a significance level of p < 0.05.ResultsSignificant correlations were found between serum biomarkers and periodontal clinical parameters. Phosphorus, creatinine, albumin, ferritin, and creatinine levels correlated significantly with the Plaque Index (p < 0.001, p < 0.001, p = 0.015, p = 0.018, and p = 0.03). While the Ferritin level showed significant correlations with both the Plaque Index and Miller Classes (r = 0.281, p = 0.018 and r = 0.258, p = 0.031), respectively. The Calcium level showed a significant correlation with the Gingival Index (r = 0.266, p = 0.027). Cystatin C level was statistically correlated with mobility (r = 0.258, p = 0.031). Also, the result showed a significant correlation between Creatinine levels and Periodontitis (r = 0.26, p = 0.03).ConclusionThis study provides evidence of a strong association between periodontal disease and chronic kidney disease in Yemeni haemodialysis patients. The findings emphasize the significance of maintaining good oral health in the care of haemodialysis patients.

Effect of a Phytochemical-Rich Olive-Derived Extract on Anthropometric, Hematological, and Metabolic Parameters.

Extra virgin olive oil is a fundamental component of the Mediterranean diet. It contains several molecules that sustain human well-being by modulating cellular metabolism and exerting antioxidant, anti-inflammatory, and anti-ageing effects to protect normal tissues, and it can exert anti-angiogenic and pro-apoptotic effects on cancer cells. Metabolites found in different parts of the olive tree, including leaves, also possess properties that might help in cancer prevention and promote wellness in aging. Olive mill wastewater (OMWW), a liquid residue produced during olive oil extraction, represents an environmental issue. However, it is rich in phytochemicals with potential beneficial properties. Dietary supplements based on OMWW can be produced for nutritional supplementation with advantages to the ecology. This work aims to measure hematochemical, anthropometric, and metabolomic parameters in volunteers taking an OMWW dietary supplement, Oliphenolia® (OMWW-OL). The supplementation of OMWW-OL 25 mL twice daily for 30 days was tested on a pilot cohort of volunteers with characteristics close to metabolic syndrome. Hematochemical, anthropometric, serum biomarkers and serum metabolomic parameters were analyzed before the intervention, at 30 days, and 30 days after stopping consumption. A total of 29 volunteers were enrolled, and 23 completed the study. The participants' parameters at baseline were measured, and then twice daily at 30 days of treatment and 30 days after assumption discontinuation. Although treatment was with an olive derivative, their weight did not increase. Their body mass index, instead of augmenting, slightly decreased, particularly in the women. Also, hydration increased, especially in the women, while blood pressure, glycemia, and insulin decreased. Cholesterol, high-density lipoproteins, and triglycerides were stable, and LDL levels decreased, while vitamin D levels, alongside calcium, perceptibly increased. Albumin also increased. All the values were in support of an equilibrium, with no damaging effects. By mass spectrometry analysis, we also found favorable changes in the vitamin D/histamine and homocysteine/methionine ratios, an increase in a new metabolite of unknown formula, and the vitamin D/unknown metabolite ratio. Supplementation of OMWW-OL has no detrimental effects and might imply the beneficial modulation of several biological parameters. Although this is a small pilot study, with limited potency, it preliminarily suggests that the OMWW extract use could be potentially valuable for people at risk of metabolic syndrome. Some of these parameters could also be relevant in supporting healthy ageing and in cancer prevention.

Cytomegalovirus immune responses are associated with lower serum NfL and disability accumulation risk at multiple sclerosis onset

Background: Infection by cytomegalovirus (HCMV) and Epstein–Barr virus (EBV) play a prognostic role in multiple sclerosis (MS). Objectives: To explore whether humoral immune responses to HCMV and EBV at disease onset were associated with changes in serum and cerebrospinal fluid (CSF) levels of inflammatory and neurodegeneration biomarkers. Methods: Ninety-eight MS patients with a median follow-up of 20 years were included in the study. The levels of a panel of nine biomarkers were measured in serum (N = 60) and CSF (N = 61) samples of patients at the time of the first demyelinating event. Results: Immune responses to HCMV inversely correlated with serum neurofilament light chain (sNfL) levels (rho = −0.367; p = 0.039). sNfL levels were reduced in patients with high immune responses to HCMV (p = 0.006). Elevated sNfL levels were associated with higher risk of Expanded Disability Status Scale (EDSS) 3.0 (p = 0.016), 4.0 (p = 0.009) and 6.0 (p = 0.003), and with higher risk of developing secondary progressive MS (p = 0.003) and to receive treatment (p = 0.032). Serum soluble CD21 levels were increased in patients with high immune responses to EBV nuclear antigen 1 (p = 0.020). Conclusions: High immune responses to HCMV are associated with limited disease progression and central nervous system (CNS) injury in MS patients. These findings reinforce the protective role of HCMV infection in MS.

