Serum Protein Research Articles (Page 1)

Unveiling the immunomodulatory mechanisms of fever-range whole-body hyperthermia in humans: Insights from miRNA and protein mediators.

Liquid biopsy noninvasively characterizes diseases by analyzing biomarker proteins in biofluids, which provide valuable insights into physiological and pathological processes. In this study, we conducted an analysis of the differences between atypical endometrial hyperplasia or endometrial cancer (AH/EC) patients after fertility-sparing treatment with different RNA-Seq-based endometrial receptivity test (rsERT) results ("receptive" versus "pre-receptive"), to investigate the proteomic connections among tissue, serum, and urine samples. Samples of endometrial tissue, serum, and urine from 40 rsERT "pre-receptive" and 10 rsERT "receptive" patients were analyzed for proteomic profiling. We integrated differentially expressed proteins from three sample types to investigate endometrial receptor (ER)-related molecular changes. Our findings indicated that both serum and urine proteomes can serve as indicators of functional changes in endometrial tissue. In serum, proteins associated with cholesterol metabolism, immune response, and coagulation exhibited a differential expression. In urine, proteins related to immune function and metabolic processes demonstrated varying levels of expression. The differentially expressed proteins in both serum and urine were associated with the immune response and metabolism. In conclusion, biofluids serve as a reflection of functional changes in endometrial tissue, which will facilitate a deeper understanding of endometrial receptivity and the discovery of potential clinical biomarkers.

Small extracellular vesicles (sEVs) are lipid nanoparticles secreted from mammalian cells that are involved in the transfer of information or therapeutically effective substances between cells. Although the scope of research on sEVs as biocompatible carriers for drug delivery to diseased tissues and cells is expanding, there is still room for improvement in the efficiency of drug loading on and in sEVs and their subsequent uptake into cells. It is desirable to alleviate the energy barriers associated with the cellular uptake of sEVs and minimize the perturbation of sEVs when loading drugs onto them. In this study, we developed a simple drug-loading system for sEVs using a dimeric curvature-sensing peptide, which enhances sEV accumulation on the cell surface by acting as an adhesive, subsequently inducing endocytic uptake of sEVs through a clathrin-mediated pathway. The dimeric curvature-sensing peptide selectively binds to the sEV surface within 10 min, even in the presence of serum proteins, and functions as a membrane interfactant to reduce the energy barriers for the cellular uptake of sEVs. The cellular uptake of sEVs and the dimeric curvature-sensing peptide under coexisting conditions increased to over 5-fold and 20-fold, respectively, compared with those administered alone. Furthermore, the dimeric curvature-sensing peptide can efficiently load anticancer drugs onto the surface of sEVs, and the system effectively induces apoptosis in two types of cancer cells. Dimeric curvature-sensing peptide is a technique with potential applications in drug delivery.

Significant alterations in biochemical and haematological markers primarily characterise the development of malaria. The objective of this study was to analyse the serum lipid and protein profiles, as well as some haematological markers, in children under the age of five who are infected with the malaria parasite. The study was conducted at the Department of Paediatric, Ahmadu Bello University Teaching Hospital in Zaria, Kaduna state. A cross-sectional study was performed on a sample of 316 children with malaria and 100 children who were seemingly healthy and under the age of five. Among the 316 patients, 50 (15.8%) tested positive for malaria, while 20 samples from persons who appeared to be in good health were examined. Significant reductions (p<0.05) in cholesterol (mean±SD: 0.450±0.026 mmol/L vs. 0.907±0.069 mmol/L), triglycerides (mean±SD: 0.326±0.058 mmol/L vs. 0.461±0.123 mmol/L), and albumin (mean±SD: 5.23±2.82 g/L vs. 2.82±2.18 g/L) were observed in malaria-positive children compared to healthy controls, indicating potential biomarkers for malaria severity.

Immunoprophylactic potential of parasite-derived antigens for controlling Lernaea cyprinacea infection in Ctenopharyngodon idella.