Core-fucose-specific Pholiota squarrosa lectin decreased hepatic inflammatory macrophage infiltration in steatohepatitis mice.

Recent findings in glycobiology revealed direct evidence of the involvement of oligosaccharide changes in human diseases, including liver diseases. Fucosylation describes the attachment of a fucose residue to a glycan or glycolipid. We demonstrated that fucosylated proteins are useful serum biomarkers for nonalcoholic fatty liver disease. Among fucosyltransferases, expression of alpha-1, 6-fucosyltransferase (Fut8), which produces core fucose, is frequently elevated during the progression of human chronic liver diseases. Previously, we discovered core-fucose-specific Pholiota squarrosa lectin (PhoSL) from Japanese mushroom Sugitake. Lectins are bioactive compounds that bind to glycan specifically, and various kinds of lectin have a variety of biological functions. Using high-fat and high-cholesterol (HFHC)-fed steatohepatitic mice, we found that core fucosylation increases in hepatic inflammatory macrophages. Antibody drugs bind to specific antigens and block protein function. We hypothesized that, like antibody drugs, PhoSL could have inhibitory effects on glycoproteins involved in steatohepatitis progression. PhoSL administration dramatically decreased hepatic macrophage infiltration and liver fibrosis-related gene expression. Using mouse macrophage-like cell RAW264.7, we found that PhoSL enhanced core-fucose-mediated activation of macrophage cell death by blocking interferon-γ/signal transducer and activator of transcription 1 (STAT1) signaling. Core-fucose-mediated cell death is a mechanism for the anti-inflammatory effects and anti-fibrotic effects of PhoSL on activated macrophages in steatohepatitic liver. In addition, PhoSL provides an anti-fibrotic effect by blocking transforming growth factor-β/SMAD family member 3 signaling in hepatic stellate cells. In conclusion, we found core-fucose-specific PhoSL administration could suppress steatohepatitis progression by decreasing inflammatory macrophage infiltration and fibrotic signaling in hepatic stellate cells.

Serum neutrophil gelatinase-associated lipocalin and cystatin C is associated with blood pressure in ex-preterm children and adolescents.

As preterm birth is a risk factor for hypertension (HTN), biomarkers for early prediction of HTN in childhood is an emerging need. The aims of the study were to evaluate serum biomarkers in ex-preterm children and examine for associations with office peripheral and central SBP (cSBP), ambulatory BP parameters and pulse wave velocity (PWV). This case-control study included children and adolescents born prematurely (ex-preterms) and at full term (controls). All participants underwent office and ambulatory BP monitoring, assessment of cSBP, PWV and serum biomarkers at the same visit. Neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-2, metalloproteinase-9 (MMP-2, MMP-9) and Cystatin C (CysC) were measured using ELISA. The study population included 52 ex-preterm individuals and 26 controls. Mean age was 10.7 ± 3.6 years. NGAL, MMP-2, MMP-9, and CysC levels were similar between the ex-preterm and the control group. In the ex-preterm group, NGAL is associated with office SBP z score (β = 1.007, 95% CI 1.001-0.014, P = 0.049), CysC with office DBP z score (β = 1.003, 95% CI 1.001-0.005, P = 0.018) and cSBP z score (β = 1.003, 95% CI 1.001-0.005, P = 0.006) independently of age, sex and BMI z score. Among ex-preterm children and adolescents 17% had ambulatory HTN and 31% had white-coat HTN. NGAL levels were higher in ex-preterm children with WCH compared with children with normal BP [57.9 (IQR 50.8) versus 34.6 (IQR 46.2)], P = 0.018]. WCH is common in ex-preterm children and adolescents and is associated with higher NGAL levels and CysC presents positive association with cSBP. The findings in this study provides preliminary evidence that NGAL and CysC may have a role in predicting the risk of developing hypertension later in life. Further studies are warranted.

Metabolomics Unveils Disrupted Pathways in Parkinson's Disease: Toward Biomarker-Based Diagnosis.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by diverse symptoms, where accurate diagnosis remains challenging. Traditional clinical observation methods often result in misdiagnosis, highlighting the need for biomarker-based diagnostic approaches. This study utilizes ultraperformance liquid chromatography coupled to an electrospray ionization source and quadrupole time-of-flight untargeted metabolomics combined with biochemometrics to identify novel serum biomarkers for PD. Analyzing a Brazilian cohort of serum samples from 39 PD patients and 15 healthy controls, we identified 15 metabolites significantly associated with PD, with 11 reported as potential biomarkers for the first time. Key disrupted metabolic pathways include caffeine metabolism, arachidonic acid metabolism, and primary bile acid biosynthesis. Our machine learning model demonstrated high accuracy, with the Rotation Forest boosting model achieving 94.1% accuracy in distinguishing PD patients from controls. It is based on three new PD biomarkers (downregulated: 1-lyso-2-arachidonoyl-phosphatidate and hypoxanthine and upregulated: ferulic acid) and surpasses the general 80% diagnostic accuracy obtained from initial clinical evaluations conducted by specialists. Besides, this machine learning model based on a decision tree allowed for visual and easy interpretability of affected metabolites in PD patients. These findings could improve the detection and monitoring of PD, paving the way for more precise diagnostics and therapeutic interventions. Our research emphasizes the critical role of metabolomics and machine learning in advancing our understanding of the chemical profile of neurodegenerative diseases.

Heart-type fatty acid binding protein (H-FABP) as an early biomarker in sepsis-induced cardiomyopathy: a prospective observational study

BackgroundSepsis-induced cardiomyopathy (SICM) is a common and life-threatening complication of sepsis, significantly contributing to elevated mortality. This study aimed to identify crucial indicators for the prompt and early assessment of SICM.MethodsPatients diagnosed with sepsis or SICM within 24 h of intensive care unit (ICU) admission were enrolled in this prospective observational study. Patients were assigned to the training set, validation set and external test set. The primary endpoint was 7-day ICU mortality, and the secondary endpoint was 28-day ICU mortality. Three machine learning algorithms were utilized to identify relevant indicators for diagnosing SICM, incorporating 64 indicators including serum biomarkers associated with cardiac, renal, and liver function, lipid metabolism, coagulation, and inflammation. Internal and external validations were performed on the screening results. Patients were then stratified based on the cut-off value of the most diagnostically effective biomarker identified, and their prognostic outcomes were observed and analyzed.ResultsA total of 270 patients were included in the training and validation set, and 52 patients were included in the external test set. Age, sex, and comorbidities did not significantly differ between the sepsis and SICM groups (P > 0.05). The support vector machine (SVM) algorithm identified six indicators with an accuracy of 84.5%, the random forest (RF) algorithm identified six indicators with an accuracy of 81.9%, and the logistic regression (LR) algorithm screened out seven indicators. Following rigorous selection, a diagnostic model for sepsis-induced cardiomyopathy was established based on heart-type fatty acid binding protein (H-FABP) (OR 1.308, 95% CI 1.170–1.462, P < 0.001) and retinol-binding protein (RBP) (OR 1.020, 95% CI 1.006–1.034, P < 0.05). H-FABP alone exhibited the highest diagnostic performance in both the internal (AUROC 0.689, P < 0.05) and external sets (AUROC 0.845, P < 0.05). Patients with SICM were further stratified based on an H-FABP diagnostic cut-off value of 8.335 ng/mL. Kaplan–Meier curve analysis demonstrated that elevated H-FABP levels at admission were associated with higher 7-day ICU mortality in patients with SICM (P < 0.05).ConclusionsThis study revealed that H-FABP concentrations measured within 24 h of patient admission could serve as a crucial biomarker for the early and rapid diagnosis and short-term prognostic evaluation of SICM.

Vascular Cytokines and Atherosclerosis: Differential Serum Levels of TRAIL, IL-18, and OPG in Obstructive Coronary Artery Disease.