The study was conducted during June, 2024–September, 2024 at College of Veterinary Science & A.H., Durg, Chhattisgarh, India aimed to research the effects of L-ascorbic acid and Zinc oxide nanoparticles supplementation to reduce transport induced stress in birds of Sonali breed. A total of 120, 6–7 weeks birds of sonali breed were divided into four different groups. Birds of group I were loaded in vehicle but not transported whereas Group II, III and IV were transported for a distance of 200km at 35–40kmh-1. Group III and IV birds received treatment of Zinc oxide nanoparticles (ZnONPs)in drinking water at 100µgml-1 and L-ascorbic acid (AA) at 82µgml-1, two days before the transportation. Blood samples were investigated for serum lipid profile and oxidative stress markers. A significant increase (p<0.05) in cortisol level, heterophil to lymphocyte ratio, total serum protein values were reported in birds of following transportation stress. Significant altered (p<0.01) serum lipid profile was recorded in birds of T2 group. The content of MDA in thigh muscle homogenate was significantly decreased (P=0.001) whereas increased antioxidant enzymes were recorded with the treatment of ZnONP and Ascorbic acid. Our results implied that supplementation of antioxidants before transportation of birds could be helpful to reduce stress in birds with improved meat quality attributes.

Introduction: Heart failure (HF) is a complex, heterogeneous disease. Identifying circulating proteins linked to cardiac structure, function, and HF subtypes may reveal new therapeutic targets. Mendelian randomization (MR) using protein quantitative trait loci (pQTL) and cardiac magnetic resonance imaging (cMRI) phenotypes enables systematic evaluation of proteomic influences on cardiac traits and HF subtypes. Methods: We performed proteome-wide univariable MR analyses to investigate potential causal effects of 1,715 serum proteins on eight cMRI traits of left and right ventricular function (LVEF, LVESV, LVEDV, SV, RVEF, RVESV, RVEDV, and RVSV) and four HF subtypes (all-cause HF, non-ischemic cardiomyopathy [NICM], dilated cardiomyopathy [DCM], and hypertrophic cardiomyopathy [HCM]). Genetic instruments were derived from pQTL data in 34,557 UK Biobank participants. Outcome data included cMRI traits (36,041 individuals), HF/NICM (153,174 cases), HCM (5,900 cases) and DCM (9,365 cases). MR was performed using the inverse-variance weighted method. We visualized significant (q < 0.05) associations across traits to highlight differences and overlap, and used a heatmap to depict Pearson correlations of z-score MR estimates across traits. Results: Proteome-wide MR identified 60-112 significant associations per trait. Visualization revealed both distinct and overlapping protein signatures, suggesting pleiotropic influences on cardiac remodeling and HF phenotypes. Trait-trait correlation analysis revealed significant positive correlations between protein effects on NICM and HF (r=0.67, p < 0.05), while protein effects on HCM and DCM displayed an inverse relationship (r=–0.18, p < 0.05), indicating divergent proteomic pathways in these cardiomyopathies. Ventricular volume traits (LVESV, LVEDV, RVEDV, RVESV) were highly intercorrelated (r>0.6), indicating proteomic drivers of ventricular remodeling may be conserved. Pathway analysis of proteins significantly associated with ≥4 traits revealed enrichment in protein processing, immune response, and lipid transport. Proteins associated with ≥6 traits included known and novel markers: SPON1, ABO, CNTN2, ENG, PDCD6, PLA2G2A, TGFBI, TLR1, TPSD1, and VSNL1. Conclusion: This analysis highlights both distinct and shared circulating proteins associated with cardiac structure, function, and HF phenotypes. Further exploration of these proteins and pathways could inform novel therapeutic strategies conserved across HF etiologies.

The study aimed to investigate the acute effects of a single leg press resistance training sessions that differed in training intensity on blood serum proteins using differential scanning calorimetry (DSC), circular dichroism (CD), and fluorescence spectra. Seven men with strength training experience participated in a randomized crossover trial, performing two experimental sessions. Each session included four sets of leg press-to-fall exercises, using loads equivalent to either 30% or 70% of their one-repetition maximum (1RM), with a 3 min rest interval between sets. Aqueous solutions of serum from blood samples taken at baseline (BA) and immediately postexercise (POST) were analyzed. The measurement techniques used allowed to observe postexercise changes in blood serum. Changes were observed in DSC profiles of blood serum, 3D fluorescence maps, and CD spectra. Statistically significant differences between stages "before" and "after" effort have been found for parameters of the endothermic transition associated with the denaturation of serum proteins. The results demonstrate the possibility of monitoring the effect of exercise on serum changes using DSC, CD, and fluorescence.