The risk-factor-based prediction of atherosclerotic coronary artery disease (CAD) remains suboptimal, particularly in the absence of any of the standard modifiable cardiovascular risk factors (SMuRFs), making the discovery of biomarkers that correlate with atherosclerosis burden critically important. We hypothesized that cytokines and receptors associated with inflammation in CAD-tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), interleukin-18 (IL-18), and osteoprotegerin (OPG)-would be independently associated with CAD. To determine this, we measured the serum biomarker levels of 993 participants from the BioHEART study who had CT coronary angiograms that were scored for severity of stenosis and plaque composition. We found that the quartiles of TRAIL, OPG, and IL-18 were significantly associated with disease scores, and that the IL-18/TRAIL and OPG/TRAIL ratios demonstrated significant differences between no CAD vs. STEMI whereas only the OPG/TRAIL ratio showed differences between no CAD and obstructive CAD (stenosis > 50%). However, these associations did not persist after adjustment for age, sex, SMuRFs, and a family history of CAD. In conclusion, TRAIL, IL-18, and OPG and the derived ratios of IL-18/TRAIL and OPG/TRAIL demonstrate significant associations with raw disease scores and risk factors, but these markers are not discriminatory biomarkers for the prediction of CAD when incorporated into multi-variable risk models.

6'-Sialyllactose Alleviates Muscle Fatigue through Reduced Blood Lactate Level after Treadmill Exercise in Mice.

6'-Sialyllactose (6'-SL), found in human breast milk, exhibits anti-inflammatory, immune function-enhancing, brain development-promoting, and gut health-improving effects. However, its effects on muscle fatigue remain unknown. Here, we aimed to investigate the effects of 6'-SL on blood lactate level, muscle fiber type, and oxidative phosphorylation protein complexes (OXPHOS) in muscle after exercise using C57BL/6J male mice. C57BL/6J mice were randomly assigned to control or 100 mg/kg 6'-SL. After 12 weeks of 6'-SL administration, the mice were made to perform treadmill exercise; their blood lactate and glucose levels were measured at the basal level (rest) and 0, 5, and 10 min after treadmill exercise. Results showed that 6'-SL treatment in C57BL/6J mice significantly reduced blood lactate level and improved blood glucose level. Moreover, 6'-SL increased the expression of slow-myosin heavy chain (MHC) and OXPHOS in gastrocnemius muscle. In addition, 6'-SL treatment for 12 weeks did not affect food intake, serum biomarkers of tissue injury, and lipid profiles compared with those of the controls. These findings indicate that non-toxic 6'-SL suppressed muscle fatigue during exercise by promoting protein expression of muscle fibers, especially slow-twitch muscle fibers characterized by abundant OXPHOS complexes and decreased blood lactate level. This study suggests that 6'-SL holds promise as a nutritional supplement in exercise and clinical settings, subject to further validation.

Unveiling novel serum biomarkers in intrahepatic cholangiocarcinoma: a pilot proteomic exploration.

Recent advancements in proteomics have shown promise in identifying biomarkers for various cancers. Our study is the first to compare the serum proteomes of intrahepatic cholangiocarcinoma (iCCA) with cirrhosis (CIR), primary sclerosing cholangitis (PSC), and hepatocellular carcinoma (HCC), aiming to identify a proteomic signature that can effectively distinguish among these conditions. Utilizing high-throughput mass spectrometry on serum samples, we identified 845 proteins, of which 646 were suitable for further analysis. Unique clustering patterns were observed among the five groups, with significant proteomic differences. Our key findings include: S100 calcium-binding protein A9 (S100A9) and haptoglobin (HP) were more abundant in iCCA, while intercellular adhesion molecule 2 (ICAM2) was higher in HCC. Serum amyloid A1 (SAA1) and A4 (SAA4) emerged as potential biomarkers, with SAA1 significantly different in the iCCA vs healthy controls (HC) comparison, and SAA4 in the HCC vs HC comparison. Elevated levels of vascular cell adhesion molecule 1 (VCAM-1) in HCC suggested its potential as a differentiation and diagnostic marker. Angiopoietin-1 receptor (TEK) also showed discriminatory and diagnostic potential in HCC. ELISA validation corroborated mass spectrometry findings. Our study underscores the potential of proteomic profiling in distinguishing iCCA from other liver conditions and highlights the need for further validation to establish robust diagnostic biomarkers.

Correlation between salivary and serum biomarkers of kidney function in chronic kidney disease patients attending the nephrology clinics at Teaching Hospital Karapitiya, Sri Lanka

The present study was designed to determine the correlation between salivary and serum levels of creatinine and urea in patients with chronic kidney disease (CKD) and to propose the use of saliva as an alternative medium for the analysis of biochemical parameters of kidney function. Accordingly, an analytical cross-sectional study was carried out using 100 CKD patients attending the Nephrology Clinics at Teaching Hospital Karapitiya, Sri Lanka. Saliva and serum samples were collected from the patients for the estimation of creatinine and urea using spectrophotometric assay kits. Of the total, the majority of the patients were found within CKD stage 3 (82%). The salivary and serum concentrations of creatinine varied within the range of 0.20 - 2.10 mg/dL and 1.54 – 11.6 mg/dL, whereas the salivary and serum concentrations of urea varied within the range of 68.04 – 127.59 mg/dL and 60.14 – 168.25 mg/dL respectively within the study population. Significant positive correlations were observed between the salivary and serum concentrations of creatinine (r= 0.985, p=0.01), and urea (r= 0.942, p=0.01), and between salivary concentrations of creatinine and urea (r=0.887, p=0.01). A significant difference was observed in the salivary biomarkers between mild to moderate stages of CKD patients and severe to end-stage CKD patients. No significant association was observed in the salivary markers with the age and sex of the patients. The area under curve values in the receiver operating characteristic analysis was&gt;0.9 (95% CI). These findings revealed high levels of diagnostic accuracy in salivary biomarkers suggesting the potential use of saliva for the assessment of kidney function in CKD patients.

Serum targeted metabolomics uncovering specific amino acid signature for diagnosis of intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (iCCA) is a hepatobiliary malignancy which accounts for approximately 5–10 % of primary liver cancers and has a high mortality rate. The diagnosis of iCCA remains significant challenges owing to the lack of specific and sensitive diagnostic tests available. Hence, improved methods are needed to detect iCCA with high accuracy. In this study, we evaluated the efficacy of serum amino acid profiling combined with machine learning modeling for the diagnosis of iCCA. A comprehensive analysis of 28 circulating amino acids was conducted in a total of 140 blood samples from patients with iCCA and normal individuals. We screened out 6 differentially expressed amino acids with the criteria of |Log2(Fold Change, FC)| > 0.585, P-value < 0.05, variable importance in projection (VIP) > 1.0 and area under the curve (AUC) > 0.8, in which amino acids L-Asparagine and Kynurenine showed an increasing tendency as the disease progressed. Five frequently used machine learning algorithms (Logistic Regression, Random Forest, Supporting Vector Machine, Neural Network and Naïve Bayes) for diagnosis of iCCA based on the 6 circulating amino acids were established and validated with high sensitivity and good overall accuracy. The resulting models were further improved by introducing a clinical indicator, gamma-glutamyl transferase (GGT). This study introduces a new approach for identifying potential serum biomarkers for the diagnosis of iCCA with high accuracy.

Leukocyte cell-derived chemotaxin 2 (LECT2) regulates liver ischemia–reperfusion injury

Background and aimHepatic ischemia–reperfusion injury (IRI) is a significant challenge in liver transplantation, trauma, hypovolemic shock, and hepatectomy, with limited effective interventions available. This study aimed to investigate the role of leukocyte cell-derived chemotaxin 2 (LECT2) in hepatic IRI and assess the therapeutic potential of Lect2-short hairpin RNA (shRNA) delivered through adeno-associated virus (AAV) vectors. Materials and methodsThis study analyzed human liver and serum samples from five patients undergoing the Pringle maneuver. Lect2-knockout and C57BL/6J mice were used. Hepatic IRI was induced by clamping the hepatic pedicle. Treatments included recombinant human LECT2 (rLECT2) and AAV-Lect2-shRNA. LECT2 expression levels and serum biomarkers including alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and blood urea nitrogen (BUN) were measured. Histological analysis of liver necrosis and quantitative reverse-transcription polymerase chain reaction were performed. ResultsSerum and liver LECT2 levels were elevated during hepatic IRI. Serum LECT2 protein and mRNA levels increased post reperfusion. Lect2-knockout mice had reduced weight loss; hepatic necrosis; and serum ALT, AST, creatinine, and BUN levels. rLECT2 treatment exacerbated weight loss, hepatic necrosis, and serum biomarkers (ALT, AST, creatinine, and BUN). AAV-Lect2-shRNA treatment significantly reduced weight loss, hepatic necrosis, and serum biomarkers (ALT, AST, creatinine, and BUN), indicating therapeutic potential. ConclusionsElevated LECT2 levels during hepatic IRI increased liver damage. Genetic knockout or shRNA-mediated knockdown of Lect2 reduced liver damage, indicating its therapeutic potential. AAV-mediated Lect2-shRNA delivery mitigated hepatic IRI, offering a potential new treatment strategy to enhance clinical outcomes for patients undergoing liver-related surgeries or trauma.