Introduction: Psychosocial stressors in early pregnancy are associated with a higher risk of adverse pregnancy outcomes (APOs), including hypertensive disorders of pregnancy (HDP), gestational diabetes, and preterm birth. However, the biological pathways underlying these associations are not well delineated. This study aims to investigate proteomic markers that may underlie the association between early pregnancy psychosocial stress and APOs. Methods: Data were from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be, a prospective study conducted from 2010-13. Participants were selected using a case-control design (508 HDP cases and 1081 controls). An aptamer-based assay was used to quantify 6,894 proteins in blood serum collected at the first-trimester study visit. Psychosocial stress during the month preceding the same visit was defined as a score greater than 13 on the 10-item Perceived Stress Scale. We used linear regression, adjusted for age and gestational age, to estimate the associations between stress and proteomic analytes. We then used logistic regression models to estimate the associations of these analytes with APOs. To identify potential biological pathways, we constructed a knowledge graph integrating Human Phenotype Ontology terms and STRING protein-protein interactions. Results: Among 1,589 pregnant participants, the mean (SD) age was 27 (6) years and 42% reported psychosocial stress. Heparan sulfate 6-O-sulfotransferase 3 (HS6ST3) was significantly associated with both stress and APOs after FDR correction. Higher psychosocial stress was associated with lower expression of HS6ST3 (-0.27 [95% CI -0.32, -0.22]). Also, a lower expression in HS6ST3 was associated with higher risk of HDP (aOR 0.72 [0.61, 0.85]), gestational diabetes (aOR 0.59 [0.48, 0.71]), and preterm birth (aOR 0.75 [0.61, 0.92]). Proteomic values were expressed in SD units of log2-transformed SomaScan measurements. A knowledge graph was created, which identified close connections between anxiety (phenotype term closest to stress), APOs, and HS6ST3 with shared biological pathways, including GPC* gene clusters, SHH, LYN, and PTCH1 ( Figure ). Conclusions: Early pregnancy psychosocial stress was significantly associated with lower HS6ST3 expression and increased risk of APOs. Genes known to interact with HS6ST3, which are involved in neuroimmune signaling, placental development, and vascular function, may represent plausible pathways linking psychosocial stress to APOs.

Background: While chronic pathological substrates of sudden cardiac death (SCD) are well-known, the molecular triggers that predispose individuals to fatal arrhythmias that day remain undefined, posing a barrier to near-term prevention. We recently reported the first transcriptome study of human myocardium sampled at autopsy-confirmed SCD to demonstrate upregulation of active fibrosis and selected channel dysregulation as a vulnerable substrate for lethal arrhythmias via candidate gene approach. Here, the study of comprehensive proteomes in autopsy-confirmed SCD samples enables unbiased discovery of novel pro-arrhythmic pathways and biomarkers. Hypothesis: The paired myocardium and circulating blood of autopsy-defined SCDs exhibit distinct proteomes compared to non-cardiac sudden deaths and trauma deaths that reflect their vulnerable myocardial state and its associated circulating biomarkers in the hours to days before SCD. Aims: Define the proteome of coupled myocardial tissue, neat serum, and enriched serum of autopsy-confirmed sudden deaths. Methods: We conducted unbiased, quantitative proteomics via LC-MS on paired LV myocardium and serum samples from 13 arrhythmic SCDs (5 acute MI, 3 CAD, 3 DCM, 2 LVH) vs. 7 non-arrhythmic sudden deaths (occult overdose, myocardial rupture, and traumas) to define the arrhythmic substrate. Results: Comprehensive proteomics resolved 5,979 proteins from myocardial tissue and 6,013 proteins from serum, representing a 3-fold increase in proteome depth vs. previous reports. Among these ~6,000 proteins, 2,088 were upregulated and 662 downregulated in Arrhythmic vs. Non-arrhythmic deaths. Arrhythmic myocardium exhibited 3-fold higher fibrosis-associated proteins (POSTN, LUM, FMOD, COL1A1) and 2-fold lower contraction-related proteins (TNNC1, TNNI3, MYLK3, MYL4). Our novel enrichment method resolved 3,645 proteins otherwise undetectable in the neat fraction (POSTN and COL1A1). Reactome analysis of overlapping differentially expressed proteins in myocardium and enriched serum revealed coordinated upregulation of extracellular matrix remodeling, metabolic dysfunction, and immune response. Conclusion: The proteome of myocardium and serum at SCD reveals systemic and cardiac-specific molecular changes which together may exacerbate existing fibrosis and contribute to electrical instability and acutely vulnerable arrhythmogenic substrate. These findings provide candidate biomarkers for near-term risk assessment of fatal arrhythmias.