Systemic C-Reactive Protein Predicts Cerebral Vasospasm and Delayed Cerebral Ischemia Following Aneurysmal Subarachnoid Hemorrhage: A Retrospective Observational Study

Aneurysmal subarachnoid hemorrhage (aSAH) is often complicated by cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI), which significantly impact patient outcomes. The study aimed to investigate the predictive value of systemic serum biomarker levels for CVS and DCI following aSAH. We retrospectively analyzed data for 450 aSAH patients admitted to University Hospital Düsseldorf between January 2011 and October 2021. Serum biomarkers were measured on admission. The occurrence of CVS and DCI was assessed based on clinical and radiological criteria. Multivariate logistic regression analysis was performed to determine the independent association of serum biomarkers with CVS and DCI. We compared the predictive values of various models using the area under the receiver operating characteristic curve. Of the 450 patients, 126 (28.0%) developed CVS, 123 (27.3%) developed DCI, and 62 (13.8%) developed co-occurring CVS and DCI. Patients with CVS, DCI, or both had significantly higher admission C-reactive protein (CRP) levels than those without these complications (P<0.001). Elevated CRP levels were independently associated with an increased risk of CVS, DCI, and co-occurring CVS and DCI (P<0.05). CRP demonstrated a higher predictive value for CVS (area under the curve [AUC]: 0.811) and co-occurring CVS and DCI (AUC: 0.802) compared to DCI alone (AUC: 0.690). Our findings suggest that admission systemic CRP levels can serve as a more valuable predictor for developing CVS than DCI following aSAH. Incorporating CRP into clinical assessments may aid in risk stratification and early intervention strategies for patients at high risk of these complications.

Differences in Acute Graft-Versus-Host Disease (GVHD) Severity and Its Outcomes Between Black and White Patients

Acute graft-versus-host disease (GVHD) is a significant complication following hematopoietic stem cell transplantation (HCT). Although recent advancements in GVHD prophylaxis have resulted in successful HCT across HLA barriers and expanded access to HCT for racial minorities, less is known about how race affects the severity and outcomes of acute GVHD. This study examines differences in the clinical course of acute GVHD and the prognostic value of GVHD biomarkers for Black and White recipients. We conducted a retrospective analysis of patients in the Mount Sinai Acute GVHD International Consortium (MAGIC) database who underwent HCT between 2014 and 2021 to describe the difference in clinical course of acute GVHD and significance of GVHD biomarkers between Black and White recipients. We used propensity score matching to generate a 1:3 matched cohort of 234 Black patients and 702 White patients with similar baseline characteristics. In the first year after HCT Black patients experienced a higher cumulative incidence of grade III-IV acute GVHD (17% versus 12%, P = 0.050), higher nonrelapse mortality (NRM; 18% versus 12%, P = .009), and lower overall survival that trended toward statistical significance (73% versus 79%, P = .071) compared to White patients. The difference in NRM in the first year was even greater among Black patients who developed GVHD than White patients (24% versus 14%, P = .041). The distribution of low, intermediate, and high MAGIC biomarker scores at the time of treatment was similar across racial groups (P = .847), however, Black patients with high biomarker scores experienced significantly worse NRM than White patients (71% versus 32%, P = .010). Our data indicate that Black patients are at a higher risk of NRM following HCT, primarily from a higher incidence of severe GVHD. Serum biomarkers at treatment initiation can stratify patients for risk of NRM across races, however Black patients with high biomarker scores had a significantly greater NRM risk. These results suggest a need for strategies that mitigate the higher risk for poor GVHD outcomes among Black patients.

Prognostic impact of right atrial strain in systemic lupus erythematosus with pulmonary arterial hypertension.