Identification of serum protein biomarkers for clear cell renal cell carcinoma using patient-derived xenografts

Sepsis is a syndrome caused by a dysregulated host response to pathogens, representing the leading cause of death from infection. Various murine models of sepsis have shown a time-dependent response based on the time of induction. Mice stimulated with high doses of bacterial lipopolysaccharide (LPS) at the end of the day exhibit a higher mortality rate (~80%) compared with those inoculated in the middle of the night (~30%). In this work, we assessed the differences in serum proteins of septic mice during the day and night. Through this proteomic study, we found significant variations in metabolic pathways, including glucose metabolism, which were associated with a better prognosis. Therefore, we studied the glucose response to LPS during the day and night. In this context, we found an early peak of LPS-induced glucose exclusively at the time of worse prognosis. We also observed a hypoglycemic response to LPS, which was independent of the time of sepsis induction. Finally, we performed a set of metabolic manipulations to study how hyperglycemia influences sepsis severity in mice. We observed that suppressing the glucose peak during the day, through metformin administration, reduced sepsis severity. In contrast, nocturnal glucose administration with LPS was rapidly metabolized and also decreased sepsis severity. In conclusion, sepsis severity may be influenced by the metabolic state at the time of the stimulus. Metabolic rhythms could lead to differences in early glucose management, affecting the outcome of this pathology.

Elucidating the binding mechanism between macluraxanthone and bovine serum albumin: multi-spectroscopic, computational, and biological insights.

Impact of diverse sleep characteristics on long-term skeletal muscle loss: A cohort study.

Interaction between airway inflammation and gut microbiota dysbiosis caused by high temperatures (40°C) and traffic-PM2.5 in mouse model.

Effects of Saccharomyces cerevisiae fermentation product (SCFP) and phytogenic feed additive as alternatives to antibiotic growth promoters on pathogen mitigation, immunomodulation and production performance in commercial broiler chickens.

ABSTRACTHepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) insertion constitutes a frequent and severe complication. However, there is a lack of robust predictive biomarkers for post‐TIPS HE, so far. This study evaluated the usefulness of neurofilament light chains (NfL) and glial fibrillary acidic protein (GFAP) in serum for predicting post‐TIPS HE. Around 144 patients with cirrhosis from three centers were prospectively included and monitored for the occurrence of post‐TIPS overt HE, liver transplantation, and death. Serum NfL and GFAP were evaluated before TIPS insertion using the single molecule array technology. In a subgroup of patients sequential NfL and GFAP levels were assessed at 30‐ and 180‐days post‐TIPS. While higher NfL levels (sHR 1.01, p = 0.036) were independently associated with post‐TIPS OHE after adjusting for other risk factors, GFAP levels had no predictive ability. Consistently, only elevated NfL levels were associated with a higher risk of death/liver transplantation in multivariable analyses. Sequential measurements of NfL at 30 and 180 days after TIPS revealed that NfL levels remain constant until Day 30 followed by a decrease at day 180. Notably, GFAP levels did not change over time. Thus, NfL could be a valuable biomarker for identifying high‐risk patients for post‐TIPS HE.

Genetic Associations with Placental and Pregnancy Proteins in Maternal Serum Identify Biomarkers for Hypertension in Pregnancy.

A rapid screening method for detection of ampicillin residues in dairy milk.

Osteochondral allograft transplantation (OCAT) is safe and effective for the treatment of large articular defects in the knee. Yet, there are no quantitative methods for predicting OCAT outcomes. This study was designed to analyze serum and urine biomarkers collected prior to OCAT to determine their capabilities for predicting outcomes with respect to functional graft survival. Prospectively collected data for patients undergoing primary multisurface knee OCAT, enrolled in an outcomes registry, were analyzed for graft survival. Blood and urine samples were collected prior to surgery for biomarker analyses. Biomarker concentrations were analyzed for the capability to predict OCAT failures (revision or arthroplasty) that occurred within the first 2 years. Fifty consecutive patients were included for analysis; the 2-year graft survival (success) rate was 80%. In samples obtained prior to OCAT, concentrations of serum hyaluronan (HA) and urine cross-linked C-telopeptide of type II collagen (CTX-II) were significantly higher for failure patients. A urinary biomarker panel containing cross-linked C-telopeptide of type I collagen (CTX-I), CTX-II, HA, IL-8, MMP-2, MMP-3, MMP-13, osteoprotegrin (OPG), and osteopontin (OPN) was able to predict the likelihood of treatment failure with an area under the curve (AUC) of 0.895, sensitivity of 85.3%, and specificity of 93.8%. Preoperative concentrations of urine CTX-II and urine MMP-3 were significantly associated with a higher risk for OCAT treatment failure. Serum and urine protein biomarkers analyzed prior to surgery have the potential to predict functional graft survival at 2 years following complex multisurface OCAT surgery in the knee. With further validation, these biomarkers may be useful as a component of the shared decision-making process for patients and health care teams to evaluate this treatment option. Level of Evidence 2, prospective cohort study.