The aim of this study was to assess right atrial (RA) function, including RA phase strain, via speckle-tracking echocardiography (STE) in a cohort of systemic lupus erythematosus (SLE) patients with pulmonary arterial hypertension (PAH) and in particular to explore the relationship between RA phase strain and the occurrence of cardiovascular events. STE analyses of RA function were evaluated in patients with SLE-PAH and in 33 healthy control subjects. Clinical associations, serum biomarkers, echocardiographic data, survival times, and adverse cardiovascular events were evaluated. A total of 66 patients with SLE-PAH were enrolled; they were divided into two groups based on the occurrence of adverse clinical events. RA phase strain was significantly reduced in patients with events than in patients without events. The endpoint was defined as the combined outcome of all-cause mortality, right heart failure, and rehospitalization due to disease progression. During a mean follow-up of 17.2±9.9 months, 23 patients (35%) reached the endpoint. Compared with patients with RA reservoir strain (RASr) ≥33.45%, patients with RASr<33.45% had more adverse long-term outcomes (log rank p<.0001). RASr was independently associated with adverse clinical outcomes according to multivariate analysis (p=.010). Our data suggest that RA function has prognostic value for SLE-PAH patients, and strain analysis revealed that the worse the RA function is, the worse the prognosis.

Untargeted Metabolomic Analyses of Body Fluids to Differentiate TBI DOC and NTBI DOC.

To investigate the metabolomic differences between Traumatic brain injury (TBI) disorder of consciousness (DOC) patients and non-traumatic brain injury (NTBI) DOC patients by using cerebrospinal fluid (CSF), serum and urine samples beneficial to understand the pathological mechanism differences between the two etiologies, provide potential clues for the subsequent treatment and prognosis, and investigate the metabolome differences and similarities between TBI and NTBI among three different body fluids. In total, 24 TBI DOC subjects and 29 NTBI DOC subjects were enrolled. CSF, serum and urine samples from TBI DOC and NTBI DOC patients were collected and analyzed by performing UPLC-MS. The statistical methods and pathway analyses were applied to discover potential biomarkers and altered metabolic functions. When comparing TBI DOC and NTBI DOC, 36, 31 and 52 differential metabolites were obtained in CSF, serum and urine, respectively. The functional analysis of differential metabolites obtained in CSF, serum and urine were all related to amino acid metabolism. Except for amino acid metabolism, metabolic biomarkers in CSF, serum and urine mainly focus on central function, cognitive function, necrosis and apoptosis and neurological function, respectively. In CSF, the highest AUC was 0.864 (Isoproturon) and 0.816 (Proline betaine). Then, the AUC of NFurfurylformamide in serum was 0.941, while the AUC of Dihydronepetalactone and Doxepin N-oxide glucuronide were 1.0 in urine. CSF, serum and urine metabolomic analyses could differentiate TBI DOC from NTBI DOC and functional analyses showed a metabolic change difference between TBI DOC and NTBI DOC.

High-throughput peptide array analysis and computational techniques for serological profiling of flavivirus infections: Implications for diagnostics and vaccine development.

Arthropod-borne viruses, such as dengue virus (DENV), pose significant global health threats, with DENV alone infecting around 400 million people annually and causing outbreaks beyond endemic regions. This study aimed to enhance serological diagnosis and discover new drugs by identifying immunogenic protein regions of DENV. Utilizing a comprehensive approach, the study focused on peptides capable of distinguishing DENV from other flavivirus infections through serological analyses. Over 200 patients with confirmed arbovirus infection were profiled using high-density pan flavivirus peptide arrays comprising 6253 peptides and the computational method matrix of local coupling energy (MLCE). Twenty-four peptides from nonstructural and structural viral proteins were identified as specifically recognized by individuals with DENV infection. Six peptides were confirmed to distinguish DENV from Zika virus (ZIKV), West Nile virus (WNV), Yellow Fever virus (YFV), Usutu virus (USUV), and Chikungunya virus (CHIKV) infections, as well as healthy controls. Moreover, the combination of two immunogenic peptides emerged as a potential serum biomarker for DENV infection. These peptides, mapping to highly accessible regions on protein structures, show promise for diagnostic and prophylactic strategies against flavivirus infections. The described methodology holds broader applicability in the serodiagnosis of infectious diseases.